WorldWideScience

Sample records for willebrand factor activity

  1. Comparison of automated von Willebrand factor activity assays

    DEFF Research Database (Denmark)

    Timm, Annette; Hillarp, Andreas; Philips, Malou

    2015-01-01

    INTRODUCTION: Von Willebrand Disease (VWD) is the most common inherited bleeding disorder. Measurement of von Willebrand factor (VWF) activity in plasma is often based on platelet agglutination stimulated by the ristocetin cofactor activity. Novel assays, based on latex beads with recombinant...

  2. Active Von Willebrand Factor, thrombocytopenia and thrombosis

    NARCIS (Netherlands)

    Hulstein, J.J.J.

    2006-01-01

    Platelets and von Willebrand factor (VWF) are unable to interact in circulation. To induce an interaction, a conversion of VWF to a platelet-binding conformation is required. At higher shear stresses, the first step in thrombus formation is binding of VWF to the subendothelium. This results in

  3. Is the activated partial thromboplastin time suitable to screen for von Willebrand factor deficiencies?

    Science.gov (United States)

    Lippi, Giuseppe; Franchini, Massimo; Poli, Giovanni; Salvagno, Gian Luca; Montagnana, Martina; Guidi, Gian Cesare

    2007-06-01

    The diagnostic approach to von Willebrand factor deficiencies is challenging and requires discretionary use of laboratory resources. Although extensive preoperative testing is not recommended, the activated partial thromboplastin time may be useful, especially in selected categories of patients. To establish the diagnostic sensitivity of this test to identify isolate von Willebrand factor deficiencies, 204 consecutive patients underwent a routine preoperative screening consisting of activated partial thromboplastin time, von Willebrand factor antigen, intrinsic pathway clotting factors activity, lupus anticoagulants and thrombin time. Thirty-seven patients were diagnosed with haemostasis disturbances other than von Willebrand factor deficiencies and were excluded from the evaluation. Isolated von Willebrand factor deficiency was diagnosed in 11 of the remaining 167 patients. A significant correlation was observed between von Willebrand factor antigen and activated partial thromboplastin time. Receiver operating characteristic curve analysis showed an area under the curve of 0.982 (95% confidence interval: 0.972-0.992; P thromboplastin time, sensitivity and specificity were 100 and 85%, respectively, with negative and positive predictive values of 100 and 31%, respectively. These results demonstrate that activated partial thromboplastin time has an excellent diagnostic sensitivity and a satisfactory specificity for identifying isolated von Willebrand factor deficiencies.

  4. Organization of von Willebrand factor on surface-activated platelets.

    Science.gov (United States)

    Escolar, G; White, J G

    1993-12-01

    The distribution and organization of von Willebrand factor (vWF) multimers on platelets after surface activation have not been fully characterized. In the present study, washed human platelets were allowed to interact with Formvar-coated, electron microscope grids for 20 minutes at 37 degrees C and then fixed. After fixation, cells were washed and then incubated with buffer alone, human plasma, human plasma preincubated with ristocetin (1.2 mg/mL), purified human vWF plus ristocetin, or bovine plasma. Macromolecular complexes were revealed by ultrastructural immunocytochemistry employing a polyclonal antibody against vWF and protein A-gold (PAG) as the electron-dense probe. vWF multimers were not present in discoid platelets but appeared on the central zone of dendritic cells and over larger central areas of fully spread platelets. Exposure to human plasma alone did not affect the distribution of electron-dense probes for vWF in central regions of surface-activated cells. Incubation of spread platelets with ristocetin-activated human plasma or bovine plasma resulted in the appearance of randomly dispersed, mottled areas of increased density covering the surface from edge to edge. Exposure to vWF antibody and PAG resulted in specific labeling of the dense areas in a serpentine, linear array. The gold-probe distribution suggested that the vWF multimers were not superimposed and were distributed in a random, irregular manner from edge to edge with label-free, clear areas between them. The results extend previous observations demonstrating that glycoprotein Ib-IX receptors are not spontaneously cleared from the plasma membranes of surface-activated platelets by showing that the receptor function of glycoprotein Ib-IX complex remains unchanged.

  5. Flow-induced elongation of von Willebrand factor precedes tension-dependent activation.

    Science.gov (United States)

    Fu, Hongxia; Jiang, Yan; Yang, Darren; Scheiflinger, Friedrich; Wong, Wesley P; Springer, Timothy A

    2017-08-23

    Von Willebrand factor, an ultralarge concatemeric blood protein, must bind to platelet GPIbα during bleeding to mediate hemostasis, but not in the normal circulation to avoid thrombosis. Von Willebrand factor is proposed to be mechanically activated by flow, but the mechanism remains unclear. Using microfluidics with single-molecule imaging, we simultaneously monitored reversible Von Willebrand factor extension and binding to GPIbα under flow. We show that Von Willebrand factor is activated through a two-step conformational transition: first, elongation from compact to linear form, and subsequently, a tension-dependent local transition to a state with high affinity for GPIbα. High-affinity sites develop only in upstream regions of VWF where tension exceeds ~21 pN and depend upon electrostatic interactions. Re-compaction of Von Willebrand factor is accelerated by intramolecular interactions and increases GPIbα dissociation rate. This mechanism enables VWF to be locally activated by hydrodynamic force in hemorrhage and rapidly deactivated downstream, providing a paradigm for hierarchical mechano-regulation of receptor-ligand binding.Von Willebrand factor (VWF) is a blood protein involved in clotting and is proposed to be activated by flow, but the mechanism is unknown. Here the authors show that VWF is first converted from a compact to linear form by flow, and is subsequently activated to bind GPIbα in a tension-dependent manner.

  6. Differential proteolytic activation of factor VIII-von Willebrand factor complex by thrombin

    Energy Technology Data Exchange (ETDEWEB)

    Hill-Eubanks, D.C.; Parker, C.G.; Lollar, P. (Univ. of Vermont, Burlington (USA))

    1989-09-01

    Blood coagulation factor VIII (fVIII) is a plasma protein that is decreased or absent in hemophilia A. It is isolated as a mixture of heterodimers that contain a variably sized heavy chain and a common light chain. Thrombin catalyzes the activation of fVIII in a reaction that is associated with cleavages in both types of chain. The authors isolated a serine protease from Bothrops jararacussu snake venom that catalyzes thrombin-like heavy-chain cleavage but not light-chain cleavage in porcine fVIII as judged by NaDodSO{sub 4}/PAGE and N-terminal sequence analysis. Using a plasma-free assay of the ability of activated {sup 125}I-fVIII to function as a cofactor in the activation of factor X by factor IXa, they found that fVIII is activated by the venom enzyme. The venom enzyme-activated fVIII was isolated in stable form by cation-exchange HPLC. von Willebrand factor inhibited venom enzyme-activated fVIII but not thrombin-activated fVIII. These results suggest that the binding of fVIII to von Willebrand factor depends on the presence of an intact light chain and that activated fVIII must dissociate from von Willebrand factor to exert its cofactor effect. Thus, proteolytic activation of fVIII-von Willebrand factor complex appears to be differentially regulated by light-chain cleavage to dissociate the complex and heavy-chain cleavage to activate the cofactor function.

  7. Towards improved diagnosis of von Willebrand disease: comparative evaluations of several automated von Willebrand factor antigen and activity assays.

    Science.gov (United States)

    Favaloro, Emmanuel J; Mohammed, Soma

    2014-12-01

    von Willebrand disease (VWD) is reportedly the most common bleeding disorder and arises from deficiency and/or defects of von Willebrand factor (VWF). Laboratory diagnosis and typing has important management implications and requires a wide range of tests, including VWF activity and antigen, and involves differential identification of qualitative vs quantitative defects. We have assessed several VWF antigen and activity assays (collagen binding [VWF:CB], ristocetin cofactor [VWF:RCo] and the new Siemens INNOVANCE assay [VWF:Ac], employing latex particles and gain of function recombinant glycoprotein Ib to facilitate VWF binding and agglutination without need for ristocetin) using different instrumentation, including the new Sysmex CS-5100, with a large sample test set (n=600). We included retrospective plus prospective study designs, and also evaluated desmopressin responsiveness plus differential sensitivity to high molecular weight VWF. VWF:Ag and VWF:RCo results from different methods were respectively largely comparable, although some notable differences were evident, including one high false normal VWF:Ag value (105 U/dL) on a type 3 VWD sample, possibly due to heterophile antibody interference in the latex-based CS-5100 methodology. VWF:Ac was largely comparable to VWF:RCo, but VWF:CB showed discrepant findings to both VWF:RCo and VWF:Ac with some patients, most notably patients with type 2M VWD. (a) VWF:Ag on different platforms are largely interchangeable, as are VWF:RCo on different platforms, except for occasional (some potentially important) differences, and manufacturer recommended methods may otherwise require some assay optimization; (b) VWF:RCo and VWF:Ac are largely interchangeable, except for occasional differences that may also relate to assay design (differing optimizations); (c) VWF:CB provides an additional activity to supplement VWF:RCo or VWF:Ac activity assays, and is not interchangeable with either. Crown Copyright © 2014. Published by

  8. Von Willebrand factor and aging.

    Science.gov (United States)

    Konkle, Barbara A

    2014-09-01

    von Willebrand factor (VWF) plays critical roles in initiating primary hemostasis and extending the half-life of coagulation factor VIII in circulation. VWF levels increase with age and elevated levels are associated with an increased risk of venous thromboembolism and cardiovascular disease (CVD). Patients with von Willebrand disease (VWD) due to a deficiency or dysfunction of VWF may have symptoms that ameliorate with aging or may have exacerbation of their disease. Bleeding sites of particular challenge in the aging patient include gastrointestinal bleeding and hematuria. Some medications used to treat VWD should be used with special precaution in older patients, including desmopressin and VWF-containing factor concentrates. Patients with VWD may have some protection from CVD, but in those patients who develop CVD, management is very challenging, given the role of antiplatelet therapy as the mainstay of treatment. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  9. A comparative evaluation of a new automated assay for von Willebrand factor activity.

    Science.gov (United States)

    Lawrie, A S; Stufano, F; Canciani, M T; Mackie, I J; Machin, S J; Peyvandi, F

    2013-03-01

    The ristocetin cofactor assay (VWF:RCo) is the reference method for assessing von Willebrand factor (VWF) activity in the diagnosis of von Willebrand's Disease (VWD). However, the assay suffers from poor reproducibility and sensitivity at low levels of VWF and is labour intensive. We have undertaken an evaluation of a new immunoturbidimetric VWF activity (VWF:Ac) assay (INNOVANCE(®) VWF Ac. Siemens Healthcare Diagnostics, Marburg, Germany) relative to an established platelet-based VWF:RCo method. Samples from 50 healthy normal subjects, 80 patients with VWD and 50 samples that exhibited 'HIL' (i.e. Haemolysis, Icterus or Lipaemia) were studied. VWF:Ac, VWF:RCo and VWF:Ag were performed on a CS-analyser (Sysmex UK Ltd, Milton Keynes, UK), all reagents were from Siemens Healthcare Diagnostics. The VWF:Ac assay, gave low intra- and inter-assay imprecision (over a 31-day period, n = 200 replicate readings) using commercial normal (Mean 96.2 IU dL(-1), CV < 3.0%) and pathological (Mean 36.1 IU dL(-1), CV < 3.5%) control plasmas. The normal and clinical samples exhibited good correlation between VWF:RCo (range 3-753 IU dL(-1)) and VWF:Ac (rs = 0.97, P < 0.0001), with a mean bias of 5.6 IU dL(-1). Ratios of VWF:Ac and VWF:RCo to VWF:Ag in the VWD samples were comparable, although VWF:Ac had a superior lower level of detection to that of VWF:RCo (3% and 5% respectively). A subset (n = 97) of VWD and HIL samples were analysed for VWF:Ac at two different dilutions to assess the effect on relative potency, no significant difference was observed (P = 0.111). The INNOVANCE(®) VWF Ac assay was shown to be reliable and precise. © 2012 Blackwell Publishing Ltd.

  10. Laboratory Testing for Von Willebrand Factor Multimers.

    Science.gov (United States)

    Oliver, Susan; Lau, Kun Kan Edwin; Chapman, Kent; Favaloro, Emmanuel J

    2017-01-01

    Von Willebrand disease (VWD) is reportedly the most common inherited bleeding disorder and can also arise as an acquired syndrome (AVWS). These disorders develop due to defects and/or deficiency of the plasma protein von Willebrand factor (VWF). Laboratory testing for the VWF-related disorders requires assessment of both VWF level and VWF activity, the latter requiring multiple assays because of the many functions carried out by VWF to help prevent bleeding. As an additional step, an evaluation of VWF structural features by multimer analysis is useful in selective investigations. The current paper therefore describes a protocol for assessment of VWF multimers by gel electrophoresis, thus enabling identification of protein bands that represent differently sized multimers. The sample protocol described in this chapter is the methodology developed by Sebia.

  11. von Willebrand disease phenotype and von Willebrand factor marker genotype in Doberman Pinschers.

    Science.gov (United States)

    Brooks, M B; Erb, H N; Foureman, P A; Ray, K

    2001-03-01

    To define the relationship between clinical expression of a type-1 von Willebrand disease phenotype and genotype at 2 von Willebrand factor marker loci in Doberman Pinschers. 102 client-owned Doberman Pinschers. Dogs were recruited on the basis of plasma von Willebrand factor concentration, clinical history, and pedigree. Blood samples and response to a history questionnaire were obtained for each dog. Plasma von Willebrand factor concentration was measured by use of an ELISA, and genotyping was performed via polymerase chain reaction for 1 intragenic and 1 extragenic von Willebrand factor marker. Amplification product size was determined by use of polyacrylamide gel electrophoresis (intragenic marker) or automated sequence analysis (extragenic marker). Western blots were prepared from a subset of dogs with low plasma von Willebrand factor concentration to evaluate multimer distribution. Strong associations were detected between plasma von Willebrand factor concentration and von Willebrand factor marker genotype. Twenty-five dogs had substantial reduction in plasma von Willebrand factor concentration and multiple hemorrhagic events. All were homozygous for a 157-base-pair intragenic marker allele and homozygous or compound heterozygous for 1 of 4 extragenic marker alleles. These marker genotypes were exclusively detected in dogs with low plasma von Willebrand factor concentration, although some dogs with these genotypes did not have abnormal bleeding. Type-1 von Willebrand disease in Doberman Pinschers is associated with the von Willebrand factor gene locus; however, the expression pattern in this breed appears more complex than that of a simple recessive trait.

  12. Alterations in hemostatic parameters during hemodialysis with dialyzers of different membrane composition and flow design. Platelet activation and factor VIII-related von Willebrand factor during hemodialysis.

    Science.gov (United States)

    Schmitt, G W; Moake, J L; Rudy, C K; Vicks, S L; Hamburger, R J

    1987-09-01

    The effect of dialyzer membrane and design on hemostatic parameters during hemodialysis were evaluated in a prospective controlled study. This study demonstrated that hemodialysis is associated with significant platelet activation and loss, which are influenced by both dialyzer configuration and membrane composition. In addition, use of the cuprophan membrane is associated with greater perturbations of the vascular endothelium, as reflected in changes in factor VIII-related von Willebrand factor and 6-keto-prostaglandin F1 alpha concentrations not seen with the polyacrylonitrile membrane. Of the dialyzers studied, the polyacrylonitrile membrane in a hollow-fiber configuration appears to minimize platelet loss and activation, and to minimize increases in factor VIII-related von Willebrand factor and 6-keto-prostaglandin F1 alpha.

  13. Differential proteolytic activation of factor VIII-von Willebrand factor complex by thrombin.

    OpenAIRE

    Hill-Eubanks, D C; Parker, C G; Lollar, P

    1989-01-01

    Blood coagulation factor VIII (fVIII) is a plasma protein that is decreased or absent in hemophilia A. It is isolated as a mixture of heterodimers that contain a variably sized heavy chain and a common light chain. Thrombin catalyzes the activation of fVIII in a reaction that is associated with cleavages in both types of chain. We isolated a serine protease from Bothrops jararacussu snake venom that catalyzes thrombin-like heavy-chain cleavage but not light-chain cleavage in porcine fVIII as ...

  14. Molecular mechanisms of von Willebrand Factor mechanoregulation

    NARCIS (Netherlands)

    Jakobi, A.J.|info:eu-repo/dai/nl/311489621

    2012-01-01

    Von Willebrand factor (VWF) multimers mediate primary adhesion and aggregation of platelets. The potency to recruit platelets critically depends on the size of VWF multimers, which is regulated by a feedback mechanism involving shear-induced unfolding of the A2 domain in VWF and cleavage by the

  15. Diurnal variation of von Willebrand factor in plasma

    DEFF Research Database (Denmark)

    Timm, Annette; Fahrenkrug, Jan; Jørgensen, Henrik L

    2014-01-01

    BACKGROUND: Quantitation of von Willebrand factor (VWF) in plasma is a central element in assessing von Willebrand disease (VWD). VWF activity is known to vary, which has partly been ascribed to biological and preanalytical variation. However, a possible diurnal expression of VWF has not been...... of light and 9 h of darkness); the plasma concentration of melatonin was used as an internal control to confirm the normal 24-h rhythms of the individual participants. RESULTS: The data, analyzed by rhythmometric statistics, revealed a significant variation (P = 0.02) and total amplitude of 22.6% in VWF...... and VWF and (ii) VWF propeptide and VWF was determined. Taken together, the data suggest changes in release and not in clearance. CONCLUSIONS: Diurnal variation in von Willebrand antigen and activity in plasma represents an important aspect of the biological variation. Standardized time-of-day plasma...

  16. [Structure and function of the factor VIII/von Willebrand factor complex].

    Science.gov (United States)

    Müller, G

    1990-03-01

    In the blood plasma factor VIII is bound to the von Willebrand factor. The primary structure of the two proteins were clarified by gene clonation. Factor VIII descends from a precursor protein with 2,351 amino acids by splitting of 19 amino acid residues and is activated by partial proteolysis. In the blood coagulation factor VIII acts as co-factor for the activation of factor X by factor IX in the presence of phospholipids and Ca++ within the intrinsic coagulation system. The formation of the von Willebrand factor takes place by splitting of 22 and 741 amino acid residues, respectively, from pre-pro-von Willebrand factor via pro-von Willebrand factor. The subunits of the von Willebrand factor consist od 2,050 amino acid residues. In the blood plasma the von Willebrand factor is existing as a mixture of multimeres. Receptors of the von Willebrand factor on the thrombocytic membrane are the glycoproteins GPIb and GPIIb/GPIIIa, by means of which the adhesion of thrombocytes at the subendoethelium of the vascular wall and the aggregation of thrombocytes are mediated.

  17. Subclinical Atherosclerosis in Patients with Rheumatoid Arthritis and Low Cardiovascular Risk: The Role of von Willebrand Factor Activity.

    Science.gov (United States)

    Ristić, Gorica G; Subota, Vesna; Lepić, Toplica; Stanisavljević, Dejana; Glišić, Branislava; Ristić, Arsen D; Petronijević, Milan; Stefanović, Dušan Z

    2015-01-01

    To evaluate association between von Willebrand factor (vWF) activity, inflammation markers, disease activity, and subclinical atherosclerosis in patients with rheumatoid arthritis (RA) and low cardiovascular risk. Above mentioned parameters were determined in blood samples of 74 non-diabetic, normotensive, female subjects, with no dyslipidemia(42 patients, 32 matched healthy controls, age 45.3±10.0 vs. 45.2±9.8 years). Intima-media thickness (IMT) was measured bilaterally, at common carotid, bifurcation, and internal carotid arteries. Subclinical atherosclerosis was defined as IMT>IMTmean+2SD in controlsat each carotid level and atherosclerotic plaque as IMT>1.5 mm. Majority of RA patients were on methotrexate (83.3%), none on steroids >10 mg/day or biologic drugs. All findings were analysed in the entire study population and in RA group separately. RA patients with subclinical atherosclerosis had higher vWF activity than those without (133.5±69.3% vs. 95.3±36.8%, psubclinical atherosclerosis was confirmed by logistic regression. vWF activity correlated significantly with erythrocyte sedimentation rate, fibrinogen, modified disease activity scores (mDAS28-ESR, mDAS28-CRP), modified Health Assessment Questionnaire (psubclinical atherosclerosis (130±68% vs. 97±38%, psubclinical atherosclerosis in low-risk RA patients as well as its correlation with inflammation markers, all parameters of disease activity, and seropositivity. Therefore, vWF might be a valuable marker of early atherosclerosis in RA patients.

  18. Space and Time Resolved Detection of Platelet Activation and von Willebrand Factor Conformational Changes in Deep Suspensions.

    Science.gov (United States)

    Biasetti, Jacopo; Sampath, Kaushik; Cortez, Angel; Azhir, Alaleh; Gilad, Assaf A; Kickler, Thomas S; Obser, Tobias; Ruggeri, Zaverio M; Katz, Joseph

    2017-01-01

    Tracking cells and proteins' phenotypic changes in deep suspensions is critical for the direct imaging of blood-related phenomena in in vitro replica of cardiovascular systems and blood-handling devices. This paper introduces fluorescence imaging techniques for space and time resolved detection of platelet activation, von Willebrand factor (VWF) conformational changes, and VWF-platelet interaction in deep suspensions. Labeled VWF, platelets, and VWF-platelet strands are suspended in deep cuvettes, illuminated, and imaged with a high-sensitivity EM-CCD camera, allowing detection using an exposure time of 1 ms. In-house postprocessing algorithms identify and track the moving signals. Recombinant VWF-eGFP (rVWF-eGFP) and VWF labeled with an FITC-conjugated polyclonal antibody are employed. Anti-P-Selectin FITC-conjugated antibodies and the calcium-sensitive probe Indo-1 are used to detect activated platelets. A positive correlation between the mean number of platelets detected per image and the percentage of activated platelets determined through flow cytometry is obtained, validating the technique. An increase in the number of rVWF-eGFP signals upon exposure to shear stress demonstrates the technique's ability to detect breakup of self-aggregates. VWF globular and unfolded conformations and self-aggregation are also observed. The ability to track the size and shape of VWF-platelet strands in space and time provides means to detect pro- and antithrombotic processes.

  19. A model for the conformational activation of the structurally quiescent metalloprotease ADAMTS13 by von willebrand factor

    Science.gov (United States)

    South, Kieron; Freitas, Marta O.; Lane, David A.

    2017-01-01

    Blood loss is prevented by the multidomain glycoprotein von Willebrand factor (VWF), which binds exposed collagen at damaged vessels and captures platelets. VWF is regulated by the metalloprotease ADAMTS13, which in turn is conformationally activated by VWF. To delineate the structural requirements for VWF-mediated conformational activation of ADAMTS13, we performed binding and functional studies with a panel of truncated ADAMTS13 variants. We demonstrate that both the isolated CUB1 and CUB2 domains in ADAMTS13 bind to the spacer domain exosite of a truncated ADAMTS13 variant, MDTCS (KD of 135 ± 1 0.1 nm and 86.9 ± 9.0 nm, respectively). However, only the CUB1 domain inhibited proteolytic activity of MDTCS. Moreover, ADAMTS13ΔCUB2, unlike ADAMTS13ΔCUB1-2, exhibited activity similar to wild-type ADAMTS13 and could be activated by VWF D4-CK. The CUB2 domain is, therefore, not essential for maintaining the inactive conformation of ADAMTS13. Both CUB domains could bind to the VWF D4-CK domain fragment (KD of 53.7 ± 2.1 nm and 84.3 ± 2.0 nm, respectively). However, deletion of both CUB domains did not prevent VWF D4-CK binding, suggesting that competition for CUB-domain binding to the spacer domain is not the dominant mechanism behind the conformational activation. ADAMTS13ΔTSP8-CUB2 could no longer bind to VWF D4-CK, and deletion of TSP8 abrogated ADAMTS13 conformational activation. These findings support an ADAMTS13 activation model in which VWF D4-CK engages the TSP8-CUB2 domains, inducing the conformational change that disrupts the CUB1-spacer domain interaction and thereby activates ADAMTS13. PMID:28209710

  20. Subclinical Atherosclerosis in Patients with Rheumatoid Arthritis and Low Cardiovascular Risk: The Role of von Willebrand Factor Activity.

    Directory of Open Access Journals (Sweden)

    Gorica G Ristić

    Full Text Available To evaluate association between von Willebrand factor (vWF activity, inflammation markers, disease activity, and subclinical atherosclerosis in patients with rheumatoid arthritis (RA and low cardiovascular risk.Above mentioned parameters were determined in blood samples of 74 non-diabetic, normotensive, female subjects, with no dyslipidemia(42 patients, 32 matched healthy controls, age 45.3±10.0 vs. 45.2±9.8 years. Intima-media thickness (IMT was measured bilaterally, at common carotid, bifurcation, and internal carotid arteries. Subclinical atherosclerosis was defined as IMT>IMTmean+2SD in controlsat each carotid level and atherosclerotic plaque as IMT>1.5 mm. Majority of RA patients were on methotrexate (83.3%, none on steroids >10 mg/day or biologic drugs. All findings were analysed in the entire study population and in RA group separately.RA patients with subclinical atherosclerosis had higher vWF activity than those without (133.5±69.3% vs. 95.3±36.8%, p<0.05. Predictive value of vWF activity for subclinical atherosclerosis was confirmed by logistic regression. vWF activity correlated significantly with erythrocyte sedimentation rate, fibrinogen, modified disease activity scores (mDAS28-ESR, mDAS28-CRP, modified Health Assessment Questionnaire (p<0.01 for all, duration of smoking, number of cigarettes/day, rheumatoid factor concentration (p<0.05 for all, and anti-CCP antibodies (p<0.01. In the entire study population, vWF activity was higher in participants with subclinical atherosclerosis (130±68% vs. 97±38%, p<0.05 or atherosclerotic plaques (123±57% vs. 99±45%, p<0.05 than in those without. Duration of smoking was significantly associated with vWF activity (β 0.026, p = 0.039.We demonstrated association of vWF activity and subclinical atherosclerosis in low-risk RA patients as well as its correlation with inflammation markers, all parameters of disease activity, and seropositivity. Therefore, vWF might be a valuable marker of

  1. ADAMTS13 deficiency with elevated levels of ultra-large and active von Willebrand factor in P. falciparum and P. vivax malaria.

    NARCIS (Netherlands)

    Mast, Q. de; Groot, E. de; Asih, P.B.; Syafruddin, D.; Oosting, M.; Sebastian, S.; Ferwerda, B.; Netea, M.G.; Groot, P.G. de; Ven, A.J.A.M. van der; Fijnheer, R.

    2009-01-01

    A deficiency in ADAMTS13 (a von Willebrand factor [VWF] cleaving protease) is associated with accumulation of prothrombogenic unusually large VWF multimers (UL-VWF) in plasma. We studied VWF release and proteolysis in patients with symptomatic Plasmodium falciparum or P. vivax malaria on the

  2. An ELISA for the quantitation of von Willebrand Factor

    DEFF Research Database (Denmark)

    Vinholt, Pernille Just; Overgaard, Martin; Diederichsen, Axel Cosmus Pyndt

    2013-01-01

    BACKGROUND: Von Willebrand factor (VWF) is pivotal in arterial thrombosis, and osteoprotegerin (OPG) is besides being a bone protein also related to cardiovascular diseases. OPG can bind VWF, but the significance of this interaction is not known. OBJECTIVES: The aim was to develop an assay...... for measurement of von Willebrand factor-osteoprotegerin complex (VWF:OPG) in human plasma. Furthermore, the significance of VWF:OPG complex as a marker of cardiovascular disease (CVD) was evaluated. PATIENTS/METHODS: A sandwich ELISA for quantification of VWF:OPG was developed using a polyclonal rabbit anti...

  3. Molecular characterization of exon 28 of von Willebrand's factor ...

    African Journals Online (AJOL)

    Background: Polymorphisms in von Willebrand factor (VWF) gene are an important contributor to the expression of VWF gene and differences in ethnic distribution of these single nucleotide polymorphisms (SNPs) exists. Aims: Our objective was to molecularly characterize the exon 28 of the VWF gene in the three major ...

  4. Molecular characterization of exon 28 of von Willebrand's factor ...

    African Journals Online (AJOL)

    2016-05-12

    May 12, 2016 ... two probable cases among 95 patients with hemophilia A and 11 with hemophilia B between 1980 and 1986, but full investigation and family studies were not performed. In. Nigeria, we have been unable to find documented cases of. Molecular characterization of exon 28 of von Willebrand's factor gene in ...

  5. von Willebrand Factor and Prekallikrein in Plasma Are Associated With Thrombus Volume in Abdominal Aortic Aneurysms

    DEFF Research Database (Denmark)

    Ghulam, Qasam M; Bredahl, Kim; Gram, Jørgen Brodersen

    2016-01-01

    was consecutively obtained from 38 patients with asymptomatic infrarenal abdominal aortic aneurysm. von Willebrand factor activity, thrombin generation time, factor XII, and prekallikrein concentration were measured in plasma on automated and in-house platforms. In total, 8 patients were excluded due to ongoing...

  6. The cooperative activity between the carboxyl-terminal TSP1 repeats and the CUB domains of ADAMTS13 is crucial for recognition of von Willebrand factor under flow.

    Science.gov (United States)

    Zhang, Ping; Pan, Weilan; Rux, Ann H; Sachais, Bruce S; Zheng, X Long

    2007-09-15

    ADAMTS13 cleaves von Willebrand factor (VWF) between Tyr(1605) and Met(1606) residues at the central A2 subunit. The amino-terminus of ADAMTS13 protease appears to be sufficient to bind and cleave VWF under static and denatured condition. However, the role of the carboxyl-terminus of ADAMTS13 in substrate recognition remains controversial. Present study demonstrates that ADAMTS13 cleaves VWF in a rotation speed- and protease concentration-dependent manner on a mini vortexer. Removal of the CUB domains (delCUB) or truncation after the spacer domain (MDTCS) significantly impairs its ability to cleave VWF under the same condition. ADAMTS13 and delCUB (but not MDTCS) bind VWF under flow with dissociation constants (K(D)) of about 50 nM and about 274 nM, respectively. The isolated CUB domains are neither sufficient to bind VWF detectably nor capable of inhibiting proteolytic cleavage of VWF by ADAMTS13 under flow. Addition of the TSP1 5-8 (T5-8CUB) or TSP1 2-8 repeats (T2-8CUB) to the CUB domains restores the binding affinity toward VWF and the inhibitory effect on cleavage of VWF by ADAMTS13 under flow. These data demonstrate directly and quantitatively that the cooperative activity between the middle carboxyl-terminal TSP1 repeats and the distal carboxyl-terminal CUB domains may be crucial for recognition and cleavage of VWF under flow.

  7. Polymorphism in the promoter region of von Willebrand factor gene and von Willebrand disease type 1

    Directory of Open Access Journals (Sweden)

    Daniel Simon

    2003-12-01

    Full Text Available The -1185A/G polymorphism in the 5'-regulatory region of the von Willebrand factor (VWF gene was associated with VWF plasma levels in a normal population. This study was undertaken to evaluate whether there is a relationship between this polymorphism and type 1 von Willebrand disease (VWD, a disorder characterized by a quantitative deficiency of VWF. The association between this polymorphism and plasma VWF levels in normal Brazilian individuals was also analyzed. Control subjects (n = 460 and type 1 VWD patients (n = 41 were studied. Polymerase chain reaction (PCR amplification of the 864-bp VWF promoter region followed by AccII restriction-digestion was used to identify the -1185A/G genotypes. The -1185G allele frequency was 57% in normal individuals and 63% in type 1 VWD patients, this difference was not significant (p = 0.29. No significant association was observed between -1185A/G genotypes and VWF plasma levels in normal individuals, although VWF levels were in the same direction as those reported by another study, with subjects carrying the G allele having the lower levels. These results suggest that -1185A/G polymorphism is not associated with the partial deficiency of VWF in type 1 VWD patients.

  8. Assembly and activation of alternative complement components on endothelial cell-anchored ultra-large von Willebrand factor links complement and hemostasis-thrombosis.

    Directory of Open Access Journals (Sweden)

    Nancy A Turner

    Full Text Available Vascular endothelial cells (ECs express and release protein components of the complement pathways, as well as secreting and anchoring ultra-large von Willebrand factor (ULVWF multimers in long string-like structures that initiate platelet adhesion during hemostasis and thrombosis. The alternative complement pathway (AP is an important non-antibody-requiring host defense system. Thrombotic microangiopathies can be associated with defective regulation of the AP (atypical hemolytic-uremic syndrome or with inadequate cleavage by ADAMTS-13 of ULVWF multimeric strings secreted by/anchored to ECs (thrombotic thrombocytopenic purpura. Our goal was to determine if EC-anchored ULVWF strings caused the assembly and activation of AP components, thereby linking two essential defense mechanisms.We quantified gene expression of these complement components in cultured human umbilical vein endothelial cells (HUVECs by real-time PCR: C3 and C5; complement factor (CF B, CFD, CFP, CFH and CFI of the AP; and C4 of the classical and lectin (but not alternative complement pathways. We used fluorescent microscopy, monospecific antibodies against complement components, fluorescent secondary antibodies, and the analysis of >150 images to quantify the attachment of HUVEC-released complement proteins to ULVWF strings secreted by, and anchored to, the HUVECs (under conditions of ADAMTS-13 inhibition. We found that HUVEC-released C4 did not attach to ULVWF strings, ruling out activation of the classical and lectin pathways by the strings. In contrast, C3, FB, FD, FP and C5, FH and FI attached to ULVWF strings in quantitative patterns consistent with assembly of the AP components into active complexes. This was verified when non-functional FB blocked the formation of AP C3 convertase complexes (C3bBb on ULVWF strings.AP components are assembled and activated on EC-secreted/anchored ULVWF multimeric strings. Our findings provide one possible molecular mechanism for clinical

  9. CHANGES OF VON WILLEBRAND FACTOR DURING PREGNANCY IN WOMEN WITHOUT AND WITH VON WILLEBRAND DISEASE

    Directory of Open Access Journals (Sweden)

    Giancarlo Castaman

    2013-07-01

    Full Text Available Delivery in von Willebrand disease (VWD represents a significant hemostatic challenge because of the variable pattern of changes observed during pregnancy of von Willebrand factor (VWF  and factor VIII (FVIII, the protein carried by VWF. The wide heterogeneity of phenotypes and of the underlying pathophysiological mechanisms associated with this disorder prompt a careful evaluation of pregnant women with VWD to plan the most appropriate treatment at time of parturition. VWF and FVIII increase significantly during pregnancy in normal women, already within the first trimester, reaching levels by far > 100 U/dL by the time of parturition. In women with VWD, levels at baseline of VWF and FVIII > 30 U/dL are usually associated with a high likelihood to achieve normal levels at the end of pregnancy and specific anti-hemorrhagic prophylaxis is seldom required. Women with basal level < 20 U/dL usually have a poor increase since most of these women carry mutations associated with increased VWF clearance or are compound heterozygous for different VWF mutations which prevent the achievement of satisfactory hemostatic levels. While women with mutations associated with increased clearance show a full, albeit transitory correction of their hemostatic deficiency after desmopressin administration, compound heterozygous need replacement therapy because they do not respond well to this agent. Patients with abnormal VWF:RCo/VWF:Ag ratio at baseline (e.g. < 0.6, typically associated with type 2 VWD, maintain the abnormality throughout pregnancy and VWF:RCo usually does not attain safe levels ³ 50 U/dL. These women require replacement therapy with VWF-FVIII concentrates. Delayed post-partum bleeding may occur when replacement therapy is not continued for some days. Tranexamic acid may be useful at discharge to avoid excessive lochia.

  10. Von Willebrand factor for menorrhagia: a survey and literature review.

    Science.gov (United States)

    Ragni, M V; Machin, N; Malec, L M; James, A H; Kessler, C M; Konkle, B A; Kouides, P A; Neff, A T; Philipp, C S; Brambilla, D J

    2016-05-01

    von Willebrand disease (VWD) is the most common congenital bleeding disorder. In women, menorrhagia is the most common bleeding symptom, and is disabling with iron deficiency anaemia, high health cost and poor quality of life. Current hormonal and non-hormonal therapies are limited by ineffectiveness and intolerance. Few data exist regarding von Willebrand factor (VWF), typically prescribed when other treatments fail. The lack of effective therapy for menorrhagia remains the greatest unmet healthcare need in women with VWD. Better therapies are needed to treat women with menorrhagia. We conducted a survey of US haemophilia treatment centres (HTCs) and a literature review using medical subject heading (MeSH) search terms 'von Willebrand factor,' 'menorrhagia' and 'von Willebrand disease' to assess the use of VWF in menorrhagia. Analysis was by descriptive statistics. Of 83 surveys distributed to HTC MDs, 20 (24.1%) provided sufficient data for analysis. Of 1321 women with VWD seen during 2011-2014, 816 (61.8%) had menorrhagia, for which combined oral contraceptives, tranexamic acid and desmopressin were the most common first-line therapies for menorrhagia, whereas VWF was third-line therapy reported in 13 women (1.6%). Together with data from 88 women from six published studies, VWF safely reduced menorrhagia in 101 women at a dose of 33-100 IU kg(-1) on day 1-6 of menstrual cycle. This represents the largest VWD menorrhagia treatment experience to date. VWF safely and effectively reduces menorrhagia in women with VWD. A prospective clinical trial is planned to confirm these findings. © 2016 John Wiley & Sons Ltd.

  11. Modeling Shear Induced Von Willebrand Factor Binding to Collagen

    Science.gov (United States)

    Dong, Chuqiao; Wei, Wei; Morabito, Michael; Webb, Edmund; Oztekin, Alparslan; Zhang, Xiaohui; Cheng, Xuanhong

    2017-11-01

    Von Willebrand factor (vWF) is a blood glycoprotein that binds with platelets and collagen on injured vessel surfaces to form clots. VWF bioactivity is shear flow induced: at low shear, binding between VWF and other biological entities is suppressed; for high shear rate conditions - as are found near arterial injury sites - VWF elongates, activating its binding with platelets and collagen. Based on parameters derived from single molecule force spectroscopy experiments, we developed a coarse-grain molecular model to simulate bond formation probability as a function of shear rate. By introducing a binding criterion that depends on the conformation of a sub-monomer molecular feature of our model, the model predicts shear-induced binding, even for conditions where binding is highly energetically favorable. We further investigate the influence of various model parameters on the ability to predict shear-induced binding (vWF length, collagen site density and distribution, binding energy landscape, and slip/catch bond length) and demonstrate parameter ranges where the model provides good agreement with existing experimental data. Our results may be important for understanding vWF activity and also for achieving targeted drug therapy via biomimetic synthetic molecules. National Science Foundation (NSF),Division of Mathematical Sciences (DMS).

  12. Polyphosphate binds to human von Willebrand factor in vivo and modulates its interaction with glycoprotein Ib.

    Science.gov (United States)

    Montilla, M; Hernández-Ruiz, L; García-Cozar, F J; Alvarez-Laderas, I; Rodríguez-Martorell, J; Ruiz, F A

    2012-11-01

    Polyphosphate, a phosphate polymer released by activated platelets, has recently been described as a potent modulator of blood coagulation and fibrinolysis. In blood plasma, polyphosphate binds to and alters the biological functions of factor XII, fibrin(ogen), thrombin and factor VII activating protease. The aim of the present study is to investigate whether polyphosphate also binds to von Willebrand factor (VWF) and alters some of its activities. When studying patients with type 1 von Willebrand disease (VWD) and their healthy relatives, we discovered a significant correlation between von Willebrand factor (VWF) and platelet polyphosphate levels. We have also found polyphosphate in preparations of VWF isolated from normal platelets and plasma. Surface plasmon resonance and electrophoretic mobility assays indicated that polyphosphate interacts with VWF in a dose- and time-dependent manner. Treatment of normal plasma with active exopolyphosphatase decreased the VWF ristocetin cofactor (VWF:RCo) activity, a functional measure of VWF binding to platelet glycoprotein receptor Ib. VWF collagen binding and multimerization were unaltered after polyphosphate depletion. Moreover, addition of polyphosphate increased the deficient VWF:RCo activity presented by plasma from patients with type 1 VWD. Our results reveal that a new role is played by polyphosphate in hemostasis by its interaction with VWF, and suggest that this polymer may be effective in the treatment of some types of VWD. © 2012 International Society on Thrombosis and Haemostasis.

  13. Exercise induced hypercoagulability, increased von Willebrand factor and decreased thyroid hormone concentrations in sled dogs

    DEFF Research Database (Denmark)

    Krogh, Anne Kirstine Havnsøe; Legind, Pernille; Kjelgaard-Hansen, Mads

    2014-01-01

    Sled dogs performing endurance races have been reported to have a high incidence of gastric erosions or ulcerations and an increased risk of gastro intestinal bleeding leading to death in some cases. In addition, these dogs also become hypothyroid during training and exercise. Canine hypothyroidi......, activated partial thromboplastin time (aPTT), prothrombin time (PT), fibrinogen, von Willebrand factor (vWf), D-dimer, platelet number, thyroid hormones, hematocrit and C-reactive protein (CRP)....

  14. von Willebrand factor, Jedi knight of the bloodstream.

    Science.gov (United States)

    Springer, Timothy A

    2014-08-28

    When blood vessels are cut, the forces in the bloodstream increase and change character. The dark side of these forces causes hemorrhage and death. However, von Willebrand factor (VWF), with help from our circulatory system and platelets, harnesses the same forces to form a hemostatic plug. Force and VWF function are so closely intertwined that, like members of the Jedi Order in the movie Star Wars who learn to use "the Force" to do good, VWF may be considered the Jedi knight of the bloodstream. The long length of VWF enables responsiveness to flow. The shape of VWF is predicted to alter from irregularly coiled to extended thread-like in the transition from shear to elongational flow at sites of hemostasis and thrombosis. Elongational force propagated through the length of VWF in its thread-like shape exposes its monomers for multimeric binding to platelets and subendothelium and likely also increases affinity of the A1 domain for platelets. Specialized domains concatenate and compact VWF during biosynthesis. A2 domain unfolding by hydrodynamic force enables postsecretion regulation of VWF length. Mutations in VWF in von Willebrand disease contribute to and are illuminated by VWF biology. I attempt to integrate classic studies on the physiology of hemostatic plug formation into modern molecular understanding, and point out what remains to be learned. © 2014 by The American Society of Hematology.

  15. Clinical measurement of von Willebrand factor by fluorescence correlation spectroscopy.

    Science.gov (United States)

    Torres, Richard; Genzen, Jonathan R; Levene, Michael J

    2012-06-01

    Identification of von Willebrand factor (vWF) abnormalities in a variety of conditions is hampered by the limitations of currently available diagnostic tests. Although direct multimer visualization by immunoelectrophoresis is a commonly used method, it is impractical as a routine clinical test. In this study, we used a biophysical analysis tool, fluorescence correlation spectroscopy (FCS), to measure vWF distributions. The goals were to develop a method that is quicker and simpler than vWF gel electrophoresis and to evaluate the potential of FCS as a clinical diagnostic technique. We analyzed plasma from 12 patients with type 1 von Willebrand disease (vWD), 14 patients with type 2 vWD, and 10 healthy controls using a fluctuation-based immunoassay approach. FCS enabled identification and proper classification of type 1 and type 2 vWD, producing quantitative results that correspond to qualitative gel multimer patterns. FCS required minimal sample preparation and only a 5-min analysis time. This study represents the first implementation of FCS for clinical diagnostics directly on human plasma. The technique shows potential for further vWF studies and as a generally applicable laboratory test method.

  16. Interference from lupus anticoagulant on von Willebrand factor measurement in splenic marginal zone lymphoma

    DEFF Research Database (Denmark)

    Vinholt, Pernille J; Nybo, Mads

    2015-01-01

    We present a case concerning a patient with splenic marginal zone lymphoma (SMZL) and isolated prolonged activated partial thromboplastin time (aPTT) caused by lupus anticoagulant. Von Willebrand factor (VWF) activity and antigen were immeasurable by latex particle immunoturbidimetric assays......, and several coagulation factor levels were decreased. However, VWF activity and antigen were normal when analyzed by other methods. Also, coagulation factor levels were normal if an aPTT reagent with low lupus anticoagulant sensitivity or a chromogenic method was applied. Altogether, the initial findings were...

  17. The effect of exercise on von Willebrand factor and ADAMTS-13 in individuals with type 1 and type 2B von Willebrand disease

    NARCIS (Netherlands)

    Stakiw, J.; Bowman, M.; Hegadorn, C.; Pruss, C.; Notley, C.; Groot, E.; Lenting, P. J.; Rapson, D.; Lillicrap, D.; James, P.

    Background: The effect of exercise on von Willebrand factor (VWF) and ADAMTS-13 levels in individuals with von Willebrand disease (VWD) has never been reported. Objectives: The aim was to quantify the effect of a standardized exercise protocol on individuals with type 1 and type 2B VWD.

  18. SNAP23 Regulates Endothelial Exocytosis of von Willebrand Factor.

    Science.gov (United States)

    Zhu, Qiuyu Martin; Zhu, Qiuyu; Yamakuchi, Munekazu; Lowenstein, Charles J

    2015-01-01

    Endothelial exocytosis regulates vascular thrombosis and inflammation. The trafficking and release of endothelial vesicles is mediated by SNARE (Soluble NSF Attachment protein REceptors) molecules, but the exact identity of endothelial SNAREs has been unclear. Three SNARE molecules form a ternary complex, including isoforms of the syntaxin (STX), vesicle-associated membrane protein (VAMP), and synaptosomal-associated protein (SNAP) families. We now identify SNAP23 as the predominant endothelial SNAP isoform that mediates endothelial exocytosis of von Willebrand Factor (VWF). SNAP23 was localized to the plasma membrane. Knockdown of SNAP23 decreased endothelial exocytosis, suggesting it is important for endothelial exocytosis. SNAP23 interacted with the endothelial exocytic machinery, and formed complexes with other known endothelial SNARE molecules. Taken together, these data suggest that SNAP23 is a key component of the endothelial SNARE machinery that mediates endothelial exocytosis.

