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

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.

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

Journal of Medical Microbiology ◽

10.1099/jmm.0.46998-0 ◽

2007 ◽

Vol 56 (6) ◽

pp. 803-808 ◽

Cited By ~ 17

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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Evidence of prolonged disturbances in the haemostatic, hemorheologic and inflammatory profiles in transmural myocardial infarction survivors

Thrombosis and Haemostasis ◽

10.1055/s-0037-1613477 ◽

2003 ◽

Vol 89 (05) ◽

pp. 892-903 ◽

Cited By ~ 13

Author(s):

Carlota Saldanha ◽

José Monteiro ◽

Carlos Perdigão ◽

João Martins eSilva ◽

Luis Sargento

Keyword(s):

Myocardial Infarction ◽

Protein C ◽

Leukocyte Count ◽

Plasma Viscosity ◽

Erythrocyte Aggregation ◽

First Year ◽

Plasminogen Activator Inhibitor 1 ◽

Cross Sectional ◽

Pai 1 ◽

Over Time

SummaryHaemostatic, hemorheologic and inflammatory disturbances have been associated with acute coronary syndromes. Most knowledge is reported in cross sectional studies and are without time dependent evolution of these profiles.The aim of this study was to evaluate, during the first year, the evolution of the haemostatic, hemorheologic and inflammatory profiles determined at hospital discharge in survivors with transmural myocardial infarction (MI).Eighty eight (79 male; 9 female) mean age of 58 ± 11 years, survivors of a transmural MI were prospectively studied at discharge, 6 months and one year after the event. Haemostatic (protein C, antithrombin III and plasminogen activator inhibitor 1), hemorheologic (blood fluidity and components) and inflammatory profiles (polymorphonuclear elastase and leukocyte count) were determined using standard methodology.The results of the study can be summarized as follows: (1) Protein C decreased (p < 0.05) over time while PAI-1 only varied significantly until 6th month. (2) Plasma viscosity and fibrinogen (p < 0.001) decrease over time, while erythrocyte aggregation (p < 0.001) and haematocrit increased. Whole blood viscosity did not vary. (3) Leukocyte decreased (p < 0.001) and elastase did not (4). Those patients with cardiovascular events (n = 7) had higher PAI-1 concentration (p<0.05) and leukocyte count (p < 0.01), at discharge (5) Left ventricle ejection fraction correlated significantly with plasma viscosity (r = 0.35 p < 0.05). The results of this longitudinal study show dynamic modifications of the haemostatic, hemorheologic and inflammatory profiles during the first year of a transmural myocardial infarction. In addition, there are interrelations between them and the clinical profile that could help to explain the clinical evolution of this group of patients.

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Excess Costs and Utilization Associated with Methicillin Resistance for Patients with Staphylococcus aureus Infection

Infection Control and Hospital Epidemiology ◽

10.1086/651094 ◽

2010 ◽

Vol 31 (4) ◽

pp. 365-373 ◽

Cited By ~ 101

Author(s):

Gregory A. Filice ◽

John A. Nyman ◽

Catherine Lexau ◽

Christine H. Lees ◽

Lindsay A. Bockstedt ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Methicillin Resistance ◽

Medical Center ◽

Patient Characteristics ◽

Veterans Affairs ◽

Department Of Veterans Affairs ◽

Accounting Systems ◽

Excess Costs ◽

Mrsa Infection ◽

Mssa Infection

Objective.To determine differences in healthcare costs between cases of methicillin-susceptible Staphylococcus aureus (MSSA) infection and methicillin-resistant S. aureus (MRSA) infection in adults.Design.Retrospective study of all cases of S. aureus infection.Setting.Department of Veterans Affairs hospital and associated clinics.Patients.There were 390 patients with MSSA infections and 335 patients with MRSA infections.Methods.We used medical records, accounting systems, and interviews to identify services rendered and costs for Minneapolis Veterans Affairs Medical Center patients with S. aureus infection with onset during the period from January 1, 2004, through June 30, 2006. We used regression analysis to adjust for patient characteristics.Results.Median 6-month unadjusted costs for patients infected with MRSA were $34,657, compared with $15,923 for patients infected with MSSA. Patients with MRSA infection had more comorbidities than patients with MSSA infection (mean Charlson index 4.3 vs 3.2; P < .001). For patients with Charlson indices of 3 or less, mean adjusted 6-month costs derived from multivariate analysis were $51,252 (95% CI, $46,041–$56,464) for MRSA infection and $30,158 (95% CI, $27,092–$33,225) for MSSA infection. For patients with Charlson indices of 4 or more, mean adjusted costs were $84,436 (95% CI, $79,843–$89,029) for MRSA infection and $59,245 (95% CI, $56,016–$62,473) for MSSA infection. Patients with MRSA infection were also more likely to die than were patients with MSSA infection (23.6% vs 11.5%; P < .001). MRSA infection was more likely to involve the lungs, bloodstream, and urinary tract, while MSSA infection was more likely to involve bones or joints; eyes, ears, nose, or throat; surgical sites; and skin or soft tissue (P < .001).Conclusions.Resistance to methicillin in S. aureus was independently associated with increased costs. Effective antimicrobial stewardship and infection prevention programs are needed to prevent these costly infections.

