bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of the endothelial plasminogen activator system by fluvastatin
Authors: Dunoyer-Geindre Sylvie , Fish Richard , Kruithof Egbert 
Published: December 2010

SummaryStatins are cholesterol-lowering drugs that exert pleiotropic effects which include changes in the plasminogen activation (PA) system of endothelial cells (EC). It was the objective of this study to investigate the signal transduction pathways by which statins increase the expression of tissue-type PA (t-PA) and decrease PA inhibitor type 1 (PAI-1) in human umbilical vein EC. Fluvastatin treatment increased t-PA expression more than 10-fold and reduced PAI-1 expression up to fivefold. This effect was mimicked by geranylgeranyl transferase inhibition. The role of geranylgeranylated small G-proteins of the Rho family was assessed by adenovirus-mediated expression of dominant negative (DN) RhoA, Cdc42 and Rac1 and by siRNA-mediated suppression of these proteins. DN-Cdc42 and DN-Rac1, as well as siRNA for Cdc42, increased t-PA expression, while DN-RhoA and DN-Rac1 decreased PAI-1 expression. Latrunculin B, an inhibitor of actin polymerisation, in-creased t-PA mRNA and reduced PAI-1 mRNA to the same extent as fluvastatin. Inhibition of p38, as well as p38α or p38β siRNA, reversed the effects of fluvastatin on t-PA expression. Treatment with p38β siRNA partially reversed the effect of fluvastatin on PAI-1, whereas p38α siRNA had no significant effect. Inhibition of jun kinase reduced basal and fluvastatin-induced t-PA expression to the same extent and increased PAI-1. MEK/ERK inhibition had no effect. In human EC, the fluvastatin-induced increase in t-PA is mediated by Cdc42 and, as with t-PA induced by inhibition of actin polymerisation, requires activation of p38MAP kinase. The mechanisms by which fluvastatin treatment reduces PAI-1 are different from those that increase t-PA.
Inhibition of von Willebrand factor by ARC1779 in patients with acute thrombotic thrombocytopenic purpura
Authors: Jilma Bernd , Siller-Matula Jolanta , Gilbert James , Knöbl Paul , Jilma-Stohlawetz Petra , Gorczyca Monika 
Published: December 2010

SummaryThrombotic thrombocytopenic purpura (TTP) can cause severe organ damage due to enhanced platelet aggregation by ultra-large von Wille-brand factor (VWF) multimers. Thus inhibition of VWF by the anti-VWF ARC1779 might potentially be beneficial for TTP patients. This prospective trial tested the safety, pharmacokinetics and pharmacodynamics of the anti-VWF aptamer ARC1779 added to plasma exchange therapy (PEX) in patients with acute TTP. Seven patients received bolus primed continuous i.v. infusions of ARC1779 (1–2 μg/kg/min) in addition to PEX until remission of TTP was induced or for 14 days. Mean steady state ARC1779 plasma concentrations of 9.9 μg/ml reduced VWF activity to 5% (mean baseline activity was 125% in TTP patients compared to a reference plasma). PEX reduced ARC1779 levels by 50%, but steady state concentrations were restored rapidly with a mini-bolus. After discontinuation of PEX, ARC1779 alone further increased platelet counts in one patient. Stopping ARC1779 was associated with an immediate drop of platelet counts in this patient. This suggests that ARC1779 can block the progression of TTP in patients with severe ADAMTS13 is deficiency. ARC1779 was generally well tolerated without any signs of bleeding. Pharmacokinetics and pharmacodynamics of ARC1779 were well predictable and in agreement with those observed in a previous trial with healthy volunteers. Based on its mechanism of action and the observed effect on platelet counts, ARC1779 used as an adjunctive to PEX may help accelerate recovery from organ dysfunction.
Degradation of the endothelial glycocalyx is associated with chylomicron leakage in mouse cremaster muscle microcirculation
Authors: Constantinescu Alina , Spaan Jos , Arkenbout E. Karin , Vink Hans , VanTeeffelen Jurgen 
Published: December 2010