  19. Value of Von Willebrand Factor as a Predictor for Osteoporosis Development in Women with Hypothyroidism

    Directory of Open Access Journals (Sweden)

    I.V. Pankiv

    2015-08-01

    Full Text Available The paper presents the study of the value of von Willebrand factor as a marker of endothelial dysfunction for osteoporosis development and for prediction of risk of its formation in women with hypothyroidism. Postmenopausal women with hypothyroidism have significant increase of von Willebrand factor at lumbar osteopenia. High concentrations of von Willebrand factor in women with hypothyroidism follows to consider it as a predictor for osteoporosis development. Increased level of С-reactive protein belongs to the unfavorable prognostic signs in relation to the decline of bone mineral density for patients with primary hypothyroidism.

  20. Differential localization of P-selectin and von Willebrand factor during megakaryocyte maturation

    DEFF Research Database (Denmark)

    Zingariello, M; Fabucci, M E; Bosco, D

    2010-01-01

    Willebrand factor are two proteins present in the alpha-granules that recognize P-selectin glycoprotein ligand on neutrophils and collagen in the subendothelial matrix. These proteins may play an important role in determining the differential release of the alpha-granule contents in response to external....... These observations support the hypothesis that P-selectin and von Willebrand factor may ensure differential release of the alpha-granule content in response to external stimuli....

  1. Cooperation within von Willebrand factors enhances adsorption mechanism.

    Science.gov (United States)

    Heidari, Maziar; Mehrbod, Mehrdad; Ejtehadi, Mohammad Reza; Mofrad, Mohammad R K

    2015-08-06

    von Willebrand factor (VWF) is a naturally collapsed protein that participates in primary haemostasis and coagulation events. The clotting process is triggered by the adsorption and conformational changes of the plasma VWFs localized to the collagen fibres found near the site of injury. We develop coarse-grained models to simulate the adsorption dynamics of VWF flowing near the adhesive collagen fibres at different shear rates and investigate the effect of factors such as interaction and cooperativity of VWFs on the success of adsorption events. The adsorption probability of a flowing VWF confined to the receptor field is enhanced when it encounters an adhered VWF in proximity to the collagen receptors. This enhancement is observed within a wide range of shear rates and is mostly controlled by the attractive van der Waals interactions rather than the hydrodynamic interactions among VWF monomers. The cooperativity between the VWFs acts as an effective mechanism for enhancing VWF adsorption to the collagen fibres. Additionally, this implies that the adsorption of such molecules is nonlinearly dependent on the density of flowing VWFs. These findings are important for studies of primary haemostasis as well as general adsorption dynamics processes in polymer physics. © 2015 The Author(s).

  2. Von Willebrand Factor Gene Variants Associate with Herpes simplex Encephalitis.

    Directory of Open Access Journals (Sweden)

    Nada Abdelmagid

    Full Text Available Herpes simplex encephalitis (HSE is a rare complication of Herpes simplex virus type-1 infection. It results in severe parenchymal damage in the brain. Although viral latency in neurons is very common in the population, it remains unclear why certain individuals develop HSE. Here we explore potential host genetic variants predisposing to HSE. In order to investigate this we used a rat HSE model comparing the HSE susceptible SHR (Spontaneously Hypertensive Rats with the asymptomatic infection of BN (Brown Norway. Notably, both strains have HSV-1 spread to the CNS at four days after infection. A genome wide linkage analysis of 29 infected HXB/BXH RILs (recombinant inbred lines-generated from the prior two strains, displayed variable susceptibility to HSE enabling the definition of a significant QTL (quantitative trait locus named Hse6 towards the end of chromosome 4 (160.89-174Mb containing the Vwf (von Willebrand factor gene. This was the only gene in the QTL with both cis-regulation in the brain and included several non-synonymous SNPs (single nucleotide polymorphism. Intriguingly, in human chromosome 12 several SNPs within the intronic region between exon 43 and 44 of the VWF gene were associated with human HSE pathogenesis. In particular, rs917859 is nominally associated with an odds ratio of 1.5 (95% CI 1.11-2.02; p-value = 0.008 after genotyping in 115 HSE cases and 428 controls. Although there are possibly several genetic and environmental factors involved in development of HSE, our study identifies variants of the VWF gene as candidates for susceptibility in experimental and human HSE.

  3. The impact of von Willebrand factor on factor VIII memory immune responses

    OpenAIRE

    Chen, Juan; Schroeder, Jocelyn A.; Luo, Xiaofeng; Shi, Qizhen

    2017-01-01

    Immune tolerance induction (ITI) with aggressive infusion of factor VIII (FVIII) is the current strategy used to eradicate FVIII inhibitors and restore normal FVIII pharmacokinetics in inhibitor patients. Whether the use of FVIII products containing von Willebrand factor (VWF) will affect the efficacy of ITI is still controversial. In this study, we explored the impact of VWF on FVIII memory immune responses in hemophilia A (HA) mice. A T-cell proliferation assay and cytokine profile analysis...

  4. Molecular characterization of exon 28 of von Willebrand's factor gene in Nigerian population.

    Science.gov (United States)

    Ezigbo, E D; Ukaejiofo, E O; Nwagha, T U

    2017-02-01

    Polymorphisms in von Willebrand factor (VWF) gene are an important contributor to the expression of VWF gene and differences in ethnic distribution of these single nucleotide polymorphisms (SNPs) exists. Our objective was to molecularly characterize the exon 28 of the VWF gene in the three major ethnic groups of Nigeria. We recruited 90 subjects, 45 had a history of bleeding. Questions included those used in the Zimmerman Program for the Molecular and Clinical Biology of von Willebrand disease (VWD), and the bleeding scores were calculated using the Molecular and Clinical Markers for the Diagnosis and Management of type 1 VWD scoring system. Full blood count, coagulation profile, VWF:antigen level and VWF:collagen-binding activities were carried out. Data were analyzed using GraphPad Prism (5.03). GraphPad Software, Inc USA. The BigDye terminator chemistry was used to determine the nucleotide sequences of VWF gene (exon 28). Eight SNPs were identified, rs 216310 (T1547), rs 1800385 (V1565L), rs1800384 (A1515), rs1800383 (D1472H), rs 1800386 (Y1584C), rs 216311 (T1381A), rs 216312 (intronic) and rs 1800381 (P1337). The SNPs rs 216311, rs 1800383 and rs 1800386 associated significantly with bleeding in study subjects. rs1800386 occurred in all with bleeding history, no ethnic variations were noted.

  5. Diagnostic Differentiation of von Willebrand Disease Types 1 and 2 by von Willebrand Factor Multimer Analysis and DDAVP Challenge Test.

    Science.gov (United States)

    Michiels, Jan Jacques; Smejkal, Petr; Penka, Miroslav; Batorova, Angelika; Pricangova, Tatiana; Budde, Ulrich; Vangenechten, Inge; Gadisseur, Alain

    2017-09-01

    The European Clinical Laboratory and Molecular (ECLM) classification of von Willebrand disease (vWD) is based on the splitting approach which uses sensitive and specific von Willebrand factor (vWF) assays with regard to the updated molecular data on structure and function of vWF gene and protein defects. A complete set of FVIII:C and vWF ristocetine cofactor, collagen binding, and antigen, vWF multimeric analysis in low- and medium-resolution gels, and responses to desmopressin (DDAVP) of FVIII:C and vWF parameters are mandatory. The ECLM classification distinguishes recessive types 1 and 3 vWD from recessive vWD 2C due to mutations in the D1 and D2 domains and vWD 2N due to mutations in the D'-FVIII-binding domain of vWF. The ECLM classification differentiates between mild vWD type 1 with variable penetrance of bleedings from symptomatic dominant type 1 vWD secretion defect and/or clearance defect with normal vWF multimers versus vWD 1M and 2M with normal or smeary vWF multimers in low- and medium-resolution gels. High-quality multimeric analysis of vWF in medium-resolution gels based on a DDAVP challenge test clearly delineates and distinguishes each of the dominant type 2 vWDs 1/2E, 2M, 2B, 2A, and 2D caused by vWF gene mutations in the D3 multimerization domain, loss or gain-of-function mutations in the glycoprotein Ib receptor A1 domain, gene mutations in the A2 proteolytic domain, and the C-terminal dimerization domain, respectively.

  6. Detailed von Willebrand factor multimer analysis in patients with von Willebrand disease in the European study, molecular and clinical markers for the diagnosis and management of type 1 von Willebrand disease (MCMDM-1VWD)

    DEFF Research Database (Denmark)

    Budde, U.; Schneppenheim, R.; Eikenboom, J.

    2008-01-01

    BACKGROUND: Type 1 von Willebrand disease (VWD) is a congenital bleeding disorder characterized by a partial quantitative deficiency of plasma von Willebrand factor (VWF) in the absence of structural and/or functional VWF defects. Accurate assessment of the quantity and quality of plasma VWF...... is difficult but is a prerequisite for correct classification. OBJECTIVE: To evaluate the proportion of misclassification of patients historically diagnosed with type 1 VWD using detailed analysis of the VWF multimer structure. Patients and methods: Previously diagnosed type 1 VWD families and healthy controls...

  7. Von Willebrand factor availability in platelet concentrates stored for 5 days.

    Science.gov (United States)

    Cesar, J M; García-Avello, A; Monteagudo, J; Espinosa, J I; Lodos, J C; Castillo, R; Navarro, J L

    1994-02-01

    Von Willebrand factor (vWF) availability was assessed in platelet concentrates (PCs). After 5 days of storage, 82 +/- 9% of basal levels of ristocetin cofactor activity (vWF:RCo) remained in PCs. vWF antigen (vWF:Ag) increased up to 166 +/- 38% (P < 0.05) in the same period. Autoradiograph pattern of vW:Ag showed an increase in low molecular weight multimers, and fast migrating multimeric forms were visualized by crossed immunoelectrophoresis on day 5. Studies carried out in platelet free plasma stored as PCs showed similar changes in vWF:RCo but increments in vWF:Ag were not detected. These data indicate that PCs maintain vWF:RCo levels of clinical value even after 5 days of storage and suggest that vWF comes out from platelets to plasma during storage.

  8. Small GTP-binding protein Ral modulates regulated exocytosis of von Willebrand factor by endothelial cells

    NARCIS (Netherlands)

    de Leeuw, H. P.; Fernandez-Borja, M.; Reits, E. A.; Romani de Wit, T.; Wijers-Koster, P. M.; Hordijk, P. L.; Neefjes, J.; van Mourik, J. A.; Voorberg, J.

    2001-01-01

    Weibel-Palade bodies are endothelial cell-specific organelles, which contain von Willebrand factor (vWF), P-selectin, and several other proteins. Recently, we found that the small GTP-binding protein Ral is present in a subcellular fraction containing Weibel-Palade bodies. In the present study, we

  9. Efficiency of von Willebrand factor-mediated targeting of interleukin-8 into Weibel-Palade bodies

    NARCIS (Netherlands)

    Bierings, R.; van den Biggelaar, M.; Kragt, A.; Mertens, K.; Voorberg, J.; van Mourik, J. A.

    2007-01-01

    Background: After de novo synthesis in endothelial cells, the chemokine interleukin-8 (IL-8) is targeted to endothelial cell-specific storage vesicles, the Weibel-Palade bodies (WPBs), where it colocalizes with von Willebrand factor (VWF). Objective: In this study we investigated a putative

  10. Binding of von Willebrand factor and plasma proteins to the eggshell of Schistosoma mansoni

    NARCIS (Netherlands)

    Dewalick, Saskia; Hensbergen, Paul J; Bexkens, Michiel L; Grosserichter-Wagener, Christina; Hokke, Cornelis H; Deelder, André M; de Groot, Philip G; Tielens, Aloysius G M; van Hellemond, Jaap J

    Schistosoma mansoni eggs have to cross the endothelium and intestinal wall to leave the host and continue the life cycle. Mechanisms involved in this essential step are largely unknown. Here we describe direct binding to the S. mansoni eggshell of von Willebrand factor and other plasma proteins

  11. Altered glycosylation of platelet-derived von Willebrand factor confers resistance to ADAMTS13 proteolysis

    NARCIS (Netherlands)

    McGrath, Rachel T.; van den Biggelaar, Maartje; Byrne, Barry; O'Sullivan, Jamie M.; Rawley, Orla; O'Kennedy, Richard; Voorberg, Jan; Preston, Roger J. S.; O'Donnell, James S.

    2013-01-01

    Platelet-von Willebrand factor (VWF) is stored within α-granules and accounts for ∼20% of total VWF in platelet-rich plasma. This platelet-VWF pool is distinct from plasma-VWF and is enriched in high molecular weight multimers (HMWM). Previous studies have described significant functional

  12. ADAMTS-13 and von Willebrand factor predict venous thromboembolism in patients with cancer

    NARCIS (Netherlands)

    Pepin, M.; Kleinjan, A.; Hajage, D.; Buller, H. R.; Di Nisio, M.; Kamphuisen, P. W.; Salomon, L.; Veyradier, A.; Stepanian, A.; Mahe, I.

    Essentials Cancer patients are at high risk of venous thromboembolism (VTE). In this study, cases and controls were cancer patients who did or did not develop VTE. von Willebrand factor (VWF) levels were higher if compared with controls and correlated with cancer stage. VWF and ADAMTS-13 are

  13. Mutant botrocetin-2 inhibits von Willebrand factor-induced platelet agglutination.

    Science.gov (United States)

    Matsui, T; Hori, A; Hamako, J; Matsushita, F; Ozeki, Y; Sakurai, Y; Hayakawa, M; Matsumoto, M; Fujimura, Y

    2017-03-01

    Essentials Botrocetin-2 (Bot2) binds to von Willebrand factor (VWF) and induces platelet agglutination. We identified Bot2 residues that are required for binding to VWF and glycoprotein (GP) Ib. We produced a mutant Bot2 that binds to VWF but inhibits platelet agglutination. Mutant Bot2 could be used as a potential anti-thrombotic reagent to block VWF-GPIb interaction. Background Botrocetin-2 (Bot2) is a botrocetin-like protein composed of α and β subunits that have been cloned from the snake Bothrops jararaca. Bot2 binds specifically to von Willebrand factor (VWF), and the complex induces glycoprotein (GP) Ib-dependent platelet agglutination. Objectives To exploit Bot2's VWF-binding capacity in order to attempt to create a mutant Bot2 that binds to VWF but inhibits platelet agglutination. Methods and Results Several point mutations were introduced into Bot2 cDNA, and the recombinant protein (recombinant Bot2 [rBot2]) was purified on an anti-botrocetin column. The mutant rBot2 with either Ala at Asp70 in the β subunit (Aspβ70Ala), or Argβ115Ala and Lysβ117Ala, showed reduced platelet agglutination-inducing activity. rBot2 with Aspβ70Ala showed little binding activity towards immobilized VWF on an ELISA plate, whereas rBot2 with Argβ115Ala/Lysβ117Ala showed reduced binding activity towards GPIb (glycocalicin) after forming a complex with VWF. rBot2 point-mutated to oppositely charged Glu at both Argβ115 and Lysβ117 showed normal binding activity towards VWF but no platelet-agglutinating activity. Furthermore, this doubly mutated protein inhibited ristocetin-induced or high shear stress-induced platelet aggregation, and restrained thrombus formation under flow conditions. Conclusions Asp70 in the β subunit of botrocetin is important for VWF binding, and Arg115 and Lys117 in the β subunit are essential for interaction with GPIb. Doubly mutated rBot2, with Argβ115Glu and Lysβ117Glu, repels GPIb and might have potential as an antithrombotic reagent that

  14. Storage of factor VIII variants with impaired von Willebrand factor binding in Weibel-Palade bodies in endothelial cells

    NARCIS (Netherlands)

    van den Biggelaar, Maartje; Bouwens, Eveline A. M.; Voorberg, Jan; Mertens, Koen

    2011-01-01

    Point mutations resulting in reduced factor VIII (FVIII) binding to von Willebrand factor (VWF) are an important cause of mild/moderate hemophilia A. Treatment includes desmopressin infusion, which concomitantly increases VWF and FVIII plasma levels, apparently from storage pools containing both

  15. Requirements for cellular co-trafficking of factor VIII and von Willebrand factor to Weibel-Palade bodies

    NARCIS (Netherlands)

    van den Biggelaar, M.; Bierings, R.; Storm, G.; Voorberg, J.; Mertens, K.

    2007-01-01

    von Willebrand factor (VWF) serves a critical role as a carrier of factor (F)VIII in circulation. While it is generally believed that FVIII and VWF assemble in circulation after secretion from different cells, an alternative view is that cells should exist that co-express FVIII and VWF. In this

  16. Assembly of multimeric von Willebrand factor directs sorting of P-selectin

    NARCIS (Netherlands)

    Hop, C.; Guilliatt, A.; Daly, M.; de Leeuw, H. P.; Brinkman, H. J.; Peake, I. R.; van Mourik, J. A.; Pannekoek, H.

    2000-01-01

    We designed a model system to study the role of von Willebrand factor (vWF) in the sorting of P-selectin and the biogenesis of Weibel-Palade body (WPB)-like organelles. For that purpose, a human epithelial cell line (T24) that synthesizes P-selectin mRNA, but which is devoid of vWF mRNA synthesis

  17. von Willebrand Factor and Oxidative Stress Parameters in Acute Coronary Syndromes

    Directory of Open Access Journals (Sweden)

    Zoran Koprivica

    2011-01-01

    Full Text Available Considering the role of von Willebrand factor (vWf in hemostasis, and the role of oxidative stress in the development of endothelial dysfunction and atherosclerotic disease, the aim of our study was to investigate the relationship between vWf, parameters of oxidative stress and different types of acute coronary syndromes (ACS. Levels of vWf activity (vWfAct, vWf antigen (vWfAg, nitric oxide (estimated through nitrites–NO2 −, superoxide anion radical (O2 −, hydrogen peroxide (H2O2, index of lipid peroxidation (estimated through thiobarbituric acid reactive substances–TBARS, superoxide dismutase (SOD and catalase (CAT activity of 115 patients were compared with those of 40 healthy controls. ACS patients had significantly higher vWfAct and vWfAg levels, as well as TBARS levels, while their levels of NO2 −, H2O2, SOD and CAT activities were lower than controls'. vWfAg showed high specificity and sensitivity as a test to reveal healthy or diseased subjects. Multivariant logistic regression marked only vWfAg and TBARS as parameters that were under independent effect of ACS type. The results of our study support the implementation of vWf in clinical rutine and into therapeutic targets, and suggest that ACS patients are in need of antioxidant supplementation to improve their impaired antioxidant defence.

  18. Factor VIII alters tubular organization and functional properties of von Willebrand factor stored in Weibel-Palade bodies

    NARCIS (Netherlands)

    Bouwens, Eveline A. M.; Mourik, Marjon J.; van den Biggelaar, Maartje; Eikenboom, Jeroen C. J.; Voorberg, Jan; Valentijn, Karine M.; Mertens, Koen

    2011-01-01

    In endothelial cells, von Willebrand factor (VWF) multimers are packaged into tubules that direct biogenesis of elongated Weibel-Palade bodies (WPBs). WPB release results in unfurling of VWF tubules and assembly into strings that serve to recruit platelets. By confocal microscopy, we have previously

  19. Thrombin-dependent Incorporation of von Willebrand Factor into a Fibrin Network*

    Science.gov (United States)

    Miszta, Adam; Pelkmans, Leonie; Lindhout, Theo; Krishnamoorthy, Ganeshram; de Groot, Philip G.; Hemker, Coenraad H.; Heemskerk, Johan W. M.; Kelchtermans, Hilde; de Laat, Bas

    2014-01-01

    Attachment of platelets from the circulation onto a growing thrombus is a process involving multiple platelet receptors, endothelial matrix components, and coagulation factors. It has been indicated previously that during a transglutaminase reaction activated factor XIII (FXIIIa) covalently cross-links von Willebrand factor (VWF) to polymerizing fibrin. Bound VWF further recruits and activates platelets via interactions with the platelet receptor complex glycoprotein Ib (GPIb). In the present study we found proof for binding of VWF to a fibrin monomer layer during the process of fibrinogen-to-fibrin conversion in the presence of thrombin, arvin, or a snake venom from Crotalus atrox. Using a domain deletion mutant we demonstrated the involvement of the C domains of VWF in this binding. Substantial binding of VWF to fibrin monomers persisted in the presence of the FXIIIa inhibitor K9-DON, illustrating that cross-linking via factor XIII is not essential for this phenomenon and suggesting the identification of a second mechanism through which VWF multimers incorporate into a fibrin network. Under high shear conditions, platelets were shown to adhere to fibrin only if VWF had been incorporated. In conclusion, our experiments show that the C domains of VWF and the E domain of fibrin monomers are involved in the incorporation of VWF during the polymerization of fibrin and that this incorporation fosters binding and activation of platelets. Fibrin thus is not an inert end product but partakes in further thrombus growth. Our findings help to elucidate the mechanism of thrombus growth and platelet adhesion under conditions of arterial shear rate. PMID:25381443

  20. Heritability of plasma von Willebrand factor antigen concentration in German Wirehaired pointers.

    Science.gov (United States)

    Brooks, M B; Castillo-Juarez, H; Oltenacu, P

    2001-07-01

    We applied quantitative genetic analyses to a population of German Wirehaired pointer dogs affected with type 2 von Willebrand disease. Plasma von Willebrand factor (vWF) protein concentration measured as vWF antigen (vWF:Ag), clinical history, and pedigree data were compiled for 331 dogs over a 5-year test period. Eight dogs had histories of abnormal bleeding and had markedly decreased plasma vWF:Ag concentrations (dogs were inbred, with an average inbreeding of 2.52%. The estimated heritability of plasma vWF concentration was 0.52. We found a major gene effect on vWF concentration. Using a single gene locus model and two different prediction methods, the upper threshold value for the aa genotype was less than 1% vWF:Ag, and the optimal threshold value for discrimination between the AA and Aa genotypes was between 68% and 72% vWF:Ag. Our analyses indicate that phenotype, assigned on the basis of a single vWF:Ag determination, is heritable and can be applied for selective breeding in a von Willebrand disease test programme.

  1. Homocisteína plasmática total e fator von Willebrand no diabete melito experimental Total plasmatic homocysteine and von Willebrand factor in experimental diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Renato Delascio Lopes

    2007-04-01

    Full Text Available OBJETIVOS: Determinar os valores plasmáticos de homocisteína e fator von Willebrand, como marcador de disfunção endotelial, em ratos com diabete melito induzido por estreptozotocina. MÉTODOS: Trinta e cinco ratos (rattus norvegicus albinus, machos, adultos (180-200 g, randomizados em três grupos: controle (n=10 não receberam agente ou veículo; sham (n=10 receberam solução veículo da estreptozotocina; e diabético (n=15 receberam estreptozotocina. Após oito semanas de indução do diabete melito, os animais foram pesados, anestesiados e tiveram sangue colhido da aorta abdominal para determinação dos valores de homocisteína plasmática total, fator von Willebrand e glicemia. RESULTADOS: O modelo experimental foi reprodutível em 100% dos animais. A média das concentrações plasmáticas de homocisteína foi: 7,9 µmol/l (controle; 8,6 µmol/l (sham e 6,1 µmol/l (diabético, com diferença entre os grupos (pOBJECTIVES: To determine the plasma homocysteine and von Willebrand factor levels as markers of endothelial dysfunction in rats with diabetes mellitus induced by streptozotocin. METHODS: Thirty-five adult male rats (Rattus norvegicus albinus (weight between 180-200g were randomized into three groups: control group (n=10, which received no drugs or vehicles; sham group (n=10, which received streptozotocin solution; and diabetic group (n=15, which received streptozotocin. Eight weeks after diabetes mellitus induction, the animals were weighed and anesthesized; blood samples were collected from abdominal aorta for plasma total homocysteine, von Willebrand factor and glucose levels. RESULTS: The experimental model was reproducible in 100% of animals. The mean plasma homocysteine levels were: 7.9 µmol/l (control, 8.6µmol/l (sham and 6.1µmol/l (diabetic, with difference among the groups (p<0.01. Multiple comparison analysis among the groups showed that values in the diabetic group were lower than in the sham group (p<0.01. The mean

  2. Comparative analysis of von Willebrand factor profiles after implantation of left ventricular assist device and total artificial heart.

    Science.gov (United States)

    Reich, H J; Morgan, J; Arabia, F; Czer, L; Moriguchi, J; Ramzy, D; Esmailian, F; Lam, L; Dunhill, J; Volod, O

    2017-08-01

    Essentials Bleeding is a major source of morbidity during mechanical circulatory support. von Willebrand factor (VWF) multimer loss may contribute to bleeding. Different patterns of VWF multimer loss were seen with the two device types. This is the first report of total artificial heart associated VWF multimer loss. Background Bleeding remains a challenge during mechanical circulatory support and underlying mechanisms are incompletely understood. Functional von Willebrand factor (VWF) impairment because of loss of high-molecular-weight multimers (MWMs) produces acquired von Willebrand disease (VWD) after left ventricular assist device (LVAD). Little is known about VWF multimers with total artificial hearts (TAHs). Here, VWF profiles with LVADs and TAHs are compared using a VWD panel. Methods VWD evaluations for patients with LVAD or TAH (2013-14) were retrospectively analyzed and included: VWF activity (ristocetin cofactor, VWF:RCo), VWF antigen (VWF:Ag), ratio of VWF:RCo to VWF:Ag, and quantitative VWF multimeric analysis. Results Twelve patients with LVADs and 12 with TAHs underwent VWD evaluation. All had either normal (47.8%) or elevated (52.2%) VWF:RCo, normal (26.1%) or elevated (73.9%) VWF:Ag and 50.0% were disproportional (ratio ≤ 0.7). Multimeric analysis showed abnormal patterns in all patients with LVADs: seven with high MWM loss; five with highest MWM loss. With TAH, 10/12 patients had abnormal patterns: all with highest MWM loss. High MWM loss correlated with presence of LVAD and highest MWM loss with TAH. Increased low MWMs were detected in 22/24. Conclusion Using VWF multimeric analysis, abnormalities after LVAD or TAH were detected that would be missed with measurements of VWF level alone: loss of high MWM predominantly in LVAD, loss of highest MWM in TAH, and elevated levels of low MWM in both. This is the first study to describe TAH-associated highest MWM loss, which may contribute to bleeding. © 2017 International Society on Thrombosis and

  3. Plasmatic ADAMTS-13 metalloprotease and von Willebrand factor in children with cyanotic congenital heart disease.

    Science.gov (United States)

    Soares, R P S; Bydlowski, S P; Nascimento, N M; Thomaz, A M; Bastos, E N M; Lopes, A A

    2013-04-01

    Changes in plasma von Willebrand factor concentration (VWF:Ag) and ADAMTS-13 activity (the metalloprotease that cleaves VWF physiologically) have been reported in several cardiovascular disorders with prognostic implications. We therefore determined the level of these proteins in the plasma of children with cyanotic congenital heart disease (CCHD) undergoing surgical treatment. Forty-eight children were enrolled (age 0.83 to 7.58 years). Measurements were performed at baseline and 48 h after surgery. ELISA, collagen-binding assays and Western blotting were used to estimate antigenic and biological activities, and proteolysis of VWF multimers. Preoperatively, VWF:Ag and ADAMTS-13 activity were decreased (65 and 71% of normal levels considered as 113 (105-129) U/dL and 91 ± 24% respectively, P membranes, followed by proteolytic cleavage. A low preoperative ADAMTS-13 activity, a longer activated partial thromboplastin time and the need for cardiopulmonary bypass correlated with postoperative bleeding (P < 0.05). Postoperatively, ADAMTS-13 activity increased but less extensively than VWF:Ag (respectively, 2.23 and 2.83 times baseline, P < 0.0001), resulting in an increased VWF:Ag/ADAMTS-13 activity ratio (1.20 to 1.54, respectively, pre- and postoperative median values, P = 0.0029). ADAMTS-13 consumption was further confirmed by decreased ADAMTS-13 antigenic concentration (0.91 ± 0.30 to 0.70 ± 0.25 µg/mL, P < 0.0001) and persistent proteolysis of VWF multimers. We conclude that, in pediatric CCHD, changes in circulating ADAMTS-13 suggest enzyme consumption, associated with abnormal structure and function of VWF.

  4. Plasmatic ADAMTS-13 metalloprotease and von Willebrand factor in children with cyanotic congenital heart disease

    Energy Technology Data Exchange (ETDEWEB)

    Soares, R.P.S. [Fundação Pró-Sangue Hemocentro de São Paulo, São Paulo, SP (Brazil); Bydlowski, S.P.; Nascimento, N.M. [Laboratório de Investigação Médica-31, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Thomaz, A.M.; Bastos, E.N.M.; Lopes, A.A. [Faculdade de Medicina, Instituto do Coração, Universidade de São Paulo, São Paulo, SP (Brazil)

    2013-04-05

    Changes in plasma von Willebrand factor concentration (VWF:Ag) and ADAMTS-13 activity (the metalloprotease that cleaves VWF physiologically) have been reported in several cardiovascular disorders with prognostic implications. We therefore determined the level of these proteins in the plasma of children with cyanotic congenital heart disease (CCHD) undergoing surgical treatment. Forty-eight children were enrolled (age 0.83 to 7.58 years). Measurements were performed at baseline and 48 h after surgery. ELISA, collagen-binding assays and Western blotting were used to estimate antigenic and biological activities, and proteolysis of VWF multimers. Preoperatively, VWF:Ag and ADAMTS-13 activity were decreased (65 and 71% of normal levels considered as 113 (105-129) U/dL and 91 ± 24% respectively, P < 0.003) and correlated (r = 0.39, P = 0.0064). High molecular weight VWF multimers were not related, suggesting an interaction of VWF with cell membranes, followed by proteolytic cleavage. A low preoperative ADAMTS-13 activity, a longer activated partial thromboplastin time and the need for cardiopulmonary bypass correlated with postoperative bleeding (P < 0.05). Postoperatively, ADAMTS-13 activity increased but less extensively than VWF:Ag (respectively, 2.23 and 2.83 times baseline, P < 0.0001), resulting in an increased VWF:Ag/ADAMTS-13 activity ratio (1.20 to 1.54, respectively, pre- and postoperative median values, P = 0.0029). ADAMTS-13 consumption was further confirmed by decreased ADAMTS-13 antigenic concentration (0.91 ± 0.30 to 0.70 ± 0.25 µg/mL, P < 0.0001) and persistent proteolysis of VWF multimers. We conclude that, in pediatric CCHD, changes in circulating ADAMTS-13 suggest enzyme consumption, associated with abnormal structure and function of VWF.

  5. Aging and ABO blood type influence von Willebrand factor and factor VIII levels through interrelated mechanisms.

    Science.gov (United States)

    Albánez, S; Ogiwara, K; Michels, A; Hopman, W; Grabell, J; James, P; Lillicrap, D

    2016-05-01

    Essentials von Willebrand factor (VWF) and factor VIII (FVIII) levels are modulated by age and ABO status. The effect of aging and ABO blood type on VWF and FVIII was assessed in 207 normal individuals. Aging and ABO blood type showed combined and bidirectional influences on VWF and FVIII levels. Aging and ABO blood type influence VWF levels through both secretion and clearance mechanisms. Background The effect of aging and ABO blood type on plasma levels of von Willebrand factor (VWF) and factor VIII (FVIII) have been widely reported; however, a comprehensive analysis of their combined effect has not been performed and the mechanisms responsible for the age-related changes have not been determined. Objectives To assess the influence of aging and ABO blood type on VWF and FVIII levels, and to evaluate the contribution of VWF secretion and clearance to the age-related changes. Methods A cross-sectional observational study was performed in a cohort of 207 normal individuals, whose levels of VWF, FVIII, VWF propeptide (VWFpp), VWFpp/VWF:Ag ratio and blood type A antigen content on VWF (A-VWF) were quantified. Results Aging and ABO blood type exerted interrelated effects on VWF and FVIII plasma levels, because the age-related increase in both proteins was significantly higher in type non-O individuals (β = 0.011 vs. 0.005). This increase with age in non-O subjects drove the differences between blood types in VWF levels, as the mean difference increased from 0.13 U/mL in the young to 0.57 U/mL in the old. Moreover, A-VWF was associated with both VWF antigen (β = 0.29; 95% confidence interval [CI], 0.09, 0.50) and VWF clearance (β = -0.15; 95% CI, -0.25, -0.06). We also documented an effect of ABO blood type on VWF secretion with aging, as old individuals with blood type non-O showed higher levels of VWFpp (mean difference 0.29 U/mL). Conclusions Aging and ABO blood type have an interrelated effect on VWF and FVIII levels, where the effect of one is significantly

  6. Complex changes in von Willebrand factor-associated parameters are acquired during uncomplicated pregnancy.

    Directory of Open Access Journals (Sweden)

    Danielle N Drury-Stewart

    Full Text Available The coagulation protein von Willebrand Factor (VWF is known to be elevated in pregnancy. However, the timing and nature of changes in VWF and associated parameters throughout pregnancy are not well understood.To better understand the changes in VWF provoked by pregnancy, we studied VWF-associated parameters in samples collected over the course of healthy pregnancies.We measured VWF antigen (VWF:Ag, VWF propeptide (VWFpp, Factor VIII (FVIII, and ADAMTS13 activity in samples collected from 46 women during pregnancy and at non-pregnant baseline. We also characterized pregnant vs. non-pregnant VWF multimer structure in 21 pregnancies, and performed isoelectric focusing (IEF of VWF in two pregnancies which had samples from multiple trimesters.VWF:Ag and FVIII levels were significantly increased during pregnancy. ADAMTS13 activity was unchanged. VWFpp levels increased much later in pregnancy than VWF:Ag, resulting in a progressive decrease in VWFpp:Ag ratios. FVIII:VWF ratios also decreased in pregnancy. Most pregnancies exhibited a clear loss of larger VWF multimers and altered VWF triplet structure. Further evidence of acquired VWF qualitative changes in pregnancy was found in progressive, reversible shifts in VWF IEF patterns over gestation.These data support a new view of pregnancy in which VWF can acquire qualitative changes associated with advancing gestational age. Modeling supports a scenario in which both increased VWF production and doubling of the VWF half-life would account for the data observed. We propose that gestation induces a prolongation in VWF survival, which likely contributes to increased total VWF levels and altered VWF structure.

  7. Secretion of von Willebrand factor by endothelial cells links sodium to hypercoagulability and thrombosis.

    Science.gov (United States)

    Dmitrieva, Natalia I; Burg, Maurice B

    2014-04-29

    Hypercoagulability increases risk of thrombi that cause cardiovascular events. Here we identify plasma sodium concentration as a factor that modulates blood coagulability by affecting the production of von Willebrand factor (vWF), a key initiator of the clotting cascade. We find that elevation of salt over a range from the lower end of what is normal in blood to the level of severe hypernatremia reversibly increases vWF mRNA in endothelial cells in culture and the rate of vWF secretion from them. The high NaCl increases expression of tonicity-regulated transcription factor NFAT5 and its binding to promoter of vWF gene, suggesting involvement of hypertonic signaling in vWF up-regulation. To elevate NaCl in vivo, we modeled mild dehydration, subjecting mice to water restriction (WR) by feeding them with gel food containing 30% water. Such WR elevates blood sodium from 145.1 ± 0.5 to 150.2 ± 1.3 mmol/L and activates hypertonic signaling, evidenced from increased expression of NFAT5 in tissues. WR increases vWF mRNA in liver and lung and raises vWF protein in blood. Immunostaining of liver revealed increased production of vWF protein by endothelium and increased number of microthrombi inside capillaries. WR also increases blood level of D-dimer, indicative of ongoing coagulation and thrombolysis. Multivariate regression analysis of clinical data from the Atherosclerosis Risk in Communities Study demonstrated that serum sodium significantly contributes to prediction of plasma vWF and risk of stroke. The results indicate that elevation of extracellular sodium within the physiological range raises vWF sufficiently to increase coagulability and risk of thrombosis.

  8. Conventional rapid latex agglutination in estimation of von Willebrand factor: method revisited and potential clinical applications.

    Science.gov (United States)

    Mahat, Marianor; Abdullah, Wan Zaidah; Hussin, Che Maraina Che

    2014-01-01

    Measurement of von Willebrand factor antigen (VWF : Ag) levels is usually performed in a specialised laboratory which limits its application in routine clinical practice. So far, no commercial rapid test kit is available for VWF : Ag estimation. This paper discusses the technical aspect of latex agglutination method which was established to suit the purpose of estimating von Willebrand factor (VWF) levels in the plasma sample. The latex agglutination test can be performed qualitatively and semiquantitatively. Reproducibility, stability, linearity, limit of detection, interference, and method comparison studies were conducted to evaluate the performance of this test. Semiquantitative latex agglutination test was strongly correlated with the reference immunoturbidimetric assay (Spearman's rho = 0.946, P agglutination test and the reference assay. Using the scoring system for the rapid latex test, no agglutination is with 0% VWF : Ag (control negative), 1+ reaction is equivalent to 150% VWF : Ag (when comparing with immunoturbidimetric assay). The findings from evaluation studies suggest that latex agglutination method is suitable to be used as a rapid test kit for the estimation of VWF : Ag levels in various clinical conditions associated with high levels and low levels of VWF : Ag.

  9. von Willebrand Disease

    Science.gov (United States)

    ... the condition. For example, the school nurse, teacher, daycare provider, coach, or any leader of afterschool activities ... MedlinePlus) Von Willebrand Disease (MedlinePlus) Building 31 31 Center Drive Bethesda, MD 20892 Learn more about getting ...

  10. Functional variation in the arginine vasopressin 2 receptor as a modifier of human plasma von Willebrand factor levels

    DEFF Research Database (Denmark)

    Nossent, Anne Yaël; Robben, J H; Deen, P M T

    2010-01-01

    SUMMARY OBJECTIVES: Stimulation of arginine vasopressin 2 receptor (V2R) with arginine vasopressin (AVP) results in a rise in von Willebrand factor (VWF) and factor VIII plasma levels. We hypothesized that gain-of-function variations in the V2R gene (AVPR2) would lead to higher plasma levels of V...

  11. Immunoprotective effect of von Willebrand factor towards therapeutic factor VIII in experimental haemophilia A.

    Science.gov (United States)

    Delignat, S; Repessé, Y; Navarrete, A-M; Meslier, Y; Gupta, N; Christophe, O D; Kaveri, S V; Lacroix-Desmazes, S

    2012-03-01

    The development of inhibitory anti-factor VIII (FVIII) antibodies in patients with haemophilia A following replacement therapy is associated with several types of risk factors. Among these, the purity of FVIII concentrates, and in particular the presence of von Willebrand factor (VWF), was controversially proposed to influence the immunogenicity of exogenous FVIII. We re-assessed in vivo and in vitro the immuno-protective effect of VWF towards FVIII. The immuno-protective effect of VWF towards FVIII was investigated in vivo, in a model of haemophilia A. We studied the endocytosis of FVIII by murine bone marrow-derived dendritic cells and evaluated the capacity of VWF to block the internalization of FVIII. We characterized the relevance of VWF for the accumulation of FVIII in the marginal zone of the spleen, a secondary lymphoid organ where the immune response to therapeutically administered FVIII initiates. Our results confirm that VWF reduces the immunogenicity of FVIII in FVIII-deficient mice. Paradoxically, VWF is important for the accumulation of FVIII in the marginal zone of the spleen. We propose that VWF exerts at least two non-mutually exclusive immunoprotective roles towards FVIII in haemophilic mice: VWF prevents the endocytosis of FVIII by professional antigen-presenting cells by blocking the interaction of FVIII with as yet unidentified endocytic receptor(s). Hypothetically, VWF, by virtue of increasing the half-life of FVIII in the circulation, may allow an increased contact time with tolerogenic marginal zone B cells in the spleen. © 2011 Blackwell Publishing Ltd.

  12. Characterization of Zebrafish von Willebrand Factor Reveals Conservation of Domain Structure, Multimerization, and Intracellular Storage

    Directory of Open Access Journals (Sweden)

    Arunima Ghosh

    2012-01-01

    Full Text Available von Willebrand disease (VWD is the most common inherited human bleeding disorder and is caused by quantitative or qualitative defects in von Willebrand factor (VWF. VWF is a secreted glycoprotein that circulates as large multimers. While reduced VWF is associated with bleeding, elevations in overall level or multimer size are implicated in thrombosis. The zebrafish is a powerful genetic model in which the hemostatic system is well conserved with mammals. The ability of this organism to generate thousands of offspring and its optical transparency make it unique and complementary to mammalian models of hemostasis. Previously, partial clones of zebrafish vwf have been identified, and some functional conservation has been demonstrated. In this paper we clone the complete zebrafish vwf cDNA and show that there is conservation of domain structure. Recombinant zebrafish Vwf forms large multimers and pseudo-Weibel-Palade bodies (WPBs in cell culture. Larval expression is in the pharyngeal arches, yolk sac, and intestinal epithelium. These results provide a foundation for continued study of zebrafish Vwf that may further our understanding of the mechanisms of VWD.

  13. Regulation of plasma von Willebrand factor [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Karl C Desch

    2018-01-01

    Full Text Available Von Willebrand factor (VWF is a multimeric plasma glycoprotein that plays a central role in the initiation of blood coagulation. Through interactions between its specific functional domains, the vascular wall, coagulation factor VIII, and platelet receptors, VWF maintains hemostasis by binding to platelets and delivering factor VIII to the sites of vascular injury. In the healthy human population, plasma VWF levels vary widely. The important role of VWF is illustrated by individuals at the extremes of the normal distribution of plasma VWF concentrations where individuals with low VWF levels are more likely to present with mucocutaneous bleeding. Conversely, people with high VWF levels are at higher risk for venous thromboembolic disease, stroke, and coronary artery disease. This report will summarize recent advances in our understanding of environmental influences and the genetic control of VWF plasma variation in healthy and symptomatic populations and will also highlight the unanswered questions that are currently driving this field of study.

  14. Insights into the mechanism(s) of von Willebrand factor degradation during mechanical circulatory support.

    Science.gov (United States)

    Bartoli, Carlo R; Dassanayaka, Sujith; Brittian, Kenneth R; Luckett, Andrew; Sithu, Srinivas; Siess, Thorsten; Raess, Daniel H; Spence, Paul A; Koenig, Steven C; Dowling, Robert D; D'Souza, Stanley E

    2014-05-01

    Left ventricular assist device support produces a bleeding diathesis. Evidence suggests a major role for von Willebrand factor (vWF). We examined vWF metabolism in a preclinical model of short-term mechanical circulatory support. In 25 calves (weight, 80-110 kg), the inflow/outflow graft of the Symphony Heart Assist System was sewn end-to-side to the carotid artery. Support was initiated (acute, n = 4; 1 week, n = 16; 2 weeks, n = 5). Acutely, carotid artery pressure and flow were measured to evaluate the hemodynamic changes near the anastomosis. At baseline and after ≤2 weeks of support, platelet aggregometry with adenosine 5'-diphosphate, collagen, and ristocetin was performed. Gel electrophoresis and wet immunoblotting qualitatively evaluated vWF multimers and quantified plasma ADAMTS-13, the vWF-cleaving protease. Carotid arterial rings near the anastomosis were studied with immunohistochemical staining for ADAMTS-13 and were cultured to quantify endothelial ADAMTS-13 production. Fluorescent resonance energy transfer was used to evaluate the enzymatic activity of ADAMTS-13 in the plasma and in supernatant from cultured carotid arterial rings. Plasma interleukin-6, which inhibits ADAMTS-13 activity, was measured using an enzyme-linked immunosorbent assay. During support, statistically significant (P < .05) changes in the carotid endothelium arterial hemodynamics were observed. The highest molecular weight vWF multimers were absent, and the vWF-ristocetin platelet aggregation pathway was significantly impaired. A modest but significant increase in plasma ADAMTS-13 protein and activity was observed. ADAMTS-13 decreased significantly in the carotid near the anastomosis but increased significantly in supernatant from cultured carotid arterial rings. The plasma interleukin-6 levels did not change significantly. Hemodynamic activation of vWF and increased plasma ADAMTS-13 activity may have reduced high-molecular-weight vWF multimers and thereby impaired the

  15. Von Willebrand Factor, ADAMTS13 and D-Dimer Are Correlated with Different Levels of Nephropathy in Type 1 Diabetes Mellitus.

    Directory of Open Access Journals (Sweden)

    Caroline Pereira Domingueti

    Full Text Available We have investigated whether von Willebrand factor, ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13, and D-Dimer were associated with different levels of renal function in patients with type 1 diabetes. Patients were classified according to level of renal function through estimated glomerular filtration rate: ≥90 and <130mL/min/1,73m2, n=52 (control group, ≥60 and <90mL/min/1,73m2, n=29 (mild renal dysfunction group, <60mL/min/1,73m2, n=28 (severe renal dysfunction group; and through urinary albumin excretion: normoalbuminuria, microalbuminuria and macroalbuminuria. Von Willebrand factor, ADAMTS13, and D-Dimer plasma levels were determined by enzyme-linked immunosorbent assay. ADAMTS13 activity was determined by fluorescence resonance energy transfer assay. Von Willebrand factor levels were increased in patients with mild (P=0.001 and severe (P<0.001 renal dysfunction as compared to the control group. ADAMTS13 levels were also increased in mild (P=0.029 and severe (P=0.002 renal dysfunction groups in comparison to the control group, while ADAMTS13 activity was increased only in the severe renal dysfunction group as compared to the control group (P=0.006. No significant differences were observed among the groups regarding von Willebrand factor/ADAMTS13 ratio. ADAMTS13 activity/ADAMTS13 levels ratio was reduced in patients with mild (P=0.013 and severe (P=0.015 renal dysfunction as compared to the control group. D-Dimer levels were increased in patients with mild (P=0.006 and severe (P<0.001 renal dysfunction as compared to the control group; it was also higher in patients with severe renal dysfunction as compared to the mild renal dysfunction group (P=0.019. Similar results were found for albuminuria classification. Increased von Willebrand factor, ADAMTS13, and D-Dimer levels and decreased ADAMTS13 activity/ADAMTS13 levels ratio are associated with renal dysfunction in patients with type 1 diabetes

  16. Von Willebrand factor in patients on mechanical circulatory support - a double-edged sword between bleeding and thrombosis.

