bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association study between polymorphims in GAS6-TAM genes and carotid atherosclerosis
Authors: Hurtado Begoña , Abasolo Nerea , Muñoz Xavier , García Nadia , Benavente Yolanda , Rubio Francisco , de Frutos Pablo García , Krupinski Jerzy , Sala Núria 
Published: July 2010

SummaryCarotid atherosclerosis (CA) is one of the most common causes of stroke, and recent studies suggest that pathways initiated by the interaction of the plasma vitamin K-dependent protein GAS6 with the tyrosine kinase receptors TYRO3, AXL and MERTK (TAM) may have a relevant role in atherogenesis. Furthermore, our previous studies indicated an association between GAS6 and stroke. The aim of this study was to analyse the genetic association between SNPs and haplotypes in GAS6-TAM genes and CA. We performed a case-control study with 233 CA patients confirmed by nuclear magnetic resonance angiography and 202 patients who suffered from cardioembolic (non atherogenic) stroke. For all included subjects information on established risk factors was available. Genotyping of 16 selected tagSNPs was performed by real-time PCR, using either FRET or TaqMan probes. Adjusted logistic regression (LR) analyses indicated that rs2289743 in TYRO3 and rs869016 in MERTK were associated to CA, decreasing its risk (OR [95%CI]=0.39 [0.16–0.94] and OR [95%CI]=0.31 [0.14–0.69], respectively). Linkage disequilibrium results were consistent with the haplotype blocks described in HapMap and adjusted LR analyses revealed that the haplotype ACAA in MERTK, containing the minor allele of the associated SNP, was also associated to CA. No association was observed with GAS6 and AXL variants, which suggests that CA is not the mechanism underlying the reported association between GAS6 and stroke. The association between TYRO3 and MERTK variants and carotid atherosclerosis found in this study reinforces a physiological role of the GAS6-TAM pathway in atherogenesis.
Differential sensitivity and kinetics of response of different ex vivo tests monitoring functional variability of platelet response to clopidogrel
Authors: Sollier Claire Bal dit , Berge Natacha , Boval Bernadette , Dubar Michel , Drouet Ludovic 
Published: July 2010

SummaryWe previously showed that variability of response to clopidogrel is linked to occupancy of the P2Y12 receptor by clopidogrel active-metabolite, and that maximal platelet aggregation intensity (MAI) measured by light transmission aggregometry (LTA) correlates with occupancy. The present study compared a range of ex vivo platelet tests at various levels of P2Y12 occupancy. After screening with clopidogrel 75 mg/day for seven days, subjects were selected to obtain ‘low’, ‘average’ and ‘high’ responders and randomised to clopidogrel (75 mg/day days 1–10; 300 mg day 11), or placebo. Assays were LTA in platelet-rich plasma using 2, 5 and 20 μM ADP, VerifyNow® P2Y12, flow cytometric analysis of platelet activation markers and vasodilator-stimulated phospho-protein (VASP) index, and a thromboelastographic test that is sensitive to clopidogrel. The reference test was P2Y12 receptor occupancy, measured by binding of 33P-2MeS-ADP to platelets. MAI showed the best correlation with P2Y12 occupancy. Similar results were seen with different ADP concentrations and when LTA data were expressed as inhibition of platelet aggregation. A plot of free receptors/cell versus VASP index was biphasic, with poor correlation for low-level P2Y12 occupancy. Sensitivity of the VerifyNow P2Y12 assay decreased at higher clopidogrel responses. Thromboelastography and P-selectin expression had poor correlation with receptor occupancy. In conclusion, LTA data correlate best with P2Y12 occupancy, the gold standard for detecting clopidogrel’s effect at the receptor level. Our results highlight a limitation of the VASP index, which appears unable to distinguish low, average and high responders early after clopidogrel initiation when P2Y12 occupancy is still low.
Factor XIII-A is involved in the regulation of gene expression in alternatively activated human macrophages
Authors: Töröcsik Dániel , Széles Lajos , Paragh György , Rákosy Zsuzsa , Bárdos Helga , Nagy László , Balázs Margit , Inbal Aida , Ádány Róza 
Published: July 2010