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Space Time Trends of Community Onset Staphylococcus Aureus Infections in Children Living in Southeastern United States: 2002-2010

10.21203/rs.3.rs-59691/v1 ◽

2020 ◽

Author(s):

Lilly Immergluck ◽

Ruijin Geng ◽

Chaohua Li ◽

Mike Edelson ◽

Lance Waller ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Census Tract ◽

Metropolitan Statistical Area ◽

Infection Group ◽

Census Tracts ◽

Mrsa Infection ◽

Very High ◽

Community Onset ◽

The U.S ◽

Mssa Infection

Abstract Background Staphylococcus aureus (S. aureus) remains a serious cause of infections in the U.S. and worldwide. Non antibiotic resistant Staphylococcus aureus (methicillin susceptible or MSSA) is the cause of half of all health care–associated staphylococcal infections, and methicillin resistant Staphylococcus aureus (MRSA) still is the leading cause of community onset skin and soft tissue infections in the U.S. This is the first study to spatially look at trends of both community onset MRSA and MSSA infections over nine years and determine ‘best’ to ‘worst’ infection trends over a nine year period (2002-2010),which spanned when community onset MRSA infections were occurring in epidemic proportions across the U.S. MethodsRetrospective study from 2002-2010, using electronic health records of children living in the southeastern U.S. (Atlanta, Georgia) with S. aureus infections and relevant U.S. census data (at the census tract level). The Proc Traj for SAS was applied to generate community onset MRSA and MSSA trajectory infection groups (low, high, very high, or deviant trends), and then, mapping of these trajectory groups using census tract boundaries.ResultsFrom community onset MRSA infection trend patterns (low, high, very high), only 0.8% of the census tracts showed a dramatic increase from 2002-2007 and then a gradual decline from 2008 to 2010. From community onset MSSA infection trend patterns (low and high), 85.7% of ‘high infection’ group persisted throughout the nine year period, compared to 14.3% of ‘low infection’ group over this same period. Low community onset MRSA and MSSA trend patterns were seen throughout the 20 counties of Atlanta, Georgia’s metropolitan statistical area, but more often seen in those counties less densley populated. Census tracts reflecting Atlanta’s ‘innercity’ had the highest proportion of the worst infection trend pattern (community onset MRSA-Very High-CO-MSSA-High or community onset MRSA-High-CO-MSSA-High). The deviant trend of community onset MRSA Very High- CO-MSSA Low infection were in census tracts east of downtown Atlanta. Conclusions ‘Trends’ of S. aureus infection patterns, stratified by antibiotic resistance, over geographic areas and time identify communities with higher risks for community onset MRSA infection compared to community onset MSSA infection.

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MRSA Infection and Mortality Rate in California

10.20944/preprints201810.0293.v1 ◽

2018 ◽

Author(s):

Haydar Witwit

Keyword(s):

Staphylococcus Aureus ◽

Mortality Rate ◽

Bacterial Infection ◽

Female Patient ◽

Methicillin Resistant Staphylococcus Aureus ◽

P Value ◽

Mortality Incidence ◽

Mrsa Infection ◽

Males And Females ◽

Mssa Infection

Average of 41,900 patients are diagnosed annually with staphylococcus bacterial infection in California, 24,089 patients have Methicillin-resistant Staphylococcus Aureus (MRSA) and 17,810 patients have Methicillin-Sensitive Staphylococcus (MSSA). This paper demonstrates that there is a difference in mortality rate due to staphylococcus infection between males and females (P-value<0.05, CI 95%). Male patient diagnosed with S. aureus has 1.3 chance of mortality incidence than female patient. In addition, MRSA infection rate is 1.4 times MSSA infection (P-value<0.05, CI 95%), but the gap of infection is decreasing; however, mortality of both infections combined are more than threefold greater compared to three decades ago.

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Dynamic changes of coagulation and fibrinolytic biomarkers in perioperaive arthroplasty patients

Journal of the Pakistan Medical Association ◽

10.47391/jpma.748 ◽

2020 ◽

Author(s):

Cong Wang ◽

Songjie Ji ◽

Zhifang Chen ◽

Zhiwei Liu ◽

Heng Zhou ◽

...