    Science.gov (United States)

    Hudzik, Bartosz; Kaczmarski, Jacek; Pacholewicz, Jerzy; Zakliczynski, Michal; Gasior, Mariusz; Zembala, Marian

    2015-09-01

    Mechanical circulatory support (MCS) is an umbrella term describing the various technologies used in both short- and long-term management of patients with either end-stage chronic heart failure (HF) or acute HF. Most often, MCS has emerged as a bridge to transplantation, but more recently it is also used as a destination therapy. Mechanical circulatory support includes left ventricular assist device (LVAD) or bi-ventricular assist device (Bi-VAD). Currently, 2- to 3-year survival in carefully selected patients is much better than with medical therapy. However, MCS therapy is hampered by sometimes life-threatening complications including bleeding and device thrombosis. Von Willebrand factor (vWF) has two major functions in haemostasis. First, it plays a crucial role in platelet-subendothelium adhesion and platelet-platelet interactions (aggregation). Second, it is the carrier of factor VIII (FVIII) in plasma. Von Willebrand factor prolongs FVIII half-time by protecting it from proteolytic degradation. It delivers FVIII to the site of vascular injury thus enhancing haemostatic process. On one hand, high plasma levels of vWF have been associated with an increased risk of thrombosis. On the other, defects or deficiencies of vWF underlie the inherited von Willebrand disease or acquired von Willebrand syndrome. Here we review the pathophysiology of thrombosis and bleeding associated with vWF.

  17. Novel antiplatelet agents: ALX-0081, a Nanobody directed towards von Willebrand factor.

    Science.gov (United States)

    Bartunek, Jozef; Barbato, Emanuele; Heyndrickx, Guy; Vanderheyden, Marc; Wijns, William; Holz, Josefin-Beate

    2013-06-01

    This manuscript reviews the studies performed with ALX-0081 (INN: caplacizumab), a Nanobody targeting von Willebrand factor, in the context of current antithrombotic therapy in coronary artery disease. ALX-0081 specifically inhibits platelet adhesion to the vessel wall, and may control platelet aggregation and subsequent clot formation without increasing bleeding risk. A substantial number of antithrombotics are aimed at this cascade; however, their generally indiscriminative mode of action can result in a narrow therapeutic window, defined by the risk for bleeding complications, and thrombotic events. Nonclinically, ALX-0081 compared favorably to several antithrombotics. In Phase I studies in healthy subjects and stable angina patients undergoing percutaneous coronary intervention (PCI), ALX-0081 was well tolerated, and effectively inhibited pharmacodynamic markers. Following these results, a phase II study was initiated in high-risk acute coronary syndrome patients undergoing PCI. Based on its mechanism of action, ALX-0081 is also being developed for acquired thrombotic thrombocytopenic purpura.

  18. Platelet function analyser (PFA-100) results and von Willebrand factor deficiency: a 16-year 'real-world' experience.

    Science.gov (United States)

    Ardillon, L; Ternisien, C; Fouassier, M; Sigaud, M; Lefrançois, A; Pacault, M; Ribeyrol, O; Fressinaud, E; Boisseau, P; Trossaërt, M

    2015-09-01

    The platelet function analyser (PFA-100) is a biological tool designed to explore primary haemostasis. This system has thus been widely demonstrated as reliable in detecting von Willebrand factor (VWF) deficiency. However, most studies were based on patients benefitting from regular medical care and accurate diagnosis, and it would seem probable that the results were somewhat optimistic, and do not reflect its performances in 'real-world' situations. We have chosen to study the reliability of PFA-100 for screening VWF ristocetin cofactor (VWF:RCo) deficiency. We retrospectively analysed the results (n = 6431) of 4027 patients referred to our centre between October 1997 and June 2013 and in whom PFA-Epi, PFA-ADP, and VWF:RCo activity had been evaluated. We studied the influence of blood group on the results and the performances of each method in a subgroup of 213 patients with genetically confirmed von Willebrand disease. We have shown that the PFA-100 system, in our experience, constitutes an excellent screening test for detecting VWF:RCo deficiency, whatever the clinical situation, in 'real-world' conditions. The negative predictive value (NPV), the positive predictive value, the sensitivity and the specificity were respectively: 0.98, 0.51, 0.98 and 0.40. When values adjusted for blood group are used, NPV and sensitivity are inferior to those using normal values which have not been adjusted for blood group. We have shown the PFA-100 method to be more efficient in screening for VWF deficiency than the VWF:RCo technique. © 2015 John Wiley & Sons Ltd.

  19. Elevated preoperative von Willebrand factor is associated with perioperative thrombosis in infants and neonates with congenital heart disease.

    Science.gov (United States)

    Hunt, R; Hoffman, C M; Emani, S; Trenor, C C; Emani, S M; Faraoni, D; Kimchi-Sarfaty, C; Ibla, J C

    2017-12-01

    Essentials Perioperative thrombosis is a major cause of morbidity and mortality in congenital heart disease. Neonates and infants undergoing repair of congenital heart lesions were prospectively followed. Elevated von Willebrand factor (VWF) to ADAMTS-13 activity ratios typified the postoperative period. Thrombosis was associated with preoperative VWF activity and cryoprecipitate transfusion SUMMARY: Background The surgical repair of congenital heart malformations is frequently complicated by perioperative thrombosis of unclear etiology. An imbalance between von Willebrand factor (VWF) and ADAMTS-13 is an emerging variable in thrombosis. Objectives To describe perioperative changes to VWF, ADAMTS-13 and NETosis, and evaluate clinical and biochemical associations with postoperative thrombosis. Methods Neonates and infants undergoing palliation or definitive surgical repair of congenital heart malformations were recruited (n = 133). Preoperative and postoperative plasma levels of VWF, ADAMTS-13 and markers of NETosis were determined. Patients were followed for up to 30 days for the occurrence of thrombosis. Univariate and multivariate logistic regression analyses were conducted to identify variables associated with thrombosis. Results We identified significant postoperative increases in VWF activity, VWF level, DNA-histone complexes and cell-free DNA with an overall decrease in ADAMTS-13 activity. Patients experiencing postoperative thrombotic events (9%) were characterized by surgery performed at a lower intraoperative temperature, higher preoperative lactic acid levels, and higher preoperative VWF activity and level. A multivariate logistic regression model identified preoperative VWF activity (odds ratio (OR) 8.39 per IU mL-1 , 95% confidence interval [CI] 1.73-40.55) and transfusion of cryoprecipitate (OR 1.10 per mL kg-1 , 95% CI 1.03-1.17) as being associated with thrombosis. Conclusions Pediatric patients undergoing surgical repair of congenital

  20. The markers of platelet functions and Von Willebrand factor serum content from patients with type 2 diabetes mellitus and ishemic stroke

    Directory of Open Access Journals (Sweden)

    Tetiana Tsarenko

    2016-03-01

    Full Text Available Introduction: The est and #1110;mated number of people with diabetes worldwide in 2015 is 415 million persons, up to 91% of adults hadtype 2 diabetes and the crude incidence of stroke among patients with diabetes of the 2ndtype can be more than 3 times that in the general population. It is known platelet activation and aggregation are critical in the pathogenesis of acute ischemic cerebrovascular diseases. Thus to examine the evidence of platelet functioning such as platelet count,aggregation in response to ADP, coagulation von Willebrand factor and serotonin content, monoamine oxidase (MAO activity in the blood of patients with ischemic stroke and with ischemic stroke complicated with the 2ndtype diabetes are the aim of the present study. Methods: The platelet aggregation was assayed for photo-optical aggregometer, von Willebrand factor was determined by Elisa, serotonin determination included ion-exchange chromatography and fluorescence spectrophotometry. Determination of monoamine-oxidase serum activity was spectophotometry. Results: The investigation has shown an increase of serotonin and Von Willebrand factor blood content in both groups of patients with ischemic stroke andtype 2 diabetes and stroke alone compared with the values of the control group. The monoamine oxidase activity and platelet count were reduced in blood of patients with diabetes of the 2ndtype with ischemic stroke against to the values from the group of healthy donors. Platelet aggregation in response to ADP increased under the investigated pathologies. Conclusions: These obtained data suggested a significant imbalance in vascular platelet element of hemostasis under the ischemic stroke and amplification of negative changes under the stroke with the 2ndtype diabetes. [Biomed Res Ther 2016; 3(3.000: 542-547

  1. Von Willebrand factor, a key protein in the exposure of CD62P on platelets.

    Science.gov (United States)

    Broberg, M; Nygren, H

    2001-09-01

    When a biomaterial is introduced into the body water, electrolytes, and proteins adsorb to the surface. Platelets are then the first cells to interact with the surface adsorbed protein layer. We have studied the role of von Willebrand factor (vWF) for platelet-protein interaction by measuring different platelet responses to protein- and plasma-coated hydrophobic glass surfaces. A high exposure of CD62P on the platelet surface was seen after 10 min of incubation on platelets interacting with vWF and normal plasma-coated surfaces (79 and 67%, respectively). On the surfaces coated with albumin and factor VIII deficient plasma, the exposure was low (11 and 27%, respectively). A higher formation of filipodial extensions on the platelets was seen on the surfaces coated with vWF and normal plasma than on the surfaces coated with albumin or factor VIII deficient plasma. No significant differences were seen between the surfaces regarding the platelet release of PF4, ATP, or phospholipids. As shown by these results, vWF is a specific regulator of the exposure of CD62P by platelets and hence important for the interaction between platelets and later arriving neutrophils at biomaterial surfaces.

  2. Time course of soluble P-selectin and von Willebrand factor levels in trauma patients: a prospective observational study.

    Science.gov (United States)

    Tang, Ning; Yin, Shiyu; Sun, Ziyong; Pan, Yingying

    2013-09-14

    Coagulopathy often develops in patients with serious trauma and is correlated with the clinical outcome. The contribution of platelet activity and endothelial dysfunction to trauma-induced coagulopathy remain to be defined. The purpose of this study was to investigate the time courses of soluble P-selectin (sPsel, an index of platelet activation) and von Willebrand factor (VWF, an index of endothelial dysfunction) in trauma patients and elucidate their relationship to coagulation parameter levels, the presence of coagulopathy, and patient outcome. This prospective observational study, which took place in a university hospital intensive care unit (ICU), included 82 severely injured trauma patients. The sPsel, VWF antigen, protein C, and factor VII levels were measured and routine coagulation tests were performed upon admission to ICU and daily within the first week. The 30-day mortality rate was also determined. Thirty-seven (45.1%) patients developed coagulopathy upon admission to the ICU, and the 30-day mortality rate was 20.7% (n = 17). Both the admission sPsel and VWF levels were lower in patients with coagulopathy than in those without (p trauma patients in the ICU, lower levels of sPsel and VWF on admission were associated with the presence of coagulopathy and might not predict a better outcome. An increase in the VWF level at the end of the first week after admission to ICU was associated with increased 30-day mortality.

  3. PROTEOLYTIC PROCESSING OF VON WILLEBRAND FACTOR BY ADAMTS13 AND LEUKOCYTE PROTEASES

    Directory of Open Access Journals (Sweden)

    Stefano Lancellotti

    2013-09-01

    Full Text Available ADAMTS13 is a 190 kDa zinc protease encoded by a gene located on chromosome 9q34.   This protease specifically hydrolyzes von Willebrand factor (VWF multimers, thus causing VWF size reduction. ADAMTS13 belongs to the A Disintegrin And Metalloprotease with ThromboSpondin type 1 repeats (ADAMTS family, involved in proteolytic processing of many matrix proteins. ADAMTS13 consists of numerous domains including a metalloprotease domain, a disintegrin domain, several thrombospondin type 1 (TSP1 repeats, a cysteine-rich domain, a spacer domain and 2 CUB (Complement c1r/c1s, sea Urchin epidermal growth factor, and Bone morphogenetic protein domains. ADAMTS13 cleaves a single peptide bond (Tyr1605-Met1606 in the central A2 domain of the VWF molecule. This proteolytic cleavage is essential to reduce the size of ultra-large VWF polymers, which, when exposed to high shear stress in the microcirculation, are prone to form with platelets clumps, which cause severe syndromes called thrombotic microangiopathies (TMAs. In this review, we a discuss the current knowledge of structure-function aspects of ADAMTS13 and its involvement in the pathogenesis of TMAs, b address the recent findings concerning proteolytic processing of VWF multimers by different proteases, such as the leukocyte-derived serine and metallo-proteases and c indicate the direction of future investigations

  4. A rapid, automated VWF ristocetin cofactor activity assay improves reliability in the diagnosis of Von Willebrand disease.

    Science.gov (United States)

    Bowyer, Annette E; Shepherd, Fiona; Kitchen, Stephen; Makris, Michael

    2011-04-01

    The effective diagnosis and monitoring of Von Willebrand Disease (VWD) requires an accurate assessment of ristocetin co-factor activity (VWF:RCo). Current methodologies include automated platelet aggregometry and manual visual agglutination both of which are laborious to perform and notoriously subject to a high degree of inter and intra assay variation. We have evaluated an automated VWF:RCo assay (BC Von Willebrand Reagent, Siemens, Marberg, Germany) for use on the Sysmex CS2100i analyser (Milton Keynes, UK) and retrospectively compared the results with an in-house manual visual agglutination assay and VWF antigen (Siemens) in normal subjects and in 53 patients with various types of VWD and 23 patients following VWF therapeutic treatment. The intra and interassay CV was improved with the automated assay (2.3% and 3.8% respectively) compared to 7% with the manual VWF:RCo assay. Good correlation was found between the two assays (r=0.91) in 53 patients with VWD. The mean manual VWF:RCo was 0.25IU/ml and mean automated VWF:RCo was 0.27IU/ml. A comparable increase in VWF:RCo following treatment, mostly with Desmopressin, was found in 13 patients with type 1 VWD (mean 3.9 fold increase with manual VWF:RCo and 3.1 fold with the automated VWF:RCo). In 13 patients with type 2 or 3 VWD following treatment mostly with concentrate , a higher increase was found with the automated VWF:RCo assay than the manual assay (mean 11.9 fold manually and mean 20.3 automated). The automated VWF:RCo assay shows enhanced precision and analysis time in this difficult and time consuming laboratory test and its introduction should greatly improve the reliability of VWF testing. Copyright © 2010. Published by Elsevier Ltd.

  5. The membrane-proximal intermolecular disulfide bonds in glycoprotein Ib influence receptor binding to von Willebrand factor.

    Science.gov (United States)

    Mo, X; Luo, S-Z; Munday, A D; Sun, W; Berndt, M C; López, J A; Dong, J-F; Li, R

    2008-10-01

    In the platelet glycoprotein (GP)Ib-IX complex, the binding site for its ligand von Willebrand factor (VWF) is restricted to the N-terminal domain of the GPIbalpha subunit. How the other subunits in the complex, GPIbbeta and GPIX, regulate the GPIbalpha-VWF interaction is not clear. As GPIbalpha connects with two GPIbbeta subunits via disulfide bonds, we tested whether these intersubunit covalent links were important to the proper VWF-binding activity of the GPIb-IX complex by characterizing the structure and VWF-binding activity of a mutant GPIb-IX complex that lacked the GPIbalpha-GPIbbeta disulfide bonds. Mutating both Cys484 and Cys485 of GPIbalpha to serine prevents GPIbalpha from forming covalent disulfide bonds with GPIbbeta, while maintaining the integrity of the complex in the membrane. The mutations cause two GPIbbeta subunits to form a disulfide bond between themselves. As compared to Chinese hamster ovary (CHO) cells stably expressing the wild-type GPIb-IX complex at a comparable level, CHO cells stably expressing the mutant GPIb-IX complex bind to significantly less soluble VWF in the presence of ristocetin and roll on the immobilized VWF under flow at a higher velocity. The disulfide bonds between GPIbalpha and GPIbbeta are necessary for optimal GPIbalpha binding to VWF. The structural plasticity around the disulfide bonds may also help to shed light on the inside-out mechanism underlying GPIbbeta modulation of VWF binding.

  6. Role of 14-3-3ζ in Platelet Glycoprotein Ibα-von Willebrand Factor Interaction-Induced Signaling

    Directory of Open Access Journals (Sweden)

    Kesheng Dai

    2012-05-01

    Full Text Available The interaction of platelet glycoprotein (GP Ib-IX with von Willebrand factor (VWF exposed at the injured vessel wall or atherosclerotic plaque rupture initiates platelet transient adhesion to the injured vessel wall, which triggers intracellular signaling cascades leading to platelet activation and thrombus formation. 14-3-3ζ has been verified to regulate the VWF binding function of GPIb-IX by interacting with the cytoplasmic domains of GPIb-IX. However, the data regarding the role of 14-3-3ζ in GPIb-IX-VWF interaction-induced signaling still remain controversial. In the present study, the data indicate that the S609A mutation replacing Ser609 of GPIbα with alanine (S609A significantly prevented the association of 14-3-3ζ with GPIbα before and after the VWF binding to GPIbα. GPIb-IX-VWF interaction-induced activations of Src family kinases and protein kinase C were clearly reduced in S609A mutation. Furthermore, S609A mutation significantly inhibited GPIb-IX-VWF interaction-induced elevation of cytoplasmic Ca2+ levels in flow cytometry analysis. Taken together, these data indicate that the association of 14-3-3ζ with the cytoplasmic domain of GPIbα plays an important role in GPIb-IX-VWF interaction-induced signaling.

  7. Safety of a pasteurized plasma-derived Factor VIII and von Willebrand factor concentrate: analysis of 33 years of pharmacovigilance data.

    Science.gov (United States)

    Kouides, Peter; Wawra-Hehenberger, Kathrin; Sajan, Anna; Mead, Henry; Simon, Toby

    2017-10-01

    Haemate-P/Humate-P (Humate-P) is a pasteurized human plasma-derived concentrate containing both Factor VIII and von Willebrand factor for treatment of hemophilia A and von Willebrand disease (VWD). We analyzed the safety of Humate-P based on more than 33 years of postmarketing pharmacovigilance data, representing an estimated exposure of approximately 25,000 patient-years. The analysis comprises reports of potential adverse drug reactions (ADRs) from all sources, reported as part of routine pharmacovigilance at CSL Behring. ADRs considered clinically relevant or potential risks of Humate-P were identified based on defined and standardized Medical Dictionary for Regulatory Activities queries. Recognizing the limitations of spontaneous reporting, we also reviewed the literature, including clinical trials with mandatory reporting. From 1982 to 2015, a total of 670 postmarketing cases had been reported via pharmacovigilance, for an overall reporting rate of approximately one ADR per 3900 administered standard doses. Of these cases, 343 involved ADRs considered clinically relevant risks (33 thromboembolic complications, 97 inhibitor formation, 110 hypersensitivity or allergic reactions) or potential risks (103 suspected virus transmissions) for Humate-P. Most thromboembolic complications occurred in patients undergoing surgery or with other known risk factors. Inhibitor formation occurred mostly in patients with hemophilia A (24 cases were high titer). Most patients with hypersensitivity or allergic reactions had VWD. None of the reported suspected virus transmission cases were confirmed to be associated with Humate-P. Reported results of company-sponsored studies showed a low incidence of adverse events possibly or probably related to Humate-P. More than 33 years of pharmacovigilance data continue to support the safety of Humate-P. © 2017 The Authors. Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.

  8. Mechanism and functional impact of CD40 ligand-induced von Willebrand factor release from endothelial cells.

    Science.gov (United States)

    Möller, Kerstin; Adolph, Oliver; Grünow, Jennifer; Elrod, Julia; Popa, Miruna; Ghosh, Subhajit; Schwarz, Manuel; Schwale, Chrysovalandis; Grässle, Sandra; Huck, Volker; Bruehl, Claus; Wieland, Thomas; Schneider, Stefan W; Nobiling, Rainer; Wagner, Andreas H; Hecker, Markus

    2015-05-01

    Co-stimulation via CD154 binding to CD40, pivotal for both innate and adaptive immunity, may also link haemostasis to vascular remodelling. Here we demonstrate that human platelet-bound or recombinant soluble CD154 (sCD154) elicit the release from and tethering of ultra-large (UL) von Willebrand factor (vWF) multimers to the surface of human cultured endothelial cells (ECs) exposed to shear stress. This CD40-mediated ULVWF multimer release from the Weibel-Palade bodies was triggered by consecutive activation of TRAF6, the tyrosine kinase c-Src and phospholipase Cγ1 followed by inositol-1,4,5 trisphosphate-mediated calcium mobilisation. Subsequent exposure to human washed platelets caused ULVWF multimer-platelet string formation on the EC surface in a shear stress-dependent manner. Platelets tethered to these ULVWF multimers exhibited P-selectin on their surface and captured labelled monocytes from the superfusate. When exposed to shear stress and sCD154, native ECs from wild-type but not CD40 or vWF-deficient mice revealed a comparable release of ULVWF multimers to which murine washed platelets rapidly adhered, turning P-selectin-positive and subsequently capturing monocytes from the perfusate. This novel CD154-provoked ULVWF multimer-platelet string formation at normal to fast flow may contribute to vascular remodelling processes requiring the perivascular or intravascular accumulation of pro-inflammatory macrophages such as arteriogenesis or atherosclerosis.

  9. Allelic associations of two polymorphic microsatellites in intron 40 of the human von Willebrand factor gene

    Energy Technology Data Exchange (ETDEWEB)

    Pena, S.D.J.; De Souza, K.T. (Nucleo de Genetica Medica de Minas Gerais, Belo Horizonte (Brazil)); De Andrade, M.; Chakraborty, R. (Univ. of Texas Graduate School of Biomedical Sciences, Houston, TX (United States))

    1994-01-18

    At intron 40 of the von Willebrand factor (vWF) gene, two GATA-repeat polymorphic sites exist that are physically separated by 212 bp. At the first site (vWF1 locus), seven segregating repeat alleles were observed in a Brazilian Caucasian population, and at the second (vWF2 locus) there were eight alleles, detected through PCR amplifications of this DNA region. Haplotype analysis of individuals revealed 36 different haplotypes in a sample of 338 chromosomes examined. Allele frequencies between generations and gender at each locus were not significantly different, and the genotype frequencies were consistent with their Hardy-Weinberg expectations. Linkage disequilibrium between loci is highly significant with positive allele size association; that is, large alleles at the loci tend to occur together, and so do the same alleles. Variability at each locus appeared to have arisen in a stepwise fashion, suggesting replication slippage as a possible mechanism of production of new alleles. However, the authors observed an increased number of haplotypes, in contrast with the predictions of a stepwise production of variation in the entire region, suggesting some form of cooperative changes between loci that could be due to either gene conversion, or a common control mechanism of production of new variation at these repeat polymorphism sites. The high degree of polymorphism (gene diversity values of 72% and 78% at vWF1 and vWF2, respectively, and of 93% at the haplotype level) makes these markers informative for paternity testing, genetic counseling, and individual-identification purposes.

  10. von Willebrand factor deficiency leads to impaired blood flow recovery after ischaemia in mice.

    Science.gov (United States)

    de Vries, Margreet R; Peters, Erna A B; Quax, Paul H A; Nossent, A Yaël

    2017-06-28

    Neovascularisation, i. e. arteriogenesis and angiogenesis, is an inflammatory process. Therefore attraction and extravasation of leukocytes is essential for effective blood flow recovery after ischaemia. Previous studies have shown that von Willebrand factor (VWF) is a negative regulator of angiogenesis. However, it has also been shown that VWF facilitates leukocyte attraction and extravasation. We aimed to investigate the role of VWF in arteriogenesis and angiogenesis during post-ischaemic neovascularisation. Wild-type (WT) and VWF deficient (VWF -/- ) C57BL/6 mice were subjected to hindlimb ischaemia via double ligation of the left femoral artery, and blood flow recovery was followed over time, using Laser Doppler Perfusion Imaging. Blood flow recovery was impaired in VWF -/- mice. After 10 days, VWF -/- mice showed a 43 ± 5 % recovery versus 68 ± 5 % in WT. Immunohistochemistry revealed that both arteriogenesis in the adductor muscles and angiogenesis in the gastrocnemius muscles were reduced in VWF -/- mice. Furthermore, leukocyte infiltration in the affected adductor muscles was reduced in VWF -/- mice. Residual paw perfusion directly after artery ligation was also reduced in VWF -/- mice, indicating a decrease in pre-existing collateral arteriole density. When we quantified collateral arterioles, we observed a 31 % decrease in the average number of collateral arterioles in the pia mater compared to WT mice (57 ± 3 in WT vs 40 ± 4 pial collaterals in VWF -/- ). We conclude that VWF facilitates blood flow recovery in mice. VWF deficiency hampers both arteriogenesis and angiogenesis in a hindlimb ischaemia model. This is associated with impaired leukocytes recruitment and decreased pre-existing collateral density in the absence of VWF.

  11. Increased deposition of von Willebrand factor in the rat heart after local ionizing irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Boerma, M.; Loenen, M.M. van; Klein, H.R.; Bart, C.I.; Wondergem, J. [Dept. of Clinical Oncology (K1-P), Leiden Univ. Medical Center (Netherlands); Kruse, J.J.C.M. [Dept. of Clinical Oncology (K1-P), Leiden Univ. Medical Center (Netherlands); Dept. of Experimental Therapy (H6), Netherlands Cancer Inst., Amsterdam (Netherlands); Zurcher, C. [Dept. of Clinical Oncology (K1-P), Leiden Univ. Medical Center (Netherlands); Dept. of Pathology, Faculty of Veterinary Medicine, Univ. of Utrecht (Netherlands)

    2004-02-01

    Background and purpose: von willebrand factor (vWf), a glycoprotein involved in blood coagulation, is synthesized by endothelial cells. Increased amounts of vWf in blood plasma or tissue samples are indicative of damaged endothelium. In the present study, mRNA expression and localization of vWf were determined in irradiated rat heart tissue. Material and methods: sprague-dawley rats received local heart irradiation with a single dose of 0, 15, or 20 Gy. Hearts were dissected at different time points (up to 16 months) after irradiation. In a second experiment, rats were injected with the radioprotector amifostine (160 mg/kg, i.p.) 15-20 min before irradiation and sacrificed after 6 months. Immunohistochemistry was performed using a polyclonal anti-vWf antibody. Serial sections were subjected to a general rat endothelial cell immunostaining (RECA-1) or a collagen staining (picrosirius red). mRNA expression was determined by using PCR. Results: in control tissue, all endothelial cells lining the lumen of the endocardium and coronary arteries, but not capillary endothelial cells, were stained for vWf. 1 month after irradiation with both 15 and 20 Gy, myocardial capillaries became immunoreactive. From 3 months onward, staining was observed also within the extracellular matrix (ECM) of fibrotic areas. At mRNA level, no changes in vWf could be observed at all time points after irradiation, suggesting that vWf deposition was not due to increased biosynthesis of the protein. In sections of amifostine-treated rat hearts, vWf staining was increased to a lesser extent. Conclusion: these dose- and time-dependent increases in deposition of vWf indicate the presence of damaged endothelium in the irradiated rat heart. These increases in vWf accumulation precede development of fibrosis in the subendocardial layer and myocardium of the left ventricles, right ventricles, and atria. (orig.)

  12. In vivo analysis of the role of O-glycosylations of von Willebrand factor.

    Directory of Open Access Journals (Sweden)

    Idinath Badirou

    Full Text Available The objective of this project was to study the function of O-glycosylations in von Willebrand factor (VWF life cycle. In total, 14 different murine Vwf cDNAs mutated on one or several O-glycosylations sites were generated: 9 individual mutants, 2 doublets, 2 clusters and 1 mutant with all 9 murine glycosylation sites mutated (Del-O-Gly. We expressed each mutated cDNA in VWF deficient-mice by hydrodynamic injection. An immunosorbent assay with Peanut Agglutinin (PNA was used to verify the O-glycosylation status. Wild-type (WT VWF expressed by hepatocytes after hydrodynamic injection was able to bind PNA with slightly higher affinity than endothelial-derived VWF. In contrast, the Del-O-Gly VWF mutant did not bind PNA, demonstrating removal of O-linked glycans. All mutants displayed a normal multimeric pattern. Two mutants, Del-O-Gly and T1255A/T1256A, led to expression levels 50% lower than those induced by WT VWF and their half-life in vivo was significantly reduced. When testing the capacity of each mutant to correct the bleeding time of VWF-deficient mice, we found that S1486A, T1255A, T1256A and the doublet T1255A/T1256A were unable to do so. In conclusion we have shown that O-glycosylations are dispensable for normal VWF multimerization and biosynthesis. It also appears that some O-glycosylation sites, particularly the T1255 and T1256 residues, are involved in the maintenance of VWF plasma levels and are essential for normal haemostasis. As for the S1486 residue, it seems to be important for platelet binding as demonstrated in vitro using perfusion experiments.

  13. An external quality assessment program for von Willebrand factor laboratory analysis: an overview from the European concerted action on thrombosis and disabilities foundation.

    Science.gov (United States)

    Meijer, Piet; Haverkate, Frits

    2006-07-01

    The laboratory diagnosis of von Willebrand disease (vWD) is complex and requires a panel of different laboratory tests. Because of this complexity, a proper quality control process is necessary. Since 2003, the European Concerted Action on Thrombosis and Disabilities Foundation has provided an external quality control program for several laboratory tests included in the diagnosis of vWD. Currently, ~180 different laboratories participate in this program, of which the vast majority perform both von Willebrand factor (vWF):antigen (Ag) and activity tests. The lowest between-laboratory variation was observed for the vWF antigen assay (10 to 24%), with a better performance for the latex immunoassay (8 to 24%) than the enzyme immunoassay (13 to 25%). Both the ristocetin cofactor activity assay (RCo) and the collagen-binding assay showed a higher between-laboratory variation (20 to 40% and 17 to 29%, respectively). We have observed that the within-laboratory repeatability for normal samples ranged from 0 to 40% for the antigen assay and from 0 to 86% for the ristocetin cofactor activity assay. Normal samples were interpreted correctly by the majority of the participants. However, type 1 vWD samples were wrongly interpreted by 20 to 40% of the participants, which was mainly caused by a discordance in the vWF:RCo/vWF:Ag ratio. It can be concluded that further improvement in the laboratory diagnosis of vWD is necessary.

  14. Clinical and laboratory diagnosis of von Willebrand disease : A synopsis of the 2008 NHLBI/NIH guidelines

    NARCIS (Netherlands)

    Nichols, William L.; Rick, Margaret E.; Ortel, Thomas L.; Montgomery, Robert R.; Sadler, J. Evan; Yawn, Barbara P.; James, Andra H.; Hultin, Mae B.; Manco-Johnson, Marilyn J.; Weinstein, Mark

    Von Willebrand factor (VWF) mediates blood platelet adhesion and accumulation at sites of blood vessel injury, and also carries coagulation factor VIII (FVIII) that is important for generating procoagulant activity. Von Willebrand disease (VWD), the most common inherited bleeding disorder, affects

  15. Genome-wide linkage analysis of von Willebrand factor plasma levels: results from the GAIT project.

    Science.gov (United States)

    Souto, Juan Carlos; Almasy, Laura; Soria, Jose Manuel; Buil, Alfonso; Stone, William; Lathrop, Mark; Blangero, John; Fontcuberta, Jordi

    2003-03-01

    High plasma levels of von Willebrand factor (vWF) have been associated with the risk of thromboembolic disease. As a complex trait, this phenotype must be influenced by genetic and environmental factors. Among the genetic factors, only the ABO gene located on chromosome 9q34 has been clearly linked to the plasma levels of vWF. This locus explains about 30-40% of the genetic variability. Therefore, the source of the majority of the genetic component remains to be identified. To search for these unknown loci, we conducted a genomewide linkage screen for genes affecting normal variation in vWF levels in 21 Spanish families as part of the GAIT (Genetic Analysis of Idiopathic Thrombophilia) Project. The results showed that the strongest linkage signal (LOD =3.46, p = 0.00003) for vWF was found on chromosome 9q34 at the DNA marker D9S290, where the ABO gene is located. Additional suggestive linkage signals were found on chromosomes 2q23.2 (LOD = 1.65, p = 0.003) and 1p36.13 (LOD =1.32, p = 0.007). After refining the linkage analysis, conditional to the ABO genotype, three additional loci on chromosomes 5, 6 and 22 showed LOD scores higher than 1, suggesting the presence of other genes linked to vWF levels. Curiously, no linkage signals were detected in other chromosome regions previously associated with vWF levels (like the structural VWF gene on 12p13.2 or Lewis blood group gene on 19q13). These results indicate that these loci are not important genetic determinants of the normal variation of vWF levels. Our results indicate that the ABO locus is the major genetic determinant of the plasma levels of the vWF in Spanish population. It is possible that there are other potential regions on chromosomes 1, 2, 5, 6 and 22 that influence this thrombosis risk factor. However, the structural vWF gene itself has a very low influence (if any) on the plasma levels of vWF.

  16. Living with von Willebrand Disease

    Science.gov (United States)

    ... the condition. For example, the school nurse, teacher, daycare provider, coach, or any leader of afterschool activities ... MedlinePlus) Von Willebrand Disease (MedlinePlus) Building 31 31 Center Drive Bethesda, MD 20892 Learn more about getting ...

  17. Neutrophil Protease Cleavage of Von Willebrand Factor in Glomeruli - An Anti-thrombotic Mechanism in the Kidney.

    Science.gov (United States)

    Tati, Ramesh; Kristoffersson, Ann-Charlotte; Manea Hedström, Minola; Mörgelin, Matthias; Wieslander, Jörgen; van Kooten, Cees; Karpman, Diana

    2017-02-01

    Adequate cleavage of von Willebrand factor (VWF) prevents formation of thrombi. ADAMTS13 is the main VWF-cleaving protease and its deficiency results in development of thrombotic microangiopathy. Besides ADAMTS13 other proteases may also possess VWF-cleaving activity, but their physiological importance in preventing thrombus formation is unknown. This study investigated if, and which, proteases could cleave VWF in the glomerulus. The content of the glomerular basement membrane (GBM) was studied as a reflection of processes occurring in the subendothelial glomerular space. VWF was incubated with human GBMs and VWF cleavage was assessed by multimer structure analysis, immunoblotting and mass spectrometry. VWF was cleaved into the smallest multimers by the GBM, which contained ADAMTS13 as well as neutrophil proteases, elastase, proteinase 3 (PR3), cathepsin-G and matrix-metalloproteinase 9. The most potent components of the GBM capable of VWF cleavage were in the serine protease or metalloprotease category, but not ADAMTS13. Neutralization of neutrophil serine proteases inhibited GBM-mediated VWF-cleaving activity, demonstrating a marked contribution of elastase and/or PR3. VWF-platelet strings formed on the surface of primary glomerular endothelial cells, in a perfusion system, were cleaved by both elastase and the GBM, a process blocked by elastase inhibitor. Ultramorphological studies of the human kidney demonstrated neutrophils releasing elastase into the GBM. Neutrophil proteases may contribute to VWF cleavage within the subendothelium, adjacent to the GBM, and thus regulate thrombus size. This anti-thrombotic mechanism would protect the normal kidney during inflammation and could also explain why most patients with ADAMTS13 deficiency do not develop severe kidney failure. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

  18. Von Willebrand factor and fibrinolytic parameters during the desmopressin test in patients with Cushing's disease

    Science.gov (United States)

    Giraldi, Francesca Pecori; Ambrogio, Alberto G; Fatti, Letizia M; Rubini, Valentina; Cozzi, Giovanna; Scacchi, Massimo; Federici, Augusto B; Cavagnini, Francesco

    2011-01-01

    AIMS Desmopressin, a vasopressin analogue, is used for various clinical purposes, including haemostasis and, in recent times, the diagnostic work-up of patients with Cushing's syndrome, a condition associated with a known prothrombotic profile. We decided to evaluate whether and to what extent a diagnostic dose of desmopressin induces significant changes in endothelial parameters in patients with Cushing's disease (CD) and obese and normal weight controls. METHODS Twelve patients with CD, 10 obese and five normal weight controls were studied. Von Willebrand antigen (VWF : Ag), tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were measured at baseline and up to 4 h after 10 µg desmopressin i.v. RESULTS Desmopressin 10 µg transiently increased VWF : Ag and t-PA and decreased PAI-1 in all subjects. The magnitude of the VWF : Ag and t-PA increases after desmopressin was comparable in the three groups (VWF : Ag peak-to-basal ratio 1.9 ± 0.17, 1.5 ± 0.11 and 1.8 ± 0.13 and t-PA peak-to-basal ratio 1.6 ± 0.18, 1.6 ± 0.20 and 1.8 ± 0.24 for CD, obese and controls, respectively, all NS). The PAI-1 decrease observed in patients with CD was comparable with obese (0.7 ± 0.07 and 0.6 ± 0.09, NS) and controls (0.7 ± 0.07 vs. 0.4 ± 0.09, P = 0.08). CONCLUSIONS Administration of desmopressin to patients with CD for diagnostic purposes induces a transitory increase in VWF : Ag counterbalanced by a decrease in PAI-1 and increase in t-PA. The magnitude of these changes is largely comparable with that observed in obese and normal weight controls. Our data show that testing with desmopressin does not induce disease-specific changes in endothelial markers in patients with CD. PMID:21143510

  19. The study of the effect of splicing mutations in von Willebrand factor using RNA isolated from patients' platelets and leukocytes.

    Science.gov (United States)

    Corrales, I; Ramírez, L; Altisent, C; Parra, R; Vidal, F

    2011-04-01

    In von Willebrand factor (VWF) the effect of mutations potentially affecting mRNA processing or splicing is less predictable than that of other mutations (e.g. nonsense or missense substitutions). Bioinformatic tools can provide a valuable means to determine the consequences of potential splice site mutations (PSSM), but functional studies are mandatory to elucidate the true effect of the variation detected. After identification of PSSM in VWD patients, we began a systematic study of their in vivo effect in RNA extracted from the patients' platelets and leukocytes. Thirteen pairs of primers were designed for full amplification of VWF mRNA by RT-PCR that, after sequencing of aberrant products, enabled elucidation of the PSSM consequences for mRNA processing. This procedure was used to study seven different PSSM identified in four patients demonstrating diverse molecular mechanisms such as exon skipping (c.533-2A>G and c.8155+3G>C) and the activation of a cryptic splice site (c.7730-1G>C). No visible effect was evident for c.1533+15G>A and c.5170+10C>T and the consequence of c.[546G>A;7082-2A>G] was hidden by nonsense-mediated mRNA decay (NMD). Results were compared with in silico predictions of four splice-site analysis tools. We demonstrate selective degradation of VWF mRNA bearing PSSM by NMD for several mutations, which suggests that NMD represents a general mechanism for truncating mutations in VWF. Furthermore, because NMD efficiency varies between cell types, use of RNA from both platelets and leukocytes for in vivo study of VWF PSSM offers complementary results, particularly in cases in which NMD occurs in the allele carrying the mutation. © 2011 International Society on Thrombosis and Haemostasis.

  20. The spider hemolymph clot proteome reveals high concentrations of hemocyanin and von Willebrand factor-like proteins.

    Science.gov (United States)

    Sanggaard, Kristian W; Dyrlund, Thomas F; Bechsgaard, Jesper S; Scavenius, Carsten; Wang, Tobias; Bilde, Trine; Enghild, Jan J

    2016-02-01

    Arthropods include chelicerates, crustaceans, and insects that all have open circulation systems and thus require different properties of their coagulation system than vertebrates. Although the clotting reaction in the chelicerate horseshoe crab (Family: Limulidae) has been described in details, the overall protein composition of the resulting clot has not been analyzed for any of the chelicerates. The largest class among the chelicerates is the arachnids, which includes spiders, ticks, mites, and scorpions. Here, we use a mass spectrometry-based approach to characterize the spider hemolymph clot proteome from the Brazilian whiteknee tarantula, Acanthoscurria geniculata. We focused on the insoluble part of the clot and demonstrated high concentrations of proteins homologous to the hemostasis-related and multimerization-prone von Willebrand factor. These proteins, which include hemolectins and vitellogenin homologous, were previously identified as essential components of the hemolymph clot in crustaceans and insects. Their presence in the spider hemolymph clot suggests that the origin of these proteins' function in coagulation predates the split between chelicerates and mandibulata. The clot proteome reveals that the major proteinaceous component is the oxygen-transporting and phenoloxidase-displaying abundant hemolymph protein hemocyanin, suggesting that this protein also plays a role in clot biology. Furthermore, quantification of the peptidome after coagulation revealed the simultaneous activation of both the innate immune system and the coagulation system. In general, many of the identified clot-proteins are related to the innate immune system, and our results support the previously suggested crosstalk between immunity and coagulation in arthropods. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Homocisteína plasmática total e fator von Willebrand no diabete melito experimental Total plasmatic homocysteine and von Willebrand factor in experimental diabetes mellitus

    OpenAIRE

    Renato Delascio Lopes; Lindalva Batista Neves; Vânia D'Almeida; Gleice Margarete de Souza Conceição; Alexandre Gabriel Junior

    2007-01-01

    OBJETIVOS: Determinar os valores plasmáticos de homocisteína e fator von Willebrand, como marcador de disfunção endotelial, em ratos com diabete melito induzido por estreptozotocina. MÉTODOS: Trinta e cinco ratos (rattus norvegicus albinus), machos, adultos (180-200 g), randomizados em três grupos: controle (n=10) não receberam agente ou veículo; sham (n=10) receberam solução veículo da estreptozotocina; e diabético (n=15) receberam estreptozotocina. Após oito semanas de indução do diabete me...

  2. Structural specializations of A2, a force-sensing domain in the ultralarge vascular protein von Willebrand factor

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Qing; Zhou, Yan-Feng; Zhang, Cheng-Zhong; Zhang, Xiaohui; Lu, Chafen; Springer, Timothy A.; Harvard-Med

    2009-06-30

    The lengths of von Willebrand factor (VWF) concatamers correlate with hemostatic potency. After secretion in plasma, length is regulated by hydrodynamic shear force-dependent unfolding of the A2 domain, which is then cleaved by a specific protease. The 1.9-{angstrom} crystal structure of the A2 domain demonstrates evolutionary adaptations to this shear sensor function. Unique among VWF A (VWA) domains, A2 contains a loop in place of the {alpha}4 helix, and a cis-proline. The central {beta}4-strand is poorly packed, with multiple side-chain rotamers. The Tyr-Met cleavage site is buried in the {beta}4-strand in the central hydrophobic core, and the Tyr structurally links to the C-terminal {alpha}6-helix. The {alpha}6-helix ends in 2 Cys residues that are linked by an unusual vicinal disulfide bond that is buried in a hydrophobic pocket. These features may narrow the force range over which unfolding occurs and may also slow refolding. Von Willebrand disease mutations, which presumably lower the force at which A2 unfolds, are illuminated by the structure.

  3. Cerebral venous thrombosis and plasma concentrations of factor VIII and von Willebrand factor: a case control study.

    Science.gov (United States)

    Bugnicourt, Jean-Marc; Roussel, Bertrand; Tramier, Blaise; Lamy, Chantal; Godefroy, Olivier

    2007-07-01

    High plasma concentrations of factor VIII (FVIII) and von Willebrand factor (VWF) have been recently associated with a moderately increased risk of venous thrombosis, but their roles in cerebral sinus and venous thrombosis (CSVT) have not been addressed. To determine whether elevation of FVIII and VWF is more frequent in CSVT, we analysed plasma levels of FVIII and VWF in a case control study. The study population consisted of 25 consecutive patients (of whom nine were excluded) admitted for CSVT to the Department of Neurology, Amiens University Hospital, France, from January 1997 to December 2002, for a general screening for thrombophilia. Sixty-four healthy subjects matched for age and sex formed the group control. Mean FVIII (CSVT: 167.3 (SD 48.8) IU/dl; control group: 117.9 (39.8) IU/dl; p = 0.001) and VWF levels (CSVT: 165.4 (76.5)%; control group: 108.5 (27.8)%; p = 0.01) were significantly higher in the CSVT group. Using the 95th percentile of the control group as the cut off value, elevated FVIII (>190 IU/dl) occurred in 25% (4/16) (p = 0.005) and elevated VWF (>168%) in 37.5% (6/16) of patients with CSVT (p150 IU/dl or >150%) showed the same results (FVIII: p = 0.005; VWF: p = 0.009). Our study suggests that elevation of plasma factor VIII levels is the most common prothrombotic risk factor for CSVT. Elevation of VWF is also associated with an increased risk of CSVT but its effect seems to be partly mediated through FVIII.

  4. Storage of factor VIII variants with impaired von Willebrand factor binding in Weibel-Palade bodies in endothelial cells.