SummaryFactor XIII subunit A (FXIII-A) is one of the most overrepresented genes that is expressed during the alternative activation of macrophages. Based on its substrate profile and its cellular localisation, FXIII-A is thought to function as an intracellular/intranuclear transglutaminase. Our aim was to find role for the intracellular FXIII-A by comparing the microarray profiles of alternatively activated monocyte-derived macrophages. Microarray analyses of FXIII-A-deficient patients and healthy controls were evaluated, followed by functional clustering of the differentially expressed genes. After a 48-hour differentiation in the presence of interleukin 4 (IL4), 1,017 probes out of the 24,398 expressed in macrophages from FXIII-A- deficient samples were IL4 sensitive, while only 596 probes were IL4 sensitive in wild-type samples. Of these genes, 307 were induced in both the deficient and the wild-type macrophages. Our results revealed that FXIII-A has important role(s) in mediating gene expression changes in macrophages during alternative activation. Functional clustering of the target genes carried out using Cytoscape/BiNGO and Ingenuity Pathways Analysis programs showed that, in the absence of FXIII-A, the most prominent differences are related to immune functions and to wound response. Our findings suggest that functional impairment of macrophages at the level of gene expression regulation plays a role in the wound healing defects of FXIII-A-deficient patients.
Phosphate and vascular calcification: Emerging role of the sodium-dependent phosphate co-transporter PiT-1
Authors: Lau Wei Ling , Festing Maria , Giachelli Cecilia 
Published: July 2010

SummaryElevated serum phosphate is a risk factor for vascular calcification and cardiovascular events in kidney disease as well as in the general population. Elevated phosphate levels drive vascular calcification, in part, by regulating vascular smooth muscle cell (VSMC) gene expression, function, and fate. The type III sodium-dependent phosphate co-transporter, PiT-1, is necessary for phosphate-induced VSMC osteochondrogenic phenotype change and calcification, and has recently been shown to have unexpected functions in cell proliferation and embryonic development.
Differential effects of TAK-442, a novel orally active direct factor Xa inhibitor, and ximelagatran, a thrombin inhibitor, on factor V-mediated feedback on coagulation cascade and bleeding
Authors: Konishi Noriko , Hiroe Katsuhiko , Kawamura Masaki 
Published: July 2010

SummaryThrombin amplifies the blood coagulation via factor V (FV)-mediated positive feedback loop. We hypothesised that factor Xa (FXa) inhibitors would interfere more gradually with this feedback activation loop than thrombin inhibitors, thereby achieving a better balance between haemostasis and prevention of thrombosis. In this study, we compared the effects of TAK-442, a novel FXa inhibitor, versus ximelagatran, a thrombin inhibitor, on FV-mediated positive feedback, venous thrombosis and bleeding. In normal plasma, TAK-442 delayed the onset of tissue factor-induced thrombin generation and prolonged prothrombin time (PT) with more gradual concentration-response curve than melagatran, the active form of ximelagatran. The effect of melagatran on the onset of thrombin generation decreased in an FVa-concentration-dependent manner in FV-deficient plasma supplemented with FVa. Furthermore, in FV-deficient plasma, the PT-prolonging potency of melagatran was markedly increased with a change in its concentration-response curve from steep to gradual. In the rat venous thrombosis model, TAK-442 (10 mg/kg, p.o.) prevented thrombus formation by 55% with 1.2 times prolongation of PT; a similar effect was observed in ximelagatran-treated (3 mg/kg, p.o.) rats. TAK-442 at 100 mg/kg prolonged PT by only 2.1 times with no change in bleeding time (BT), whereas ximelagatran at 10 mg/kg prolonged PT by 3.9 times and significantly increased BT. These results suggest that the differential effects of the two agents on FV-mediated amplification of thrombin generation may underlie the observation of a wider therapeutic window for TAK-442 than for ximelagatran.
Shear stress regulates inflammatory and thrombogenic gene transcripts in cultured human endothelial progenitor cells
Authors: Lund Trine , Hermansen Stig , Andreasen Thomas , Olsen Jan , Østerud Bjarne , Myrmel Truls , Ytrehus Kirsti 
Published: July 2010

SummaryShear stress has an established effect on mature endothelial cells, but less is known about how shear stress regulates endothelial progenitor cells (EPCs). In vitro expanded EPCs isolated from adult human blood represent a novel tool in regenerative vessel therapy. However, in vitro culturing may generate cells with unfavourable properties. The aim of the present study was therefore to assess whether shear stress may influence the inflammatory and thrombotic phenotype of in vitro expanded EPCs. In late outgrowth EPCs, 6 hours of shear stress (6.0 dynes/ cm2) significantly reduced the mRNA levels of IL-8, COX2, and tissue factor (TF) compared to static controls. This was associated with a reduced TF activity. In contrast, mRNA expression of NOS3 was significantly increased following 6 and 24 hours of shear stress. In accordance with this, NOS3 protein expression was increased following 24 hours of shear stress. Overall stimulation with the proinflammatory mediator, TNFα, for the final 2 hours increased the mRNA expression of IL-6, IL-8, MCP-1, ICAM1, and TF. However exposure to 6 hours of shear stress significantly suppressed the inductory potential of TNFα to increase the mRNA levels of IL-6, IL-8, COX2, and TF. Additionally, TNFα increased TF activity approximately 10 times, an effect that was also significantly reduced by exposure to 6 and 24 hours of shear stress. The effect of shear on the gene levels of TF and NOS3 were not blocked by the NOS inhibitor L-NAME. These observations suggest that EPCs are capable of functionally responding to shear stress.
A splice variant of ADAMTS13 is expressed in human hepatic stellate cells and cancerous tissues
Authors: Hunt Ryan , Hershko Klilah , Pommier Elie , Geetha S. , Blaisdell Adam , Marple Andrew , Roma Isabella , Newell Jordan , Allen Courtni , Friedman Scott , Shomron Noam , Hamasaki-Katagiri Nobuko , Kimchi-Sarfaty Chava 
Published: July 2010