SummaryA thick endothelial glycocalyx contributes to the barrier function of vascular endothelium in macro- and microcirculation. We hypothesised in the current study that diet-induced hyperlipidaemia perturbs the glycocalyx, resulting in decreased dimensions of this layer and increased transendothelial lipoprotein leakage in capillaries. Glycocalyx thickness was measured in mouse cremaster muscle capillaries by intravital microscopy from the distance between flowing red blood cells and the endothelial surface. In control C57BL/6 mice on standard chow, glycocalyx thickness measured 0.58 ± 0.01 (mean ± SEM) μm, and no lipo-proteins were observed in the tissue. After three months administration of an either mild or severe high-fat / high-cholesterol diet (HFC) to C57BL/6 and ApoE3-Leiden mice, circulating large lipoproteins appeared into the subendothelial space in an increasing proportion of cre-master capillaries, and these capillaries displayed reduced glycocalyx dimensions of 0.40 ± 0.02 and 0.30 ± 0.01 μm (C57BL/6 mice), and 0.37 ± 0.01 and 0.28 ± 0.01 μm (ApoE3-Leiden mice), after the mild and severe HFC diet, respectively. The chylomicron nature of the accumulated lipoproteins was confirmed by observations of subendothelial deposition of DiI-labeled chylomicrons in capillaries after inducing acute glycocalyx degradation by heparitinase in normolipidaemic C57BL/6 mice. It is concluded that while under control conditions the endothelial glycocalyx contributes to the vascular barrier against transvascular lipoprotein leakage in the microcirculation, diet-induced hyperlipidaemia reduces the thickness of the glycocalyx, thereby facilitating leakage of chylomicrons across the capillary wall.
Pre-analytical and analytical issues in the analysis of blood microparticles
Authors: Yuana Yuana , Bertina Rogier , Osanto Susanne 
Published: December 2010

SummaryResults of plasma microparticles (MPs) measurements reported in the literature vary widely. This is clearly not only related to the lack of well-standardised MP assays, but also to variations in pre-analytical conditions. In this review we will discuss the pre-analytical variables related to plasma and MP preparation which may affect MP analysis. Additionally we will address several analytical issues in commonly used MP as-says and briefly discuss some novel approaches for the detection and characterisation of MPs. Ideally MP measurements should be performed in plasma, freshly prepared directly after blood withdrawal. As platelet contamination seems to be one of the major pre-analytical problems in processing plasma for MP measurement, the use of platelet-free plasma may be preferred. When frozen-thawed plasma is used, especially PMP and annexinV-positive MP counts should be interpreted with caution. When flow cytometry is chosen as a method for quantifi-cation of MPs, some analytical conditions should be standardised, e.g. settings of the flow cytometer, quality of the antibodies, and use of counting beads. Fluorescence-nanoparticle tracking analysis and atomic force microscopy can accurately count nanosized MPs, but unfortunately the operational procedures of both methods are still time consuming and they give no information on the functional properties of MPs. The MP-TF activity assay provides information on MPs carrying active TF, regardless of their parental origin. Ultimately, standardisation of pre-analytical procedures and the introduction of reliable and rapid methods for the measurement of MPs are urgently needed to facilitate their use as biomarker in the pathophysiology of diseases.
Association between γ′ fibrinogen levels and inflammation
Authors: Alexander Kristine , Madden Theresa , Farrell David 
Published: December 2010

SummaryThe γ’ fibrinogen isoform produces clots that are stiffer and more resistant to breakdown than the more common fibrinogen isoform, γA. Increased levels of γ’ fibrinogen are associated with several forms of cardiovascular disease. The purpose of this cross-sectional study was to investigate the relationship between γ’ fibrinogen, an emerging risk factor for cardiovascular disease, and inflammatory markers in subjects with a chronic inflammatory state. The 284 subjects for this study came from the Periodontitis And Vascular Events (PAVE) study, and γ’ fibrinogen and total fibrinogen in plasma were measured by ELISA. Information on patient demographics and health status, as well as levels of C-reactive protein (CRP), an inflammatory marker, have previously been collected for this study. The mean (SE) γ’ fibrinogen level in the subjects was 0.622 (0.017) mg/ml. Levels of γ’ fibrinogen were correlated with CRP (p = 0.006), with a one unit increase in CRP associated with a 1.9% increase in γ’ fibrinogen, after adjustment for potential confounders. Total fibrinogen was not correlated with γ’ fibrinogen in these subjects. The number of dental sites with evidence of tissue inflammation was also significantly associated with γ’ fibrinogen levels. These results provide an important step in the evolution of γ’ fibrinogen not only as a general risk factor for cardiovascular disease, but as a potentially useful biomarker for assessing a patient’s inflammatory state and associated cardiovascular disease risk.
Venous thromboembolism and bleeding after total knee and hip arthroplasty
Authors: Guijarro Ricardo , Montes Julio , Roman Carlos San , Arcelus Juan Ignacio , Barillari Giovanni , Granero Xavier , Monreal Manuel 
Published: December 2010