    Directory of Open Access Journals (Sweden)

    Maartje van den Biggelaar

    Full Text Available BACKGROUND: Point mutations resulting in reduced factor VIII (FVIII binding to von Willebrand factor (VWF are an important cause of mild/moderate hemophilia A. Treatment includes desmopressin infusion, which concomitantly increases VWF and FVIII plasma levels, apparently from storage pools containing both proteins. The source of these VWF/FVIII co-storage pools and the mechanism of granule biogenesis are not fully understood. METHODOLOGY/PRINCIPAL FINDINGS: We studied intracellular trafficking of FVIII variants implicated in mild/moderate hemophilia A together with VWF in HEK293 cells and primary endothelial cells. The role of VWF binding was addressed using FVIII variants displaying reduced VWF interaction. Binding studies using purified FVIII proteins revealed moderate (Arg2150His, Del2201, Pro2300Ser to severe (Tyr1680Phe, Ser2119Tyr VWF binding defects. Expression studies in HEK293 cells and primary endothelial cells revealed that all FVIII variants were present within VWF-containing organelles. Quantitative studies showed that the relative amount of FVIII storage was independent of various mutations. Substantial amounts of FVIII variants are co-stored in VWF-containing storage organelles, presumably by virtue of their ability to interact with VWF at low pH. CONCLUSIONS: Our data suggest that the potential of FVIII co-storage with VWF is not affected in mild/moderate hemophilia A caused by reduced FVIII/VWF interaction in the circulation. These data support the hypothesis that Weibel-Palade bodies comprise the desmopressin-releasable FVIII storage pool in vivo.

  5. Dogs with hearth diseases causing turbulent high-velocity blood flow have changes in patelet function and von Willebrand factor multimer distribution

    DEFF Research Database (Denmark)

    Tarnow, Inge; Kristensen, Annemarie Thuri; Olsen, Lisbeth Høier

    2005-01-01

    The purpose of this prospective study was to investigate platelet function using in vitro tests based on both high and low shear rates and von Willebrand factor (vWf) multimeric composition in dogs with cardiac disease and turbulent high-velocity blood flow. Client-owned asymptomatic, untreated d...

  6. Function of von Willebrand factor in children with diarrhea-associated hemolytic-uremic syndrome (D+ HUS).

    Science.gov (United States)

    Sutor, A H; Thomas, K B; Prüfer, F H; Grohmann, A; Brandis, M; Zimmerhackl, L B

    2001-06-01

    Reports on von Willebrand factor (vWF) in hemolytic-uremic syndrome (HUS) are not unequivocal. Because of potential pathogenic implications, we examined the ability of vWF to bind to collagen in vitro, which reflects its function. Plasma vWF antigen (vWF:Ag) and collagen-binding activity (vWF:CBA) were measured by enzyme-linked immunosorbent assay in children with (1) diarrhea-associated (D+) HUS (n = 27), (2) chronic renal insufficiency (CRI) (n = 8), (3) gastroenteritis (GE) not associated with HUS (n = 15), (4) immune thrombocytopenia (ITP) (n = 40) and from controls (n = 35). Structural vWF was evaluated by multimer analysis. Children with D+ HUS had vWF:Ag of 2.53 and vWF:CBA of 1.98 U/mL. The corresponding values for patients with ITP were 1.35 and 1.82 U/mL, with CRI 1.55 and 1.55 U/mL, and with GE 1.68 and 2.10 U/mL; all values were higher than in controls (1.04 and 1.16 U/mL). The mean ratio of vWF:CBA to vWF:Ag ratio in controls was 1.13; only children with HUS had a dysfunctional vWF, as indicated by a low ratio of 0.78; the ratio was elevated in children with ITP (1.36) and GE (1.27) and was normal in those with CRI (1.06). No ultralarge molecular multimers of vWF were detected in any group, including HUS. The very high concentration of plasma vWF:Ag in HUS probably reflects endothelial cell damage or irritation. In contrast to all other groups, only children with HUS had a dysfunctional vWF, caused either by a primary (due to enterohemorrhagic Escherichia coli) or secondary (due to consumption of functionally active vWF) process. This abnormality was not obvious as structural anomaly by multimer analysis.

  7. Factor VIII and von Willebrand factor co-delivery by endothelial cells

    NARCIS (Netherlands)

    Bouwens, E.A.M.

    2011-01-01

    A defect in coagulation factor VIII (FVIII) results in the inherited bleeding disorder hemophilia A. Current treatment of hemophilia A is hampered by the need of frequent administration of costly FVIII products. Therefore gene therapy is an attractive alternative for protein replacement to treat

  8. von Willebrand Factor-Rich Platelet Thrombi in the Liver Cause Sinusoidal Obstruction Syndrome following Oxaliplatin-Based Chemotherapy.

    Directory of Open Access Journals (Sweden)

    Naoto Nishigori

    Full Text Available Oxaliplatin-based chemotherapy is widely used to treat advanced colorectal cancer (CRC. Sinusoidal obstruction syndrome (SOS due to oxaliplatin is a serious type of chemotherapy-associated liver injury (CALI in CRC patients. SOS is thought to be caused by the sinusoidal endothelial cell damage, which results in the release of unusually-large von Willebrand factor multimers (UL-VWFMs from endothelial cells. To investigate the pathophysiology of CALI after oxaliplatin-based chemotherapy, we analyzed plasma concentration of von Willebrand factor (VWF and the distribution of VWFMs in CRC patients. Twenty-three patients with advanced CRC who received oxaliplatin-based chemotherapy with (n = 6 and without (n = 17 bevacizumab were analyzed. CALI (n = 6 and splenomegaly (n = 9 were found only in patients who did not treated with bevacizumab. Plasma VWF antigen (VWF:Ag and serum aspartate aminotransferase (AST levels increased after chemotherapy only in patients without bevacizumab. VWFM analysis in patients who did not receive bevacizumab showed the presence of UL-VWFMs and absence of high molecular weight VWFMs during chemotherapy, especially in those with CALI. In addition, plasma VWF:Ag and AST levels increased after chemotherapy in patients with splenomegaly (n = 9, but not in patients without splenomegaly (n = 14. Histological findings in the liver tissue of patients who did not receive bevacizumab included sinusoidal dilatation and microthrombi in the sinusoids. Many microthrombi were positive for both anti-IIb/IIIa and anti-VWF antibodies. Plasma UL-VWFM levels might be increased by damage to endothelial cells as a result of oxaliplatin-based chemotherapy. Bevacizumab could prevent CALI and splenomegaly through inhibition of VWF-rich platelet thrombus formation.

  9. Evaluation of von Willebrand factor phenotypes and genotypes in Hemophilia A patients with and without identified F8 mutations.

    Science.gov (United States)

    Boylan, B; Rice, A S; De Staercke, C; Eyster, M E; Yaish, H M; Knoll, C M; Bean, C J; Miller, C H

    2015-06-01

    Hemophilia A (HA) is an X-linked bleeding disorder caused by a deficiency in factor VIII (FVIII). von Willebrand disease (VWD) is characterized by a quantitative or qualitative defect in von Willebrand factor (VWF). Patients with VWD with severely low VWF or VWD Type 2N (VWD2N), a VWD subtype distinguished by defective VWF binding to FVIII, may have reduced FVIII levels secondary to their VWD. These patients superficially resemble patients with HA and pose a potential for misdiagnosis. To investigate the unexplained cause of bleeding in HA patients without known FVIII mutations by assessing plasma VWF antigen (VWF:Ag), FVIII binding capacities and VWF genotypes. Thirty-seven of 1027 patients with HA studied as part of the Hemophilia Inhibitor Research Study lacked identifiable F8 mutations. These patients (cases) and 73 patients with identified F8 mutations (controls) were evaluated for VWF:Ag, a patient's VWF capacity to bind FVIII (VWF:FVIIIB) and VWF sequence. Four cases had VWF:Ag < 3 IU dL(-1) and VWF mutations consistent with Type 3 VWD. Six cases and one control were heterozygous for mutations previously reported to cause Type 1 VWD (VWD1) (n = five cases and one control) or predicted to be deleterious by Polyphen2 and SIFT prediction tools (n = 1 case). One control had VWF:Ag < 30 IU dL(-1) and seven patients (four cases and three controls), including two cases who were heterozygous for a known VWD2N mutation, had reduced VWF:FVIIIB. These data emphasize that some patients diagnosed with HA require VWF assessments in order to achieve a comprehensive diagnosis and an optimal treatment strategy. © 2015 International Society on Thrombosis and Haemostasis.

  10. Distinct roles of Ser-764 and Lys-773 at the N terminus of von Willebrand factor in complex assembly with coagulation factor VIII.

    Science.gov (United States)

    Castro-Núñez, Lydia; Bloem, Esther; Boon-Spijker, Mariëtte G; van der Zwaan, Carmen; van den Biggelaar, Maartje; Mertens, Koen; Meijer, Alexander B

    2013-01-04

    Complex formation between coagulation factor VIII (FVIII) and von Willebrand factor (VWF) is of critical importance to protect FVIII from rapid in vivo clearance and degradation. We have now employed a chemical footprinting approach to identify regions on VWF involved in FVIII binding. To this end, lysine amino acid residues of VWF were chemically modified in the presence of FVIII or activated FVIII, which does not bind VWF. Nano-LC-MS analysis showed that the lysine residues of almost all identified VWF peptides were not differentially modified upon incubation of VWF with FVIII or activated FVIII. However, Lys-773 of peptide Ser-766-Leu-774 was protected from chemical modification in the presence of FVIII. In addition, peptide Ser-764-Arg-782, which comprises the first 19 amino acid residues of mature VWF, showed a differential modification of both Lys-773 and the α-amino group of Ser-764. To verify the role of Lys-773 and the N-terminal Ser-764 in FVIII binding, we employed VWF variants in which either Lys-773 or Ser-764 was replaced with Ala. Surface plasmon resonance analysis and competition studies revealed that VWF(K773A) exhibited reduced binding to FVIII and the FVIII light chain, which harbors the VWF-binding site. In contrast, VWF(S764A) revealed more effective binding to FVIII and the FVIII light chain compared with WT VWF. The results of our study show that the N terminus of VWF is critical for the interaction with FVIII and that Ser-764 and Lys-773 have opposite roles in the binding mechanism.

  11. Associations Between Diabetic Retinopathy and Plasma Levels of High-sensitive C-reactive Protein or Von Willebrand Factor in Long-term Type 1 Diabetic Patients

    DEFF Research Database (Denmark)

    Laursen, Jonas Vejvad Nørskov; Hoffmann, Stine Skovbo; Green, Anders

    2013-01-01

    a population-based cohort from Fyn County, Denmark. Plasma levels of hs-CRP and von Willebrand factor antigen were measured and related to the level of diabetic retinopathy (DR) as evaluated by dilated nine-field 45 degree monoscopic fundus photos captured by Topcon TRC-NWS6 and graded according to the Early...... Treatment Diabetic Retinopathy Study (ETDRS) adaptation of the modified Airlie House classification of DR. Results: Median age and duration of diabetes were 58.7 and 43 years, respectively. Median levels (10th-90th percentile) of hs-CRP and von Willebrand factor antigen were 1.31 mg/l (0.37-13.3 mg/l) and 1......Purpose: To evaluate high-sensitive C-reactive protein (hs-CRP) and von Willebrand factor as possible plasma markers of diabetic retinopathy in a population-based cohort of type 1 diabetic patients. Materials and Methods: This was a cross-sectional study of 201 type 1 diabetic patients from...

  12. Distribution of von Willebrand factor levels in young women with and without bleeding symptoms: influence of ABO blood group and promoter haplotypes

    DEFF Research Database (Denmark)

    Lethagen, S.; Hillarp, A.; Ekholm, C.

    2008-01-01

    The normal distribution of von Willebrand factor (VWF) levels is wide. Low levels are associated with bleeding symptoms and von Willebrand disease (VWD). We have recently described a high prevalence of bleeding symptoms in a whole age group of young females (n = 1,019) from Malmo, Sweden....... It was the objective of the present study to evaluate the distribution of VWF levels in young females with or without bleeding symptoms in this population, and the influence of ABO blood group and promoter haplotypes on VWF levels and to identify a possible increased prevalence of VWD in females with bleeding symptoms....... A random selection of the female age group (n = 246), into a study group (n = 176) with, and a control group (n = 70) without bleeding symptoms, was evaluated. Eighteen girls had VWF:RCo below the reference range, of which 17 belonged to the study group (17/176, 9.7%), and one to the control group (1/70, 1...

  13. Analysis of von Willebrand factor A domain-related protein (WARP polymorphism in temperate and tropical Plasmodium vivax field isolates

    Directory of Open Access Journals (Sweden)

    Zakeri Sedigheh

    2009-06-01

    Full Text Available Abstract Background The identification of key molecules is crucial for designing transmission-blocking vaccines (TBVs, among those ookinete micronemal proteins are candidate as a general class of malaria transmission-blocking targets. Here, the sequence analysis of an extra-cellular malaria protein expressed in ookinetes, named von Willebrand factor A domain-related protein (WARP, is reported in 91 Plasmodium vivax isolates circulating in different regions of Iran. Methods Clinical isolates were collected from north temperate and southern tropical regions in Iran. Primers have been designed based on P. vivax sequence (ctg_6991 which amplified a fragment of about 1044 bp with no size variation. Direct sequencing of PCR products was used to determine polymorphism and further bioinformatics analysis in P. vivax sexual stage antigen, pvwarp. Results Amplified pvwarp gene showed 886 bp in size, with no intron. BLAST analysis showed a similarity of 98–100% to P. vivax Sal-I strain; however, Iranian isolates had 2 bp mismatches in 247 and 531 positions that were non-synonymous substitution [T (ACT to A (GCT and R (AGA to S (AGT] in comparison with the Sal-I sequence. Conclusion This study presents the first large-scale survey on pvwarp polymorphism in the world, which provides baseline data for developing WARP-based TBV against both temperate and tropical P. vivax isolates.

  14. Expression of von Willebrand factor, pulmonary intravascular macrophages, and Toll-like receptors in lungs of septic foals

    Science.gov (United States)

    Harrison, Jacqueline M. E.; Quanstrom, Leah M.; Robinson, Alex R.; Wobeser, Bruce; Anderson, Stacy L.

    2017-01-01

    Sepsis causes significant mortality in neonatal foals; however, there is little data describing the cellular and molecular pathways of lung inflammation in septic foals. This study was conducted to characterize lung inflammation in septic foals. Lung tissue sections from control (n = 6) and septic (n = 17) foals were compared using histology and immunohistology. Blinded pathologic scoring of hematoxylin and eosin stained samples revealed increased features of lung inflammation such as thickened alveolar septa and sequestered inflammatory cells in septic foals. Septic foal lungs showed increased expression of von Willebrand factor in blood vessels, demonstrating vascular inflammation. Use of MAC387 antibody to detect calprotectin as a reflection of mononuclear cell infiltration revealed a significant increase in their numbers in alveolar septa of lungs from septic foals compared to those from control foals. The mononuclear cells appeared to be mature macrophages and were located in the septal capillaries, suggesting they were pulmonary intravascular macrophages (PIMs). Finally, lungs from septic foals showed increased expression of Toll-like receptor 4 and 9 in mononuclear cells relative to the control. Taken together, this study is the first to show the expression of inflammatory molecules and an increase in PIMs in lungs from foals that died from sepsis. PMID:27297419

  15. Influences of ABO blood group, age and gender on plasma coagulation factor VIII, fibrinogen, von Willebrand factor and ADAMTS13 levels in a Chinese population

    Directory of Open Access Journals (Sweden)

    Zongkui Wang

    2017-03-01

    Full Text Available Background ABO blood group is a hereditary factor of plasma levels of coagulation factor VIII (FVIII and von Willebrand factor (VWF. Age and gender have been shown to influence FVIII, VWF, fibrinogen (Fbg, and ADAMTS13 (A disintegrin and metalloprotease with thrombospondin type 1 motif, 13. We investigated the effects of ABO type, age, and gender on plasma levels of FVIII, Fbg, VWF, and ADAMTS13 in a Chinese population. Methods A total of 290 healthy volunteers were eligible for this study. ABO blood group was determined by indirect technique. FVIII:C and Fbg were measured by clotting assays. VWF antigen (VWF:Ag, collagen-binding activity (VWF:CBA, and ADAMTS13 antigen were assessed by ELISA, whereas VWF ristocetin cofactor activity (VWF:Rcof was performed by agglutination of platelets with ristocetin. Results Mean FVIII:C and VWF levels (VWF:Ag, VWF:CBA, and VWF:Rcof were significantly higher in non-O than in O type subjects (p < 0.05 for all comparison. ADAMTS13 antigen decreased with increasing age, whereas the other parameters increased. Other than ADAMTS13 (p < 0.01, no gender-related variations were observed in the other parameters. Moreover, FVIII:C, Fbg, VWF:Ag, VWF:CBA, and VWF:Rcof showed significant and positive relationships with age (r = 0.421, 0.445, 0.410, 0.401, and 0.589, resp.; all p < 0.001, whereas a negative relationship was observed for ADAMTS13 antigen (r = 0.306; p = 0.006. Furthermore, FVIII:C were strongly correlated with VWF:Ag, VWF:CBA, and VWF:Rcof (r = 0.746, r = 0.746, and r = 0.576, resp.; p < 0.0001. VWF parameters were also strongly correlated with each other (r = 0.0.847 for VWF:Ag and VWF:CBA; r = 0.722 for VWF:Ag and VWF:Rcof; p < 0.0001. Conclusions ABO blood group, age, and gender showed different effects on plasma levels of FVIII:C, Fbg, VWF:Ag, VWF:CBA, VWF:Rcof, and ADAMTS13 antigen. These new data on a Chinese population are quite helpful to compare with other ethnic groups.

  16. How Is von Willebrand Disease Treated?

    Science.gov (United States)

    ... the condition. For example, the school nurse, teacher, daycare provider, coach, or any leader of afterschool activities ... MedlinePlus) Von Willebrand Disease (MedlinePlus) Building 31 31 Center Drive Bethesda, MD 20892 Learn more about getting ...

  17. How Is von Willebrand Disease Diagnosed?

    Science.gov (United States)

    ... the condition. For example, the school nurse, teacher, daycare provider, coach, or any leader of afterschool activities ... MedlinePlus) Von Willebrand Disease (MedlinePlus) Building 31 31 Center Drive Bethesda, MD 20892 Learn more about getting ...

  18. Von Willebrand factor and alkaline phosphatase predict re-transplantation-free survival after the first liver transplantation.

    Science.gov (United States)

    Wannhoff, Andreas; Rauber, Conrad; Friedrich, Kilian; Rupp, Christian; Stremmel, Wolfgang; Weiss, Karl Heinz; Schemmer, Peter; Gotthardt, Daniel N

    2017-02-01

    After liver transplantation (LT), there are liver-related, infectious and cardiovascular complications that contribute to reduced graft survival. These conditions are associated with an increase in the Von Willebrand factor antigen (VWF-Ag), which was previously correlated with survival in cirrhotic patients. Evaluate VWF-Ag as a predictive marker of re-transplantation-free survival in patients after LT. We measured VWF-Ag in patients after first LT and then followed them prospectively with regard to the primary endpoint, namely re-transplantation-free survival. There were 6 out of 80 patients who died or received re-LT during follow-up. In these patients, the median VWF-Ag was 510.6%, which was significantly higher (p = 0.001) than in the patients who were alive at the end of follow-up (with a median VWF-Ag = 186.8%). At a cut-off of 286.8%, VWF-Ag was significantly correlated with re-transplantation-free survival (p alkaline phosphatase (ALP), but not the model of end-stage liver disease (MELD) score, donor age, nor cold ischemia time. A score combining VWF-Ag and ALP showed an impressive capability in the receiver operating characteristic (ROC) analysis (with area under the curve (AUC) = 0.958) to distinguish between patients with regard to the primary endpoint. VWF-Ag is a non-invasive marker that can predict outcome in patients after LT. Its diagnostic performance increased when combined with ALP in a newly developed scoring system.

  19. Contrast ultrasound imaging of the aorta alters vascular morphology and circulating von Willebrand factor in hypercholesterolemic rabbits.

    Science.gov (United States)

    Smith, Brendon W; Simpson, Douglas G; Sarwate, Sandhya; Miller, Rita J; Blue, James P; Haak, Alexander; O'Brien, William D; Erdman, John W

    2012-05-01

    Ultrasound contrast agents (UCAs) are intravenously infused microbubbles that add definition to ultrasonic images. Ultrasound contrast agents continue to show clinical promise in cardiovascular imaging, but their biological effects are not known with confidence. We used a cholesterol-fed rabbit model to evaluate these effects when used in conjunction with ultrasound (US) to image the descending aorta. Male New Zealand White rabbits (n = 41) were weaned onto an atherogenic diet containing 1% cholesterol, 10% fat, and 0.11% magnesium. At 21 days, rabbits were exposed to contrast US at 1 of 4 pressure levels using either the UCA Definity (Lantheus Medical Imaging, Inc, North Billerica, MA) or a saline control (n = 5 per group). Blood samples were collected and analyzed for lipids and von Willebrand factor (vWF), a marker of endothelial function. Animals were euthanized at 42 days, and tissues were collected for histologic analysis. After adjustment for pre-exposure vWF, high-level US (in situ [at the aorta] peak rarefactional pressure of 1.4 or 2.1 MPa) resulted in significantly lower vWF 1 hour post exposure (P = .0127; P(adj) < .0762). This difference disappeared within 24 hours. Atheroma thickness in the descending aorta was lower in animals receiving the UCA compared to animals receiving saline. Contrast US affected the descending aorta, as evidenced by two separate outcome measures. These results may be a first step in elucidating a previously unknown biological effect of UCAs. Further research is warranted to characterize the effects of this procedure.

  20. DEEP VEIN THROMBOSIS IN PATIENT WITH VON WILLEBRAND DISEASE

    Directory of Open Access Journals (Sweden)

    V. A. Elykomov

    2016-01-01

    Full Text Available Objective: to identify the possible factors of thrombogenic risk and ways of its prevention in patients with von Willebrand disease.Case description. Patient X., 42 years old, who suffers from von Willebrand disease type 3 with 5-years of age. Asked on reception to the traumatologist in the polyclinic of the Regional Hospital with pain in the left hip joint. Recommended planned operative treatment in the Altai Regional Clinical Hospital. Preoperative preparation included the infusion of concentrate of von Willebrand factor and coagulation factor VIII. Operation – cement total arthroplasty of the left hip joint. In the postoperative period analgesic treatment, elastic compression of the lower extremities, iron supplements, also conducted infusion of concentrate of von Willebrand factor and coagulation factor VIII for 20 days and thromboprophylactic with dabigatran. On the 3rd day after the operation the patient revealed deep vein thrombosis of the femoral segment (floating clot.Results. The patient was operated for emergency indications in the Department of endovascular surgery – installation of venous cava filter “Volan”. Dabigatran is cancelled, appointed clexane for 3 months. In our clinical example the patient lacked risk factors of pulmonary embolism as obesity, age, smoking, prolonged immobilization, estrogen therapy. Overdose of factor VIII were not observed – the level of factor did not exceed 135 % on transfusions. At the same time, the patient was found polymorphisms in the genes ITGA2, FGB, MTHFR, MTR – heterozygote, MTRR – mutant homozygote, which may indicate the genetic factors of thrombogenic risk. Also a significant risk factor was massive surgical intervention (total hip replacement. Despite preventive measures (elastic compression, thromboprophylactic dabigatran, early activation we cannot to avoid thrombotic complications.Conclusion. This article presents a case demonstrating a thrombotic complication in patients

  1. Platelets, inflammatory cells, von Willebrand factor, syndecan-1, fibrin, fibronectin, and bacteria co-localize in the liver thrombi of Bacillus anthracis-infected mice.

    Science.gov (United States)

    Popova, Taissia G; Millis, Bryan; Bailey, Charles; Popov, Serguei G

    2012-01-01

    Vascular dysfunction and thrombosis have been described in association with anthrax infection in humans and animals but the mechanisms of these dysfunctions, as well as the components involved in thrombi formation are poorly understood. Immunofluorescent microscopy was used to define the composition of thrombi in the liver of mice challenged with the Bacillus anthracis Sterne spores. Lethal infection with the toxigenic Sterne strain, in contrast to the non-lethal, non-toxigenic delta-Sterne strain, demonstrated time-dependent increase in the number of vegetative bacteria inside the liver sinusoids and central vein. Massive appearance of thrombi typically occluding the lumen of the vessels coincided with the sudden death of infected animals. Bacterial chains in the thrombi were stained positive for syndecan-1 (SDC-1), fibronectin, and were surrounded by fibrin polymers, GPIIb-positive platelets, von Willebrand Factor (vWF), CD45-positive leukocytes, and massive amount of shed SDC-1. Experiments with human umbilical vein endothelial cells (HUVECs) demonstrated the active role of the host response to the secreted pathogenic factors of bacteria during the onset of the pro-thrombotic condition. The bacterial culture supernatants, as well as the isolated proteins (the pore-forming toxin anthrolysin O and phospholipase C) induced release of vWF, while anthrolysin O, sphingomyelinase and edema toxin induced release of thrombin from HUVECs and polymerization of fibrin in the presence of human plasma. Our findings suggest that activation of endothelium in response to infection can contribute to the formation of occlusive thrombi consisting of aggregated bacteria, vWF, shed SDC-1, fibrin, activated platelets, fibronectin and leukocytes. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Insulin resistance is accompanied by increased von Willebrand factor levels in nondiabetic women: a study of offspring of type 2 diabetic subjects compared to offspring of nondiabetic subjects

    DEFF Research Database (Denmark)

    Foss, Anne-Catherine; Vestbo, Else; Frøland, Anders

    2002-01-01

    : We compared vWF, fibrinogen and fibronectin in 88 nondiabetic offspring of type 2 diabetic subjects (relatives) and 103 offspring of nondiabetic subjects (controls). Other measurements included urinary albumin excretion rate, blood pressure, lipid profile and insulin resistance using homeostasis......OBJECTIVES: To examine whether levels of von Willebrand factor (vWF), fibrinogen and fibronectin are related to a parental history of type 2 diabetes and to determine possible explanatory factors for high versus low vWF and fibrinogen. DESIGN: Cross-sectional study. SUBJECTS, MAIN OUTCOME MEASURES...

  3. Plasma concentration of von Willebrand factor predicts mortality in patients on chronic renal replacement therapy

    NARCIS (Netherlands)

    Péquériaux, Nathalie C.; Fijnheer, Rob; Gemen, Eugenie F.; Barendrecht, Arjan D.; Dekker, Friedo W.; Krediet, Raymond T.; Beutler, Jaap J.; Boeschoten, Elisabeth W.; Roest, Mark

    2012-01-01

    Background. Traditional cardiovascular risk factors do not explain the high incidence of cardiovascular mortality and morbidity in patients with end-stage renal disease. A prothrombotic state could accelerate the process of vascular disease in these patients. Methods. In this study, four platelet

  4. Elevated levels of plasma von Willebrand factor and the risk of macro- and microvascular disease in type 2 diabetic patients with microalbuminuria

    DEFF Research Database (Denmark)

    Gaede, P; Vedel, P; Parving, H H

    2001-01-01

    according to baseline plasma von Willebrand factor levels below or above the median. The main outcome was cardiovascular disease (cardiovascular mortality, non-fatal stroke, non-fatal myocardial infarction, coronary artery bypass graft and revascularization or amputation of legs), progression to diabetic...... nephropathy or progression in diabetic retinopathy. RESULTS: At baseline the two groups were comparable for HbA(1c), fasting levels of s-total-cholesterol, s-HDL-cholesterol and s-triglycerides, systolic and diastolic blood pressure, gender, known diabetes duration, smoking habits, previous cardiovascular...

  5. Protein replacement therapy and gene transfer in canine models of hemophilia A, hemophilia B, von willebrand disease, and factor VII deficiency.

    Science.gov (United States)

    Nichols, Timothy C; Dillow, Aaron M; Franck, Helen W G; Merricks, Elizabeth P; Raymer, Robin A; Bellinger, Dwight A; Arruda, Valder R; High, Katherine A

    2009-01-01

    Dogs with hemophilia A, hemophilia B, von Willebrand disease (VWD), and factor VII deficiency faithfully recapitulate the severe bleeding phenotype that occurs in humans with these disorders. The first rational approach to diagnosing these bleeding disorders became possible with the development of reliable assays in the 1940s through research that used these dogs. For the next 60 years, treatment consisted of replacement of the associated missing or dysfunctional protein, first with plasma-derived products and subsequently with recombinant products. Research has consistently shown that replacement products that are safe and efficacious in these dogs prove to be safe and efficacious in humans. But these highly effective products require repeated administration and are limited in supply and expensive; in addition, plasma-derived products have transmitted bloodborne pathogens. Recombinant proteins have all but eliminated inadvertent transmission of bloodborne pathogens, but the other limitations persist. Thus, gene therapy is an attractive alternative strategy in these monogenic disorders and has been actively pursued since the early 1990s. To date, several modalities of gene transfer in canine hemophilia have proven to be safe, produced easily detectable levels of transgene products in plasma that have persisted for years in association with reduced bleeding, and correctly predicted the vector dose required in a human hemophilia B liver-based trial. Very recently, however, researchers have identified an immune response to adeno-associated viral gene transfer vector capsid proteins in a human liver-based trial that was not present in preclinical testing in rodents, dogs, or nonhuman primates. This article provides a review of the strengths and limitations of canine hemophilia, VWD, and factor VII deficiency models and of their historical and current role in the development of improved therapy for humans with these inherited bleeding disorders.

  6. von Willebrand Disease

    Science.gov (United States)

    ... for type 1 von Willebrand disease is called desmopressin. It causes a temporary increase in the von ... injection or by being sniffed into the nose. Desmopressin may also help some people with type 2 ...

  7. Successful immune tolerance induction consisting of high-dose factor VIII rich in von Willebrand factor and pulsed intravenous immunoglobulin: a case report

    Directory of Open Access Journals (Sweden)

    Kubisz Peter

    2012-10-01

    Full Text Available Abstract Introduction The development of factor VIII inhibitors is a serious complication of replacement therapy in patients with congenital hemophilia A. Immune tolerance induction has been accepted as the only clinically proven treatment allowing antigen-specific tolerance to factor VIII. However, some of its issues, such as patient selection, timing, factor VIII dosing, use of immunosuppressive or immunomodulatory procedures, still remain the subject of debate. Case presentation A case of a 3-year-old Caucasian boy with severe congenital hemophilia A, intron 22 inversion of the F8 gene and high-titer inhibitor, who underwent an immune tolerance induction according to the modified Bonn regimen (high doses of plasma-derived factor VIII rich in von Willebrand factor and pulsed intravenous immunoglobulin is presented. The treatment lasted for 13 months and led to the eradication of inhibitor. Conclusion Addition of intravenous immunoglobulin did not negatively affect the course of immune tolerance induction and led to the rapid eradication of factor VIII inhibitor.

  8. von Willebrand disease and aging : an evolving phenotype

    NARCIS (Netherlands)

    Sanders, Y. V.; Giezenaar, M. A.; Laros-van Gorkom, B. A. P.; Meijer, K.; van der Bom, J. G.; Cnossen, M. H.; Nijziel, M. R.; Ypma, P. F.; Fijnvandraat, K.; Eikenboom, J.; Mauser-Bunschoten, E. P.; Leebeek, F. W. G.

    Background: Because the number of elderly von Willebrand disease (VWD) patients is increasing, the pathophysiology of aging in VWD has become increasingly relevant. Objectives: To assess age-related changes in von Willebrand factor (VWF) and factor VIII (FVIII) levels and to compare age-related

  9. The important role of von Willebrand factor in platelet-derived FVIII gene therapy for murine hemophilia A in the presence of inhibitory antibodies.

    Science.gov (United States)

    Shi, Q; Schroeder, J A; Kuether, E L; Montgomery, R R

    2015-07-01

    Our previous studies have demonstrated that targeting FVIII expression to platelets results in FVIII storage together with von Willebrand factor (VWF) in platelet α-granules and that platelet-derived FVIII (2bF8) corrects the murine hemophilia A phenotype even in the presence of high-titer anti-FVIII inhibitory antibodies (inhibitors). To explore how VWF has an impact on platelet gene therapy for hemophilia A with inhibitors. 2bF8 transgenic mice in the FVIII(-/-) background (2bF8(tg+/-) F8(-/-) ) with varying VWF phenotypes were used in this study. Animals were analyzed by VWF ELISA, FVIII activity assay, Bethesda assay and tail clip survival test. Only 18% of 2bF8(tg+/-) F8(-/-) VWF(-/-) animals, in which VWF was deficient, survived the tail clip challenge with inhibitor titers of 3-8000 BU mL(-1) . In contrast, 82% of 2bF8(tg+/-) F8(-/-) VWF(+/+) mice, which had normal VWF levels, survived tail clipping with inhibitor titers of 10-50,000 BU mL(-1) . All 2bF8(tg+/-) F8(-/-) VWF(-/-) mice without inhibitors survived tail clipping and no VWF(-/-) F8(-/-) mice survived this challenge. Because VWF is synthesized by endothelial cells and megakaryocytes and is distributed in both plasma and platelets in peripheral blood, we further investigated the effect of each compartment of VWF on platelet-FVIII gene therapy for hemophilia A with inhibitors. In the presence of inhibitors, 42% of animals survived tail clipping in the group with plasma-VWF and 50% survived in the platelet-VWF group. VWF is essential for platelet gene therapy for hemophilia A with inhibitors. Both platelet-VWF and plasma-VWF are required for optimal platelet-derived FVIII gene therapy for hemophilia A in the presence of inhibitors. © 2015 International Society on Thrombosis and Haemostasis.

  10. von Willebrand Factor Test

    Science.gov (United States)

    ... Hormone Binding Globulin (SHBG) Shiga toxin-producing Escherichia coli Sickle Cell Tests Sirolimus Smooth Muscle Antibody (SMA) ... Ratio Valproic Acid Vancomycin Vanillylmandelic Acid (VMA) VAP Vitamin A Vitamin B12 and Folate Vitamin D Tests ...

  11. Inhibition of ADAMTS-13 by Doxycycline Reduces von Willebrand Factor Degradation During Supraphysiological Shear Stress: Therapeutic Implications for Left Ventricular Assist Device-Associated Bleeding.

    Science.gov (United States)

    Bartoli, Carlo R; Kang, Jooeun; Restle, David J; Zhang, David M; Shabahang, Cameron; Acker, Michael A; Atluri, Pavan

    2015-11-01

    The aim of this study was to investigate a potential therapy for left ventricular assist device (LVAD)-associated bleeding. Nonsurgical bleeding is the most frequent complication of LVAD support. Recent evidence has demonstrated that supraphysiological shear stress from continuous-flow LVADs accelerates von Willebrand factor (vWF) metabolism by the action of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS-13) (the vWF protease). An acquired vWF deficiency causes bleeding. This suggests that ADAMTS-13 is a clinical target to reduce vWF degradation. We tested the hypothesis that inhibition of ADAMTS-13 with doxycycline, an inexpensive, clinically approved drug, reduces vWF degradation during shear stress. Whole blood was collected from human donors (n = 15), and purified, recombinant ADAMTS-13 protein was obtained. An enzyme-linked immunosorbent assay (ELISA) was used to quantify the dose relationship between doxycycline and ADAMTS-13 activity prior to shear stress (n = 10). To determine the effect of shear stress, plasma and recombinant ADAMTS-13 were exposed to LVAD-like supraphysiological shear stress (approximately 175 dyne/cm(2)). vWF multimers and degradation fragments were characterized with electrophoresis and immunoblotting (n = 10). Förster resonance energy transfer was used to quantify plasma ADAMTS-13 activity (n = 10). An ELISA was used to quantify vWF:collagen binding activity. Platelet aggregometry was performed with adenosine 5'-diphosphate, collagen, and ristocetin (vWF-platelet pathway) agonism (n = 10). Doxycycline significantly decreased plasma ADAMTS-13 activity (p = 0.01) and the activity of recombinant human ADAMTS-13 protein by 21%. After plasma was exposed to shear stress, the same pattern of vWF degradation was observed as previously reported for LVAD patients, and vWF:collagen binding activity decreased significantly (p = 0.002). Doxycycline significantly decreased ADAMTS-13 activity (p = 0.04) and

  12. Characterization of recessive severe type 1 and 3 von willebrand disease (vwd), asymptomatic heterozygous carriers versus bloodgroup o-related von willebrand factor deficiency, and dominant type 1 VWD

    NARCIS (Netherlands)

    J.J. Michiels (Jan); Z. Berneman (Zwi); A. Gadisseur (Alain); M. van der Planken (Marc); W. Schroyens (Wilfried); A. van de Velde (Ann); H.H.D.M. van Vliet (Huib)

    2006-01-01

    textabstractRecessive type 3 von Willebrand disease (VWD) is caused by homozygosity or double heterozygosity for two non-sense mutations (null alleles). Type 3 VWD is easy to diagnose by the combination of a strongly prolonged bleeding time (BT), absence of ristocetine-induced platelet aggregation

  13. Screening of Von Willebrand Disease in Iranian Women With Menorrhagia

    Science.gov (United States)

    Rahbar, Nahid; Faranoush, Mohammad; Ghorbani, Raheb; Sadr Alsadat, Bahare

    2015-01-01

    Background: Menorrhagia is a common health problem in women, particularly those with bleeding disorders. Little is known about the course of menorrhagia or other bleeding symptoms in women with the most common congenital bleeding disorder, von Willebrand disease (vWD). Objectives: The aim of this study was to estimate the prevalence of vWD in women with diagnosed menorrhagia. Materials and Methods: In this cross-sectional study, a total of 460 consecutive patients, presenting menorrhagia, were analyzed. The initial screening and confirmation tests for the diagnosis of vWD included determination of prothrombin time (PT), partial thromboplastin time (PTT), bleeding time (BT), fibrinogen, factor VIII, vWF antigen, and vWF activity. A questionnaire was filled for every patient. The data were then analyzed using the SPSS software. Results: Mean age of our patients was 32.5 ± 10.6 years. The level of von Willebrand factor in 22.5% and von Willebrand activity in 19.6% of patients was abnormal. The prevalence of vWD among patients with menorrhagia was 24%. Conclusions: The high prevalence of vWD among our patients was the same as other previous reports, suggesting low awareness about this disease and under diagnosis of mild cases. PMID:25763275

  14. Factor VIII/V C-domain swaps reveal discrete C-domain roles in factor VIII function and intracellular trafficking

    OpenAIRE

    Ebberink, Eduard H T M; Bouwens, Eveline A. M.; Bloem, Esther; Boon-Spijker, Mariëtte; van den Biggelaar, Maartje; Voorberg, Jan; Alexander B. Meijer; Mertens, Koen

    2017-01-01

    Factor VIII C-domains are believed to have specific functions in cofactor activity and in interactions with von Willebrand factor. We have previously shown that factor VIII is co-targeted with von Willebrand factor to the Weibel-Palade bodies in blood outgrowth endothelial cells, even when factor VIII carries mutations in the light chain that are associated with defective von Willebrand factor binding. In this study, we addressed the contribution of individual factor VIII C-domains in intrace...

  15. Doença de von Willebrand e anestesia Enfermedad de von Willebrand y anestesia Von Willebrand's disease and anesthesia

    Directory of Open Access Journals (Sweden)

    Fabiano Timbó Barbosa

    2007-06-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A doença de von Willebrand ocorre devido à mutação no cromossomo 12 e é caracterizada por deficiência qualitativa ou quantitativa do fator de von Willebrand. A diversidade de mutações leva ao aparecimento das mais variadas manifestações clínicas possibilitando a divisão dos pacientes em vários tipos e subtipos clínicos. A coagulopatia se manifesta basicamente através da disfunção plaquetária associada à diminuição dos níveis séricos do fator VIII coagulante. O objetivo dessa revisão foi mostrar os cuidados relacionados aos pacientes portadores da doença de von Willebrand durante o período perioperatório. CONTEÚDO: Foram definidas as características da doença de von Willebrand quanto à fisiopatologia, à classificação, ao diagnóstico laboratorial, ao tratamento atual e aos cuidados com o manuseio do paciente no período perioperatório. CONCLUSÕES: A doença de von Willebrand é o distúrbio hemorrágico hereditário mais comum, porém ela é subdiagnosticada pela complexidade da própria doença. A correta classificação do paciente, o uso apropriado da desmopressina e a transfusão do fator de von Willebrand são medidas fundamentais para a realização do procedimento anestésico bem-sucedido.JUSTIFICATIVA Y OBJETIVOS: La enfermedad de von Willebrand ocurre debido a la mutación en el cromosoma 12 y se caracteriza por la deficiencia cualitativa o cuantitativa del factor de von Willebrand. La diversidad de mutaciones conlleva al aparecimiento de las más variadas manifestaciones clínicas posibilitando la división de los pacientes en varios tipos y subtipos clínicos. La coagulopatía se manifiesta básicamente a través de la disfunción plaquetaria asociada con la disminución de los niveles séricos del factor VIII coagulante. El objetivo de esa revisión fue mostrar los cuidados relacionados con las pacientes portadoras de la enfermedad de von Willebrand durante el per

  16. VON WILLEBRAND DISEASE: DIAGNOSIS AND TREATMENT

    Directory of Open Access Journals (Sweden)

    Majda Benedik Dolničar

    2004-12-01

    Full Text Available Background. Von Willebrand disease (VWD is a most frequently inborn bleeding disorder caused by quantitative or qualitative defects of von Willebrand factor (VWF. VWF promotes platelet-vessel wall (adhesion and plateletplatelet interaction (aggregation. It is also the carrier for factor VIII (F VIII in plasma. A deficiency of VWF may results in impairment of both, primary and secondary haemostasis. Therefore, patients with VWD can have bleeding symptoms typical fot the defect in primary haemostasis (mucocutaneous haemorrhages. In severe deficiency of VWF there are also haemarthroses and haematomas typical for patients with coagulation defects. Several types and subtypes of VWD have been described. The diagnosis is based on measurements of VWF concentration and activity and F VIII activity in plasma. The tests identifying VWD subtypes are ristocetin induced platelet agglutination (RIPA, multimeric analysis of VWF and measurement of the binding of VWF to F VIII.Conclusions. Due to heterogeneity of VWF defects, the correct diagnosis of types and subtypes is sometimes difficult but is important for appropriate treatment. There are two main therapeutic options for patients with VWD: desmopressin and blood derived concentrates of F VIII/VWF. In certain cases antifibrinolytics and hormones can be suitable treatment. Desmopressin is the treatment of choice in patients with type 1 VWD. It raises endogenous F VIII and VWF and thereby corrects the intrinsic coagulation defect as well as the prolonged bleeding time (BT or closure time (CT-PFA100 in most type 1 VWD patients. In type 3 and in the majority of type 2 patients desmopressin is not effective and it is necessary to use concentrates containing F VIII and VWF. These are always effective in raising of F VIII activity, whereas the BT/CT may not be completely corrected, but the normalisation of the BT/CT is not always necessary.

  17. Endothelial markers in malignant vascular tumours of the liver: superiority of QB-END/10 over von Willebrand factor and Ulex europaeus agglutinin 1.

    Science.gov (United States)

    Anthony, P P; Ramani, P

    1991-01-01

    A new monoclonal antibody, QB-END/10, raised against the CD34 antigen in human endothelial cell membranes and haemopoietic progenitor cells, was studied for its usefulness as a marker of neoplastic vascular cells in 21 angiosarcomas and seven malignant haemangioendotheliomas of the liver. QB-END/10 was both more sensitive and more specific than Von Willebrand factor (VWF) and Ulex europaeus 1 agglutinin (UEA-1) in labelling endothelial cells and it did not cross react with epithelia as UEA-1 often does. Staining was uniformly strong and clear in all histological variants of these two tumours. QB-END/10 should prove particularly useful in the differential diagnosis of malignant vascular tumours of the liver. Images PMID:1705261

  18. Consumption of nattokinase is associated with reduced blood pressure and von Willebrand factor, a cardiovascular risk marker: results from a randomized, double-blind, placebo-controlled, multicenter North American clinical trial

    Directory of Open Access Journals (Sweden)

    Jensen GS

    2016-10-01

    Full Text Available Gitte S Jensen,1 Miki Lenninger,1 Michael P Ero,2 Kathleen F Benson,1 1NIS Labs, Klamath Falls, OR, 2Machaon Diagnostics, Inc., Oakland, CA, USA Objective: The objective of this study is to evaluate the effects of consumption of nattokinase on hypertension in a North American hypertensive population with associated genetic, dietary, and lifestyle factors. This is in extension of, and contrast to, previous studies on Asian populations.Materials and methods: A randomized, double-blind, placebo-controlled, parallel-arm clinical study was performed to evaluate nattokinase (NSK-SD, a fermented soy extract nattō from which vitamin K2 has been removed. Based on the results from previous studies on Asian populations, 79 subjects were enrolled upon screening for elevated blood pressure (BP; systolic BP ≥130 or diastolic BP ≥90 mmHg who consumed placebo or 100 mg nattokinase/d for the 8-week study duration. Blood collections were performed at baseline and 8 weeks for testing plasma renin activity, von Willebrand factor (vWF, and platelet factor-4. Seventy-four people completed the study with good compliance.Results: Consumption of nattokinase was associated with a reduction in both systolic and diastolic BP. The reduction in systolic BP was seen for both sexes but was more robust in males consuming nattokinase. The average reduction in diastolic BP in the nattokinase group from 87 mmHg to 84 mmHg was statistically significant when compared to that in the group consuming placebo, where the average diastolic BP remained constant at 87 mmHg (P<0.05, and reached a high level of significance for males consuming nattokinase, where the average diastolic BP dropped from 86 mmHg to 81 mmHg (P<0.006. A decrease in vWF was seen in the female population consuming nattokinase (P<0.1. In the subpopulation with low plasma renin activity levels at baseline (<0.29 ng/mL/h, an increase was seen for 66% of the people after 8-week consumption of nattokinase (P

  19. Revascularization Operation for Moyamoya Disease with Concurrent von Willebrand Disease.

    Science.gov (United States)

    Miki, Kenji; Arimura, Koichi; Nishimura, Ataru; Yoshimoto, Koji; Sayama, Tetsuro; Iihara, Koji

    2017-12-01

    Although extracranial-intracranial (EC-IC) bypass is an effective treatment strategy for symptomatic moyamoya disease, surgeons need to be cautious regarding the possibility of postoperative hemorrhagic complications in patients with a concurrent coagulation disorder. Here, we describe a case of EC-IC bypass for moyamoya disease concurrent with von Willebrand disease type 1. Following perioperative replacement of the von Willebrand factor, the patient showed an uneventful and uncomplicated clinical course. This is the first reported case of EC-IC bypass being performed for moyamoya disease in a patient with concurrent von Willebrand disease. We emphasize the importance of appropriate management with replacement of the von Willebrand factor during the perioperative period to avoid hemorrhagic complications. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Von Willebrand factor antigen predicts response to double dose of aspirin and clopidogrel by PFA-100 in patients undergoing primary angioplasty for ST elevation myocardial infarction.