SummaryAlthough ADAMTS13, the von Willebrand factor (VWF)-cleaving protease, is expressed in a range of tissues, the physiological significance of tissue-specific ADAMTS13 alternative splicing isoforms have yet to be clarified. Screening a panel of human tissues and cell lines revealed a spliced ADAMTS13 transcript in hepatic stellate cells and a hepatoma cell line that retains the 25th intron. A nonsense codon within the intron truncates the protease, which gains 64 novel amino acids in lieu of both CUB domains. This isoform, while retaining VWF-cleaving capability, accumulates intracellularly and its biological inaccessibility may prevent its participation in regulating haemostasis and other physiologic functions.
The effect of ethanol and its metabolism on fibrinolysis
Authors: Vorster Hester , Jerling Johann , Venter Christine , Kotze Retha , Bornman Elsabe , Malfliet Joyce , Rijken Dingeman , Pieters Marlien 
Published: July 2010

SummaryThe role of ethanol metabolism in possible haemostatic cardioprotective effects has not yet been determined. To this end, we investigated the effect of a moderate dose of ethanol (35 g) and its metabolism, on haemostatic variables over 14 hours (h). Eighteen Caucasian males participated in a placebo-controlled, randomised, cross-over study. Blood was collected prior to alcohol consumption, and at 10 time points for 14 h. Blood ethanol peaked at 1 h and was cleared after 8 h following ethanol consumption, significantly increasing plasma acetate (p=0.0028). Ethanol did not influence the coagulation factors significantly. PAI-1act increased (p<0.0001) and tPAact (p=0.047) decreased following alcohol consumption, reaching maximum (0.69 to 22.2 IU/ml) and minimum (0.88 to 0.33 IU/ml) levels at 5 h, respectively. Significantly increased plasma clot lysis times (46.8 to 67.6 minutes) and reduced global fibrinolytic capacity of whole blood, measured as D-dimer production during incubation of blood clots (2.26 to 0.29 μg/ml), were found at 5 h. Except for PAI-1act (borderline significance; p=0.05), there was no significant difference in the fibrinolytic markers between the two groups the following morning. Moderate ethanol consumption resulted in a significant temporary fibrinolysis inhibition. Any protective effects of moderate ethanol consumption on cardiovascular disease do not appear to be due to improvement in fibrinolytic potential within the first 14 h following consumption. The use of global fibrinolytic assays is recommended for determining the true effect of ethanol on fibrinolysis.
CYP1A1, smoking and venous thromboembolism
Authors: Kong Fan-Cui , Zhang Wei-Juan , Zhu Jin , Zheng Wen-Jie , Wang He-Yao , Wang Chen 
Published: July 2010

SummarySince CYP1A1 enzyme is involved in metabolism of tobacco carcinogens, the CYP1A1 gene may be of relevance to smoking-induced differences in the risks of venous thromboembolism (VTE). We conducted a case-control study to investigate genetic polymorphisms in CYP1A1 that might modify the risk of developing VTE. A total of 425 Chinese patients with VTE and 527 VTE-free control individuals, matched by age and gender, were included in this analysis. The MspI and Ile462Val polymorphisms in CYP1A1 gene were analysed using the Amplification Refractory Mutation System (ARMS) method. The Ile462Val AG variant and combined AG and GG variant was significantly associated with VTE, adjusted for age, gender, weight and contraceptives (OR=1.362, 95%CI 1.026, 1.809, p=0.033; OR=1.420, 95% CI 1.081, 1.865, p=0.012, respectively); The AG and GG combined variant was still significantly associated with VTE when adjusting further for smoking (OR=1.344, 95%CI 1.019,1.772, p=0.036) A more than two-fold increase for VTE was associated with the Ile462Val combined variant of AG+GG (OR of 2.805, 95% CI 1.250, 6.293, p=0.012) in the smokers. Genetic variations of CYP1A1 Ile462Val contribute to susceptibility to smoking-induced VTE in the Chinese populations. A two-fold increase in the risk in the smokers in the patients who carry CYP1A1 Ile462Val variant alleles has demonstrated the importance of gene-environment interactions in the development of this disease.
Clinical decision rule and D-dimer have lower clinical utility to exclude pulmonary embolism in cancer patients
Authors: van Sluis Geerte , Kamphuisen Pieter , Söhne Maaike , Leebeek Frank , Bossuyt Patrick , Büller Harry , Douma Renée 
Published: July 2010