Keyword(s):

Plasminogen Activator ◽

Total Joint Arthroplasty ◽

Protein C ◽

Specific Inhibitor ◽

Joint Arthroplasty ◽

Enzyme Linked Immunosorbent Assay ◽

Endothelial Protein C Receptor ◽

Coagulation Parameters ◽

At Iii ◽

Pai 1

Abstract Objective: To evaluate Coagulation and fibrinolytic parameters after total joint arthroplasty (TJA) and provide evidence for optimization of timing of perioperative anticoagulation medicine. Methods: The prospective study was conducted at the Jishuitan Hospital of Peking University from January to April in 2016, and comprised patients who were scheduled consecutively to undergo primary total knee arthroplasty (TKA) or total hip arthroplasty (THA). Blood samples were obtained at day 1 preoperatively and day1, day 3 postoperatively. Antigenic levels of protein C (PC), endothelial protein C receptor (EPCR), tissue factor pathway inhibitor (TFPI), antithrombin III (AT-III), plasminogen activator inhibitor 1 (PAI-1) and tissue plasminogen activator (tPA) were measured with commercially available enzyme-linked immunosorbent assay kits. Results: Postoperative levels of coagulation parameters TFPI and AT-III were increased compared to preoperative values (118.7±34.6 vs 70.0±20.5 ?g/ml for AT-III, and 26.37±7.91vs 16.68±8.92 ?g/l for TFPI), while postoperative levels of coagulation parameters PC and EPCR were decreased (0.88±0.30 vs 2.03±0.66 ?g/ml for PC, and 100.8±31.0 vs 199.4±57.4 ?g/ml for EPCR). Postoperative levels of fibrinolytic parameter tPA was increased compared to preoperative values (2.87±0.83 vs 2.03±1.03 ?g/l), while its specific inhibitor PAI-1 was decreased (0.88±0.30 vs 2.03±0.66 ?g/l). Conclusion: These results demonstrated the perturbation of the coagulation and fibrinolytic system of patients undergoing TJA. Hypercoagulation and hyperfibrinolysis were observed in postoperative patients, which suggested anticoagulant therapy is effective and necessary. Keywords?Total joint arthroplasty, anticoagulation, fibrinolysis

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

10.21203/rs.3.rs-772089/v1 ◽

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.

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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 ◽

10.1210/en.2010-0323 ◽

2010 ◽

Vol 151 (9) ◽

pp. 4455-4466 ◽

Cited By ~ 37

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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Involvement of p300/CBP and epigenetic histone acetylation in TGF-β1-mediated gene transcription in mesangial cells

AJP Renal Physiology ◽

10.1152/ajprenal.00523.2012 ◽

2013 ◽

Vol 304 (5) ◽

pp. F601-F613 ◽

Cited By ~ 88

Author(s):

Hang Yuan ◽

Marpadga A. Reddy ◽

Guangdong Sun ◽

Linda Lanting ◽

Mei Wang ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Histone Acetylation ◽

Transforming Growth Factor ◽

Mesangial Cells ◽

Mrna Levels ◽

Creb Binding Protein ◽

Diabetic Mice ◽

Plasminogen Activator Inhibitor 1 ◽

Tgf Β1 ◽

Pai 1

Transforming growth factor-β1 (TGF-β1)-induced expression of plasminogen activator inhibitor-1 (PAI-1) and p21 in renal mesangial cells (MCs) plays a major role in glomerulosclerosis and hypertrophy, key events in the pathogenesis of diabetic nephropathy. However, the involvement of histone acetyl transferases (HATs) and histone deacetylases (HDACs) that regulate epigenetic histone lysine acetylation, and their interaction with TGF-β1-responsive transcription factors, are not clear. We evaluated the roles of histone acetylation, specific HATs, and HDACs in TGF-β1-induced gene expression in rat mesangial cells (RMCs) and in glomeruli from diabetic mice. Overexpression of HATs CREB binding protein (CBP) or p300, but not p300/CBP-activating factor, significantly enhanced TGF-β1-induced PAI-1 and p21 mRNA levels as well as transactivation of their promoters in RMCs. Conversely, they were significantly attenuated by HAT domain mutants of CBP and p300 or overexpression of HDAC-1 and HDAC-5. Chromatin immunoprecipitation assays showed that TGF-β1 treatment led to a time-dependent enrichment of histone H3-lysine9/14-acetylation (H3K9/14Ac) and p300/CBP occupancies around Smad and Sp1 binding sites at the PAI-1 and p21 promoters. TGF-β1 also enhanced the interaction of p300 with Smad2/3 and Sp1 and increased Smad2/3 acetylation. High glucose-treated RMCs exhibited increased PAI-1 and p21 levels, and promoter H3K9/14Ac, which were blocked by TGF-β1 antibodies. Furthermore, increased PAI-1 and p21 expression was associated with elevated promoter H3K9/14Ac levels in glomeruli from diabetic mice. Thus TGF-β1-induced PAI-1 and p21 expression involves interaction of p300/CBP with Smads and Sp1, and increased promoter access via p300/CBP-induced H3K9/14Ac. This in turn can augment glomerular dysfunction linked to diabetic nephropathy.

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

Blood ◽

10.1182/blood.v110.11.3952.3952 ◽

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* (<60%) Protein S* (<60%) AT III (<80%) Homocysteine (>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 (>42) ng/ml) APC Resistance (<2.1) VIII:c & VIII:vW (>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)

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