    Science.gov (United States)

    Gianetti, Jacopo; Parri, Maria Serena; Della Pina, Francesca; Marchi, Federica; Koni, Endrin; De Caterina, Alberto; Maffei, Stefano; Berti, Sergio

    2013-01-01

    Von Willebrand factor (VWF) is an emerging risk factor in acute coronary syndromes. Platelet Function Analyzer (PFA-100) with Collagen/Epinephrine (CEPI) is sensitive to functional alterations of VWF and also identifies patients with high on-treatment platelet reactivity (HPR). The objective of this study was to verify the effect of double dose (DD) of aspirin and clopidogrel on HPR detected by PFA-100 and its relation to VWF and to its regulatory metalloprotease ADAMTS-13. Between 2009 and 2011 we enrolled 116 consecutive patients with ST elevation myocardial infarction undergoing primary PCI with HPR at day 5 after PCI. Patients recruited were then randomized between a standard dose (SD, n = 58) or DD of aspirin and clopidogrel (DD, n = 58), maintained for 6 months follow-up. Blood samples for PFA-100, light transmittance aggregometry, and VWF/ADAMTS-13 analysis were collected after 5, 30, and 180 days (Times 0, 1, and 2). At Times 1 and 2 we observed a significantly higher CEPI closure times (CT) in DD as compared to SD (P myocardial infarction is reversible by DD of aspirin and clopidogrel; the response is predicted by basal levels of VWF and ADAMTS-13. PFA-100 may be a useful tool to risk stratification in acute coronary syndromes given its sensitivity to VWF.

  1. Immunohistochemial study on the expression of von Willebrand factor (vWF) after onlay autogenous iliac grafts for lateral alveolar ridge augmentation

    Science.gov (United States)

    2013-01-01

    Introduction The main problems of autogenous bone transplants are their unpredictable atrophy and their loss of structure. One key factor lies in the poor revascularization of simple onlay grafts. The the aim of this study was to evaluate the revascularization processes in autogenous bone grafts from the iliac crest to the alveolar ridge. Methods In a sheep model, autogenous bone grafts were harvested from the iliac crest. A combination of a resorbable collagen membrane (CM) and deproteinized bovine bone material (DBBM) was used to modify the bone graft (experiment 2). This was compared with a simple onlay bone graft (control group, experiment 1). The amount of vessels in bone and connective tissue (CT), and the amount of CT were analyzed. The expression of von Willebrand factor (vWF) was compared between the two experimental groups using immunohistochemical analysis. Results The ratio of the amount of vessels in bone and CT changed over time, and more vessels could be detected in bone at 12–16 weeks of graft healing. The number of vessels were significantly higher in experiment 2 than in experiment 1. More CT was found in experiment 1, whereas the amount of CT in both experiments decreased over time. Conclusion This study shows a more intensive and extensive revascularization in experiment 2, as significantly more vessels were detected. The decreased amount of CT in experiment 2 clarifies its clinical superiority. PMID:24330606

  2. Gender and age peculiarities of content changes of protein C, von Willebrand factor, vascular cell adhesion molecules sVCAM-1 in patients with acute left ventricle Q-wave myocardial infarction

    Directory of Open Access Journals (Sweden)

    S. M. Kyselov

    2015-04-01

    Full Text Available Markers of hemostasis have an influence on the state of postinfarction remodeling processes. Aim. In order to study the gender and age peculiarities, to determine the predictive value of the protein C, von Willebrand factor and vascular cell adhesion molecules sVCAM-1 concentration, we examined 76 patients with acute Q-wave myocardial infarction. Methods and results. On the 1st day of the disease, higher concentrations of protein C were detected in young women, vascular cell adhesion molecules sVCAM-1 - in men of any age. On the 10th day of the disease, both in men and women increase in the content of protein C, reducing the concentration of von Willebrand factor and vascular cell adhesion molecules sVCAM-1 were detected. Conclusion. Protein C has the highest prognostic potential in relation to the formation of heart aneurysm after Q-wave myocardial infarction in women of young age, and von Willebrand factor and vascular cell adhesion molecules sVCAM-1 - in older men.

  3. Plasma fibrinolysis is related to the degree of organ dysfunction but not to the concentration of von Willebrand Factor in critically ill patients

    Directory of Open Access Journals (Sweden)

    Vincent Jean-Louis

    2009-06-01

    Full Text Available Abstract Background Endothelial cell dysfunction, by promoting fibrin deposition, has been implicated in the development of multiple organ failure. Altered fibrinolysis during inflammation may participate in microvascular alterations. We sought to determine whether plasma fibrinolysis was related to the severity of organ dysfunction and/or to the levels of von Willebrand factor (vWF antigen, as a marker of endothelium dysfunction, in critically ill patients. Methods Forty-nine consecutive patients admitted to an adult medico-surgical intensive care unit (ICU with (18 or without sepsis (31 were included. C-reactive protein and vWF levels were measured on ICU admission and plasma fibrinolysis was assessed by the Euglobulin Clot Lysis Time (ECLT. The sequential organ failure assessment (SOFA score and the simplified acute physiology score (SAPS II were calculated on admission. Results ECLT was significantly longer in septic than in non-septic patients [1033 min (871–1372 versus 665 min (551–862, p = 0.001]. There were significant correlations between ECLT and C-reactive protein (CRP concentrations (r = 0.78, p Conclusion ECLT measurement at admission could be a marker of organ dysfunction and a prognostic indicator in critically ill patients.

  4. Adhesive Forces between A1 Domain of von Willebrand Factor and N-terminus Domain of Glycoprotein Ibα Measured by Atomic Force Microscopy.

    Science.gov (United States)

    Tobimatsu, Hiroaki; Nishibuchi, Yuichiro; Sudo, Ryo; Goto, Shinya; Tanishita, Kazuo

    2015-01-01

    von Willebrand factor (VWF) plays an important role in the regulation of hemostasis and thrombosis formation, particularly under a high shear rate. However, the adhesive force due to the molecular interaction between VWF and glycoprotein Ibα (GPIbα) has not been fully explored. Thus, we employed atomic force microscopy to directly measure the adhesive force between VWF and GPIbα. We measured the adhesive force between VWF and GPIbα at the molecular level using an atomic force microscope (AFM). An AFM cantilever was coated with recombinant N-terminus VWF binding site of GPIbα, whereas a cover glass was coated with native VWF. The adhesive force at the molecular level was measured using an AFM. In the presence of 1 μg/mL VWF, the adhesion force was nearly 200 pN. As per the Gaussian fit analysis, the adhesive force of a single bond could have been 54 or 107 pN. Our consideration with the Gaussian fit analysis proposed that the adhesive force of a single bond could be 54 pN, which is very close to that obtained by optical tweezers (50 pN).

  5. A Novel Single-Domain Antibody Against von Willebrand Factor A1 Domain Resolves Leukocyte Recruitment and Vascular Leakage During Inflammation-Brief Report.

    Science.gov (United States)

    Aymé, Gabriel; Adam, Frédéric; Legendre, Paulette; Bazaa, Amine; Proulle, Valérie; Denis, Cécile V; Christophe, Olivier D; Lenting, Peter J

    2017-09-01

    von Willebrand factor (VWF) is crucial to hemostasis, but also plays a role in inflammatory processes. Unfortunately, no proper monoclonal antibodies to study VWF function in mice are currently available. We therefore aimed to generate single-domain antibodies (sdAbs) recognizing murine VWF and blocking its function in vivo. Llama-derived sdAbs recognizing both human and murine VWF were isolated via phage display technology. One of them (designated KB-VWF-006) recognized the VWF A1 domain with picomolar affinity. This sdAb avidity was strongly enhanced via dimerization using a triple Ala linker (KB-VWF-006bi). When administered in vivo to wild-type mice, KB-VWF-006bi dose dependently induced bleeding in a tail clip model. In 2 distinct models of inflammation, KB-VWF-006bi efficiently interfered with leukocyte recruitment and vascular leakage. KB-VWF-006bi is an sdAb recognizing the A1 domain of human VWF and murine VWF that interferes with VWF-platelet interactions in vivo. By using this sdAb, we now also show that the A1 domain is pertinent to the participation of VWF in the inflammatory response. © 2017 American Heart Association, Inc.

  6. Characterization of an entomopathogenic fungi target integument protein, Bombyx mori single domain von Willebrand factor type C, in the silkworm, Bombyx mori.

    Science.gov (United States)

    Han, F; Lu, A; Yuan, Y; Huang, W; Beerntsen, B T; Huang, J; Ling, E

    2017-06-01

    The insect cuticle works as the first line of defence to protect insects from pathogenic infections and water evaporation. However, the old cuticle must be shed in order to enter the next developmental stage. During each ecdysis, moulting fluids are produced and secreted into the area among the old and new cuticles. In a previous study, the protein Bombyx mori single domain von Willebrand factor type C (BmSVWC; BGIBMGA011399) was identified in the moulting fluids of Bo. mori and demonstrated to regulate ecdysis. In this study we show that in Bo. mori larvae, BmSVWC primarily locates to the integument (epidermal cells and cuticle), wing discs and head. During the moulting stage, BmSVWC is released into the moulting fluids, and is then produced again by epidermal cells after ecdysis. Fungal infection was shown to decrease the amount of BmSVWC in the cuticle, which indicates that BmSVWC is a target protein of entomopathogenic fungi. Thus, BmSVWC is mainly involved in maintaining the integrity of the integument structure, which serves to protect insects from physical damage and pathogenic infection. © 2017 The Royal Entomological Society.

  7. Pseudo (Platelet-type von Willebrand disease in pregnancy: a case report

    Directory of Open Access Journals (Sweden)

    Grover Neetu

    2013-01-01

    Full Text Available Abstract Background Pseudo (platelet-type-von Willebrand disease is a rare autosomal dominant bleeding disorder caused by an abnormal function of the glycoprotein lb protein; the receptor for von Willebrand factor. This leads to an increased removal of VWF multimers from the circulation as well as platelets and this results in a bleeding diathesis. Worldwide, less than 50 patients are reported with platelet type von Willebrand disease (PT-VWD. Case presentation We describe the management of platelet type von Willebrand disease in pregnancy of a 26 year old Caucasian primigravida. The initial diagnosis was made earlier following a significant haemorrhage post tonsillectomy several years prior to pregnancy. The patient was managed under a multidisciplinary team which included obstetricians, haematologists, anaesthetists and neonatologists. Care plans were made for the ante- natal, intra-partum and post-partum periods in partnership with the patient. The patient’s platelet count levels dropped significantly during the antenatal period. This necessitated the active exclusion of other causes of thrombocytopenia in pregnancy. A vaginal delivery was desired and plans were made for induction of labour at 38 weeks of gestation with platelet cover in view of the progressive fall of the platelet count. The patient however went into spontaneous labour on the day of induction. She was transfused two units of platelets before delivery. She had an unassisted vaginal delivery of a healthy baby. The successful antenatal counselling has encouraged the diagnosis of the same condition in her mother and sister. We found this to be a particularly interesting case as well as challenging to manage due to its rarity. Psuedo von Willebrand disease in pregnancy can be confused with a number of other differential diagnoses, such as gestational thrombocutopenia, idiopathatic thrombocytopenia, thrombotic thrombocytopenic purpura and pre-eclampsia; all need consideration

  8. Pseudo (platelet-type) von Willebrand disease in pregnancy: a case report.

    Science.gov (United States)

    Grover, Neetu; Boama, Vincent; Chou, Munazzah Rifat

    2013-01-17

    Pseudo (platelet-type)-von Willebrand disease is a rare autosomal dominant bleeding disorder caused by an abnormal function of the glycoprotein lb protein; the receptor for von Willebrand factor. This leads to an increased removal of VWF multimers from the circulation as well as platelets and this results in a bleeding diathesis. Worldwide, less than 50 patients are reported with platelet type von Willebrand disease (PT-VWD). We describe the management of platelet type von Willebrand disease in pregnancy of a 26 year old Caucasian primigravida. The initial diagnosis was made earlier following a significant haemorrhage post tonsillectomy several years prior to pregnancy. The patient was managed under a multidisciplinary team which included obstetricians, haematologists, anaesthetists and neonatologists. Care plans were made for the ante- natal, intra-partum and post-partum periods in partnership with the patient. The patient's platelet count levels dropped significantly during the antenatal period. This necessitated the active exclusion of other causes of thrombocytopenia in pregnancy. A vaginal delivery was desired and plans were made for induction of labour at 38 weeks of gestation with platelet cover in view of the progressive fall of the platelet count. The patient however went into spontaneous labour on the day of induction. She was transfused two units of platelets before delivery. She had an unassisted vaginal delivery of a healthy baby. The successful antenatal counselling has encouraged the diagnosis of the same condition in her mother and sister. We found this to be a particularly interesting case as well as challenging to manage due to its rarity. Psuedo von Willebrand disease in pregnancy can be confused with a number of other differential diagnoses, such as gestational thrombocutopenia, idiopathatic thrombocytopenia, thrombotic thrombocytopenic purpura and pre-eclampsia; all need consideration during investigations even in a case such as this where the

  9. Treatment of patients with von Willebrand disease

    Directory of Open Access Journals (Sweden)

    Tuohy E

    2011-04-01

    Full Text Available Emma Tuohy1, Emma Litt1, Raza Alikhan1,21Department of Haematology, University Hospital of Wales, Cardiff, UK; 2Haemophilia and Thrombosis Centre, University Hospital of Wales, Cardiff, UKAbstract: Von Willebrand disease (vWD is the most common hereditary bleeding disorder. The aim of therapy is to correct the dual hemostatic defect, due to defective platelet adhesion-aggregation and abnormal coagulation due to Factor VIII (FVIII deficiency. The choice of treatment depends on a number of factors, including the severity of the bleed, the procedure planned, the subtype and severity of the disease and the age and morbidity of the patient. Desmopressin (DDAVP is the treatment of choice for type 1 vWD as it increases endogenous release of FVIII and von Willebrand factor (vWF and is also used in some subtypes of type 2 vWD. In those patients in whom DDAVP is ineffective or contraindicated, levels can be restored by infusing vWF:FVIII concentrates. The role of antifibrinolytic treatment is an important adjunct to replacement therapy during minor or major surgery involving mucosal surfaces. The dosing and timing of vWF:FVIII concentrates is important depending on the nature of the surgical procedure. The role of secondary prophylaxis needs to be further defined.Keywords: von Willebrand disease, treatment, DDAVP 

  10. Von Willebrand Factor Antigen Predicts Response to Double Dose of Aspirin and Clopidogrel by PFA-100 in Patients Undergoing Primary Angioplasty for St Elevation Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Jacopo Gianetti

    2013-01-01

    Full Text Available Von Willebrand factor (VWF is an emerging risk factor in acute coronary syndromes. Platelet Function Analyzer (PFA-100 with Collagen/Epinephrine (CEPI is sensitive to functional alterations of VWF and also identifies patients with high on-treatment platelet reactivity (HPR. The objective of this study was to verify the effect of double dose (DD of aspirin and clopidogrel on HPR detected by PFA-100 and its relation to VWF and to its regulatory metalloprotease ADAMTS-13. Between 2009 and 2011 we enrolled 116 consecutive patients with ST elevation myocardial infarction undergoing primary PCI with HPR at day 5 after PCI. Patients recruited were then randomized between a standard dose (SD, n=58 or DD of aspirin and clopidogrel (DD, n=58, maintained for 6 months follow-up. Blood samples for PFA-100, light transmittance aggregometry, and VWF/ADAMTS-13 analysis were collected after 5, 30, and 180 days (Times 0, 1, and 2. At Times 1 and 2 we observed a significantly higher CEPI closure times (CT in DD as compared to SD (P<0.001. Delta of CEPI-CT (T1-T0 was significantly related to VWF (P<0.001 and inversely related to ADAMTS-13 (0.01. Responders had a significantly higher level of VWF at T0. Finally, in a multivariate model analysis, VWF and ADAMTS-13 in resulted significant predictors of CEPI-CT response (P=0.02. HRP detected by PFA-100 in acute myocardial infarction is reversible by DD of aspirin and clopidogrel; the response is predicted by basal levels of VWF and ADAMTS-13. PFA-100 may be a useful tool to risk stratification in acute coronary syndromes given its sensitivity to VWF.

  11. Myomectomy in a case of von Willebrand's disease in a low ...

    African Journals Online (AJOL)

    Von Willebrand's disease (vWD) is an inherited bleeding disorder with an estimated prevalence of 1% in the general population. It is caused by deficiency or dysfunction of von Willebrand's factor. Surgical procedure on patients with vWD is usually associated with increased haemorrhage. Keywords: Clotting Factors ...

  12. Amount of H Antigen Expressed on Circulating von Willebrand Factor Is Modified by ABO Blood Group Genotype and Is a Major Determinant of Plasma von Willebrand Factor Antigen Levels

    National Research Council Canada - National Science Library

    O’Donnell, James; Boulton, Frank E; Manning, Richard A; Laffan, Michael A

    2002-01-01

    .... AvWF was correlated strongly with plasma levels of A transferase activity. Thus, we have clearly demonstrated a direct relationship between ABO genotype, A transferase expression, and the amount of A antigen expressed on circulating vWF...

  13. Consumption of nattokinase is associated with reduced blood pressure and von Willebrand factor, a cardiovascular risk marker: results from a randomized, double-blind, placebo-controlled, multicenter North American clinical trial

    Science.gov (United States)

    Jensen, Gitte S; Lenninger, Miki; Ero, Michael P; Benson, Kathleen F

    2016-01-01

    Objective The objective of this study is to evaluate the effects of consumption of nattokinase on hypertension in a North American hypertensive population with associated genetic, dietary, and lifestyle factors. This is in extension of, and contrast to, previous studies on Asian populations. Materials and methods A randomized, double-blind, placebo-controlled, parallel-arm clinical study was performed to evaluate nattokinase (NSK-SD), a fermented soy extract nattō from which vitamin K2 has been removed. Based on the results from previous studies on Asian populations, 79 subjects were enrolled upon screening for elevated blood pressure (BP; systolic BP ≥130 or diastolic BP ≥90 mmHg) who consumed placebo or 100 mg nattokinase/d for the 8-week study duration. Blood collections were performed at baseline and 8 weeks for testing plasma renin activity, von Willebrand factor (vWF), and platelet factor-4. Seventy-four people completed the study with good compliance. Results Consumption of nattokinase was associated with a reduction in both systolic and diastolic BP. The reduction in systolic BP was seen for both sexes but was more robust in males consuming nattokinase. The average reduction in diastolic BP in the nattokinase group from 87 mmHg to 84 mmHg was statistically significant when compared to that in the group consuming placebo, where the average diastolic BP remained constant at 87 mmHg (Pnattokinase, where the average diastolic BP dropped from 86 mmHg to 81 mmHg (Pnattokinase (Pnattokinase (Pnattokinase consumption in a North American population is associated with beneficial changes to BP in a hypertensive population, indicating sex-specific mechanisms of action of nattokinase’s effect on vWF and hypertension. PMID:27785095

  14. Consumption of nattokinase is associated with reduced blood pressure and von Willebrand factor, a cardiovascular risk marker: results from a randomized, double-blind, placebo-controlled, multicenter North American clinical trial.

    Science.gov (United States)

    Jensen, Gitte S; Lenninger, Miki; Ero, Michael P; Benson, Kathleen F

    2016-01-01

    The objective of this study is to evaluate the effects of consumption of nattokinase on hypertension in a North American hypertensive population with associated genetic, dietary, and lifestyle factors. This is in extension of, and contrast to, previous studies on Asian populations. A randomized, double-blind, placebo-controlled, parallel-arm clinical study was performed to evaluate nattokinase (NSK-SD), a fermented soy extract nattō from which vitamin K2 has been removed. Based on the results from previous studies on Asian populations, 79 subjects were enrolled upon screening for elevated blood pressure (BP; systolic BP ≥130 or diastolic BP ≥90 mmHg) who consumed placebo or 100 mg nattokinase/d for the 8-week study duration. Blood collections were performed at baseline and 8 weeks for testing plasma renin activity, von Willebrand factor (vWF), and platelet factor-4. Seventy-four people completed the study with good compliance. Consumption of nattokinase was associated with a reduction in both systolic and diastolic BP. The reduction in systolic BP was seen for both sexes but was more robust in males consuming nattokinase. The average reduction in diastolic BP in the nattokinase group from 87 mmHg to 84 mmHg was statistically significant when compared to that in the group consuming placebo, where the average diastolic BP remained constant at 87 mmHg (Pnattokinase, where the average diastolic BP dropped from 86 mmHg to 81 mmHg (Pnattokinase (Pnattokinase (Pnattokinase consumption in a North American population is associated with beneficial changes to BP in a hypertensive population, indicating sex-specific mechanisms of action of nattokinase's effect on vWF and hypertension.

  15. Pulmonary hypertension secondary to hyperviscosity in a patient with rheumatoid arthritis and acquired von Willebrand disease: a case report.

    Science.gov (United States)

    Hernández-Gilsoul, Thierry; Atisha-Fregoso, Yemil; Vargas-Ruíz, Angel G; Rivero-Sigarroa, Eduardo; Dominguez-Cherit, Guillermo; Namendys-Silva, Silvio A

    2013-10-02

    Acquired von Willebrand disease is initiated by autoantibodies and hyperviscosity syndrome caused by a massive polyclonal hypergammaglobulinemia. Acquired von Willebrand disease associated with autoimmune disease in addition to pulmonary hypertension during emergency room presentation is a rare condition. To the best of our knowledge, this is the second case reported in the literature treated with success; the first one was reported in 1987. A 28-year-old mestizo man with a 3-year history of inflammatory arthritis was admitted to our hospital. An overlap of rheumatoid arthritis with systemic lupus erythematosus was suspected; therefore methotrexate was initiated, and later changed to leflunomide because of liver toxicity. Prothrombin time, international normalized ratio and activated partial thromboplastin times were normal (11/10.4 seconds; 1.2; 31.1/26.9 seconds, respectively), von Willebrand factor activity was observed with low ristocetin cofactor at 33.6UI/dL, high von Willebrand factor antigen >200UI/dL, and a low von Willebrand factor: ristocetin cofactor to von Willebrand factor antigen ratio. He was admitted to the emergency room with a 24-hour evolution of progressive dyspnea, cough, thoracic pain, and palpitations, 104 beats/min, 60/40 mmHg, temperature of 38°C, pulse oximetric saturation 88% and 30 breaths/minute. Cold, pale and mottled skin was also observed. He was then transferred to the intensive care unit. The placement of a pulmonary artery catheter was made. The initial patterns showed a precapillary pulmonary hypertension; acute pulmonary embolism was the first choice for diagnosis. Pulmonary angiography was conducted, and when no clot was discovered, pulmonary artery hypertension associated with connective tissue disease was considered. Serum protein electrophoresis confirmed the presence of a massive polyclonal hypergammaglobulinemia, and no paraproteinemia or monoclonal cell population was found from the electrophoretic pattern of the

  16. Nordic Haemophilia Council's practical guidelines on diagnosis and management of von Willebrand disease

    DEFF Research Database (Denmark)

    Lassila, Riitta; Holme, Pål André; Landorph, Andrea

    2011-01-01

    Von Willebrand disease (VWD) is the most common inherited bleeding disorder characterized by spontaneous or tissue injury-related, mostly mucocutaneous, bleeding events. VWD affects both males and females and is caused by quantitative or qualitative deficiency of Von Willebrand factor. The diagno...

  17. Current and Emerging Options for the Management of Inherited von Willebrand Disease

    NARCIS (Netherlands)

    Heijdra, J.M. (Jessica M.); M.H. Cnossen (Marjon); F.W.G. Leebeek (Frank)

    2017-01-01

    textabstractVon Willebrand disease (VWD) is the most common inherited bleeding disorder with an estimated prevalence of ~1% and clinically relevant bleeding symptoms in approximately 1:10,000 individuals. VWD is caused by a deficiency and/or defect of von Willebrand factor (VWF). The most common

  18. Von Willebrand Disease in the Netherlands : from genetic variation to phenotypic variability

    NARCIS (Netherlands)

    Y.V. Sanders (Yvonne)

    2015-01-01

    markdownabstractAbstract Von Willebrand Disease (VWD) is the most common inherited bleeding disorder resulting in mucocutaneous bleeding, like epistaxis, oral cavity bleeding and menorrhagia. VWD is caused by reduced or dysfunctional von Willebrand Factor (VWF). VWF levels are highly variable

  19. Acquired von Willebrand syndrome: A rare disorder of heterogeneous etiology

    Directory of Open Access Journals (Sweden)

    P Kasatkar

    2013-01-01

    Full Text Available Context: Acquired von Willebrand syndrome (AVWS is a rare bleeding disorder that mimics the inherited form of von Willebrand disease (VWD in terms of laboratory findings and clinical presentation. Aims: To study the etiology of acquired VWD. Settings and Design: The patients referred from various hospitals in and out of Mumbai were included in the study. Materials and Methods: Six patients with AVWS diagnosed at this center over the last 10 years were analyzed against 171 patients with inherited VWD. The differential diagnosis of AVWS was made based on reduced levels of von Willebrand antigen and von Willebrand ristocetin cofactor, decrease in ristocetin induced platelet aggregation, absence of correction in mixing studies with no prior history of bleeding problems and a negative family history for bleeding disorders. Results: In three patients, the disease was associated with systematic lupus erythematosus, out of which one was also associated with Kikuchi lymphadenitis and second with autoimmune hemolytic anemia. Fourth case was associated with hypothyroidism and fifth was a case of dermatitis and vitiligo. The last patient was a case of hemophilia A with Burkitts lymphoma, who developed autoantibodies to von Willebrand factor. Except two patients, all other patients responded to immune suppressive therapy with corticosteroids, while the patient with hypothyroidism responded to oral thyroxine. Conclusion: AVWS is a rare condition and may often be missed or diagnosed as inherited disease associated with heterogeneous disease conditions.

  20. Long-term impact of joint bleeds in von Willebrand disease: a nested case-control study.

    Science.gov (United States)

    van Galen, Karin P M; de Kleijn, Piet; Foppen, Wouter; Eikenboom, Jeroen; Meijer, Karina; Schutgens, Roger E G; Fischer, Kathelijn; Cnossen, Marjon H; de Meris, Joke; Fijnvandraat, Karin; van der Bom, Johanna G; Laros-van Gorkom, Britta A P; Leebeek, Frank W G; Mauser-Bunschoten, Eveline P

    2017-09-01

    Patients with severe von Willebrand disease (VWD) may develop arthropathy after joint bleeds. Information on its prevalence and severity is limited. We aimed to assess the occurrence and severity of arthropathy in VWD and its impact on daily life. VWD patients with and without verified joint bleeds were matched for age, sex and Factor VIII level or von Willebrand Factor activity in a nested case-control study within the Willebrand in the Netherlands study. Assessments included the Hemophilia Joint Health Score (0-124), Pettersson score (0-13 per joint X-ray), Hemophilia Activity List score (0-100), joint pain (Visual Analog Scale 0-10), and the Impact on Participation and Autonomy questionnaire (0-20). Arthropathy was defined as a Hemophilia Joint Health Score of 10 or higher, or a Pettersson score over 3 of at least one joint. We included 48 patients with verified joint bleeds (cases) and 48 controls: 60% males, mean age 46 years (range 18-80), median von Willebrand Factor activity 5 versus 8 IU/dL and Factor VIII 24 versus 36 IU/dL. Arthropathy occurred in 40% of the cases versus 10% of the controls (PList score: 88 vs. 100, P3: 13 of 19 vs. 3 of 28, P<0.01, and median score on the participation questionnaire 6.1 vs. 0.9, P<0.01). In conclusion, arthropathy occurs in 40% of VWD patients after joint bleeds and is associated with pain, radiological abnormalities, functional limitations, and less social participation (Dutch trial register: NTR4548). Copyright© 2017 Ferrata Storti Foundation.

  1. Translational medicine advances in von Willebrand disease.

    Science.gov (United States)

    Lillicrap, D

    2013-06-01

    Following the recognition of von Willebrand disease (VWD) in 1926 and the cloning of the gene for von Willebrand factor (VWF) in 1985, significant advances have been made in our fundamental knowledge of both the disease and the protein. Some of this new knowledge has also begun to impact the clinical management of VWD. First, the progressive increase in our understanding of the molecular genetic basis of VWD has resulted in rational applications of molecular testing to complement the current range of phenotypic tests for VWD. These molecular genetic strategies are most effectively directed at the prenatal diagnosis of type 3 VWD and confirmatory testing for types 2B and 2N disease. In contrast, the use of molecular testing to clarify the diagnosis of type 1 VWD is of marginal benefit, at best. In terms of VWD therapies, a new recombinant VWF concentrate has recently completed successful clinical trials and is now awaiting more widespread application. There have even been some preclinical successes with VWF gene transfer although the clinical rationale for this therapeutic strategy needs careful consideration. Much more remains to be learnt about the biology of VWF and further translational advances for the enhancement of VWD care will inevitably be realized. © 2013 International Society on Thrombosis and Haemostasis.

  2. Diagnosing von Willebrand disease: a short history of laboratory milestones and innovations, plus current status, challenges, and solutions.

    Science.gov (United States)

    Favaloro, Emmanuel J

    2014-07-01

    von Willebrand disease (VWD) is a disorder characterized by deficiency of, or defects in, von Willebrand factor (VWF). VWD was originally identified by Erik Adolf von Willebrand, who in early 1924 investigated a large family suffering from a bleeding disorder that seemed to differ from hemophilia. Erik von Willebrand undertook some initial laboratory investigations to conclude the involvement of a plasma factor, the lack of which prolonged the bleeding time, but failed to impair coagulation times and clot retraction. By the end of the 1960s, VWD was accepted as a combined deficiency of factor VIII (FVIII) and another plasma factor responsible for normal platelet adhesion. Just how these two functions were related to each other was less clear and the diagnostic tests available at the time were poorly reproducible, cumbersome, and unreliable; thus, VWD was poorly delineated from other coagulation and platelet disorders. The early 1970s saw a revolution in diagnostics when ristocetin was identified to induce platelet aggregation, and this formed the basis of the first consistent and reliable VWF "activity" test, permitting quantification of the platelet adhesive function missing in VWD. Concurrently, immunoprecipitating techniques specific for VWF were defined, and the application of such technologies permitted a clearer understanding of both VWF and VWD heterogeneity. Continued exploration of the structure and function of VWF contributed greatly to the understanding of platelet physiology, ligand receptor interaction and pathways of cellular interaction and activation. Recently, additional assays evaluating other functions of VWF, including collagen binding, platelet glycoprotein Ib binding, and FVIII binding, have improved the diagnosis of VWD. The purpose of this narrative review is to explore the history of phenotypic VWD diagnostics, with a focus on laboratory milestones from the past as well highlighting recent and ongoing innovations, and ongoing challenges and

  3. Genetics Home Reference: von Willebrand disease

    Science.gov (United States)

    ... Jun;5(6):1165-9. Citation on PubMed Kessler CM. Diagnosis and treatment of von Willebrand disease: ... consult with a qualified healthcare professional . About Selection Criteria for Links Data Files & API Site Map Customer ...

  4. High-Affinity DNA Aptamer Generation Targeting von Willebrand Factor A1-Domain by Genetic Alphabet Expansion for Systematic Evolution of Ligands by Exponential Enrichment Using Two Types of Libraries Composed of Five Different Bases.

    Science.gov (United States)

    Matsunaga, Ken-Ichiro; Kimoto, Michiko; Hirao, Ichiro

    2017-01-11

    The novel evolutionary engineering method ExSELEX (genetic alphabet expansion for systematic evolution of ligands by exponential enrichment) provides high-affinity DNA aptamers that specifically bind to target molecules, by introducing an artificial hydrophobic base analogue as a fifth component into DNA aptamers. Here, we present a newer version of ExSELEX, using a library with completely randomized sequences consisting of five components: four natural bases and one unnatural hydrophobic base, 7-(2-thienyl)imidazo[4,5-b]pyridine (Ds). In contrast to the limited number of Ds-containing sequence combinations in our previous library, the increased complexity of the new randomized library could improve the success rates of high-affinity aptamer generation. To this end, we developed a sequencing method for each clone in the enriched library after several rounds of selection. Using the improved library, we generated a Ds-containing DNA aptamer targeting von Willebrand factor A1-domain (vWF) with significantly higher affinity (KD = 75 pM), relative to those generated by the initial version of ExSELEX, as well as that of the known DNA aptamer consisting of only the natural bases. In addition, the Ds-containing DNA aptamer was stabilized by introducing a mini-hairpin DNA resistant to nucleases, without any loss of affinity (KD = 61 pM). This new version is expected to consistently produce high-affinity DNA aptamers.

  5. Prevalence of von Willebrand disease in women with iron deficiency anaemia and menorrhagia in Taiwan.

    Science.gov (United States)

    Chen, Y-C; Chao, T-Y; Cheng, S-N; Hu, S-H; Liu, J-Y

    2008-07-01

    Iron deficiency anaemia (IDA) is a frequently encountered disease, which can be attributed to menorrhagia. Most female patients with von Willebrand disease (VWD) have menorrhagia. The aim of this study was to investigate the prevalence of VWD in women with both IDA and menorrhagia in Taiwan. From January to December 2005 and November 2006 to January 2007, 56 consecutive patients with both IDA and menorrhagia were enrolled in this study. Their median age was 41 years (range 18-53). IDA was diagnosed by anaemia plus either low ferritin or transferrin saturation. Menorrhagia was evaluated by patient's menses history. Both von Willebrand factor antigen (VWF:Ag) and ristocetin cofactor activity (VWF:RCo) were measured for each patient. Bleeding time (BT) and platelet function analyser (PFA)-100 assay were determined as ancillary tests. The VWD diagnosis was established if: (i) both VWF:Ag (menorrhagia might develop IDA at younger age (34.3 vs. 39.7, P = 0.09) and had more IDA recurrence (75% vs. 16%, P = 0.03) than those patients without VWD. Of the eight VWD patients with VWF multimer analyses, all were revealed to have type I VWD. Our study demonstrates that VWD was not uncommon in women with both IDA and menorrhagia in Taiwan.

  6. Changes in bleeding patterns in von Willebrand disease after institution of long-term replacement therapy : results from the von Willebrand Disease Prophylaxis Network

    NARCIS (Netherlands)

    Holm, Elena; Abshire, Thomas C; Bowen, Joel; Álvarez, M Teresa; Bolton-Maggs, Paula; Carcao, Manuel; Federici, Augusto B; Gill, Joan Cox; Halimeh, Susan; Kempton, Christine; Key, Nigel S; Kouides, Peter; Lail, Alice; Landorph, Andrea; Leebeek, Frank; Makris, Michael; Mannucci, Pier; Mauser-Bunschoten, Eveline P; Nugent, Diane; Valentino, Leonard A; Winikoff, Rochelle; Berntorp, Erik

    Clinically, the leading symptom in von Willebrand disease (VWD) is bleeding, chiefly of mucosal type, for example, epistaxis, gingival, or gastrointestinal bleeding, and menorrhagia. In severe forms of VWD with secondary deficiency of factor VIII, spontaneous joint bleeding, resembling that observed

  7. The metal-ion-dependent adhesion site in the Von Willebrand factor-A domain of α2δ subunits is key to trafficking voltage-gated Ca2+ channels

    Science.gov (United States)

    Cantí, C.; Nieto-Rostro, M.; Foucault, I.; Heblich, F.; Wratten, J.; Richards, M. W.; Hendrich, J.; Douglas, L.; Page, K. M.; Davies, A.; Dolphin, A. C.

    2005-01-01

    All auxiliary α2δ subunits of voltage-gated Ca2+ (CaV) channels contain an extracellular Von Willebrand factor-A (VWA) domain that, in α2δ-1 and -2, has a perfect metal-ion-dependent adhesion site (MIDAS). Modeling of the α2δ-2 VWA domain shows it to be highly likely to bind a divalent cation. Mutating the three key MIDAS residues responsible for divalent cation binding resulted in a MIDAS mutant α2δ-2 subunit that was still processed and trafficked normally when it was expressed alone. However, unlike WT α2δ-2, the MIDAS mutant α2δ-2 subunit did not enhance and, in some cases, further diminished CaV1.2, -2.1, and -2.2 currents coexpressed with β1b by using either Ba2+ or Na+ as a permeant ion. Furthermore, expression of the MIDAS mutant α2δ-2 reduced surface expression and strongly increased the perinuclear retention of CaVα1 subunits at the earliest time at which expression was observed in both Cos-7 and NG108–15 cells. Despite the presence of endogenous α2δ subunits, heterologous expression of α2δ-2 in differentiated NG108–15 cells further enhanced the endogenous high-threshold Ca2+ currents, whereas this enhancement was prevented by the MIDAS mutations. Our results indicate that α2δ subunits normally interact with the CaVα1 subunit early in their maturation, before the appearance of functional plasma membrane channels, and an intact MIDAS motif in the α2δ subunit is required to promote trafficking of the α1 subunit to the plasma membrane by an integrin-like switch. This finding provides evidence for a primary role of a VWA domain in intracellular trafficking of a multimeric complex, in contrast to the more usual roles in binding extracellular ligands in other exofacial VWA domains. PMID:16061813

  8. Van Willebrand's disease in the Western Cape

    African Journals Online (AJOL)

    Von Willebrand's disease (VWD) is a mild-ta-moderately severe bleeding disorder characterised by mucosal bleeding such as epistaxis, gingival bleeding, gastro-intestinal bleeding and menorrhagia Haemarthroses, deep subcutaneous and intramuscular haematomas, typically seen in the severe haemophilias. are ...

  9. Joint bleeding in von Willebrand disease

    NARCIS (Netherlands)

    Galen, K.P.M. van

    2017-01-01

    Von Willebrand disease (VWD) is the most common inherited bleeding disorder occurring in approximately 1/100 people. Until now, joint bleeds did not get much attention in clinical research on VWD, since mucocutaneous bleeding is predominant. However, recurrent joint bleeds lead to arthropathy, the

  10. Technological advances in diagnostic testing for von Willebrand disease: new approaches and challenges.

    Science.gov (United States)

    Hayward, C P M; Moffat, K A; Graf, L

    2014-06-01

    Diagnostic tests for von Willebrand disease (VWD) are important for the assessment of VWD, which is a commonly encountered bleeding disorder worldwide. Technical innovations have been applied to improve the precision and lower limit of detection of von Willebrand factor (VWF) assays, including the ristocetin cofactor activity assay (VWF:RCo) that uses the antibiotic ristocetin to induce plasma VWF binding to glycoprotein (GP) IbIXV on target platelets. VWF-collagen-binding assays, depending on the type of collagen used, can improve the detection of forms of VWD with high molecular weight VWF multimer loss, although the best method is debatable. A number of innovations have been applied to VWF:RCo (which is commonly performed on an aggregometer), including replacing the target platelets with immobilized GPIbα, and quantification by an enzyme-linked immunosorbent assay (ELISA), immunoturbidimetric, or chemiluminescent end-point. Some common polymorphisms in the VWF gene that do not cause bleeding are associated with falsely low VWF activity by ristocetin-dependent methods. To overcome the need for ristocetin, some new VWF activity assays use gain-of-function GPIbα mutants that bind VWF without the need for ristocetin, with an improved precision and lower limit of detection than measuring VWF:RCo by aggregometry. ELISA of VWF binding to mutated GPIbα shows promise as a method to identify gain-of-function defects from type 2B VWD. The performance characteristics of many new VWF activity assays suggest that the detection of VWD, and monitoring of VWD therapy, by clinical laboratories could be improved through adopting newer generation VWF assays. © 2014 John Wiley & Sons Ltd.

  11. Acquired von Willebrand syndrome in children with aortic and pulmonary stenosis.

    Science.gov (United States)

    Binnetoğlu, Fatih Köksal; Babaoğlu, Kadir; Filiz, Şayegan Güven; Zengin, Emine; Altun, Gürkan; Kılıç, Suar Çakı; Sarper, Nazan

    This prospective study was planned to investigate the frequency and relationship of acquired von Willebrand syndrome (AVWS) with aortic and pulmonary stenosis in patients. A total of 84 children, ranging from two to 18 years of age, were enrolled in this study. Of these, 28 had isolated aortic stenosis, 32 had isolated pulmonary stenosis and 24 were healthy. Children with aortic and pulmonary stenosis associated with other congenital heart diseases were excluded. Children with hypothyroidism, renal or liver disease, malignancy or autoimmune disease were also excluded. Wholeblood count, blood group, factor VIII level, prothrombin time (PT), activated partial thromboplastin time (aPTT), von Willebrand factor antigen (VWF:Ag), ristocetin co-factor (VWF:RCo), and bleeding time using a platelet-function analyser (PFA-100) were performed in all patients. All of the children in the study underwent a detailed physical examination and echocardiographic evaluation. A history of bleeding was positive in 18% of the aortic stenosis group, 9% of the pulmonary stenosis group, and 4% of the control group. Seven of 60 (12%) patients had laboratory findings that implied a diagnosis of AVWS, and two of these (28%) had a history of bleeding. The frequency of AVWS was 14% in patients with aortic stenosis and 9% in those with pulmonary stenosis. AVWS is not rare in stenotic obstructive cardiac diseases. A detailed history of bleeding should be taken from patients with valvular disease. Even if the history is negative, whole blood count, PT and aPTT should be performed. If necessary, PFA-100 closure time and further tests should be planned for the diagnosis of AVWS.

  12. Utility of platelet function analyzer as a screening tool for the diagnosis of von Willebrand disease in adolescents with menorrhagia.

    Science.gov (United States)

    Naik, Swati; Teruya, Jun; Dietrich, Jennifer E; Jariwala, Purvi; Soundar, Esther; Venkateswaran, Lakshmi

    2013-07-01

    Von Willebrand disease (VWD), and in particular, VWD type 1 and low VW factor (defined as Von Willebrand Ristocetin cofactor activity (RCoF) menorrhagia and both groups benefit from similar management. Platelet function analyzer (PFA-100®) is often used as a screening test to detect VWD. We analyzed the utility of PFA-100® as a screening tool in the detection of VWD type 1 and low VW factor (VWF) in an exclusive adolescent population with menorrhagia. The study population consisted of adolescents with menorrhagia who had simultaneously drawn blood samples for VWD and PFA-100®. Abnormal PFA-100® was defined as values >183 seconds for collagen/epinephrine and/or >126 seconds for collagen/ADP. Of a total of 235 patients tested, 23 patients had RCoF menorrhagia. We conclude that in the setting of adolescent menorrhagia, PFA-100® does not have utility as an initial screening test for the diagnosis of VWD and in particular, low VWF and that clinicians need to be aware of this limitation of PFA-100® while evaluating adolescents with menorrhagia. Copyright © 2013 Wiley Periodicals, Inc.

  13. Inheritance of von Willebrand's disease in a colony of Doberman Pinschers.

    Science.gov (United States)

    Riehl, J; Okura, M; Mignot, E; Nishino, S

    2000-02-01

    To determine the mode of inheritance of von Willebrand's disease (vWD) and perform linkage analysis between vWD and coat color or narcolepsy in a colony of Doberman Pinschers. 159 Doberman Pinschers. von Willebrand factor antigen (vWF:Ag) concentration was measured by use of ELISA, and results were used to classify dogs as having low ( 65%) vWF:Ag concentration, compared with results of analysis of standard pooled plasma. Buccal bleeding time was measured, and mode of inheritance of vWD was assessed by pedigree analysis. von Willebrand's disease was transmitted as a single autosomal gene defect. Results suggested that 27.04% of dogs were homozygous for vWD, 62.26% were heterozygous, and 10.69% did not have the defect. Most homozygous and some heterozygous dogs had prolonged bleeding times. Dogs with diluted coat colors (blue and fawn) were significantly overrepresented in the homozygous group, compared with black and red dogs, but a significant link between vWD and coat color was not detected. von Willebrand's disease is transmitted as an autosomal dominant trait with variable penetrance; most dogs in this colony (89.3%) were carriers of vWD. Homozygosity for vWD is not likely to be lethal. Some heterozygous dogs have prolonged bleeding times. An association between diluted coat colors and vWD may exist.

  14. Factor XII Contact Activation.

    Science.gov (United States)

    Naudin, Clément; Burillo, Elena; Blankenberg, Stefan; Butler, Lynn; Renné, Thomas

    2017-11-01

    Contact activation is the surface-induced conversion of factor XII (FXII) zymogen to the serine protease FXIIa. Blood-circulating FXII binds to negatively charged surfaces and this contact to surfaces triggers a conformational change in the zymogen inducing autoactivation. Several surfaces that have the capacity for initiating FXII contact activation have been identified, including misfolded protein aggregates, collagen, nucleic acids, and platelet and microbial polyphosphate. Activated FXII initiates the proinflammatory kallikrein-kinin system and the intrinsic coagulation pathway, leading to formation of bradykinin and thrombin, respectively. FXII contact activation is well characterized in vitro and provides the mechanistic basis for the diagnostic clotting assay, activated partial thromboplastin time. However, only in the past decade has the critical role of FXII contact activation in pathological thrombosis been appreciated. While defective FXII contact activation provides thromboprotection, excess activation underlies the swelling disorder hereditary angioedema type III. This review provides an overview of the molecular basis of FXII contact activation and FXII contact activation-associated disease states. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  15. Levonorgestrel intrauterine system as a treatment option for severe menorrhagia in adolescent with type III von Willebrand disease.