SummaryPatients with malignancy frequently present with clinically suspected pulmonary embolism (PE). However, the safe and efficient combination of a clinical decision rule (CDR) and D-dimer test to rule out PE performs less well in patients with malignancy. We examined potential explanations and analysed whether elevating the D-dimer cut-off could improve the clinical utility. We used data on consecutive patients with suspected PE included in a multicenter management study. The performance of the Wells CDR and the D-dimer test was compared between patients with and without malignancy and multivariable analysis was used to compare the weights of the CDR variables. Furthermore, we combined the CDR (cut-off ≤4) with different D-dimer cut-off levels for the exclusion of PE. Of 3,306 patients with suspected PE, 475 (14%) had cancer. The Wells rule variables were less diagnostic in cancer patients. Increasing the D-dimer cut-off level to 700 μg/l for all ages or using an age-dependent cut-off resulted in an increase in the proportion of patients in whom PE could be excluded from 8.4% to 13% and 12%, respectively. The corresponding false-negative rates were 1.6% (95% confidence interval 0.3–8.7%) and 0.0% (0.0–6.3%). The Wells CDR and D-dimer perform less well in patients with suspected PE if they have cancer. Individual variables in the Wells rule are less diagnostic in cancer patients than in non-cancer patients with suspected PE. A CDR combined with an age-dependent D-dimer cut-off shows a modest improvement of the strategy in cancer patients.
Impact of race and gender on antithrombotic therapy
Authors: Capodanno Davide , Angiolillo Dominick 
Published: July 2010

SummaryLarge randomised trials support the use of a variety of antithrombotic drugs for treatment of atherothrombotic disease processes leading to cardiovascular disease. The heterogeneous case-mix of patients enrolled in these trials, however, hamper the attempt to generalise their findings to subgroups which are not sufficiently represented in the study population, such as women and ethnic minorities. Sex- and race-specific disparities in the clinical presentation, management, and outcomes of coronary artery disease may relate to underlying differences in thrombotic profiles and response to antithrombotic therapies. The present manuscript provides an overview of the currently available data on the epidemiology of coronary artery disease based on gender and race as well as the biological considerations for their differences in thrombosis and haemostasis and effects of antithrombotic therapy.
Relationship between dietary vitamin K intake and the stability of anticoagulation effect in patients taking long-term warfarin
Authors: Kim Kyun Hee , Choi Won Suk , Lee Jang Hoon , Lee Hyejin , Yang Dong Heon , Chae Shung Chull 
Published: July 2010

SummaryLittle study has been performed on the effect of vitamin K intake on the variability of warfarin’s anticoagulant effects over long period of time. We estimated average vitamin K intake in the patients taking warfarin and evaluated its relation with the stability of anticoagulation effect. We estimated average daily vitamin K intake based on a three-day food diary in 66 patients taking warfarin regularly for ≥one year and divided them into three groups of equal number according to vitamin K intake. Stability of anticoagulant effect was compared in these groups using the coefficient of variation (CV) of the prothrombin time expressed in international normalised ratio (INR) and the CV of warfarin doses. Median daily vitamin K intake was 161.3 μg/day (31.3 μg/day – 616.6 μg/day). CVs of both INR and warfarin doses were negatively and independently correlated with dietary vitamin K intake (r=-0.293, p=0.017 and r= –0.350, p=0.004, respectively). CV of INR was significantly different among three groups of vitamin K intake (p<0.05 in ANOVA). High vitamin K intake (>195.7 μg/day) group had lower CV of INR than the low intake (<126.5 μg/day) group (19.2 ± 8.96 % vs. 25.5 ± 8.61 %, p<0.05). CV of warfarin doses was also significantly different among the groups (p<0.05 in Jonckheere-Terpstra test). However, the significance of difference between high and low vitamin intake groups was marginal (p=0.046 in Mann-Whitney test). In conclusion, long-term anticoagulation effect of warfarin is more stable in the patients who take greater than a certain amount of dietary vitamin K.Footnote: The content of this paper was submitted as partial fulfillment of the requirement for the degree of Master of Medical Science (Kim KH) to the Kyungpook National University.
Iodixanol Versus Low-Osmolar Contrast Media for Prevention of Contrast Induced Nephropathy
Authors: From Aaron M. , Al Badarin Firas J. , McDonald Furman S. , Bartholmai Brian J. , Cha Stephen S. , Rihal Charanjit S. 
Published: July 2010