SummaryThe impact of venous thromboembolism (VTE) and bleeding in patients undergoing major joint surgery has not been thoroughly studied. The Spanish National Discharge Database during the years 2005–2006 was used to assess the frequency and clinical impact of VTE and bleeding after elective total knee (TKA) or hip (THA) arthroplasty. Of 58,037 patients undergoing TKA, 0.18% (95% confidence interval [CI]: 0.15–0.22) were diagnosed with pulmonary embolism (PE), 0.57% (95% CI: 0.51–0.63) with deep-vein thrombosis (DVT), 1.20% (95% CI: 1.12–1.30) had bleeding complications, and 0.09% (95% CI: 0.07–0.12) died. Of 54 patients who died, 20.4% (95% CI: 10.7–35.4) had been diagnosed with PE, 3.70% (95% CI: 0.63–11.7) with DVT, and 13.0% (95% CI: 5.67–25.6) had bled. Of 31,769 patients undergoing elective THA, 0.23% (95% CI: 0.18–0.29) were diagnosed with PE, 0.44% (95% CI: 0.37–0.52) with DVT, 1.21% (95% CI: 1.10–1.34) bled, and 0.16% (95% CI: 0.12–0.21) died. Of 52 patients who died, 13.5% (95% CI: 6.08–24.8) had been diagnosed with PE, and 9.61% (95% CI: 3.52–21.3) had bled. On multivariable analysis, PE (odds ratio [OR]: 157; 95% CI: 75–328), DVT (OR: 6.3; 95% CI: 1.5–27) and bleeding (OR: 8.5; 95% CI: 3.6–20) were independent predictors for death after TKA. After THA, only PE (OR: 65; 95% CI: 26–160) and bleeding (OR: 6.4; 95% CI: 2.3–17) predicted the risk for death. Bleeding, DVT, and PE, arising after TKA were all independent predictors for death. Their increase in risk was, however, substantially higher for PE. After THA, only PE and bleeding independently predicted death.
CC and CXC chemokines are pivotal mediators of cerebral injury in ischaemic stroke
Authors: Viviani Giorgio Luciano , Dallegri Franco , Quercioli Alessandra , Veneselli Edvige , Mach François , Mirabelli-Badenier Marisol , Braunersreuther Vincent , Montecucco Fabrizio 
Published: December 2010

SummaryThe definition of ischaemic stroke has been recently updated as an acute episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischaemia in the presence of a cerebral infarction. This “tissular” definition has highlighted the importance of pathophysiological processes underlying cerebral damage. In particular, post-ischaemic inflammation in the brain and in the blood stream could influence crucial steps of the tissue injury/repair cascade. CC and CXC chemokines orchestrate the inflammatory response in atherosclerotic plaque vulnerability and cerebral infarction. These molecules exert their activities through the binding to selective transmembrane receptors. CC and CXC chemokines modulate crucial processes (such as inflammatory cell recruitment and activation, neuronal survival, neoangio-genesis). On the other hand, CXC chemokines could also modulate stem cell homing, thus favouring tissue repair. Given this evidence, both CC and CXC chemokines could represent promising therapeutic targets in primary and secondary prevention of ischaemic stroke. Only preliminary studies have been performed investigating treatments with selective chemokine agonists/antagonists. In this review, we will update evidence on the role and the potential therapeutic strategies targeting CC and CXC chemokines in the pathophysiology of ischaemic stroke.
Survival Comparison of the Ross Procedure and Mechanical Valve Replacement With Optimal Self-Management Anticoagulation Therapy
Authors: Mokhles M. Mostafa , Körtke Heinrich , Stierle Ulrich , Wagner Otto , Charitos Efstratios I. , Bogers Ad J.J.C. , Gummert Jan , Sievers Hans-Hinrich , Takkenberg Johanna J.M. 
Published: December 2010

Background—
It is suggested that in young adults the Ross procedure results in better late patient survival compared with mechanical prosthesis implantation. We performed a propensity score–matched study that assessed late survival in young adult patients after a Ross procedure versus that after mechanical aortic valve replacement with optimal self-management anticoagulation therapy.