    Science.gov (United States)

    Silva, Carla Donato; Geraldes, Fernanda; Silva, Isabel Santos

    2013-04-30

    The authors describe a case of an adolescent with type III von Willebrand disease and severe menorrhagia since menarche. Antifibrinolytic, hormonal (estroprogestative pill in high doses, etonogestrel implant and gonadotropin-releasing hormone agonist goserelin) and Von Willebrand Factor/Factor VIII replacement therapies were prescribed to the patient, but symptomatic control was only obtained with high doses of VWF/FVIII twice a week. In March 2012, a levonorgestrel intrauterine system was inserted in a 14-year-old. At present, the patient is asymptomatic without regular prophylaxis (VWF/FVIII replacement therapy) and has had a remarkable improvement in her quality of life.

  16. Management of type 2b von Willebrand disease in the neonatal period.

    Science.gov (United States)

    Proud, Lindsay; Ritchey, A Kim

    2017-01-01

    Von Willebrand disease (VWD) is the most common inherited bleeding disorder, affecting one in 1,000 people. Type 2b VWD is a less common subtype caused by a gain-of-function mutation in von Willebrand factor (VWF) that leads to the formation of large, ineffective VWF-platelet multimers in circulation. This unique pathophysiology creates diagnostic and treatment dilemmas. There is limited information on the management of type 2b VWD in the neonatal period. This report describes the management of a neonate with type 2b VWD with an emphasis on the added benefit of concomitant platelet transfusion and factor replacement therapy over factor replacement therapy alone. © 2016 Wiley Periodicals, Inc.

  17. Factors affecting aspartase activity.

    Science.gov (United States)

    DEPUE, R H; MOAT, A G

    1961-09-01

    Depue, Robert H. (Hahnemann Medical College, Philadelphia), and Albert G. Moat. Factors affecting aspartase activity. J. Bacteriol. 82:383-386. 1961.-Cells of Escherichia coli grown in a glucose-mineral salts medium contain about one-fifth the amount of aspartase activity observed in cells grown in a yeast extract-peptone medium. The aspartase activity of the cells grown in glucose-salts medium would appear to be too low to provide a mechanism for synthesis of amino groups. Aspartase was purified approximately eightfold by ammonium sulfate precipitation and column chromatography of cell-free extracts. The purified preparation was specific for l-aspartic acid and contained no fumarase activity. A divalent metal ion requirement was demonstrated, this requirement being satisfied by cobaltous or manganous ions. The enzyme activity was found to be dependent upon free sulfhydryl groups. Biotin did not appear to be directly involved in the aspartase reaction since high concentrations of avidin did not alter the reaction rate. The Michaelis constant for aspartase with aspartic acid as substrate was determined to be 0.033 m.

  18. Heparanase procoagulant activity, factor Xa, and plasminogen activator inhibitor 1 are increased in shift work female nurses.

    Science.gov (United States)

    Nadir, Yona; Saharov, Gleb; Hoffman, Ron; Keren-Politansky, Anat; Tzoran, Inna; Brenner, Benjamin; Shochat, Tamar

    2015-07-01

    Epidemiologic studies indicate on an increased risk of cardiovascular disease and cancer in shift workers, although the underlying mechanism is obscure. Heparanase directly enhances tissue factor (TF) activity leading to increased factor Xa production and subsequent activation of the coagulation system. In the present study, a comparison of coagulation markers among healthy shift working (SW) vs. healthy daytime working (DW) female nurses was performed. Thirty SW and 30 DW female nurses were enrolled. For each of the 60 participants, blood was drawn between 7:00 and 8:00 a.m. and at least 8 h after the last work shift. Plasma was studied for coagulation marker that included TF/heparanase procoagulant activity, TF activity, heparanase procoagulant activity, heparanase level, factor Xa level, plasminogen activator inhibitor 1 (PAI-1), plasminogen, α2-antiplasmin, fibrinogen, global protein C, von Willebrand factor, and D-dimer by chromogenic assays and enzyme-linked immunosorbent assays (ELISAs). Sleep quality was assessed by self-report according to the Pittsburgh Sleep Quality Index. The heparanase procoagulant activity increased by 2-fold and the TF/heparanase procoagulant activity increased by 1.5-fold in SW nurses compared to DW nurses (P cardiovascular and cancer morbidity.

  19. Prophylaxis escalation in severe von Willebrand disease: A prospective study from the von Willebrand Disease Prophylaxis Network

    NARCIS (Netherlands)

    T.C. Abshire (Thomas Calvin); J. Cox-Gill; C.L. Kempton; F.W.G. Leebeek (Frank); M. Carcao (M.); P. Kouides (P.); S. Donfield (S.); E. Berntorp

    2015-01-01

    textabstractBackground: Treatment of mucosal bleeding (epistaxis, gastrointestinal bleeding, and menorrhagia) and joint bleeding remains problematic in clinically severe von Willebrand disease (VWD). Patients are often unresponsive to treatment (e.g. desmopressin or antifibrinolytic therapy) and may

  20. Assessing the clinical severity of type 1 von Willebrand disease patients with a microchip flow-chamber system.

    Science.gov (United States)

    Nogami, K; Ogiwara, K; Yada, K; Shida, Y; Takeyama, M; Yaoi, H; Minami, H; Furukawa, S; Hosokawa, K; Shima, M

    2016-04-01

    The clinical phenotype of von Willebrand disease (VWD) is heterogeneous, and von Willebrand factor ristocetin cofactor activity (VWF:RCo) does not always reflect clinical severity, especially in VWD type 1. We have reported the potential of a microchip flow-chamber system (Total-Thrombus Formation Analysis System [T-TAS®]) for assessing physiologic hemostasis in VWD. Aim To evaluate the relationship between T-TAS, bleeding score (BS) and laboratory test results in type 1 VWD patients. Microchips coated with collagen (platelet chip [PL-chip]) or collagen/thromboplastin (AR-chip) were used to assess platelet thrombus formation (PTF) at high shear rates or fibrin-rich PTF at low shear rates, respectively, in whole blood from 50 patients. The times needed for the flow pressure to increase by 10 kPa and 30 kPa (T10 and T30 ) from baseline were calculated from flow pressure curves. BS was determined by the use of a standardized questionnaire. PL-T10 values correlated with BS (R(2) ~ 0.45) better than VWF:RCo (R(2) ~ 0.36), irrespective of the flow rate, whereas AR-T10 showed only a weak correlation with BS (R(2) ~ 0.18). Patients with PL-T10 > 10 min or AR-T10 > 30 min had lower VWF levels and higher BS than those with PL-T10 ≤ 10 min or AR-T10 ≤ 30 min, and the greatest differences were observed with PL-T10. Clinical severity appeared to correlate best with PL-T10 > 8 min. BS was significantly higher in patients with VWF:RCo of 8 min than in those with PL-T10 ≤ 8 min. T-TAS could be a useful technique for discriminating and predicting BS in VWD type 1 patients. © 2016 International Society on Thrombosis and Haemostasis.

  1. Decrease of hemostatic cardiovascular risk factors by aggressive vs. conventional atorvastatin treatment in patients with Type 2 diabetes mellitus.

    NARCIS (Netherlands)

    Ree, M.A. van de; Maat, M.P. de; Kluft, C.; Meinders, A.E.; Princen, H.M.; Huisman, M.V.

    2003-01-01

    BACKGROUND: Patients with Type 2 diabetes mellitus have increased levels of hemostatic risk variables for cardiovascular disease, such as fibrinogen, von Willebrand factor (VWF), factor (F)VIIa, d-dimer and plasminogen activator inhibitor-1 (PAI-1). OBJECTIVES: To evaluate the effect of aggressive

  2. Complement activation, endothelial dysfunction, insulin resistance and chronic heart failure

    DEFF Research Database (Denmark)

    Bjerre, M.; Kistorp, C.; Hansen, T.K.

    2010-01-01

    CRP), endothelial activation (soluble E-selectin, sEsel)), endothelial damage/dysfunction (von Willebrand factor, vWf) and insulin resistance (IR) and prognosis in CHF remains unknown. Design. We investigated the association(s) between plasma sMAC, hsCRP, sEsel, vWf and IR (assessed by homeostatic model assessment...

  3. Diagnosis and Treatment of von Willebrand Disease and Rare Bleeding Disorders

    Directory of Open Access Journals (Sweden)

    Giancarlo Castaman

    2017-04-01

    Full Text Available Along with haemophilia A and B, von Willebrand disease (VWD and rare bleeding disorders (RBDs cover all inherited bleeding disorders of coagulation. Bleeding tendency, which can range from extremely severe to mild, is the common symptom. VWD, due to a deficiency and/or abnormality of von Willebrand factor (VWF, represents the most frequent bleeding disorder, mostly inherited as an autosomal dominant trait. The diagnosis may be difficult, based on a bleeding history and different diagnostic assays, which evaluate the pleiotropic functions of VWF. Different treatment options are available for optimal management of bleeding and their prevention, and long-term outcomes are generally good. RBDs are autosomal recessive disorders caused by a deficiency of any other clotting factor, apart from factor XII, and cover roughly 5% of all bleeding disorders. The prevalence of the severe forms can range from 1 case in 500,000 up to 1 in 2–3 million, according to the defect. Diagnosis is based on bleeding history, coagulation screening tests and specific factor assays. A crucial problem in RBDs diagnosis is represented by the non-linear relationship between clinical bleeding severity and residual clotting levels; genetic diagnosis may help in understanding the phenotype. Replacement therapies are differently available for patients with RBDs, allowing the successful treatment of the vast majority of bleeding symptoms.

  4. The Carmat Bioprosthetic Total Artificial Heart Is Associated With Early Hemostatic Recovery and no Acquired von Willebrand Syndrome in Calves.

    Science.gov (United States)

    Smadja, David M; Susen, Sophie; Rauch, Antoine; Cholley, Bernard; Latrémouille, Christian; Duveau, Daniel; Zilberstein, Luca; Méléard, Denis; Boughenou, Marie-Fazia; Belle, Eric Van; Gaussem, Pascale; Capel, Antoine; Jansen, Piet; Carpentier, Alain

    2017-10-01

    To determine hemostasis perturbations, including von Willebrand factor (VWF) multimers, after implantation of a new bioprosthetic and pulsatile total artificial heart (TAH). Preclinical study SETTING: Single-center biosurgical research laboratory. Female Charolais calves, 2-to-6 months old, weighing 102-to-122 kg. Surgical implantation of TAH through a mid-sternotomy approach. Four of 12 calves had a support duration of several days (4, 4, 8, and 10 days), allowing for the exploration of early steps of hemostasis parameters, including prothrombin time; coagulation factor levels (II, V, VII+X, and fibrinogen); and platelet count. Multimeric analysis of VWF was performed to detect a potential loss of high-molecular weight (HMW) multimers, as previously described for continuous flow rotary blood pumps. Despite the absence of anticoagulant treatment administered in the postoperative phase, no signs of coagulation activation were detected. Indeed, after an immediate postsurgery decrease of prothrombin time, platelet count, and coagulation factor levels, most parameters returned to baseline values. HMW multimers of VWF remained stable either after initiation or during days of support. Coagulation parameters and platelet count recovery in the postoperative phase of the Carmat TAH (Camat SA, Velizy Villacoublay Cedex, France) implantation in calves, in the absence of anticoagulant treatment and associated with the absence of decrease in HMW multimers of VWF, is in line with early hemocompatibility that is currently being validated in human clinical studies. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Factor VII-activating protease

    DEFF Research Database (Denmark)

    Ramanathan, Ramshanker; Gram, Jørgen B; Sand, Niels Peter R

    2017-01-01

    : Factor VII-activating protease (FSAP) may regulate development of cardiovascular disease (CVD). We evaluated sex differences in FSAP measures and examined the association between FSAP and coronary artery calcification (CAC) in a middle-aged population. Participants were randomly selected citizens...

  6. Decreased plasma ADAMTS-13 activity as a predictor of postoperative bleeding in cyanotic congenital heart disease

    Directory of Open Access Journals (Sweden)

    Rosangela P.S. Soares

    2013-04-01

    Full Text Available OBJECTIVE: To analyze the preoperative plasma antigenic concentration and activity of von Willebrand factor and its main cleaving protease ADAMTS-13 in pediatric patients with cyanotic congenital heart disease undergoing surgical treatment and investigate possible correlations with postoperative bleeding. METHODS: Plasma antigenic concentrations (von Willebrand factor:Ag and ADAMTS-13:Ag were measured using enzyme-linked immunoassays. Collagen-binding assays were developed to measure biological activities (von Willebrand factor:collagen binding and ADAMTS-13 activity. The multimeric structure of von Willebrand factor was analyzed using Western immunoblotting. Demographic, diagnostic, and general and specific laboratory data and surgery-related variables were subjected to univariate, bivariate, and multivariate analysis for the prediction of postoperative bleeding. RESULTS: Forty-eight patients were enrolled, with ages ranging from 9 months to 7.6 years (median 2.5 years. The plasma concentrations of von Willebrand factor:Ag and ADAMTS-13:Ag were decreased by 65 and 82%, respectively, in the patients compared with the controls (p<0.001. An increased density of low-molecular-weight fractions of von Willebrand factor, which are suggestive of proteolytic degradation (p = 0.0081, was associated with decreased ADAMTS-13 activity, which was likely due to ADAMTS-13 consumption (71% of controls, p = 0.0029 and decreased von Willebrand factor:collagen binding (76% of controls, p = 0.0004. Significant postoperative bleeding occurred in 13 patients. The preoperative ADAMTS-13 activity of <64.6% (mean level for the group, preoperative activated partial thromboplastin time, and the need for cardiopulmonary bypass were characterized as independent risk factors for postoperative bleeding, with respective hazard ratios of 22.35 (95% CI 1.69 to 294.79, 1.096 (95% CI 1.016 to 1.183, and 37.43 (95% CI 1.79 to 782.73. CONCLUSION: Low plasma ADAMTS-13

  7. Decreased plasma ADAMTS-13 activity as a predictor of postoperative bleeding in cyanotic congenital heart disease

    Science.gov (United States)

    Soares, Rosangela P.S.; Bydlowski, Sérgio P.; Jatene, Marcelo B.; Hironaka, Janete Ferreira; Lopes, Antonio Augusto

    2013-01-01

    OBJECTIVE: To analyze the preoperative plasma antigenic concentration and activity of von Willebrand factor and its main cleaving protease ADAMTS-13 in pediatric patients with cyanotic congenital heart disease undergoing surgical treatment and investigate possible correlations with postoperative bleeding. METHODS: Plasma antigenic concentrations (von Willebrand factor:Ag and ADAMTS-13:Ag) were measured using enzyme-linked immunoassays. Collagen-binding assays were developed to measure biological activities (von Willebrand factor:collagen binding and ADAMTS-13 activity). The multimeric structure of von Willebrand factor was analyzed using Western immunoblotting. Demographic, diagnostic, and general and specific laboratory data and surgery-related variables were subjected to univariate, bivariate, and multivariate analysis for the prediction of postoperative bleeding. RESULTS: Forty-eight patients were enrolled, with ages ranging from 9 months to 7.6 years (median 2.5 years). The plasma concentrations of von Willebrand factor:Ag and ADAMTS-13:Ag were decreased by 65 and 82%, respectively, in the patients compared with the controls (p<0.001). An increased density of low-molecular-weight fractions of von Willebrand factor, which are suggestive of proteolytic degradation (p = 0.0081), was associated with decreased ADAMTS-13 activity, which was likely due to ADAMTS-13 consumption (71% of controls, p = 0.0029) and decreased von Willebrand factor:collagen binding (76% of controls, p = 0.0004). Significant postoperative bleeding occurred in 13 patients. The preoperative ADAMTS-13 activity of <64.6% (mean level for the group), preoperative activated partial thromboplastin time, and the need for cardiopulmonary bypass were characterized as independent risk factors for postoperative bleeding, with respective hazard ratios of 22.35 (95% CI 1.69 to 294.79), 1.096 (95% CI 1.016 to 1.183), and 37.43 (95% CI 1.79 to 782.73). CONCLUSION: Low plasma ADAMTS-13 activity is

  8. Idiopathic pulmonary hypertension causing acquired von Willebrand disease and menorrhagia.

    Science.gov (United States)

    Sokkary, Nancy A; Dietrich, Jennifer E; Venkateswaran, Lakshmi

    2011-10-01

    Von Willebrand disease (VWD) maybe inherited or acquired; both etiologies can be associated with heavy menstrual bleeding. Pulmonary arterial hypertension may result in acquired VWD due to the destruction of high molecular weight von Willebrand multimers. We report a case of menorrhagia due to acquired VWD in a patient with idiopathic pulmonary hypertension. An adolescent female with known idiopathic pulmonary hypertension developed acquired VWD. Her primary disease necessitates the use of platelet inhibitors and intermittent anticoagulation. At menarche she also developed menorrhagia due to acquired VWD. She is currently controlled with stimate and progesterone-only therapy. VWD in a patient with idiopathic pulmonary hypertension causing menorrhagia. Although VWD and menorrhagia are commonly linked, the treatment and disease process in a patient with idiopathic pulmonary arterial hypertension is incredibly complex. Published by Elsevier Inc.

  9. Consumption of nattokinase is associated with reduced blood pressure and von Willebrand factor, a cardiovascular risk marker: results from a randomized, double-blind, placebo-controlled, multicenter North American clinical trial

    OpenAIRE

    Jensen GS; Lenninger M; Ero MP; Benson KF

    2016-01-01

    Gitte S Jensen,1 Miki Lenninger,1 Michael P Ero,2 Kathleen F Benson,1 1NIS Labs, Klamath Falls, OR, 2Machaon Diagnostics, Inc., Oakland, CA, USA Objective: The objective of this study is to evaluate the effects of consumption of nattokinase on hypertension in a North American hypertensive population with associated genetic, dietary, and lifestyle factors. This is in extension of, and contrast to, previous studies on Asian populations.Materials and methods: A randomized, double-blind, placebo-...

  10. Association between Von Willebrand factor, disintegrin and metalloproteinase with thrombospondin type 1 motif member 13, d-Dimer and cystatin C levels with retinopathy in type 1 diabetes mellitus.

    Science.gov (United States)

    Domingueti, Caroline Pereira; Fuzatto, Jéssica A; Fóscolo, Rodrigo B; Reis, Janice S; Dusse, Luci M; Carvalho, Maria das Graças; Gomes, Karina B; Fernandes, Ana Paula

    2016-08-01

    We evaluated the association between plasma levels of VWF, ADAMTS13 and d-Dimer, which consist on endothelial dysfunction and hypercoagulability biomarkers, and cystatin C with retinopathy in type 1 diabetic patients. Patients were classified according to presence (n=55) or absence (n=70) of retinopathy. Plasma levels of VWF, ADAMTS13, d-Dimer and cystatin C were evaluated by ELISA and ADAMTS13 activity was evaluated by FRET. Plasma levels of VWF (p=0.033), ADAMTS13 activity (p=0.014), d-Dimer (p=0.002) and cystatin C (p1) were elevated in diabetic patients with retinopathy compared to those without this complication. The multivariate logistic regression analysis showed that ADAMTS13 activity (p=0.031) d-Dimer (p=0.015) and cystatin C (p=0.001) remained associated with retinopathy after adjustment for age, diabetes duration, use of statin, use of ACEi or angiotensin antagonist, use of acetylsalicylic acid and glomerular filtration rate. ADAMTS13 activity, d-Dimer and cystatin C are associated with retinopathy in type 1 diabetic patients and are promising biomarkers for the diagnosis and monitoring of diabetic retinopathy. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Severe Plasmodium falciparum malaria is associated with circulating ultra-large von Willebrand multimers and ADAMTS13 inhibition.

    LENUS (Irish Health Repository)

    Larkin, Deirdre

    2009-03-01

    Plasmodium falciparum infection results in adhesion of infected erythrocytes to blood vessel endothelium, and acute endothelial cell activation, together with sequestration of platelets and leucocytes. We have previously shown that patients with severe infection or fulminant cerebral malaria have significantly increased circulatory levels of the adhesive glycoprotein von Willebrand factor (VWF) and its propeptide, both of which are indices of endothelial cell activation. In this prospective study of patients from Ghana with severe (n = 20) and cerebral (n = 13) P. falciparum malaria, we demonstrate that increased plasma VWF antigen (VWF:Ag) level is associated with disproportionately increased VWF function. VWF collagen binding (VWF:CB) was significantly increased in patients with cerebral malaria and severe malaria (medians 7.6 and 7.0 IU\\/ml versus 1.9 IU\\/ml; p<0.005). This increased VWF:CB correlated with the presence of abnormal ultra-large VWF multimers in patient rather than control plasmas. Concomitant with the increase in VWF:Ag and VWF:CB was a significant persistent reduction in the activity of the VWF-specific cleaving protease ADAMTS13 (approximately 55% of normal; p<0.005). Mixing studies were performed using P. falciparum patient plasma and normal pooled plasma, in the presence or absence of exogenous recombinant ADAMTS13. These studies demonstrated that in malarial plasma, ADAMTS13 function was persistently inhibited in a time-dependent manner. Furthermore, this inhibitory effect was not associated with the presence of known inhibitors of ADAMTS13 enzymatic function (interleukin-6, free haemoglobin, factor VIII or thrombospondin-1). These novel findings suggest that severe P. falciparum infection is associated with acute endothelial cell activation, abnormal circulating ULVWF multimers, and a significant reduction in plasma ADAMTS13 function which is mediated at least in part by an unidentified inhibitor.

  12. Psychosocial factors underlying physical activity

    Directory of Open Access Journals (Sweden)

    Ji Cheng-Ye

    2007-09-01

    of physical activity on academic achievement and other factors beyond physical health; barriers of not having enough time and having too many assignments perceived to hinder frequent physical activity; and parental approval. More rigorous research on psychosocial determinants with close-ended items developed from these open-ended data and with larger sample sizes of students is necessary. Research with parents and school staff will be needed to understand the perceptions of these stakeholder groups key to creating the students' social environment.

  13. Rate-limiting roles of the tenase complex of factors VIII and IX in platelet procoagulant activity and formation of platelet-fibrin thrombi under flow.

    Science.gov (United States)

    Swieringa, Frauke; Kuijpers, Marijke J E; Lamers, Moniek M E; van der Meijden, Paola E J; Heemskerk, Johan W M

    2015-06-01

    The importance of factor Xa generation in thrombus formation has not been studied extensively so far. Here, we used mice deficient in either factor VIII or factor IX to determine the role of platelet-stimulated tenase activity in the formation of platelet-fibrin thrombi on collagen. With tissue factor present, deficiency in factor VIII or IX markedly suppressed thrombus growth, fibrin formation and platelet procoagulant activity (phosphatidylserine exposure). In either case, residual fibrin formation was eliminated in the absence of tissue factor. Effects of factor deficiencies were antagonized by supplementation of the missing coagulation factor. In wild-type thrombi generated under flow, phosphatidylserine-exposing platelets bound (activated) factor IX and factor X, whereas factor VIII preferentially co-localized at sites of von Willebrand factor binding. Furthermore, proteolytic activity of the generated activated factor X and thrombin was confined to the sites of phosphatidylserine exposure. With blood from a hemophilia A or B patient, the formation of platelet-fibrin thrombi was greatly delayed and reduced, even in the presence of high concentrations of tissue factor. A direct activated factor X inhibitor, rivaroxaban, added to human blood, suppressed both thrombin and fibrin formation. Together, these data point to a potent enforcement loop in thrombus formation due to factor X activation, subsequent thrombin and fibrin generation, causing activated factor X-mediated stimulation of platelet phosphatidylserine exposure. This implies that the factor VIII/factor IX-dependent stimulation of platelet procoagulant activity is a limiting factor for fibrin formation under flow conditions, even at high tissue factor concentrations. Copyright© Ferrata Storti Foundation.

  14. Postpartum Hemorrhage in Women with Von Willebrand Disease - A Retrospective Observational Study.

    Directory of Open Access Journals (Sweden)

    Igor Govorov

    Full Text Available von Willebrand disease (VWD is a hereditary bleeding disorder, caused by a deficiency in the levels and/or function of von Willebrand factor (VWF. Women with VWD appear to be at increased risk of experiencing postpartum hemorrhage (PPH, though the levels of VWF increase during pregnancy. There is limited knowledge of how PPH is associated with the subtype of VWD, plasma levels of other coagulations factors than VWF and given hemostatic treatment.The aims were to investigate the incidence of PPH in women with VWD and to analyse the correlation between PPH and: (1 type of VWD, (2 laboratory monitoring of VWF and FVIII and (3 hemostatic drug treatment.This was a retrospective observational study. The study participants (n = 34 were recruited from the Coagulation Unit, Karolinska University hospital. Fifty-nine deliveries, which occurred in 14 different obstetrics units (years 1995-2012 were included in the study.The incidence of primary PPH was 44%, severe primary PPH 20% and secondary PPH 12%. VWD type 3 was associated with a higher risk of experiencing severe primary PPH compared to other subtypes. FVIII:C in pregnancy was inversely correlated to blood loss during delivery. There was a significantly higher incidence of secondary PPH when the VWD diagnosis was unknown at time of delivery.The women with VWD are at higher risk of PPH, especially those with type 3 VWD or when diagnosis is unknown prior to delivery. Identification of pregnant women with undiagnosed VWD may be of importance in order to prevent PPH.

  15. Molecular cloning, expression and assembly of multimeric von Willebrand factor

    NARCIS (Netherlands)

    Pannekoek, H.; Voorberg, J.

    1989-01-01

    Recently, substantial progress has been made in our knowledge of the domains involved in correlating structure and function of vWF, as well as in the biosynthesis and assembly of multimeric vWF. These studies were greatly supported by the development of three new techniques. (1) In vitro culturing

  16. Molecular characterization of exon 28 of von Willebrand's factor ...

    African Journals Online (AJOL)

    2016-05-12

    May 12, 2016 ... two probable cases among 95 patients with hemophilia A and 11 with hemophilia B between 1980 and 1986, but full investigation and family studies were not performed. In. Nigeria, we ... bleeding symptoms are epistaxis, menorrhagia (in women), easy bruising, oral cavity bleeding, bleeding after dental.

  17. Polyphosphate accelerates factor V activation by factor XIa.

    Science.gov (United States)

    Choi, Sharon H; Smith, Stephanie A; Morrissey, James H

    2015-03-01

    Factor Va enhances the rate of prothrombin activation by factor Xa by four to five orders of magnitude. Production of initiating levels of factor Va from its precursor, factor V, is a critical event early in haemostasis, as factor V exhibits negligible cofactor activity. While thrombin is the most potent physiological back-activator of factor V, the first prothrombinase complexes require a source of factor Va prior to thrombin generation. A recent study by Whelihan et al. (J Thromb Haemost 2010; 8:1532-1539) identified factor XIa as a candidate for the initial thrombin-independent activation of factor V, although this reaction was slow and required relatively high concentrations of factors V and XIa. Activated platelets secrete polyphosphate, which we previously showed to be potently procoagulant. We now report that polyphosphate greatly accelerates factor V activation by factor XIa, and that this is supported by polyphosphate polymers of the size secreted by activated human platelets. This finding provides additional evidence that factor XIa-mediated generation of factor Va may contribute to the initiation of haemostasis.

  18. In Vitro Effect of Activated Recombinant Factor VII (rFVIIa) on Coagulation Properties of Human Blood at Hypothermic Temperatures

    Science.gov (United States)

    2007-11-01

    hemostatic defects (i.e., factor VIIa deficiency, acquired von Willebrand disease, uremia, and liver disease) for controlling acute bleeding episodes... acquired haemophilia with recombinant factor VIIa: a multicentre study. Thromb Haemost. 1997;78:1463–1467. 14. Shapiro AD, Gilchrist GS, Hoots WK...2005;3:742–751. 47. Butenas S, Brummel KE, Branda RF, Paradis SG, Mann KG. Mechanism of factor VIIa-dependent coagulation in hemophilia blood. Blood

  19. Genetic heterogeneity in a large cohort of Indian type 3 von Willebrand disease patients.

    Directory of Open Access Journals (Sweden)

    Priyanka Kasatkar

    Full Text Available Though von Willebrand disease (VWD is a common coagulation disorder, due to the complexity of the molecular analysis of von Willebrand factor gene (VWF, not many reports are available from this country. Large size of the gene, heterogeneous nature of mutations and presence of a highly homologous pseudogene region are the major impediments in the genetic diagnosis of VWD. The study is aimed at unravelling the molecular pathology in a large series of VWD patients from India using an effective strategy.We evaluated 85 unrelated Indian type 3 VWD families to identify the molecular defects using a combination of techniques i.e. PCR-RFLP, direct DNA sequencing and multiple ligation probe amplification (MLPA.Mutations could be characterized in 77 unrelated index cases (ICs. 59 different mutations i.e. nonsense 20 (33.9%, missense 13 (22%, splice site 4 (6.8%, gene conversions 6 (10.2%, insertions 2 (3.4%, duplication 1 (1.7%, small deletions 10 (17% and large deletions 3 (5.1% were identified, of which 34 were novel. Two common mutations i.e. p.R1779* and p.L970del were identified in our population with founder effect. Development of alloantibodies to VWF was seen in two patients, one with nonsense mutation (p.R2434* and the other had a large deletion spanning exons 16-52.The molecular pathology of a large cohort of Indian VWD patients could be identified using a combination of techniques. A wide heterogeneity was observed in the nature of mutations in Indian VWD patients.

  20. Cesariana em paciente com doença de von Willebrand associada à infecção pelo HIV: relato de caso Cesárea en paciente con enfermedad de von Willebrand asociada a la infección por el HIV: relato de caso Anesthesia for cesarean section in patient with von Willebrand's disease and HIV infection: case report

    Directory of Open Access Journals (Sweden)

    Vanessa Rezende Balle

    2004-12-01

    Willebrand y HIV positiva sometida a cesárea. RELATO DEL CASO: Paciente de 24 años, portadora de anemia microcítica, enfermedad de von Willebrand y HIV, llegó a la emergencia obstétrica en inicio de trabajo de alumbramiento. No realizó prenatal. Fue indicada cesárea a fin de disminuir los riesgos de transmisión vertical en paciente con carga vírica de HIV desconocida. Presentaba hematomas por el cuerpo e historia de hematoma de pared abdominal en cesárea anterior. Los tests de coagulación estaban un poco alterados. Después de infusión de concentrado de factor VIII fue realizada anestesia general. Madre y recién nacido presentaron evolución satisfactoria. CONCLUSIONES: La evaluación de manifestaciones clínicas en pacientes con coagulopatia es fundamental en la decisión del tipo de anestesia que será indicada para cada paciente. La evaluación debe ser individualizada, considerando los riesgos y beneficios de la técnica escogida. En estas pacientes, se debe siempre restringir al máximo la indicación de interrupción de la gestación por vía alta, optándose siempre por los métodos menos invasivos. La terapia con concentrado de factor VIII es actualmente la mejor opción de tratamiento, corrigiendo la deficiencia específica y dismunuyendo los riesgos de transmisión vírica.BACKGROUND AND OBJECTIVES: Von Willebrand's disease is the most common hereditary coagulation disorder in young women. The incidence of HIV infection among women has been progressively increasing, and vertical transmission may account for 25% of cases. This report aimed at describing the case of an HIV-positive patient with von Willebrand's disease scheduled for cesarean section. CASE REPORT: Female HIV-positive patient, 24 years old, with microcytic anemia and von Willebrand's disease, admitted to the emergency room in early labor. She had no pre-natal care. Cesarean section was indicated to lower vertical transmission risks since HIV viral count was unknown. Patient had hematomas

  1. [Desmopressin testing in children with von Willebrand syndrome in haemostaseologic centers of Saxonia, Saxonia-Anhalt and Thuringia].

    Science.gov (United States)

    Huhn, B; Hofmann, A; Hofmann, K; Sirb, H; Aumann, V; Kentouche, K; Sauerbrey, A; Franke, D; Kuhlisch, E; Knöfler, R

    2009-10-01

    The influence of desmopressin on hemostasis is mediated by the release of von Willebrand factor and of coagulation factor VIII from vascular endothelium. The necessity of testing desmopressin effectiveness on hemostasis is a matter of controversy and the performance of the test is not yet standardized. For this reason the desmopressin tests in 114 children with von Willebrand syndrome (type 1, n=98; type 2A, n=12; type 2M, n=2; type 2N, n=2) carried out in 7 paediatric haemostaseologic centers were retrospectively analyzed. The effectiveness of desmopressin was assessed using defined response criteria. As expected, the test performance showed a wide variation among the centers. In 99 children desmopressin was given intravenously as a short infusion at a dosage ranging from 0.25 to 0.41 microg/kg and in 15 intranasally at an absolute dose of 40 to 300 microg. The points of time for blood taking after desmopressin application ranged from 0.5 to 12 h. The absent desmopressin response in 7 patients (6%) and the partial response in 15 indicate the necessity of testing desmopressin effectiveness before the first therapeutic use. The application of desmopressin was well tolerated by the patients.

  2. Syringomyelia following surgery for a spontaneous spinal subdural hematoma in a 13-year-old girl with congenital von Willebrand disease: case report and literature review.

    Science.gov (United States)

    Ben Nsir, A; Boubaker, A; Jemel, H

    2016-04-01

    Spontaneous spinal subdural hematomas are rare. Their occurrence in a child with congenital von Willebrand disease and the complication of their surgery by a large secondary syringomyelia have never been previously reported. A 13-year-old girl with congenital von Willebrand disease presented to our emergency department in January 2011 for sudden onset of severe back pain centered in her thoracic spine rapidly aggravated by signs of acute myelopathy without any precipitating factor. MRI scan revealed a thoracic subdural collection anterior to the spinal cord at the T7-T9 level, hyperintense on T1- and T2-weighted sequences consistent with an acute spinal subdural hemorrhage. Evacuation of the subdural hematoma was realized immediately after hemostasis parameter correction, and post-operative course was uneventful with full functional recovery. One year later, the patient presented once again but with progressive and more severe myelopathy caused by a large syringomyelia extending from the T5 level to the conus medullaris. A syringopleural shunting was performed and the patient was unrolled under an intensive care and rehabilitation program. Her condition remarkably improved and she became able to walk independently within 2 weeks post-operatively. von Willebrand disease should be included as a possible factor of spontaneous spinal subdural hemorrhage. Surgery is advised in emergency and can be associated with remarkable recovery especially in children. Delayed syringomyelia can complicate the post-operative course and can be successfully addressed by syringopleural shunting. Long-term clinical and radiological follow-up is advocated.

  3. Rinoplastia em paciente com doença de Von Willebrand: relato de caso Rinoplastia en paciente con enfermedad de Von Willebrand: relato de caso Rhinoplasty in a patient with Von Willebrand disease: case report

    Directory of Open Access Journals (Sweden)

    Roberto Martins Matos Junior

    2007-12-01

    aprovado pelo FDA, tem sido uma prática utilizada somente em circunstâncias emergenciais, devido ao risco relativo de contaminação viral. A 1-desamino, 8-D-arginina vasopressina (DDAVP-desmopressina estimula o aumento da concentração do fator VIII, tendo a vantagem de eliminar a exposição aos patógenos transmitidos pelo sangue, além da possibilidade de administração por vias nasal, subcutânea e venosa.JUSTIFICATIVA Y OBJETIVOS: Los pacientes portadores de la enfermedad de von Willebrand presentan sangramiento anormal después de heridas y procedimientos quirúrgicos, ya que esta afecta la hemostasia primaria y secundaria debido a la alteración del factor VIII. El objetivo de este relato es elucidar el manoseo pre, peri y postoperatorio de pacientes con tal enfermedad. RELATO DEL CASO: Paciente del sexo femenino, 42 años, blanca, 165 cm, 61kg, ASA II, fue sometida a la evaluación preanestésica para la realización de rinoplastia, con diagnóstico previo de enfermedad de von Willebrand del tipo 1, siendo liberada para la intervención quirúrgica después de la evaluación hematológica, con test de DDAVP IN26 responsivo. El día de la operación, y después de la medicación preanestésica y del monitoreo adecuado, se le dio oxígeno por catéter nasal e infundida la solución de desmopresina (0,4 µg.kg-1 en 100 mL de NaCl a 0,9% por vía venosa 30 minutos antes de la operación. Enseguida se inició la inducción anestésica con sufentanil (1 µg.kg-1, propofol (4 mg.kg-1 y rocuronio (0,6 mg.kg-1 por vía venosa. A continuación se realizó la intubación traqueal seguida de ventilación controlada mecánica en sistema con absorción de CO2, mantenida con O2, N2O y sevoflurano. El acto quirúrgico duró noventa minutos. En el intraoperatorio la paciente se mantuvo hemodinámicamente estable, presentando sangramiento sin importancia. Al final de la operación fue extubada y llevada a la sala de recuperación post anestésica, donde permaneció por 120

  4. Acquired von Willebrand's disease and hypothyroidism: report of a case presenting with menorrhagia.

    Science.gov (United States)

    Blesing, N. E.; Hambley, H.; McDonald, G. A.

    1990-01-01

    A 17 year old woman presented with severe anaemia due to menorrhagia. On investigation, she was shown to have abnormalities of her haemostatic mechanism consistent with von Willebrand's disease Type I, although there was no family history of this disorder. In addition, she was shown to have severe primary hypothyroidism. On correction of hypothyroidism with oral thyroxine, her coagulation defects returned to normal and menorrhagia ceased. This is consistent with acquired von Willebrand's disease secondary to hypothyroidism. PMID:2217000

  5. Assessment of the olfactory function in Italian patients with type 3 von Willebrand disease caused by a homozygous 253 Kb deletion involving VWF and TMEM16B/ANO2.

    Directory of Open Access Journals (Sweden)

    Valentina Cenedese

    Full Text Available Type 3 Von Willebrand disease is an autosomal recessive disease caused by the virtual absence of the von Willebrand factor (VWF. A rare 253 kb gene deletion on chromosome 12, identified only in Italian and German families, involves both the VWF gene and the N-terminus of the neighbouring TMEM16B/ANO2 gene, a member of the family named transmembrane 16 (TMEM16 or anoctamin (ANO. TMEM16B is a calcium-activated chloride channel expressed in the olfactory epithelium. As a patient homozygous for the 253 kb deletion has been reported to have an olfactory impairment possibly related to the partial deletion of TMEM16B, we assessed the olfactory function in other patients using the University of Pennsylvania Smell Identification Test (UPSIT. The average UPSIT score of 4 homozygous patients was significantly lower than that of 5 healthy subjects with similar sex, age and education. However, 4 other members of the same family, 3 heterozygous for the deletion and 1 wild type, had a slightly reduced olfactory function indicating that socio-cultural or other factors were likely to be responsible for the observed difference. These results show that the ability to identify odorants of the homozygous patients for the deletion was not significantly different from that of the other members of the family, showing that the 253 kb deletion does not affect the olfactory performance. As other genes may compensate for the lack of TMEM16B, we identified some predicted functional partners from in silico studies of the protein-protein network of TMEM16B. Calculation of diversity for the corresponding genes for individuals of the 1000 Genomes Project showed that TMEM16B has the highest level of diversity among all genes of the network, indicating that TMEM16B may not be under purifying selection and suggesting that other genes in the network could compensate for its function for olfactory ability.

  6. Desmopressin improves platelet activity in acute intracerebral hemorrhage.

    Science.gov (United States)

    Naidech, Andrew M; Maas, Matthew B; Levasseur-Franklin, Kimberly E; Liotta, Eric M; Guth, James C; Berman, Micheal; Rosenow, Joshua M; Lindholm, Paul F; Bendok, Bernard R; Prabhakaran, Shyam; Bernstein, Richard A; Kwaan, Hau C

    2014-08-01

    Minimizing hematoma growth in high-risk patients is an attractive strategy to improve outcomes after intracerebral hemorrhage. We tested the hypothesis that desmopressin (DDAVP), which improves hemostasis through the release of von Willebrand factor, improves platelet activity after intracerebral hemorrhage. Patients with reduced platelet activity on point-of-care testing alone (5), known aspirin use alone (1), or both (8) received desmopressin 0.4 μg/kg IV. We measured Platelet Function Analyzer-epinephrine (Siemens AG, Germany) and von Willebrand factor antigen from baseline to 1 hour after infusion start and hematoma volume from the diagnostic to a follow-up computed tomographic scan. We enrolled 14 patients with of mean age 66.8±14.6 years, 11 (85%) of whom were white and 8 (57%) were men. Mean Platelet Function Analyzer-epinephrine results shortened from 192±18 seconds pretreatment to 124±15 seconds (P=0.01) 1 hour later, indicating improved plate activity. von Willebrand factor antigen increased from 242±96% to 289±103% activity (P=0.004), indicating the expected increase in von Willebrand factor. Of 7 (50%) patients who received desmopressin within 12 hours of intracerebral hemorrhage symptom onset, changes in hematoma volume were modest, -0.5 (-1.4 to 8.4) mL and only 2 had hematoma growth. One patient had low blood pressure and another had a new fever within 6 hours of desmopressin administration. Intravenous desmopressin was well tolerated and improved platelet activity after acute intracerebral hemorrhage. Larger studies are needed to determine its potential effects on reducing hematoma growth versus platelet transfusion or placebo. http://www.clinicaltrials.gov. Unique identifier: NCT00961532. © 2014 American Heart Association, Inc.

  7. Heavy menstrual bleeding and health-associated quality of life in women with von Willebrand's disease.

    Science.gov (United States)

    Govorov, Igor; Ekelund, Lena; Chaireti, Roza; Elfvinge, Petra; Holmström, Margareta; Bremme, Katarina; Mints, Miriam

    2016-05-01

    Women with the inherited bleeding disorder von Willebrand's disease (VWD) face gender-specific hemostatic challenges during menstruation. Heavy menstrual bleeding (HMB) can negatively affect their overall life activities and the health-associated quality of life. The purpose of the present study was to investigate whether women with VWD experienced HMB and an impaired health-associated quality of life. The study subjects were recruited from the Coagulation Unit of Karolinska University Hospital. Information was retrieved from various self-administered forms and medical records. Of the 30 women (18-52 years) that were included in the present study, 50% suffered from HMB, although the majority received treatment for HMB. In addition, almost all the included women perceived limitations in the overall life activities due to menstruation. The health-associated quality of life for women with HMB was significantly lower (Pwomen of the general population. In conclusion, women with VWD experienced reduced health-associated quality of life as a result of HMB. Therefore, preventing limitations in overall life activities and improving their health-associated quality of life thorough counseling on menstrual bleeding is important for women with VWD.

  8. Key factors of enterprise innovation activity

    Directory of Open Access Journals (Sweden)

    Pichugina Maryna Anatoliivna

    2015-02-01

    Full Text Available The article deals with the studies of factors and conditions that define enterprise innovative activity. It is distinguished factors that influence the orientation on innovation of a company and factors that influence the innovation ability. It is noted an interdependence between innovative ability, orientation and activity. The article is also dedicated to analyses of influence specific industry characteristics and inner view of enterprise. It is discussed the influence of such factors as knowledge base, the organizational learning mechanisms, an external openness and the structure of innovative connections on the company opportunities to innovate. It is tried to focus on the impact of the environment on enterprise capabilities.

  9. Characterization of a novel mutation in the von Willebrand factor propeptide in a distinct subtype of recessive von Willebrand disease

    DEFF Research Database (Denmark)

    Lanke, Elsa; Kristoffersson, Ann-Charlotte; Philips, Malou

    2008-01-01

    mutation in the VWFpp abolishes multimerization of VWF. The mutation probably disrupts the normal configuration of the VWFpp, which is essential for correct orientation of the protomers and ultimately multimerization. The mutant amino acid is located in a region that is highly conserved across several...

  10. Characterization of conformation-sensitive antibodies to ADAMTS13, the von Willebrand cleavage protease.

    Directory of Open Access Journals (Sweden)

    Zuben E Sauna

    2009-08-01

    Full Text Available The zinc metalloprotease ADAMTS13 is a multidomain protein that cleaves von Willebrand Factor (VWF and is implicated in Thrombotic Thrombocytopenic Purpura (TTP pathogenesis. Understanding the mechanism of this protein is an important goal. Conformation sensitive antibodies have been used to monitor protein conformation and to decipher the molecular mechanism of proteins as well as to distinguish functional and non-functional mutants.We have characterized several antibodies against ADAMTS13, both monoclonal and polyclonal. We have used flow cytometry to estimate the binding of these antibodies to ADAMTS13 and demonstrate that antibodies raised against the TSP and disintegrin domains detect conformation changes in the ADAMTS13. Thus for example, increased binding of these antibodies was detected in the presence of the substrate (VWF, mainly at 37 degrees C and not at 4 degrees C. These antibodies could also detect differences between wild-type ADAMTS13 and the catalytically deficient mutant (P475S. The flow cytometry approach also allows us to estimate the reactivity of the antibody as well as its apparent affinity.Our results suggest that these antibodies may serve as useful reagents to distinguish functional and non-functional ADAMTS13 and analyze conformational transitions to understand the catalytic mechanism.