Background—
Contrast-induced nephropathy (CIN) is associated with significant morbidity and mortality. The objective of our meta-analysis was to assess the efficacy of iodixanol compared with low-osmolar contrast media (LOCM) for prevention of CIN.

Methods and Results—

We searched MEDLINE, the Cochrane Central Register of Controlled Trials, and internet sources of cardiology trial results for individual and relevant reviews of randomized, controlled trials, for the terms contrast media, contrast nephropathy, renal failure, iodixanol, Visipaque, and low-osmolar contrast media. All studies reported an incidence rate of CIN for each study group; there was no restriction on the definition of CIN. There were no restrictions on journal type or patient population. Overall, 36 trials were identified for analysis of aggregated summary data on 7166 patients; 3672 patients received iodixanol and 3494 patients received LOCM. Overall, iodixanol showed no statistically significant reduction in CIN incidence below that observed with heterogeneous comparator agents (
P
=0.11). Analysis of patient subgroups revealed that there was a significant benefit of iodixanol when compared with iohexol alone (odds ratio, 0.25; 95% confidence interval, 0.11 to 0.55;
P
<0.001) but not when compared with LOCM other than iohexol or with other ionic dimers or among patients receiving intra-arterial contrast injections or among patients undergoing coronary angiography with or without percutaneous intervention.

Conclusions—
Analysis of aggregated summary data from multiple randomized, controlled trials of iodixanol against diverse LOCMs for heterogeneous procedures and definitions of CIN show an iodixanol-associated reduction that is suggestive but statistically nonsignificant.
Strut Coverage and Vessel Wall Response to a New-Generation Paclitaxel-Eluting Stent With an Ultrathin Biodegradable Abluminal Polymer
Authors: Guagliumi Giulio , Sirbu Vasile , Musumeci Giuseppe , Bezerra Hiram G. , Aprile Alessandro , Kyono Hiroyuki , Fiocca Luigi , Matiashvili Aleksandre , Lortkipanidze Nikoloz , Vassileva Angelina , Popma Jeffrey J. , Allocco Dominic J. , Dawkins Keith D. , Valsecchi Orazio , Costa Marco A. 
Published: July 2010

Background—
Polymer-coated drug-eluting stents are effective in preventing restenosis but have been associated with delayed healing and incomplete strut coverage. It is unknown whether paclitaxel-eluting stents (PES) with minimal biodegradable abluminal coating enhances strut coverage while preventing neointimal hyperplasia. Using optical coherence tomography (OCT) as a primary imaging modality, we assessed the proportion of uncovered struts at 6-month follow-up in PES coated with durable versus ultrathin (<1 μm) biodegradable abluminal polymers.

Methods and Results—

In this pilot trial, 60 patients with de novo lesions (≤25 mm) in native coronary vessels were randomly assigned to receive either TAXUS Liberté PES or JACTAX PES, a Liberté stent with polymer deposited abluminally as microdots (JACTAX HD: 9.2 μg each of polymer and paclitaxel per 16-mm stent; JACTAX LD: 5 μg each). OCT follow-up occurred at 6 months with clinical follow-up through 1 year. The primary end point was percent uncovered struts by OCT. An independent core laboratory blinded to stent assignment analyzed images. The 6-month rate of uncovered struts per patient was 5.3±14.7% for TAXUS Liberté, 7.0±12.2% for JACTAX HD, and 4.6±7.3% for JACTAX LD (
P
=0.81); percent malapposed struts was 1.4±4.4%, 0.8±1.9%, and 1.1±2.8%, respectively (
P
=0.86). Strut-level intimal thickness was 0.20±0.10, 0.22±0.15, and 0.24±0.15 mm (
P
=0.64); percent volume obstruction by OCT was 22.2±12.8, 22.5±16.2, and 25.8±15.2 (
P
=0.69). There were no deaths, Q-wave myocardial infarctions, or stent thromboses through 1 year.

Conclusions—
JACTAX PES with an ultrathin microdot biodegradable abluminal polymer did not result in improved strut coverage at 6 months compared with TAXUS Liberté.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00776204.