Methods and Results—

We selected 918 Ross patients and 406 mechanical valve patients 18 to 60 years of age without dissection, aneurysm, or mitral valve replacement who survived an elective procedure (1994 to 2008). With the use of propensity score matching, late survival was compared between the 2 groups. Two hundred fifty-three patients with a mechanical valve (mean follow-up, 6.3 years) could be propensity matched to a Ross patient (mean follow-up, 5.1 years). Mean age of the matched cohort was 47.3 years in the Ross procedure group and 48.0 years in the mechanical valve group (
P
=0.17); the ratio of male to female patients was 3.2 in the Ross procedure group and 2.7 in the mechanical valve group (
P
=0.46). Linearized all-cause mortality rate was 0.53% per patient-year in the Ross procedure group compared with 0.30% per patient-year in the mechanical valve group (matched hazard ratio, 1.86; 95% confidence interval, 0.58 to 5.91;
P
=0.32). Late survival was comparable to that of the general German population.

Conclusions—
In comparable patients, there is no late survival difference in the first postoperative decade between the Ross procedure and mechanical aortic valve implantation with optimal anticoagulation self-management. Survival in these selected young adult patients closely resembles that of the general population, possibly as a result of highly specialized anticoagulation self-management, better timing of surgery, and improved patient selection in recent years.
Randomized Comparison of Final Kissing Balloon Dilatation Versus No Final Kissing Balloon Dilatation in Patients With Coronary Bifurcation Lesions Treated With Main Vessel Stenting
Authors: Niemelä Matti , Kervinen Kari , Erglis Andrejs , Holm Niels R. , Maeng Michael , Christiansen Evald H. , Kumsars Indulis , Jegere Sanda , Dombrovskis Andis , Gunnes Pål , Stavnes Sindre , Steigen Terje K. , Trovik Thor , Eskola Markku , Vikman Saila , Romppanen Hannu , Mäkikallio Timo , Hansen Knud N. , Thayssen Per , Åberge Lars , Jensen Lisette O. , Hervold Anders , Airaksinen Juhani , Pietilä Mikko , Frobert Ole , Kellerth Thomas , Ravkilde Jan , Aarøe Jens , Jensen Jan S. , Helqvist Steffen , Sjögren Iwar , James Stefan , Miettinen Heikki , Lassen Jens F. , Thuesen Leif 
Published: December 2010

Background—
It is unknown whether the preferred 1-stent bifurcation stenting approach with stenting of the main vessel (MV) and optional side branch stenting using drug-eluting stents should be finalized by a kissing balloon dilatation (FKBD). Therefore, we compared strategies of MV stenting with and without FKBD.

Methods and Results—

We randomized 477 patients with a bifurcation lesion to FKBD (n=238) or no FKBD (n=239) after MV stenting. The primary end point was major adverse cardiac events: cardiac death, non–procedure-related index lesion myocardial infarction, target lesion revascularization, or stent thrombosis within 6 months. The 6-month major adverse cardiac event rates were 2.1% and 2.5% (
P
=1.00) in the FKBD and no-FKBD groups, respectively. Procedure and fluoroscopy times were longer and more contrast media was needed in the FKBD group than in the no-FKBD group. Three hundred twenty-six patients had a quantitative coronary assessment. At 8 months, the rate of binary (re)stenosis in the entire bifurcation lesion (MV and side branch) was 11.0% versus 17.3% (
P
=0.11), in the MV was 3.1% versus 2.5% (
P
=0.68), and in the side branch was 7.9% versus 15.4% (
P
=0.039) in the FKBD versus no-FKBD groups, respectively. In patients with true bifurcation lesions, the side branch restenosis rate was 7.6% versus 20.0% (
P
=0.024) in the FKBD and no-FKBD groups, respectively.

Conclusions—
MV stenting strategies with and without FKBD were associated with similar clinical outcomes. FKBD reduced angiographic side branch (re)stenosis, especially in patients with true bifurcation lesions. The simple no-FKBD procedures resulted in reduced use of contrast media and shorter procedure and fluoroscopy times. Long-term data on stent thrombosis are needed.