  11. Variable bleeding phenotype in an Amish pedigree with von Willebrand disease.

    Science.gov (United States)

    Gupta, Sweta; Heiman, Meadow; Duncan, Natalie; Hinckley, Jesse; Di Paola, Jorge; Shapiro, Amy D

    2016-10-01

    Through a cross-sectional study design, the bleeding phenotype in the Amish in Indiana (IN) and Wisconsin (WI) was described using two different bleeding scores. von Willebrand factor (VWF) testing was performed and bleeding questionnaires from Centers for Disease Control and Prevention (CDC) and European MCMDM-1 (Tosetto bleeding score (BS)) were administered to the IN and WI cohort respectively. Seven hundred and seventy nine subjects were recruited, 17% were diagnosed with VWD based on Ristocetin cofactor, VWF:RCo  T. The WI AF were much younger at a mean age 15 years vs 26 years in IN AF cohort. The AF subjects had a median VWF:RCo of 13IU/dl with a statistically significant higher median BS 1 versus 0 in the WI AF vs WI Unaffected (UA), 2 vs 1 in the IN AF vs IN UA, P Amish with VWD, despite a unifying mutation. Am. J. Hematol. 91:E431-E435, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  12. Identification and Characterization of Novel Variations in Platelet G-Protein Coupled Receptor (GPCR Genes in Patients Historically Diagnosed with Type 1 von Willebrand Disease.

    Directory of Open Access Journals (Sweden)

    Jacqueline Stockley

    Full Text Available The clinical expression of type 1 von Willebrand disease may be modified by co-inheritance of other mild bleeding diatheses. We previously showed that mutations in the platelet P2Y12 ADP receptor gene (P2RY12 could contribute to the bleeding phenotype in patients with type 1 von Willebrand disease. Here we investigated whether variations in platelet G protein-coupled receptor genes other than P2RY12 also contributed to the bleeding phenotype. Platelet G protein-coupled receptor genes P2RY1, F2R, F2RL3, TBXA2R and PTGIR were sequenced in 146 index cases with type 1 von Willebrand disease and the potential effects of identified single nucleotide variations were assessed using in silico methods and heterologous expression analysis. Seven heterozygous single nucleotide variations were identified in 8 index cases. Two single nucleotide variations were detected in F2R; a novel c.-67G>C transversion which reduced F2R transcriptional activity and a rare c.1063C>T transition predicting a p.L355F substitution which did not interfere with PAR1 expression or signalling. Two synonymous single nucleotide variations were identified in F2RL3 (c.402C>G, p.A134 =; c.1029 G>C p.V343 =, both of which introduced less commonly used codons and were predicted to be deleterious, though neither of them affected PAR4 receptor expression. A third single nucleotide variation in F2RL3 (c.65 C>A; p.T22N was co-inherited with a synonymous single nucleotide variation in TBXA2R (c.6680 C>T, p.S218 =. Expression and signalling of the p.T22N PAR4 variant was similar to wild-type, while the TBXA2R variation introduced a cryptic splice site that was predicted to cause premature termination of protein translation. The enrichment of single nucleotide variations in G protein-coupled receptor genes among type 1 von Willebrand disease patients supports the view of type 1 von Willebrand disease as a polygenic disorder.

  13. A 12.3-kb Duplication Within the VWF Gene in Pigs Affected by Von Willebrand Disease Type 3

    Directory of Open Access Journals (Sweden)

    Stefanie Lehner

    2018-02-01

    Full Text Available Von Willebrand Disease (VWD type 3 is a serious and sometimes fatal hereditary bleeding disorder. In pigs, the disease has been known for decades, and affected animals are used as models for the human disease. Due to the recessive mode of inheritance of VWD type 3, severe bleeding is typically seen in homozygous individuals. We sequenced the complete porcine VWF (Von Willebrand Factor complementary DNA (cDNA and detected a tandem duplication of exons 17 and 18, causing a frameshift and a premature termination codon (p.Val814LeufsTer3 in the affected pig. Subsequent next generation sequencing on genomic DNA proved the existence of a 12.3-kb tandem duplication associated with VWD. This duplication putatively originates from porcine Short Interspersed Nuclear Elements (SINEs located within VWF introns 16 and 18 with high identity. The premature termination truncates the VWF open reading frame by a large part, resulting in an almost entire loss of the mature peptide. It is therefore supposed to account for the severe VWD type 3. Our results further indicate the presence of strong, nonsense-mediated decay in VWF messenger RNA (mRNA containing the duplication, which was supported by the almost complete absence of the complete VWF protein in immunohistochemistry analysis of the VWD-affected pig. In the past, differentiation of wild-type and heterozygous pigs in this VWD colony had to rely on clinical examinations and additional laboratory methods. The present study provides the basis to distinguish both genotypes by performing a rapid and simple genetic analysis.

  14. Cuidados nos pacientes com hemofilia e doença de von Willebrand na cirurgia eletiva otorrinolaringológica Otolaryngology surgery: management of elective surgery in patients with haemophilia and von Willebrand disease

    Directory of Open Access Journals (Sweden)

    Marise P. C. Marques

    2003-01-01

    average age of the patients was 23.75 years (2-62 years. The study group consisted of 14 hemophiliacs, 11 with severe hemophilia A (1 female, 1 female with 30% of VIII factor (VIIIF level, 1 male with hemophilia B and 1 female with severe factor X deficiency; and 6 with vWD, 4 type 1 (3 females, 1 male type 2 A and 1 male type 3. Acquired immunodeficiency syndrome was present in 13 hemophilic patients. The mean duration of the surgical events was 1 hour and 37 minutes (15 min-12 hours. The coagulation defect was corrected with desmopressin (DDAVP, intermediate purity VIIIF concentrate 8Y, cryoprecipitated or non-activated prothrombinic complex (PPSB, according to factor levels and the severity of the surgery. Epsilon aminocaproic acid was used in association. In 1 severe hemophiliac A patient, excessive bleeding was observed in the second day of the postoperative period which ceased with elevation of the minimal level of VIIIF to 80%. In another patient, with type 3 vWD, severe postoperative bleeding occurred because of difficulty to identify the best reposition blood coagulation factor for him. After the use of intermediate purity VIIIF concentrate 8Y, the bleeding was controlled. RESULTS: The hemostatic effect in the other patients was rated as normal or excellent. CONCLUSION: It was concluded that patients with vWD or hemophilia do not have an increased operative risk if appropriate therapy is given.

  15. A systematic review of the effects of hemophilia and von Willebrand disease on arterial trombosis

    NARCIS (Netherlands)

    Biere-Rafi, Sara; Zwiers, M.; Peters, Marjolein; Van Der Meer, Jan; Rosendaal, Frits R; Buller, Harry R; Kamphuisen, Pieter W

    Background: Patients with hemophilia and von Willebrand disease (VWD) may be protected against arterial thrombosis, through a hy-pocoagulable state or atherosclerosis. We performed a systematic review to assess the association between these clotting disorders, arterial thrombosis and the prevalence

  16. Health-related quality of life among adult patients with moderate and severe von Willebrand disease.

    NARCIS (Netherlands)

    Wee, E.M. de; Mauser-Bunschoten, E.P.; Bom, J.G. Van Der; Degenaar-Dujardin, M.E.; Eikenboom, H.C.; Fijnvandraat, K.; Goede-Bolder, A. de; Laros, B.A.P.; Meijer, K.; Raat, H.; Leebeek, F.W.

    2010-01-01

    SUMMARY BACKGROUND: von Willebrand Disease (VWD) is the most frequent inherited bleeding disorder. It is unknown how this disorder affects quality of life. OBJECTIVES: This nationwide multicenter cross-sectional study determined health-related quality of life (HR-QoL) in adult patients with moderate

  17. The effect of haemophilia and von Willebrand disease on arterial thrombosis : A systematic review

    NARCIS (Netherlands)

    Biere-Rafi, S.; Zwiers, M.; Peters, M.; van der Meer, J.; Rosendaal, F. R.; Buller, H. R.; Kamphuisen, P. W.

    Background: Patients with haemophilia and von Willebrand disease (VWD) may have a reduced cardiovascular mortality, due to a hypocoagulable state or decreased atherogenesis. We performed a systematic review to assess the association between haemophilia and VWD, and fatal and nonfatal arterial

  18. Gynaecological and obstetric bleeding in moderate and severe von Willebrand disease

    NARCIS (Netherlands)

    de Wee, Eva M.; Knol, H. Marieke; Mauser-Bunschoten, Eveline P.; van der Bom, Johanna G.; Eikenboom, Jeroen C. J.; Fijnvandraat, Karin; de Goede-Bolder, Arja; Laros-van Gorkom, Britta; Ypma, Paula F.; Zweegman, Sonja; Meijer, Karina; Leebeek, Frank W. G.

    2011-01-01

    A nation-wide cross-sectional study was initiated to assess gynaecological and obstetrical symptoms in an unselected cohort of women with moderate and severe von Willebrand disease (VWD) in the Netherlands. A total of 423 women aged >= 16 years were included. Bleeding severity was measured using the

  19. Gynaecological and obstetric bleeding in moderate and severe von Willebrand disease.

    NARCIS (Netherlands)

    Wee, E.M. de; Knol, H.M.; Mauser-Bunschoten, E.P.; Bom, J.G. Van Der; Eikenboom, J.C.; Fijnvandraat, K.; Goede-Bolder, A. de; Laros-van Gorkom, B.A.P.; Ypma, P.F.; Zweegman, S.; Meijer, K.; Leebeek, F.W.

    2011-01-01

    A nation-wide cross-sectional study was initiated to assess gynaecological and obstetrical symptoms in an unselected cohort of women with moderate and severe von Willebrand disease (VWD) in the Netherlands. A total of 423 women aged >/=16 years were included. Bleeding severity was measured using the

  20. Activated human neutrophils release hepatocyte growth factor/scatter factor.

    LENUS (Irish Health Repository)

    McCourt, M

    2012-02-03

    BACKGROUND: Hepatocyte growth factor or scatter factor (HGF\\/SF) is a pleiotropic cytokine that has potent angiogenic properties. We have previously demonstrated that neutrophils (PMN) are directly angiogenic by releasing vascular endothelial growth factor (VEGF). We hypothesized that the acute inflammatory response can stimulate PMN to release HGF. AIMS: To examine the effects of inflammatory mediators on PMN HGF release and the effect of recombinant human HGF (rhHGF) on PMN adhesion receptor expression and PMN VEGF release. METHODS: In the first experiment, PMN were isolated from healthy volunteers and stimulated with tumour necrosis factor-alpha (TNF-alpha), lipopolysaccharide (LPS), interleukin-8 (IL-8), and formyl methionyl-leucyl-phenylalanine (fMLP). Culture supernatants were assayed for HGF using ELISA. In the second experiment, PMN were lysed to measure total HGF release and HGF expression in the PMN was detected by Western immunoblotting. Finally, PMN were stimulated with rhHGF. PMN CD 11a, CD 11b, and CD 18 receptor expression and VEGF release was measured using flow cytometry and ELISA respectively. RESULTS: TNF-alpha, LPS and fMLP stimulation resulted in significantly increased release of PMN HGF (755+\\/-216, 484+\\/-221 and 565+\\/-278 pg\\/ml, respectively) compared to controls (118+\\/-42 pg\\/ml). IL-8 had no effect. Total HGF release following cell lysis and Western blot suggests that HGF is released from intracellular stores. Recombinant human HGF did not alter PMN adhesion receptor expression and had no effect on PMN VEGF release. CONCLUSIONS: This study demonstrates that pro-inflammatory mediators can stimulate HGF release from a PMN intracellular store and that activated PMN in addition to secreting VEGF have further angiogenic potential by releasing HGF.

  1. Antiglucocorticoid activity of hepatocyte nuclear factor-6.

    Science.gov (United States)

    Pierreux, C E; Stafford, J; Demonte, D; Scott, D K; Vandenhaute, J; O'Brien, R M; Granner, D K; Rousseau, G G; Lemaigre, F P

    1999-08-03

    Glucocorticoids exert their effects on gene transcription through ubiquitous receptors that bind to regulatory sequences present in many genes. These glucocorticoid receptors are present in all cell types, yet glucocorticoid action is controlled in a tissue-specific way. One mechanism for this control relies on tissue-specific transcriptional activators that bind in the vicinity of the glucocorticoid receptor and are required for receptor action. We now describe a gene-specific and tissue-specific inhibitory mechanism through which glucocorticoid action is repressed by a tissue-restricted transcription factor, hepatocyte nuclear factor-6 (HNF-6). HNF-6 inhibits the glucocorticoid-induced stimulation of two genes coding for enzymes of liver glucose metabolism, namely 6-phosphofructo-2-kinase and phosphoenolpyruvate carboxykinase. Binding of HNF-6 to DNA is required for inhibition of glucocorticoid receptor activity. In vitro and in vivo experiments suggest that this inhibition is mediated by a direct HNF-6/glucocorticoid receptor interaction involving the amino-terminal domain of HNF-6 and the DNA-binding domain of the receptor. Thus, in addition to its known property of stimulating transcription of liver-expressed genes, HNF-6 can antagonize glucocorticoid-stimulated gene transcription.

  2. Placental Growth Factor Contributes to Liver Inflammation, Angiogenesis, Fibrosis in Mice by Promoting Hepatic Macrophage Recruitment and Activation

    Directory of Open Access Journals (Sweden)

    Xi Li

    2017-07-01

    Full Text Available Placental growth factor (PlGF, a member of the vascular endothelial growth factor (VEGF family, mediates wound healing and inflammatory responses, exerting an effect on liver fibrosis and angiogenesis; however, the precise mechanism remains unclear. The aims of this study are to identify the role of PlGF in liver inflammation and fibrosis induced by bile duct ligation (BDL in mice and to reveal the underlying molecular mechanism. PlGF small interfering RNA (siRNA or non-targeting control siRNA was injected by tail vein starting 2 days after BDL. Liver inflammation, fibrosis, angiogenesis, macrophage infiltration, and hepatic stellate cells (HSCs activation were examined. Our results showed that PlGF was highly expressed in fibrotic livers and mainly distributed in activated HSCs and macrophages. Furthermore, PlGF silencing strongly reduced the severity of liver inflammation and fibrosis, and inhibited the activation of HSCs. Remarkably, PlGF silencing also attenuated BDL-induced hepatic angiogenesis, as evidenced by attenuated liver endothelial cell markers CD31 and von Willebrand factor immunostaining and genes or protein expression. Interestingly, these pathological ameliorations by PlGF silencing were due to a marked reduction in the numbers of intrahepatic F4/80+, CD68+, and Ly6C+ cell populations, which were reflected by a lower expression of these macrophage marker molecules in fibrotic livers. In addition, knockdown of PlGF by siRNA inhibited macrophages activation and substantially suppressed the expression of pro-inflammatory cytokines and chemokines in fibrotic livers. Mechanistically, evaluation of cultured RAW 264.7 cells revealed that VEGF receptor 1 (VEGFR1 mainly involved in mediating the role of PlGF in macrophages recruitment and activation, since using VEGFR1 neutralizing antibody blocking PlGF/VEGFR1 signaling axis significantly inhibited macrophages migration and inflammatory responses. Together, these findings indicate

  3. Haemostasis prophylaxis using single dose desmopressin acetate and extended use epsilon aminocaproic acid for adenotonsillectomy in patients with type 1 von Willebrand disease.

    Science.gov (United States)

    Santoro, C; Hsu, F; Dimichele, D M

    2012-03-01

    In patients with confirmed or suspected type 1 von Willebrand disease (VWD), adenotonsillectomy has been reported to be associated with a rate of peri-operative hemorrhage between 8 and 23%. Desmopressin acetate (DDAVP, 1-deamino 8-D arginine- vasopressin) is the treatment of choice for type 1 patients with baseline von Willebrand factor levels of 10 IU/dL or greater. DDAVP is generally well tolerated; however, severe hyponatremia and seizures have been reported in young children less than 2 years of age, limiting its use in this age group. Antifibrinolytic therapy plays an important adjunctive role in the effective treatment of mucocutaneous bleeding, particularly in the oropharynx where the salivary concentration of fibrinolytic enzymes is high. During the past 10 years, we treated 6 pediatric patients with mild/moderate type 1 VWD undergoing an adenotonsillar procedure at our institution with the same hemostatic regimen consisting of one single dose of DDAVP and an extended use of EACA. In this small case series, the above mentioned prophylactic treatment regimen was both well tolerated and efficacious in controlling hemorrhage. Furthermore, DDAVP-related complications were avoided in a pediatric population with a higher risk of developing them. © 2011 Blackwell Publishing Ltd.

  4. GENÉTICA MOLECULAR DE LA HEMOFILIA A EN UNA FAMILIA COLOMBIANA CON DIAGNÓSTICO DE ENFERMEDAD DE VON WILLEBRAND Y DE HEMOFILIA A

    Directory of Open Access Journals (Sweden)

    Diana Carolina Polanía Villanueva

    2014-12-01

    Full Text Available El Factor von Willebrand circula en el plasma formando un complejo con el Factor VIII de coagulación por enlaces no covalentes. Esta interacción evita la degradación enzimática del Factor VIII y asegura su transporte al lugar de formación del coágulo de fibrina. Debido a su estrecha relación, la disminución de la actividad de un factor puede afectar la actividad del otro, lo que genera un diagnóstico clínico equivocado en cuanto a qué enfermedad se padece, si Hemofilia A o Enfermedad de von Willebrand. Este estudio reporta el caso de una familia colombiana que según diagnóstico clínico de su fenotipo, padecía las dos enfermedades. Sin embargo, dicha familia carecía de un estudio genético que permitiera verificar y contrastar el diagnóstico que hacen las entidades de salud. Por tal razón, se realizó un diagnóstico genético por pruebas moleculares que detectan mutaciones, como las inversiones en los intrones 1 y 22 por PCR de fragmentos largos y la secuenciación del gen del Factor VIII, esta última no aplicada y publicada en Colombia hasta el momento. Se encontraron dos mutaciones sinónimas en los exones 14 y 26 que no alteran la secuencia de aminoácidos en la proteína; por tanto, se descarta la presencia de Hemofilia A en la familia. Se plantea la posibilidad de un caso de Enfermedad de von Willebrand únicamente. El estudio demuestra la necesidad que hay en el país de ampliar las pruebas clínicas y de incluir el diagnóstico genético en casos de ambigüedad en el diagnóstico de estas coagulopatías.

  5. Factors associated with active white enamel lesions.

    Science.gov (United States)

    Ferreira, M A F; Mendes, N S

    2005-09-01

    The aim of this study was to assess the factors associated with the presence of active white enamel lesions among public school students in the city of Natal, Brazil. A convenience sample of 300 boys and girls aged between 7 and 12 years was selected among the pupils attending public schools in the city of Natal. Only those children presenting with opaque and rough-surface white lesions in a region of biofilm accumulation on the vestibular surface of permanent upper incisors were included. The investigation took the form of a cross-sectional study. A chart containing individual data was used, and a clinical examination was performed to determine the oral health status of the children, including caries (DMF-s(1), DMF-s(2), DMFdmf, dmf and total number of teeth with caries) and oral hygiene status (Gingival Bleeding Index and Visible Plaque Index). Data underwent descriptive analysis and analysis of variance, and chi-square tests were used for the comparison of continuous and dichotomous variables between groups with one, two, or three or more white lesions. On average, each child presented with 2.3 teeth affected by white lesions, relatively high indices of dental caries and poor oral hygiene, with an 85% rate of localized plaque on the surfaces of teeth with lesions. The presence of visible plaque was statistically significant between the three groups, based on the number of lesions (P = 0.006), indicating a positive association between the number of lesions and the presence of biofilm. There is a strong association between the presence of dental biofilm, high indices of caries and active white enamel lesions. Full professional effort is needed in order to motivate children to carry out oral hygiene sufficient for the adequate control of dental biofilm.

  6. Galectin-1 and Galectin-3 Constitute Novel-Binding Partners for Factor VIII.

    Science.gov (United States)

    O'Sullivan, Jamie M; Jenkins, P Vince; Rawley, Orla; Gegenbauer, Kristina; Chion, Alain; Lavin, Michelle; Byrne, Barry; O'Kennedy, Richard; Preston, Roger J S; Brophy, Teresa M; O'Donnell, James S

    2016-05-01

    Recent studies have demonstrated that galectin-1 (Gal-1) and galectin-3 (Gal-3) can bind von Willebrand factor and directly modulate von Willebrand factor-dependent early thrombus formation in vivo. Because the glycans expressed on human factor VIII (FVIII) are similar to those of von Willebrand factor, we investigated whether galectins might also bind and modulate the activity of FVIII. Immunosorbant assays and surface plasmon resonance analysis confirmed that Gal-1 and Gal-3 bound purified FVIII with high affinity. Exoglycosidase removal of FVIII N-linked glycans significantly reduced binding to both Gal-1 and Gal-3. Moreover, combined removal of both the N- and O-glycans of FVIII further attenuated Gal-3 binding. Notably, specific digestion of FVIII high-mannose glycans at N239 and N2118 significantly impaired FVIII affinity for Gal-1. Importantly Gal-1, but not Gal-3, bound to free FVIII in the plasma milieu, and significantly inhibited FVIII functional activity. Interestingly, commercial recombinant FVIII (rFVIII) concentrates are manufactured in different cell lines and differ in their glycosylation profiles. Although the biological mechanism has not been defined, recent studies in previously untreated patients with severe hemophilia A reported significant differences in inhibitor development associated with different rFVIII products. Interestingly, Gal-1 and Gal-3 both displayed enhanced affinity for BHK-rFVIII compared with CHO-rFVIII. Furthermore, binding of Gal-1 and Gal-3 to BDD-FVIII was markedly reduced compared with full-length rFVIII. We have identified Gal-1 and Gal-3 as novel-binding partners for human FVIII and demonstrated that Gal-1 binding can influence the procoagulant activity of FVIII. © 2016 American Heart Association, Inc.

  7. Characterization of the clotting activities of structurally different forms of activated factor IX. Enzymatic properties of normal human factor IXa alpha, factor IXa beta, and activated factor IX Chapel Hill.

    OpenAIRE

    Griffith, M J; Breitkreutz, L; Trapp, H; Briet, E; Noyes, C M; Lundblad, R L; Roberts, H. R.

    1985-01-01

    Two structurally different forms of activated human Factor IX (Factor IXa alpha and IXa beta) have been previously reported to have essentially identical clotting activity in vitro. Although it has been shown that activated Factor IX Chapel Hill, an abnormal Factor IX isolated from the plasma of a patient with mild hemophilia B, and normal Factor IXa alpha are structurally very similar, the clotting activity of activated Factor IX Chapel Hill is much lower (approximately fivefold) than that o...

  8. Aspects of haemostatic function in healthy subjects with microalbuminuria--a potential atherosclerotic risk factor

    DEFF Research Database (Denmark)

    Jensen, J S; Myrup, B; Borch-Johnsen, K

    1995-01-01

    : plasma concentrations of tissue plasminogen activator antigen and plasminogen activator inhibitor type 1 antigen; and endothelial factor: plasma von Willebrand factor antigen concentration. The fibrinolytic and endothelial factors were measured both before and after 10 minutes of venous occlusion.......6 micrograms/min): Coagulation factors: blood platelet count and mean volume, plasma Factor VII antigen concentration and coagulant activity, and plasma concentrations of prothrombin fragment 1 + 2, thrombin-antithrombin III complexes, fibrinogen, and fibrinopeptide A; fibrinolytic and endothelial factors...... of the arm. None of the haemostatic factors were significantly altered in the microalbuminuric group. Plasma fibrinogen concentration tended to be elevated but not statistically significant ((mean (95% C.I.) 7.8 (7.2-8.3) vs. 7.2 (6.9-7.5) mumol/l; p

  9. Characterization of the clotting activities of structurally different forms of activated factor IX. Enzymatic properties of normal human factor IXa alpha, factor IXa beta, and activated factor IX Chapel Hill.

    Science.gov (United States)

    Griffith, M J; Breitkreutz, L; Trapp, H; Briet, E; Noyes, C M; Lundblad, R L; Roberts, H R

    1985-01-01

    Two structurally different forms of activated human Factor IX (Factor IXa alpha and IXa beta) have been previously reported to have essentially identical clotting activity in vitro. Although it has been shown that activated Factor IX Chapel Hill, an abnormal Factor IX isolated from the plasma of a patient with mild hemophilia B, and normal Factor IXa alpha are structurally very similar, the clotting activity of activated Factor IX Chapel Hill is much lower (approximately fivefold) than that of normal Factor IXa beta. In the present study we have prepared activated Factor IX by incubating human Factor IX with calcium and Russell's viper venom covalently bound to agarose. Fractionation of the activated Factor IX by high-performance liquid chromatography demonstrated the presence of both Factors IXa alpha and IXa beta. On the basis of active site concentration, determined by titration with antithrombin III, the clotting activities of activated Factor IX Chapel Hill and IXa alpha were similar, but both activities were less than 20% of the clotting activity of Factor IXa beta. Activated Factor IX activity was also measured in the absence of calcium, phospholipid, and Factor VIII, by determination of the rate of Factor X activation in the presence of polylysine. In the presence of polylysine, the rates of Factor X activation by activated Factor IX Chapel Hill, Factor IXa alpha, and Factor IXa beta were essentially identical. We conclude that the clotting activity of activated Factor IX Chapel Hill is reduced when compared with that of Factor IXa beta but essentially normal when compared with that of Factor IXa alpha.

  10. Analysis of factor XIa, factor IXa and tissue factor activity in burn patients.

    Science.gov (United States)

    Shupp, Jeffrey W; Prior, Shannon M; Jo, Daniel Y; Moffatt, Lauren T; Mann, Kenneth G; Butenas, Saulius

    2017-10-09

    An elevated procoagulant activity observed in trauma patients is, in part, related to tissue factor (TF) located on blood cells and microparticles. However, analysis of trauma patient plasma indicates that there are other contributor(s) to the procoagulant activity. We hypothesize that factor (F)XIa and FIXa are responsible for an additional procoagulant activity in burn patients. Multiple time-point plasma samples from 56 burn patients (total number of samples was 471; up to 20 time-points/patient collected in 3 weeks following admission) were evaluated in a thrombin generation assay using inhibitory antibodies to TF, FIXa and FXIa. Due to the limited volume of some samples, not all were analyzed for all three proteins. At admission, 10 of 53 patients (19%) had active TF, 53 of 55 (96%) had FXIa and 48 of 55 (87%) had FIXa in their plasma. 34 patients of 56 enrolled (61%) showed TF activity at one or more time-points. All patients had FXIa and 96% had FIXa at one or more time-points. Overall, TF was observed in 99 of 455 samples analyzed (22%), FXIa in 424 of 471 (90%) and FIXa in 244 of 471 (52%). The concentration of TF was relatively low and varied between 0 and 2.1pM, whereas that of FXIa was higher, exceeding 100pM in some samples. The majority of samples with FIXa had it at sub-nanomolar concentrations. No TF, FXIa and FIXa activity was detected in plasma from healthy individuals. For the first time reported, the majority of plasma samples from burn patients have active FXIa and FIXa, with a significant fraction of them having active TF. The concentration of all three proteins varies in a wide range. Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.

  11. Antifibrinolytic therapy for preventing oral bleeding in patients with haemophilia or Von Willebrand disease undergoing minor oral surgery or dental extractions.

    Science.gov (United States)

    van Galen, Karin P M; Engelen, Eveline T; Mauser-Bunschoten, Evelien P; van Es, Robert J J; Schutgens, Roger E G

    2015-12-24

    Minor oral surgery or dental extractions (oral or dental procedures) are widely performed and can be complicated by hazardous oral bleeding, especially in people with an inherited bleeding disorder such as haemophilia or Von Willebrand disease. The amount and severity of singular bleedings depend on disease-related factors, such as the severity of the haemophilia, both local and systemic patient factors (such as periodontal inflammation, vasculopathy or platelet dysfunction) and intervention-related factors (such as the type and number of teeth extracted or the dimension of the wound surface). Similar to local haemostatic measures and suturing, antifibrinolytic therapy is a cheap, safe and potentially effective treatment to prevent bleeding complications in individuals with bleeding disorders undergoing oral or dental procedures. However, a systematic review of trials reporting outcomes after oral surgery or a dental procedure in people with an inherited bleeding disorder, with or without, the use of antifibrinolytic agents has not been performed to date. The primary objective was to assess the efficacy of local or systemic use of antifibrinolytic agents to prevent bleeding complications in people with haemophilia or Von Willebrand disease undergoing oral or dental procedures. Secondary objectives were to assess if antifibrinolytic agents can replace or reduce the need for clotting factor concentrate therapy in people with haemophilia or Von Willebrand disease and to further establish the effects of these agents on bleeding in oral or dental procedures for each of these populations. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches of the Cochrane Central Register of Controlled Trials (CENTRAL), of MEDLINE and from handsearching of journals and conference abstract books. We additionally searched the reference lists of relevant articles and reviews. We searched Pub

  12. Platelet Factor 4 Binds to Vascular Proteoglycans and Controls Both Growth Factor Activities and Platelet Activation.

    Science.gov (United States)

    Lord, Megan S; Cheng, Bill; Farrugia, Brooke L; McCarthy, Simon; Whitelock, John M

    2017-03-10

    Platelet factor 4 (PF4) is produced by platelets with roles in both inflammation and wound healing. PF4 is stored in platelet α-granules bound to the glycosaminoglycan (GAG) chains of serglycin. This study revealed that platelet serglycin is decorated with chondroitin/dermatan sulfate and that PF4 binds to these GAG chains. Additionally, PF4 had a higher affinity for endothelial-derived perlecan heparan sulfate chains than serglycin GAG chains. The binding of PF4 to perlecan was found to inhibit both FGF2 signaling and platelet activation. This study revealed additional insight into the ways in which PF4 interacts with components of the vasculature to modulate cellular events. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Physical activity and cardiovascular disease risk factors among ...

    African Journals Online (AJOL)

    Background: Cardiovascular diseases (CVD) risk factors are increasing at an unprecedented rate in developing countries. However, fewer studies have evaluated the role of physical activity in preventing CVD in these countries. We assessed level physical activity and its relationship with CVD risk factors among young and ...

  14. Opposing Effects of Platelet-Activating Factor and Lyso-Platelet-Activating Factor on Neutrophil and Platelet ActivationS⃞

    OpenAIRE

    Welch, Emily J.; Naikawadi, Ram P.; Li, Zhenyu; Lin, Phoebe; Ishii, Satoshi; Shimizu, Takao; Tiruppathi, Chinnaswamy; Du, Xiaoping; Subbaiah, Papasani V.; Ye, Richard D.

    2008-01-01

    Platelet-activating factor (PAF) is a potent, bioactive phospholipid that acts on multiple cells and tissues through its G protein-coupled receptor (GPCR). PAF is not stored but is rapidly generated via enzymatic acetylation of the precursor 1-O-hexadecyl-2-hydroxy-sn-glycero-3-phosphocholine (lysoPAF). The bioactivity of PAF is effectively and tightly regulated by PAF acetylhydrolases, which convert PAF back to lysoPAF. Previous studies report that lysoPAF is an i...

  15. Prolonged activated prothromboplastin time and breed specific variation in haemostatic analytes in healthy adult Bernese Mountain dogs

    DEFF Research Database (Denmark)

    Nielsen, Lise; Wiinberg, Bo; Kjelgaard-Hansen, Mads

    2011-01-01

    Coagulation tests are often performed in dogs suspected of haemostatic dysfunction and are interpreted according to validated laboratory reference intervals (RIs). Breed specific RIs for haematological and biochemical analytes have previously been identified in Bernese Mountain dogs, but it remains...... to be determined if breed specific RIs are necessary for haemostasis tests. Activated prothromboplastin time (aPTT), prothrombin time (PT), selected coagulation factors, D-dimers, fibrinogen, von Willebrand factor and thromboelastography (TEG) were analyzed in healthy Bernese Mountain dogs using the CLSI model...

  16. Crystallization and preliminary X-ray analysis of the complex of the first von Willebrand type C domain bound to bone morphogenetic protein 2

    Energy Technology Data Exchange (ETDEWEB)

    Qiu, Li-yan; Zhang, Jin-li [Lehrstuhl für Physiologische Chemie II, Theodor-Boveri-Institut (Biozentrum) der Universität Würzburg, Am Hubland, D-97074 Würzburg (Germany); Kotzsch, Alexander [Lehrstuhl für Molekulare Pflanzenphysiologie und Biophysik, Julius-von-Sachs Institut der Universität Würzburg, Julius-von-Sachs Platz 2, D-97082 Würzburg (Germany); Sebald, Walter [Lehrstuhl für Physiologische Chemie II, Theodor-Boveri-Institut (Biozentrum) der Universität Würzburg, Am Hubland, D-97074 Würzburg (Germany); Rudolf-Virchow-Zentrum (DFG Forschungszentrum) der Universität Würzburg, Versbacher Strasse 9, D-97070 Würzburg (Germany); Mueller, Thomas D., E-mail: mueller@botanik.uni-wuerzburg.de [Lehrstuhl für Molekulare Pflanzenphysiologie und Biophysik, Julius-von-Sachs Institut der Universität Würzburg, Julius-von-Sachs Platz 2, D-97082 Würzburg (Germany); Rudolf-Virchow-Zentrum (DFG Forschungszentrum) der Universität Würzburg, Versbacher Strasse 9, D-97070 Würzburg (Germany); Lehrstuhl für Physiologische Chemie II, Theodor-Boveri-Institut (Biozentrum) der Universität Würzburg, Am Hubland, D-97074 Würzburg (Germany)

    2008-04-01

    Crystals of the complex of the first von Willebrand type C domain (VWC1) of crossveinless 2 (CV2) bound to bone morphogenetic protein 2 (BMP2) exist in two tetragonal crystal forms belonging to either space group P4{sub 1}2{sub 1}2 or I4{sub 1}, with one complete BMP2 dimer and two CV2 VWC1 domains per asymmetric unit, and diffract to 2.6 Å resolution. Crossveinless 2 (CV2) is a member of the chordin family, a protein superfamily that modulates the activity of bone morphogenetic proteins such as BMP2. The BMPs represent a large group of secreted proteins that control many steps during embryonal development and in tissue and organ homeostasis in the adult organism. The gene encoding the first von Willebrand type C domain (VWC1) of CV2 was cloned, expressed in Escherichia coli and purified to homogeneity. The binary complex of CV2 VWC1 and BMP2 was purified and subjected to crystallization. Crystals of SeMet-labelled proteins were obtained in two different forms belonging to the tetragonal space groups P4{sub 1}2{sub 1}2 and I4{sub 1}, with unit-cell parameters a = b = 86.7, c = 139.2 Å and a = b = 83.7, c = 139.6 Å, respectively. Initial analysis suggests that a complete binary complex consisting of one BMP2 dimer bound to two CV2 VWC1 domains is present in the asymmetric unit.

  17. Long-term impact of joint bleeds in von Willebrand disease: a nested case-control study

    NARCIS (Netherlands)

    Galen, K.P. van; Kleijn, P. de; Foppen, W.; Eikenboom, J.; Meijer, K.; Schutgens, R.E.; Fischer, K.; Cnossen, M.H.; Meris, J. de; Fijnvandraat, K.; Bom, J.G. Van Der; Laros-van Gorkom, B.A.P.; Leebeek, F.W.; Mauser-Bunschoten, E.P.

    2017-01-01

    Patients with severe von Willebrand disease (VWD) may develop arthropathy after joint bleeds. Information on its prevalence and severity is limited. We aimed to assess the occurrence and severity of arthropathy in VWD and its impact on daily life. VWD patients with and without verified joint bleeds

  18. Long-term impact of joint bleeds in von Willebrand disease : A nested case-control study

    NARCIS (Netherlands)

    van Galen, Karin P.M.; de Kleijn, Piet; Foppen, Wouter; Eikenboom, Jeroen H C; Meijer, Karina; Schutgens, Roger E.G.; Fischer, Kathelijn; Cnossen, Marjon H; de Meris, Joke; Fijnvandraat, Karin; van der Bom, Johanna G; Laros-van Gorkom, Britta A P; Leebeek, Frank W G; Mauser-Bunschoten, Eveline P.

    2017-01-01

    Patients with severe von Willebrand disease (VWD) may develop arthropathy after joint bleeds. Information on its prevalence and severity is limited. We aimed to assess the occurrence and severity of arthropathy in VWD and its impact on daily life. VWD patients with and without verified joint bleeds

  19. Long-term impact of joint bleeds in von Willebrand disease : A nested case-control study

    NARCIS (Netherlands)

    van Galen, Karin P. M.; de Kleijn, Piet; Foppen, Wouter; Eikenboom, Jeroen; Meijer, Karina; Schutgens, Roger E. G.; Fischer, Kathelijn; Cnossen, Marjon H.; de Meris, Joke; Fijnvandraat, Karin; van der Bom, Johanna G.; Laros-van Gorkom, Britta A. P.; Leebeek, Frank W. G.; Mauser-Bunschoten, Eveline P.

    Patients with severe von Willebrand disease (VWD) may develop arthropathy after joint bleeds. Information on its prevalence and severity is limited. We aimed to assess the occurrence and severity of arthropathy in VWD and its impact on daily life. VWD patients with and without verified joint bleeds

  20. Long-term impact of joint bleeds in von Willebrand disease: A nested case-control study

    NARCIS (Netherlands)

    K.P.M. van Galen; P. de Kleijn; W. Foppen (Wouter); J.C.J. Eikenboom (Jeroen); K. Meijer; R. Schutgens (Roger); K. Fischer (Kathelijn); M.H. Cnossen (Marjon); J. de Meris (J.); K. Fijnvandraat; J.G. van der Bom (Anske); B.A.P. Laros-Van Gorkom (Britta); F.W.G. Leebeek (Frank); E.P. Mauser-Bunschoten (Eveline)

    2017-01-01

    textabstractPatients with severe von Willebrand disease (VWD) may develop arthropathy after joint bleeds. Information on its prevalence and severity is limited. We aimed to assess the occurrence and severity of arthropathy in VWD and its impact on daily life. VWD patients with and without verified

  1. Antiglucocorticoid activity of hepatocyte nuclear factor-6.

    OpenAIRE

    Pierreux, Christophe; Stafford, J; Demonte, D; Scott, D K; Vandenhaute, Jean; O'Brien, R M; Granner, D K; Rousseau, Guy; Lemaigre, Frédéric

    1999-01-01

    Glucocorticoids exert their effects on gene transcription through ubiquitous receptors that bind to regulatory sequences present in many genes. These glucocorticoid receptors are present in all cell types, yet glucocorticoid action is controlled in a tissue-specific way. One mechanism for this control relies on tissue-specific transcriptional activators that bind in the vicinity of the glucocorticoid receptor and are required for receptor action. We now describe a gene-specific and tissue-spe...

  2. Activation of the retroviral budding factor ALIX.

    Science.gov (United States)

    Zhai, Qianting; Landesman, Michael B; Chung, Hyo-Young; Dierkers, Adam; Jeffries, Cy M; Trewhella, Jill; Hill, Christopher P; Sundquist, Wesley I

    2011-09-01

    The cellular ALIX protein functions within the ESCRT pathway to facilitate intralumenal endosomal vesicle formation, the abscission stage of cytokinesis, and enveloped virus budding. Here, we report that the C-terminal proline-rich region (PRR) of ALIX folds back against the upstream domains and auto-inhibits V domain binding to viral late domains. Mutations designed to destabilize the closed conformation of the V domain opened the V domain, increased ALIX membrane association, and enhanced virus budding. These observations support a model in which ALIX activation requires dissociation of the autoinhibitory PRR and opening of the V domain arms.

  3. Socioeconomic Factors Influence Physical Activity and Sport in Quebec Schools

    Science.gov (United States)

    Morin, Pascale; Lebel, Alexandre; Robitaille, Éric; Bisset, Sherri

    2016-01-01

    Background: School environments providing a wide selection of physical activities and sufficient facilities are both essential and formative to ensure young people adopt active lifestyles. We describe the association between school opportunities for physical activity and socioeconomic factors measured by low-income cutoff index, school size…

  4. Platelet-activating factor in cirrhotic liver and hepatocellular carcinoma

    OpenAIRE

    Mathonnet, Muriel; Descottes, Bernard; Valleix, Denis; Truffinet, Véronique; Labrousse, François; Denizot, Yves

    2006-01-01

    AIM: Platelet-activating factor (PAF) is a pro-inflammatory and angiogenic lipid mediator. Here we aimed to investigate levels of PAF, lyso-PAF (the PAF precursor), phospholipase A2 (PLA2, the enzymatic activity generating lyso-PAF), acetylhydrolase activity (AHA, the PAF degrading enzyme) and PAF receptor (PAF-R) transcripts in cirrhotic liver and hepatocellular carcinoma (HCC).

  5. Markers of endothelial cell activation and immune activation are increased in patients with severe leptospirosis and associated with disease severity.

    Science.gov (United States)

    Goeijenbier, Marco; Gasem, M Hussein; Meijers, Joost C M; Hartskeerl, Rudy A; Ahmed, Ahmed; Goris, Marga G A; Isbandrio, Bambang; Schuller, Simone S; Osterhaus, Albert D M E; Martina, Byron E E; van Gorp, Eric C M; Nally, Jarlath E; Wagenaar, Jiri F P

    2015-10-01

    Previous studies concluded that haemorrhage is one of the most accurate prognostic factors of mortality in leptospirosis. Therefore, endothelial cell activation was investigated in relation to disease severity in severe leptospirosis. Prospective cohort study of severe leptospirosis patients. Plasma levels of sE-selectin and Von Willebrand factor (VWF) were determined. Consequently, an in vitro endothelial cell model was used to assess endothelial activation after exposure to virulent Leptospira. Finally, immune activation, as a potential contributing factor to endothelial cell activation, was determined by soluble IL2-receptor (sIL-2r) and soluble Fas-ligand (sFasL) levels. Plasma levels of sE-selectin and VWF strongly increased in patients compared to healthy controls. Furthermore, sE-selectin was significantly elevated (203 ng/ml vs. 157 ng/ml, p leptospirosis patients. Copyright © 2015 The British Infection Association. All rights reserved.

  6. Nutrition, Physical Activity, and Obesity - Behavioral Risk Factor Surveillance System

    Data.gov (United States)

    U.S. Department of Health & Human Services — This dataset includes data on adult's diet, physical activity, and weight status from Behavioral Risk Factor Surveillance System. This data is used for DNPAO's Data,...

  7. Factors associated with early sexual activity among urban adolescents.

    Science.gov (United States)

    Smith, C A

    1997-07-01

    This study uses lifespan and ecological frameworks to investigate the factors associated with early adolescent sexual activity. Data from a longitudinal study of urban teenagers of color address three issues: (1) the prevalence and pattern of sexual activity among boys and girls ages 15 and younger, (2) the link between early sexual activity and high-risk sexual behavior, and (3) the life contexts linked with early sexual activity. Results from 803 African American and Hispanic adolescents suggest a high prevalence of early sexual activity, which is associated with higher rates of childbearing and risky sexual behavior than sexual activity initiated in later adolescence. Somewhat different factors are associated with early sexual activity for boys and girls, although family composition, parent attachment, and substance use are important for both genders. Implications for intervention are discussed.

  8. Laboratory testing for von Willebrand's disease: an assessment of current diagnostic practice and efficacy by means of a multi-laboratory survey. RCPA Quality Assurance Program (QAP) in Haematology Haemostasis Scientific Advisory Panel.

    Science.gov (United States)

    Favaloro, E J; Smith, J; Petinos, P; Hertzberg, M; Koutts, J

    1999-10-01

    We report an evaluation of current laboratory practice for the diagnosis of von Willebrand's disease (VWD) by means of a multilaboratory survey. This assessment was undertaken with the RCPA Quality Assurance Program (QAP) in Haematology, which covers a wide geographic area encompassing Australia, New Zealand and Asia. A total of 25 laboratories actively involved in testing for VWD were selected to participate in a sample testing assessment exercise. Samples comprised 10 plasmas: (i) a normal plasma pool (in duplicate), (ii) this pool diluted to 50% (in duplicate), (iii) a normal individual (X1), (iv) severe Type 1 VWD (X1), (v) Type 2B VWD (x2 unrelated donors), (vi) Type 3 VWD (x1), (vii) Type 2A VWD (x1). Laboratories were asked to perform all tests available to them in order to establish a laboratory diagnosis of VWD, and then to comment on the possibility or otherwise of VWD. Overall findings indicated a wide variation in test practice, in the effectiveness of various test procedures in detecting VWD, and in the ability of various composite test panels to identify type 2 VWD subtypes. Firstly, while all laboratories (n = 25) performed tests for FVIII:C activity, von Willebrand factor 'antigen' (VWF:Ag) and a functional VWF assay [using the ristocetin cofactor assay (VWF:RCo; n = 23) and/or the collagen binding assay (VWF:CBA; n = 12)], only three laboratories carried out VWF:Multimer analysis. Secondly, for the three quantitative VWF assays, 10/25 (40%) laboratories performed all three, whereas 15/25 (60%) performed only two [VWF:Ag and VWF:RCo (n = 13); VWF:Ag and VWF:CBA (n = 2)]. Thirdly, a variety of assay methodologies were evident for VWF:Ag [ELISA, electro-immuno diffusion (EID), latex immuno-assay (LIA), and VIDAS assay] and VWF:RCo (platelet agglutination/'aggregometry' and a 'functional VWF:RCo-alternative' ELISA assay). Between method analysis for the quantitative VWF assays showed that the VWF:RCo yielded the greatest degree of inter

  9. Activity limitations and factors influencing functional outcome of ...

    African Journals Online (AJOL)

    Background: Determining the functional abilities and factors influencing outcome of patients with stroke following rehabilitation are essential for the planning of future interventions and services in order to optimise recovery. Objectives: To determine the activity limitations and factors influencing functional outcome of patients ...

  10. Allosteric activation of coagulation factor VIIa visualized by hydrogen exchange

    DEFF Research Database (Denmark)

    Rand, Kasper Dyrberg; Jørgensen, Thomas; Olsen, Ole H

    2006-01-01

    Coagulation factor VIIa (FVIIa) is a serine protease that, after binding to tissue factor (TF), plays a pivotal role in the initiation of blood coagulation. We used hydrogen exchange monitored by mass spectrometry to visualize the details of FVIIa activation by comparing the exchange kinetics...