Clinical Trial Registration—

URL:
http://clinicaltrials.gov
. Unique identifier: NCT00914199.
Tropical Plumes over Eastern North Africa as a Source of Rain in the Middle East
Authors: Rubin Shira , Ziv Baruch , Paldor Nathan 
Published: December 2010

Abstract
Tropical plumes (TPs) reflect tropical–extratropical interaction associated with the transport of moisture from the Tropics to extratropical latitudes. They are observed in satellite images as continuous narrow cloud bands ahead of upper-level subtropical troughs at times when the subtropical jet is highly perturbed. Rainstorms usually develop in the exit regions of TPs, so their presence over northern Africa has an impact on the precipitation regime in the southeastern Mediterranean. Based on satellite images and rainfall measurements from Israel, 10 TPs over eastern North Africa between 1988 and 2005 in which considerable rain was recorded were selected. Using the NCEP–NCAR reanalysis data, the structure and evolution of these TPs were characterized and their regional canonical features were identified. A typical TP that occurred in March 1991 is described in detail. The main canonical characteristics are as follows: the TP development is preceded by an incubation period, expressed either as a stationary upper-level trough, persisting 2–6 days, or as two consecutive TP pulses; the preferred location for TP origin is 5°–15°N, 5°W–15°E; the TP is separated from the underlying dry Saharan PBL; the subtropical trough undergoes a phase locking with the lower tropical trough; the cloudiness in the TP-induced rainstorm is mostly stratified with continuous moderate rain, originating from midlevel moisture; and the TP tends to be followed by a midlatitude cyclogenesis over the eastern Mediterranean. This analysis proposes several explanations for the efficiency of the TPs in transporting moisture over a 2000-km distance.
Estimating the Sensitivity of Radiative Impacts of Shallow, Broken Marine Clouds to Boundary Layer Aerosol Size Distribution Parameter Uncertainties for Evaluation of Satellite Retrieval Requirements
Authors: Fridlind Ann M. , Ackerman Andrew S. 
Published: December 2010

Abstract
A proposed objective of the planned Aerosol–Cloud–Ecosystem (ACE) satellite mission is to provide constraints on climate model representation of aerosol effects on clouds by retrieving profiles of aerosol number concentration, effective variance, and effective radius over the 0.1–1-μm radius range under humidified ambient conditions with 500-m vertical resolution and uncertainties of 100%, 50%, and 10%, respectively. Shallow, broken marine clouds provide an example of conditions where boundary layer aerosol properties would be retrieved in clear-sky gaps. To quantify the degree of constraint that proposed retrievals might provide on cloud radiative forcing (CRF) simulated by climate models under such conditions, dry aerosol size distribution parameters are independently varied here in large-eddy simulations of three well-established modeling case studies. Using the rudimentary available aerosol specifications, it is found that relative changes of total dry aerosol properties in simulations can be used as a proxy for relative changes of ambient aerosol properties targeted by ACE retrievals. The sensitivity of simulated daytime shortwave CRF to the proposed uncertainty in retrieved aerosol number concentration is −15 W m−2 in the overcast limit, roughly a factor of 2 smaller than a simple analytic estimate owing primarily to aerosol-induced reductions in simulated liquid water path across this particular set of case studies. The CRF sensitivity to proposed uncertainties in retrieved aerosol effective variance and effective radius is typically far smaller, with no corresponding analytic estimate. Generalization of the results obtained here using only three case studies would require statistical analysis of relevant meteorological and aerosol observations and quantification of observational and model uncertainties and biases.
Model-Inspired Predictors for Model Output Statistics (MOS)*
Authors: Termonia Piet , Deckmyn Alex 
Published: December 2010

Abstract
This article addresses the problem of the choice of the predictors for the multiple linear regression in model output statistics. Rather than devising a selection procedure directly aimed at the minimization of the final scores, it is examined whether taking the model equations as a guidance may render the process more rational. To this end a notion of constant fractional errors is introduced. Experimental evidence is provided that they are approximately present in the model and that their impact is sufficiently linear to be corrected by a linear regression. Of particular interest are the forcing terms in the coupling of the physics parameterization to the dynamics of the model. Because such parameterizations are estimates of subgrid processes, they are expected to represent degrees of freedom that are independent of the resolved-scale model variables. To illustrate the value of this approach, it is shown that the temporal accumulation of sensible and latent heat fluxes and net solar and thermal radiation utilized as predictors add a statistically significant improvement to the 2-m temperature scores.