  11. Plasma level of von Willebrand factor: An indicator of severity in ...

    African Journals Online (AJOL)

    Background: Sickle cell anaemia is a congenital hemolytic disorder caused by mutation in the â-globin gene at position 6 with replacement of glutamic acid by valine. Patients who arehomozygous for this mutation suffer from hemolytic anaemia and other serious complications. The underlying pathology of much of these ...

  12. Structural studies on B2-glycoprotein I and von Willebrand factor A3 domain

    NARCIS (Netherlands)

    Bouma, B.

    2000-01-01

    The integrity of blood circulation is a prerequisite for life; its malfunctioning is a leading cause of morbidity and mortality in developed countries. For that reason the haemostatic system is a critical component of homeostasis. In Chapter I an overview is given of the biophysical and biochemical

  13. Transient von Willebrand factor-mediated platelet influx stimulates liver regeneration after partial hepatectomy in mice

    NARCIS (Netherlands)

    Kirschbaum, Marc; Jenne, Craig N; Veldhuis, Zwanida J; Sjollema, Klaas A; Lenting, Peter J; Giepmans, Ben N G; Porte, Robert J; Kubes, Paul; Denis, Cécile V; Lisman, Ton

    2017-01-01

    Background & AimsIn addition to their function in thrombosis and haemostasis, platelets play an important role in the stimulation of liver regeneration. It has been suggested that platelets deliver mitogenic cargo to the regenerating liver, and accumulation of platelets in the regenerating liver has

  14. Nitric oxide level and von Willebrand factor (vWF) secretion are not ...

    African Journals Online (AJOL)

    Jane

    2011-08-15

    Aug 15, 2011 ... ACKNOWLEDEGMENTS. We are highly indebted to Dr. Haghjoo for help in NO and. vWF measurement, and Massah A. for his help in. Behjati et al. 8875 luminescence measurement. This study was funded by grant no. 287097 from Deputy of Research, Isfahan. University of Medical Sciences, Isfahan, Iran ...

  15. Leukocyte telomere length is inversely correlated with plasma Von Willebrand factor

    DEFF Research Database (Denmark)

    Hjelmborg, Jacob V B; Nzietchueng, Rosine; Kimura, Masayuki

    2010-01-01

    attrition, ultimately resulting in shortened LTL. METHODS: We studied 3 cohorts: the ADELAHYDE study (age 60-87years), the ERA study (age 41-88years) and the Longitudinal Study of Aging Danish Twins (LSADT) (age 73-94years). RESULTS: Multiple regression analysis with LTL as the dependent variable, and age...... resistance, cigarette smoking and low socio-economic status. We examined the association between LTL and VWF plasma levels to test the hypothesis that high levels of VWF promote an increase in the turnover of blood cells, including leukocytes. Such a process would heighten the rate of age-dependent LTL...

  16. Acute rejection before cytomegalovirus infection enhances von Willebrand factor and soluble VCAM-1 in blood

    NARCIS (Netherlands)

    Kas-Deelen, AM; Harmsen, MC; de Maar, EF; Oost-Kort, WW; Tervaert, JWC; van der Meer, J; van Son, WJ; The, TH

    2000-01-01

    Background. Human cytomegalovirus (HCMV) infections in transplantation patients are associated with vascular endothelial damage. This is reflected by the appearance of cytomegalic endothelial cells (CECs) and noninfected endothelial cells (ECs) in blood. To get more insight in the extent of vascular

  17. Platelet-independent adhesion of calcium-loaded erythrocytes to von Willebrand factor

    NARCIS (Netherlands)

    Smeets, M.W.J. (Michel W.J.); R. Bierings (Ruben); Meems, H. (Henriet); F.P.J. Mul (F. P J); D. Geerts (Dirk); A.P.J. Vlaar (Alexander); J. Voorberg (Jan); P.L. Hordijk (Peter )

    2017-01-01

    textabstractAdhesion of erythrocytes to endothelial cells lining the vascular wall can cause vaso-occlusive events that impair blood flow which in turn may result in ischemia and tissue damage. Adhesion of erythrocytes to vascular endothelial cells has been described in multiple hemolytic disorders,

  18. Transient von Willebrand factor-mediated platelet influx stimulates liver regeneration after partial hepatectomy in mice

    NARCIS (Netherlands)

    Kirschbaum, Marc; Jenne, Craig N; Veldhuis, Zwanida J; Sjollema, Klaas A; Lenting, Peter J; Giepmans, Ben N G; Porte, Robert J; Kubes, Paul; Denis, Cécile V; Lisman, Ton

    2017-01-01

    BACKGROUND & AIMS: In addition to their function in thrombosis and hemostasis, platelets play an important role in the stimulation of liver regeneration. It has been suggested that platelets deliver mitogenic cargo to the regenerating liver, and accumulation of platelets in the regenerating liver

  19. Cellular fibronectin and von Willebrand factor concentrations in plasma of rats treated with monocrotaline pyrrole

    NARCIS (Netherlands)

    Schultze, A.E.; Emeis, J.J.; Roth, R.A.

    1996-01-01

    The monocrotaline pyrrole (MCTP)-treated rat is a useful model for the study of certain chronic pulmonary vascular diseases. A single, i.v. administration of a low dose of MCTP causes pneumotoxicity, pulmonary vascular remodeling, sustained increases in pulmonary arterial pressure, and right

  20. Factors associated with physical activity among Canadian high school students.

    Science.gov (United States)

    Leggett, Carly; Irwin, Melinda; Griffith, Jane; Xue, Lin; Fradette, Katherine

    2012-04-01

    Identifying multi-level factors affecting physical activity (PA) levels among adolescents is essential to increasing activity to promote health within this population. This study examines the associations between PA and 11 independent factors among Manitoba high school students. The sample included 31,202 grade 9-12 students who completed the Manitoba Youth Health Survey. Associations between PA and independent factors were examined separately and through multivariate regression. Analyses were stratified by gender. Perception of athletic ability, school location, parental encouragement and number of active friends were strong predictors of activity for moderately active and active males and females. Grade was a significant predictor of PA for females at both levels of activity but only significant for males when comparing active to inactive students. Perception of schoolwork and means of transport were minimally associated with PA. Results highlight the importance of targeting multiple levels of influence to increase PA among youth. Programs should focus on older students, females and those who are inactive or moderately active. In addition, social modeling of PA and increasing self-efficacy around activity should be encouraged.

  1. Factors influencing participation in physical activity among 11- 13 ...

    African Journals Online (AJOL)

    South African adolescents, in general, are physically inactive, and obesity amongst the youth at schools has become an alarming trend. This study aimed to identify the predisposing, reinforcing and enabling factors of physical activity and to determine the strongest predictors of physical activity participation among ...

  2. food choices, physical activity levels and other factors associated ...

    African Journals Online (AJOL)

    user

    Revision 2 August 2017. Keywords dietary pattern, educators, food choices, obesity; physical activity; South Africa. Food choices, physical activity levels and other factors associated with weight gain in primary school educators. 83. BACKGROUND. Globally, deaths from non-communicable diseases (NCDs) are predicted to ...

  3. Plasma factor VII-activating protease is increased by oral contraceptives and induces factor VII activation in-vivo

    DEFF Research Database (Denmark)

    Sidelmann, Johannes J; Skouby, Sven O; Kluft, Cornelis

    2011-01-01

    Oral contraceptive (OC) use influences the hemostatic system significantly and is a risk factor for development of cardiovascular disease. Factor VII-activating protease (FSAP) has potential effects on hemostasis. The 1601GA genotype of the 1601G/A polymorphism in the FSAP gene expresses a FSAP...

  4. Activity of recombinant factor VIIa under different conditions in vitro

    DEFF Research Database (Denmark)

    Bladbjerg, Else-Marie; Jespersen, Jørgen

    2008-01-01

    investigated the in-vitro effects of pH, temperature, and haemodilution on the activity of recombinant activated factor VII. Samples from eight healthy volunteers were spiked with recombinant activated factor VII (final concentration 1.7 microg/ml) and adjusted to pH 6.0, 6.5, 7.0, and 7.4 or analysed at 30...... activity in plasma. Significant effects of pH were observed for clotting time, clot formation time, maximum clot firmness, and factor VII coagulant activity in the direction of longer clot formation times and less firm clots with decreasing pH. Temperature had significant effects on clotting time, clot......, but no effects on clotting time indicating that haemodilution does not affect clot formation, but the clot formed at high haemodilution may not be so firm. In conclusion, the activity of recombinant activated factor VII was affected in vitro by pH, temperature, and haemodilution. Additional studies are necessary...

  5. [Effects of soil factor on active components of Radix Ophiopogonis].

    Science.gov (United States)

    Zhang, Lianting; Ye, Zhengliang; Guo, Qiaosheng

    2010-06-01

    To study the effects of soil factors on the active components in Radix Ophiopogonis. The content of polysaccharide, flavonoids, saponins, water-soluble extract and inorganic elements in Radix Ophiopogonis gathered from 7 different places were compared, physical and chemical properties and inorganic elements of soil were analyzed. The path and grey connection analysis were applied for studying the effects on the active components of Radix Ophiopogonis. The concentrations of mineral elements in plant were mainly adjusted by active absorption. The active components in Radix Ophiopogonis was primarily effected by soil enzyme activity, the other important factors were potassium, pH, and organic matter. K, Fe, Mn, B, Ba, Zn of soil also had much influence on it then others inorganic elements.

  6. Regulation of tissue factor coagulant activity on cell surfaces.

    Science.gov (United States)

    Rao, L V M; Pendurthi, U R

    2012-11-01

    Tissue factor (TF) is a transmembrane glycoprotein and an essential component of the factor VIIa-TF enzymatic complex that triggers activation of the coagulation cascade. Formation of TF-FVIIa complexes on cell surfaces not only trigger the coagulation cascade but also transduce cell signaling via activation of protease-activated receptors. Tissue factor is expressed constitutively on cell surfaces of a variety of extravascular cell types, including fibroblasts and pericytes in and surrounding blood vessel walls and epithelial cells, but is generally absent on cells that come into contact with blood directly. However, TF expression could be induced in some blood cells, such as monocytes and endothelial cells, following an injury or pathological stimuli. Tissue factor is essential for hemostasis, but aberrant expression of TF leads to thrombosis. Therefore, a proper regulation of TF activity is critical for the maintenance of hemostatic balance and health in general. TF-FVIIa coagulant activity at the cell surface is influenced not only by TF protein expression levels but also independently by a variety of mechanisms, including alterations in membrane phospholipid composition and cholesterol content, thiol-dependent modifications of TF allosteric disulfide bonds, and other post-translational modifications of TF. In this article, we critically review the key literature on mechanisms by which TF coagulant activity is regulated at the cell surface in the absence of changes in TF protein levels with specific emphasis on recently published data and provide the authors' perspective on the subject. © 2012 International Society on Thrombosis and Haemostasis.

  7. Physical activity and associated factors among students attending evening classes

    Directory of Open Access Journals (Sweden)

    Fabio Luis Ceschini

    2015-03-01

    Full Text Available The aim of this study was to describe the physical activity level and associated factors among students attending evening classes in public and private schools in a region of the city of São Paulo. The sample was composed of 1,844 adolescents of both sexes aged 15-20 years. Three public and private schools in the city of São Paulo were visited. Daily physical activity level was assessed through International Physical Activity Questionnaire that classifies physical activity level. Physical activity level was divided into insufficiently active (when subject reported less than 300 minutes of moderate to vigorous physical activities per week and physically active (when subject reported more than 300 minutes of moderate to vigorous physical activities per week. Information related to risk behavior such as smoking and alcohol consumption was collected. Data were analyzed using logistic regression with three levels of data input and p<.05 as significance level. The prevalence of physically active adolescents was 36.1%. Most active subjects were: A younger boys with low socioeconomic levels; B adolescents from private schools; C adolescents that do not smoke or drink alcoholic beverages; D those who do not attend formal exercise program; E those who go to school to perform physical activities on weekends. Adolescents attending evening classes tended to be insufficiently active. We believe that school structure, working hours, and distance from home and workplace to school and risk factor should explain these data. Intervention programs could significantly contribute to increase the physical activity level among adolescents.

  8. Psychosocial factors associated with increased physical activity in insufficiently active adults with arthritis.

    Science.gov (United States)

    Peeters, G M E E Geeske; Brown, Wendy J; Burton, Nicola W

    2015-09-01

    Although physical activity can potentially reduce symptoms of arthritis, 50% of people with arthritis are insufficiently active. The aim was to identify psychosocial factors associated with increased physical activity in mid-age adults with arthritis who did not meet recommended physical activity levels. Longitudinal cohort study. Data were from 692 insufficiently active men and women (mean age 55 ± 6.6 years) with arthritis, who answered mailed surveys in 2007 and 2009 in the HABITAT study. Increased physical activity was defined as a change of ≥ 200 MET min/week in walking, moderate and vigorous activities from 2007 to 2009. Scale scores were used to measure psychosocial factors including intention, experiences, attitudes, efficacy, barriers, motivation, social support, and health professional advice. Associations between (1) 2007 psychosocial factors and (2) 2007-2009 improvement (≥ +1 standard deviation) in psychosocial factors and increased physical activity were examined with logistic regression models. Results were adjusted for education, body mass index, and self-rated health. Between 2007 and 2009, 296 participants (42.8%) increased their physical activity. Engagement, mastery and physical activity intention in 2007 were associated with this increase in physical activity (engagement OR = 1.11, 99% confidence interval (CI) = 1.05-1.17; mastery OR = 1.12, 99%CI = 1.02-1.22; physical activity intention OR = 1.29, 99%CI = 1.06-1.56). Improved scores for encouragement (OR = 2.07, CI = 1.07-4.01) and self-efficacy (OR =2 .27, CI = 1.30-3.97) were also significantly associated with increased physical activity. Positive physical activity experiences and intentions were predictors of increased physical activity among people with arthritis. Improved physical activity confidence and social support were associated with increased physical activity. It is important to consider these psychosocial factors when planning physical activity interventions for people with

  9. Surface-Energy Dependent Contact Activation of Blood Factor XII

    Science.gov (United States)

    Golas, Avantika; Parhi, Purnendu; Dimachkie, Ziad O.; Siedlecki, Christopher A.; Vogler, Erwin A.

    2009-01-01

    Contact activation of blood factor XII (FXII, Hageman factor) in neat-buffer solution exhibits a parabolic profile when scaled as a function of silanized-glass-particle activator surface energy (measured as advancing water adhesion tension τao=γlvocosθ in dyne/cm, where γlvo is water interfacial tension in dyne/cm and θ is the advancing contact angle). Nearly equal activation is observed at the extremes of activator water-wetting properties −36materials falling within the 20chemistries falling within this range are, however, a perplexingly difficult target for surface engineering because of the critical balance that must be struck between hydrophobicity and hydrophilicity. Results are interpreted within the context of blood plasma coagulation and the role of water and proteins at procoagulant surfaces. PMID:19892397

  10. Physical Activity in Adolescents following Treatment for Cancer: Influencing Factors

    Directory of Open Access Journals (Sweden)

    Marilyn Wright

    2013-01-01

    Full Text Available The purpose of this study was to examine physical activity levels and influencing individual and environmental factors in a group of adolescent survivors of cancer and a comparison group. Methods. The study was conducted using a “mixed methods” design. Quantitative data was collected from 48 adolescent survivors of cancer and 48 comparison adolescents using the Godin Leisure-Time Exercise Questionnaire, the Fatigue Scale—Adolescents, and the Amherst Health and Activity Study—Student Survey. Qualitative data was collected in individual semistructured interviews. Results. Reported leisure-time physical activity total scores were not significantly different between groups. Physical activity levels were positively correlated with adult social support factors in the group of adolescent survivors of cancer, but not in the comparison group. Time was the primary barrier to physical activity in both groups. Fatigue scores were higher for the comparison but were not associated with physical activity levels in either group. The qualitative data further supported these findings. Conclusions. Barriers to physical activity were common between adolescent survivors of cancer and a comparative group. Increased knowledge of the motivators and barriers to physical activity may help health care providers and families provide more effective health promotion strategies to adolescent survivors of pediatric cancer.

  11. Mechanisms of Hepatocyte Growth Factor Activation in Cancer Tissues

    Energy Technology Data Exchange (ETDEWEB)

    Kawaguchi, Makiko; Kataoka, Hiroaki, E-mail: mejina@med.miyazaki-u.ac.jp [Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692 (Japan)

    2014-09-29

    Hepatocyte growth factor/scatter factor (HGF/SF) plays critical roles in cancer progression through its specific receptor, MET. HGF/SF is usually synthesized and secreted as an inactive proform (pro-HGF/SF) by stromal cells, such as fibroblasts. Several serine proteases are reported to convert pro-HGF/SF to mature HGF/SF and among these, HGF activator (HGFA) and matriptase are the most potent activators. Increased activities of both proteases have been observed in various cancers. HGFA is synthesized mainly by the liver and secreted as an inactive pro-form. In cancer tissues, pro-HGFA is likely activated by thrombin and/or human kallikrein 1-related peptidase (KLK)-4 and KLK-5. Matriptase is a type II transmembrane serine protease that is expressed by most epithelial cells and is also synthesized as an inactive zymogen. Matriptase activation is likely to be mediated by autoactivation or by other trypsin-like proteases. Recent studies revealed that matriptase autoactivation is promoted by an acidic environment. Given the mildly acidic extracellular environment of solid tumors, matriptase activation may, thus, be accelerated in the tumor microenvironment. HGFA and matriptase activities are regulated by HGFA inhibitor (HAI)-1 (HAI-1) and/or HAI-2 in the pericellular microenvironment. HAIs may have an important role in cancer cell biology by regulating HGF/SF-activating proteases.

  12. Elevated plasma phospholipase A2 and platelet-activating factor acetylhydrolase activity in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Yves Denizot

    2004-01-01

    Full Text Available This clinical study reports that blood levels of the pro-inflammatory mediator platelet-activating factor (PAF did not change in colorectal cancer patients. In contrast, plasma levels of two enzymatic activities, one implicated in PAF production (i.e. phospholipase A2 and one in PAF degradation (i.e. PAF acetylhydrolase activity were significantly elevated.

  13. Cost-utility analysis of von Willebrand disease screening in adolescents with menorrhagia.

    Science.gov (United States)

    Sidonio, Robert Francis; Smith, Kenneth J; Ragni, Margaret V

    2010-09-01

    To construct a decision analysis model to evaluate the cost utility of von Willebrand disease (VWD) testing in adolescents with menorrhagia. A 20-year Markov decision analytic model was constructed to evaluate the cost utility of two strategies: testing or not testing for VWD. The model includes probabilities of remaining well, suffering an acute menorrhagia bleeding event, surgical complications, oral contraceptive pill complications, or dying. Probabilities, costs, and utilities were estimated from published literature. The prevalence of type 1 VWD in adolescent females with menorrhagia was estimated at 13%. The cost of testing adolescents with menorrhagia for VWD was $1790, versus $1251 for not testing for VWD. The effectiveness of not testing in quality-adjusted life-years (QALYs) gained (14.237 QALYs) was similar to the VWD testing strategy (14.246 QALYs). Compared with not testing for VWD, screening for VWD had an incremental cost-effectiveness ratio of $62,791 per QALY, a value typically considered economically reasonable. In adolescents with menorrhagia, testing for VWD before the initiation of oral contraceptives is cost-effective. Copyright (c) 2010 Mosby, Inc. All rights reserved.

  14. Prevalence of activated protein C resistance (Factor V Leiden) in ...

    African Journals Online (AJOL)

    ... Protein C (Factor V Leiden) is the commonest genetic defect known to confer a predisposition to thrombosis. This study aims to determine the prevalence of activated protein C resistance (APCr) in Lagos, and to determine if any association exists between APCr and ABO, Rhesus blood types, and hemoglobin phenotypes.

  15. Recombinant-activated factor VII in the paediatric cardiac surgery ...

    African Journals Online (AJOL)

    V Agarwal, KE Okonta, PS Lal. Abstract. Background: The control of excessive bleeding after paediatric cardiac surgery can be challenging. This may make the use of recombinant-activated factor VII (rFVIIa) in preventing this excessive bleeding, after adopted conventional methods have failed, desirable. Our aim is to ...

  16. factors affecting implementation of practical activities in science

    African Journals Online (AJOL)

    Temechegn

    Academically less prepared students of secondary schools prefer humanities and social sciences than science and technology in higher education. The majority of students in schools of the study area join social science. Therefore assessing factors affecting implementation of practical activities in science education in study ...

  17. Prevalence and risk factors for Active Convulsive Epilepsy in ...

    African Journals Online (AJOL)

    The self-reported treatment gap was 86.9% (95%CI: 83.5%-90.3%). Conclusion: ACE is common within the middle belt of Ghana and could be reduced with improved obstetric care and prevention of parasite infestations such as Onchocerca volvulus and Toxoplasma gondii. Keywords: Active Epilepsy, risk factors, ...

  18. Prevalence and risk factors for Active Convulsive Epilepsy in ...

    African Journals Online (AJOL)

    Introduction: epilepsy is common in sub-Saharan Africa, but there is little data in West Africa, to develop public health measures for epilepsy in this region. Methods: we conducted a three-stage cross-sectional survey to determine the prevalence and risk factors for active convulsive epilepsy (ACE), and estimated the ...

  19. Hepatocyte growth factor activator inhibitor-2 prevents shedding of matriptase

    DEFF Research Database (Denmark)

    Larsen, Brian R; Steffensen, Simon D R; Nielsen, Nis Valentin Ladefoged

    2013-01-01

    Hepatocyte growth factor activator inhibitor-2 (HAI-2) is an inhibitor of many proteases in vitro, including the membrane-bound serine protease, matriptase. Studies of knock-out mice have shown that HAI-2 is essential for placental development only in mice expressing matriptase, suggesting that HAI...

  20. Factors Influencing Research Activity among Medical Students at ...

    African Journals Online (AJOL)

    This study aimed at describing the factors that influence research among medical students in a Kenyan University. Subjects and Methods This descriptive cross sectional study involved medical students at the School of Medicine, University of Nairobi. An open questionnaire regarding research activity was administered to ...

  1. Modifiable factors associated with active pulmonary tuberculosis in a ...

    African Journals Online (AJOL)

    Conclusions: Modifiable factors associated with active PTB in Nakuru G.K prison are: HIV status, BCG vaccination, PTB case contact, poverty and poor personal hygiene. We recommend HIV counselling and testing of all PTB patients, screening for TB upon prison entry and TB contact investigation and improving personal ...

  2. Are intestinal helminths risk factors for developing active tuberculosis?

    DEFF Research Database (Denmark)

    Elias, Daniel; Mengistu, Getahun; Akuffo, Hannah

    2006-01-01

    OBJECTIVES: To determine the prevalence of intestinal helminth infections in active tuberculosis patients and their healthy household contacts and to assess its association with active TB in an area endemic for both types of infections. METHODS: Smear-positive pulmonary TB patients and healthy......: Intestinal helminth infection may be one of the risk factors for the development of active pulmonary TB in addition to HIV infection. This finding may have important implications in the control of TB in helminth endemic areas of the world....

  3. Social and Psychological Factors Associated With Adolescent Physical Activity.

    Science.gov (United States)

    Garcia, Jeanette M; Sirard, John R; Larsen, Ross; Bruening, Meg; Wall, Melanie; Neumark-Sztainer, Dianne

    2016-09-01

    The purpose of this study was to examine, using structural equation modeling, the associations between nominated friend physical activity (PA), friend social support with individual PA-related psychological factors, and adolescent PA. Data were obtained from EAT 2010 (Eating and Activity Among Teens), a large cross-sectional study conducted in 20 middle and high schools. The sample consisted of 1951 adolescents (mean age: 14.25 ± 1.96, 54% female, 68% ethnic minorities). PA, parent and friend social support (perceived social support for PA from parents and friends), and psychological measures (PA enjoyment, PA self-efficacy, and PA barriers) were assessed by self-report questionnaires. The SEM analysis consisted of 1 observed variable: friend PA, and 2 latent constructs: psychological factors, perceived social support. The model was a good fit, indicating that there were significant direct effects of both friend PA (P < .01) and psychological factors (P < .0001) on adolescent PA. In addition, psychological factors mediated the association between friend PA and adolescent PA. The results of this model suggest that psychological factors and friend PA are associated with adolescent PA, and that psychological factors may play an important role. Future studies should further examine the association of both friend PA and psychological variables with adolescent PA.

  4. Carbohydrates and Activity of Natural and Recombinant Tissue Factor*

    Science.gov (United States)

    Krudysz-Amblo, Jolanta; Jennings, Mark E.; Mann, Kenneth G.; Butenas, Saulius

    2010-01-01

    The effect of glycosylation on tissue factor (TF) activity was evaluated, and site-specific glycosylation of full-length recombinant TF (rTF) and that of natural TF from human placenta (pTF) were studied by liquid chromatography-tandem mass spectrometry. The amidolytic activity of the TF·factor VIIa (FVIIa) complex toward a fluorogenic substrate showed that the catalytic efficiency (Vmax) of the complex increased in the order rTF1–243 (Escherichia coli) carbohydrates significantly influence the activity of TF proteins. Carbohydrate analysis revealed glycosylation on asparagines 11, 124, and 137 in both rTF1–263 and pTF. The carbohydrates of rTF1–263 contain high mannose, hybrid, and fucosylated glycans. Natural pTF contains no high mannose glycans but is modified with hybrid, highly fucosylated, and sialylated sugars. PMID:19955571

  5. Tissue factor activates allosteric networks in factor VIIa through structural and dynamic changes

    DEFF Research Database (Denmark)

    Madsen, Jesper Jonasson; Persson, E.; Olsen, O. H.

    2015-01-01

    Background: Tissue factor (TF) promotes colocalization of enzyme (factorVIIa) and substrate (FX or FIX), and stabilizes the active conformation of FVIIa. Details on how TF induces structural and dynamic changes in the catalytic domain of FVIIa to enhance its efficiency remain elusive. Objective......: To elucidate the activation of allosteric networks in the catalytic domain of the FVIIa protease it is when bound to TF.MethodsLong-timescale molecular dynamics simulations of FVIIa, free and in complex with TF, were executed and analyzed by dynamic network analysis. Results: Allosteric paths of correlated...

  6. Human blood platelets lack nitric oxide synthase activity.

    Science.gov (United States)

    Böhmer, Anke; Gambaryan, Stepan; Tsikas, Dimitrios

    2015-01-01

    Reports on expression and functionality of nitric oxide synthase (NOS) activity in human blood platelets and erythrocytes are contradictory. We used a specific gas chromatography-mass spectrometry (GC-MS) method to detect NOS activity in human platelets. The method measures simultaneously [(15)N]nitrite and [(15)N]nitrate formed from oxidized (15)N-labeled nitric oxide ((15)NO) upon its NOS-catalyzed formation from the substrate l-[guanidino-(15)N2]-arginine. Using this GC-MS assay, we did not detect functional NOS in non-stimulated platelets and in intact platelets activated by various agonists (adenosine diphosphate, collagen, thrombin, or von Willebrand factor) or lysed platelets. l-[guanidino-nitro]-Arginine-inhibitable NOS activity was measured after addition of recombinant human endothelial NOS to lysed platelets. Previous and recent studies from our group challenge expression and functionality of NOS in human platelets and erythrocytes.

  7. LPS-inducible factor(s) from activated macrophages mediates cytolysis of Naegleria fowleri amoebae

    Energy Technology Data Exchange (ETDEWEB)

    Cleary, S.F.; Marciano-Cabral, F.

    1986-03-01

    Soluble cytolytic factors of macrophage origin have previously been described with respect to their tumoricidal activity. The purpose of this study was to investigate the mechanism and possible factor(s) responsible for cytolysis of the amoeba Naegleria fowleri by activated peritoneal macrophages from B6C3F1 mice. Macrophages or conditioned medium (CM) from macrophage cultures were incubated with /sup 3/H-Uridine labeled amoebae. Percent specific release of label served as an index of cytolysis. Bacille Calmette-Guerin (BCG) and Corynebacterium parvum macrophages demonstrated significant cytolysis of amoebae at 24 h with an effector to target ratio of 10:1. Treatment of macrophages with inhibitors of RNA or protein synthesis blocked amoebicidal activity. Interposition of a 1 ..mu..m pore membrane between macrophages and amoebae inhibited killing. Inhibition in the presence of the membrane was overcome by stimulating the macrophages with LPS. CM from SPS-stimulated, but not unstimulated, cultures of activated macrophages was cytotoxic for amoebae. The activity was heat sensitive and was recovered from ammonium sulfate precipitation of the CM. Results indicate that amoebicidal activity is mediated by a protein(s) of macrophage origin induced by target cell contact or stimulation with LPS.

  8. Factors of the active listening of preschool children

    Directory of Open Access Journals (Sweden)

    Purić Daliborka S.

    2016-01-01

    Full Text Available Active listening is a communication skill which is crucial for the development of cooperative relationships in the group, culture of friendship and fellowship, it is also important for the development of literacy skills and talent for speaking. Furthermore, it contributes to the improvement of the level of knowledge, skills and school achievement, as well as to the development of self-confidence of children. Developing of active listening is an important task in the activities with children of preschool age. In this paper, the author, wanting to determine the importance of the factors of active listening of preschool children, examines how preschool teachers (N = 198: (a evaluate the importance of certain elements of active listening that relate to the speaker and the listener, and (b estimate their role in the process of developing active listening skills of preschool children as an essential element of successful interpersonal communication. Results of the survey show that preschool teachers attach greater importance to the factors of active listening related to the listener (attention, listening skill, interest in the subject, than to the factors related to the speaker (motivation for listening, quality of the narrative. More than two-thirds of surveyed preschool teachers (172 or 86.9% define its impact on the stimulation of active listening of children as significant. Work experience and professional qualifications as independent variables significantly influence the attitudes of preschool teachers about the importance of their impact in stimulating active listening. Preschool teacher is a key element of the training of preschool children in the area of the basic communication skills of active listening. In this sense, the results of our survey show that in the context of academic study programs for education of preschool teachers special attention is given to the communication skills and to their role in the development of active listening

  9. Factors associated with early platelet activation in obese children.

    Science.gov (United States)

    Gómez García, Anel; Núñez, Guillermina García; Sandoval, Martha Eva Viveros; Castellanos, Sergio Gutierrez; Alvarez Aguilar, Cleto

    2014-09-01

    To investigate the factors associated with platelet activation in obese children. Cross-sectional study. Department of Pediatrics of Regional Hospital N∘ 1 of Mexican Institute of Social Security in Morelia, Michoacán, Mexico. 79 obese and 64 non-obese children between the ages of 5 and 10 years. Obese children (body mass index [BMI] >85 in growth curves for Centers for Disease Control/National Center for Health Statistics), and the control group of 64 non-obese children (percentile Obese children displayed higher plasma sP-selectin, leptin, PAI-1, and vWF than non-obese children. In the univariate logistic regression analysis, leptin, vWF, UA, and high density lipoprotein (HDL), but not with PAI-1, were factors associated with platelet activation. By stepwise linear regression analysis adjusted by sex and age, the best predictor variables for platelet activation were leptin (β:0.381; t:4.665; P=0.0001), vWF (β:0.211; t:2.926; P=0.004), UA (β:0.166; t:2.146; P=0.034), and HDL (β:-0.215; t:-2.819; P=0.006). Obese children have a higher risk of developing early platelet activation. Factors associated with platelet activation were Leptin, vWF, UA, and HDL. Further studies involving larger numbers of patients over a longer duration are needed to understand the possible molecular mechanism underlying the association between leptin, vWF, and UA and endothelial activation and/or endothelial damage/dysfunction in obese children and its influence in cardiovascular disease in adults. © 2014 Marshfield Clinic.

  10. Recombinant Factor VIIa-Mediated Activation of Prothrombin Complex Concentrates.

    Science.gov (United States)

    Sadeghi, Nasiredin; Iacobelli, Massimo; Vaziri, Behroz; Kahn, Daniel; Hoppensteadt, Debra; Guler, Nil; Fareed, Jawed

    2017-04-01

    Recombinant factor VIIa (rFVIIa) is used in the management of bleeding in patients with hemophilia. A generic biosimilar version of NovoSeven is also developed (AryoSeven). To compare the activation profile of NovoSeven and AryoSeven, 2 commercially available protein complex concentrates (PCCs) were used. Profilnine activated by RecombiPlasTin 2G resulted in conversions of prothrombin to prethrombin and thrombin at 5 to 30 minutes. However, addition of rFVIIa at final concentration range of 0.25 to 0.5 µg/mL to the same mixture resulted in total conversion of prothrombin to thrombin with a doublet at 36 kDa. Recombinant factor VIIa alone did not generate thrombin in native Beriplex, and the addition of rFVIIa to Beriplex failed to generate thrombin. Beriplex activated by RecombiPlasTin 2G resulted in complete conversion of prothrombin to thrombin. Both NovoSeven and AryoSeven exhibited similar activation profiles. These studies indicate that the activation of PCCs by both rFVIIa preparations results in comparable generation of thrombin.

  11. Risk factors for glucose intolerance in active acromegaly

    Directory of Open Access Journals (Sweden)

    Kreze A.

    2001-01-01

    Full Text Available In the present retrospective study we determined the frequency of glucose intolerance in active untreated acromegaly, and searched for risk factors possibly supporting the emergence of the diabetic condition. Among 43 patients, 8 (19%; 95% CI: 8-33% had diabetes mellitus and 2 (5%; 1-16% impaired glucose tolerance. No impaired fasting glycemia was demonstrable. The frequency of diabetes was on average 4.5 times higher than in the general Slovak population. Ten factors suspected to support progression to glucose intolerance were studied by comparing the frequency of glucose intolerance between patients with present and absent risk factors. A family history of diabetes and arterial hypertension proved to have a significant promoting effect (P<0.05, chi-square test. A significant association with female gender was demonstrated only after pooling our data with literature data. Concomitant prolactin hypersecretion had a nonsignificant promoting effect. In conclusion, the association of active untreated acromegaly with each of the three categories of glucose intolerance (including impaired fasting glycemia, not yet studied in this connection was defined as a confidence interval, thus permitting a sound comparison with the findings of future studies. Besides a family history of diabetes, female gender and arterial hypertension were defined as additional, not yet described risk factors.

  12. Factors related to impairment of activities of daily living.

    Science.gov (United States)

    Kamiyama, T; Muratani, H; Kimura, Y; Fukiyama, K; Abe, K; Fujii, J; Kuwajima, I; Ishii, M; Shiomi, T; Kawano, Y; Mikami, H; Ibayashi, S; Omae, T

    1999-09-01

    We examined the factors related to the impairment of activities of daily living (ADL). ADL was evaluated by using ADL-20, which consists of 20 items from 4 major categories of activities; mobility, self-care, instrumental, and communication. The patients' gender, birth date, clinical diagnosis, past history, life styles, physical findings, laboratory data, and details of therapy were also recorded. Patients A total of 1,163 outpatients aged 50 years or older were included. Data from 1,093 patients were analyzed. We divided the subjects into two groups; Group I having full marks of ADL-20 (n=582) and group II exhibiting an impairment of ADL (n=511). Multiple logistic analysis revealed that in both sexes age and stroke were common independent factors related to the impairment of ADL. Other factors associated with impairment of ADL were smoking in men and presence of proteinuria in women. The presence of hyperlipidemia was associated with preservation of the ADL in women. The results demonstrated significant associations of smoking in men and the presence of proteinuria in women with the impairment of ADL in elderly Japanese outpatients. There appears to be a sex difference in the risk factors of impairment of ADL.

  13. Pitfalls in Interventional Pain Medicine: Hyponatremia after DDAVP for a Patient with Von Willebrand Disease Undergoing an Epidural Steroid Injection

    Directory of Open Access Journals (Sweden)

    Talal W. Khan

    2017-01-01

    Full Text Available Desmopressin (DDAVP, a synthetic analog of vasopressin, has been used in patients with von Willebrand disease (VWD, mild hemophilia A, and platelet dysfunction to reduce the risk of bleeding associated with surgical and interventional procedures. We report the case of a patient with VWD presenting with a bulging disc and radicular pain that underwent transforaminal epidural steroid injections. Her course was complicated with the interval development of headaches and dizziness symptomatic of moderate hyponatremia, likely due to excessive fluid intake. This report highlights a relatively rare side effect of DDAVP when used for prophylaxis in patients with VWD and reinforces the need for vigilance in these patients.

  14. Activated macrophages control human adipocyte mitochondrial bioenergetics via secreted factors.

    Science.gov (United States)

    Keuper, Michaela; Sachs, Stephan; Walheim, Ellen; Berti, Lucia; Raedle, Bernhard; Tews, Daniel; Fischer-Posovszky, Pamela; Wabitsch, Martin; Hrabě de Angelis, Martin; Kastenmüller, Gabi; Tschöp, Matthias H; Jastroch, Martin; Staiger, Harald; Hofmann, Susanna M

    2017-10-01

    Obesity-associated WAT inflammation is characterized by the accumulation and local activation of macrophages (MΦs), and recent data from mouse studies suggest that macrophages are modifiers of adipocyte energy metabolism and mitochondrial function. As mitochondrial dysfunction has been associated with obesity and the metabolic syndrome in humans, herein we aimed to delineate how human macrophages may affect energy metabolism of white adipocytes. Human adipose tissue gene expression analysis for markers of macrophage activation and tissue inflammation (CD11c, CD40, CD163, CD206, CD80, MCP1, TNFα) in relationship to mitochondrial complex I (NDUFB8) and complex III (UQCRC2) was performed on subcutaneous WAT of 24 women (BMI 20-61 kg/m 2 ). Guided by these results, the impact of secreted factors of LPS/IFNγ- and IL10/TGFβ-activated human macrophages (THP1, primary blood-derived) on mitochondrial function in human subcutaneous white adipocytes (SGBS, primary) was determined by extracellular flux analysis (Seahorse technology) and gene/protein expression. Stepwise regression analysis of human WAT gene expression data revealed that a linear combination of CD40 and CD163 was the strongest predictor for mitochondrial complex I (NDUFB8) and complex III (UQCRC2) levels, independent of BMI. IL10/TGFβ-activated MΦs displayed high CD163 and low CD40 expression and secreted factors that decreased UQCRC2 gene/protein expression and ATP-linked respiration in human white adipocytes. In contrast, LPS/IFNγ-activated MΦs showed high CD40 and low CD163 expression and secreted factors that enhanced adipocyte mitochondrial activity resulting in a total difference of 37% in ATP-linked respiration of white adipocytes (p = 0.0024) when comparing the effect of LPS/IFNγ- vs IL10/TGFβ-activated MΦs. Our data demonstrate that macrophages modulate human adipocyte energy metabolism via an activation-dependent paracrine mechanism. Copyright © 2017 The Authors. Published by Elsevier

  15. Modulation of topoisomerase activities by tumor necrosis factor.

    Science.gov (United States)

    Baloch, Z; Cohen, S; Fresa, K; Coffman, F D

    1995-01-01

    A number of chemotherapeutic agents which inhibit the DNA topoisomerases markedly potentiate cell death mediated by tumor necrosis factor, suggesting a role for these enzymes in the TNF cytotoxic mechanism. To investigate this possibility, topoisomerase I and II activities were assayed following TNF addition to murine L929 cells. Topoisomerase I and II activities increased within 15 min of TNF addition and returned to baseline levels within 1 and 2 hr, respectively. The increases in both topoisomerase activities were blocked by H-7 (but not H-8) and similar increases were seen following PMA addition. However, concentrations of H-7 which blocked the increased topoisomerase activities had no effect on TNF cytotoxicity nor on the enhancement of TNF cytotoxicity by topoisomerase inhibitors. Thus, in these cells topoisomerase activities are directly modified by TNF during the initial phases of a cytotoxic response. However, neither TNF cytotoxicity nor the enhancement of TNF cytotoxicity by topoisomerase inhibitors appears to require the TNF-mediated increases in topoisomerase activities.

  16. Adolescent Physical Activity: Moderation of Individual Factors by Neighborhood Environment.

    Science.gov (United States)

    D'Angelo, Heather; Fowler, Stephanie L; Nebeling, Linda C; Oh, April Y

    2017-06-01

    Less than a third of U.S. adolescents meet federal physical activity (PA) guidelines. Understanding correlates of PA at multiple levels of the Social Ecological Model could improve PA interventions among youth. This study examines (1) associations between factors across the Social Ecological Model including psychosocial factors, perceived neighborhood physical and social environment characteristics, and adolescent moderate to vigorous PA (MVPA) and (2) whether perceived neighborhood characteristics moderate associations between psychosocial factors and MVPA. A national sample of adolescents (aged 12-17 years) in the 2014 Family Life, Activity, Sun, Health, and Eating Study was used to examine associations between psychosocial characteristics, perceived neighborhood social and physical characteristics, and self-reported weekly minutes of MVPA. Analyses were conducted in 2015. Interaction terms between psychosocial and neighborhood variables were added to multiple linear regression models to examine moderation hypotheses. Significant two-way interactions revealed that neighborhoods with features perceived as supportive of PA strengthened several psychosocial-MVPA associations. The positive associations between MVPA and friend norms, friend support, and attitudes were strengthened for adolescents living in neighborhoods with high versus low PA resource availability (all p<0.05). Furthermore, the association between controlled and autonomous motivation and MVPA was strengthened under conditions of shops/stores near (versus distant from) adolescents' homes (p<0.05). The association between some psychosocial factors and adolescent MVPA may be environment dependent. Neighborhood physical and social environments supportive of PA are important to consider when developing targeted PA interventions and may strengthen the association between psychosocial-level factors and adolescent MVPA. Copyright © 2017 American Journal of Preventive Medicine. All rights reserved.

  17. Factors Associated With Ambulatory Activity in De Novo Parkinson Disease.

    Science.gov (United States)

    Christiansen, Cory; Moore, Charity; Schenkman, Margaret; Kluger, Benzi; Kohrt, Wendy; Delitto, Anthony; Berman, Brian; Hall, Deborah; Josbeno, Deborah; Poon, Cynthia; Robichaud, Julie; Wellington, Toby; Jain, Samay; Comella, Cynthia; Corcos, Daniel; Melanson, Ed

    2017-04-01

    Objective ambulatory activity during daily living has not been characterized for people with Parkinson disease prior to initiation of dopaminergic medication. Our goal was to characterize ambulatory activity based on average daily step count and examine determinants of step count in nonexercising people with de novo Parkinson disease. We analyzed baseline data from a randomized controlled trial, which excluded people performing regular endurance exercise. Of 128 eligible participants (mean ± SD = 64.3 ± 8.6 years), 113 had complete accelerometer data, which were used to determine daily step count. Multiple linear regression was used to identify factors associated with average daily step count over 10 days. Candidate explanatory variable categories were (1) demographics/anthropometrics, (2) Parkinson disease characteristics, (3) motor symptom severity, (4) nonmotor and behavioral characteristics, (5) comorbidities, and (6) cardiorespiratory fitness. Average daily step count was 5362 ± 2890 steps per day. Five factors explained 24% of daily step count variability, with higher step count associated with higher cardiorespiratory fitness (10%), no fear/worry of falling (5%), lower motor severity examination score (4%), more recent time since Parkinson disease diagnosis (3%), and the presence of a cardiovascular condition (2%). Daily step count in nonexercising people recruited for this intervention trial with de novo Parkinson disease approached sedentary lifestyle levels. Further study is warranted for elucidating factors explaining ambulatory activity, particularly cardiorespiratory fitness, and fear/worry of falling. Clinicians should consider the costs and benefits of exercise and activity behavior interventions immediately after diagnosis of Parkinson disease to attenuate the health consequences of low daily step count.Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A170).

  18. Time-activity relationships to VOC personal exposure factors

    Science.gov (United States)

    Edwards, Rufus D.; Schweizer, Christian; Llacqua, Vito; Lai, Hak Kan; Jantunen, Matti; Bayer-Oglesby, Lucy; Künzli, Nino

    Social and demographic factors have been found to play a significant role in differences between time-activity patterns of population subgroups. Since time-activity patterns largely influence personal exposure to compounds as individuals move across microenvironments, exposure subgroups within the population may be defined by factors that influence daily activity patterns. Socio-demographic and environmental factors that define time-activity subgroups also define quantifiable differences in VOC personal exposures to different sources and individual compounds in the Expolis study. Significant differences in exposures to traffic-related compounds ethylbenzene, m- and p-xylene and o-xylene were observed in relation to gender, number of children and living alone. Categorization of exposures further indicated time exposed to traffic at work and time in a car as important determinants. Increased exposures to decane, nonane and undecane were observed for males, housewives and self-employed. Categorization of exposures indicated exposure subgroups related to workshop use and living downtown. Higher exposures to 3-carene and α-pinene commonly found in household cleaning products and fragrances were associated with more children, while exposures to traffic compounds ethylbenzene, m- and p-xylene and o-xylene were reduced with more children. Considerable unexplained variation remained in categorization of exposures associated with home product use and fragrances, due to individual behavior and product choice. More targeted data collection methods in VOC exposure studies for these sources should be used. Living alone was associated with decreased exposures to 2-methyl-1-propanol and 1-butanol, and traffic-related compounds. Identification of these subgroups may help to reduce the large amount of unexplained variation in VOC exposure studies. Further they may help in assessing impacts of urban planning that result in changes in behavior of individuals, resulting in shifts in

  19. Contribution of coagulation factor VII R353Q polymorphism to the ...

    African Journals Online (AJOL)

    Hanan Azzam

    2016-12-05

    Dec 5, 2016 ... a b s t r a c t. Background: Elevated factor VII (FVII) level is a risk factor for thromboembolic disorders. It was reported that the FVII R353Q polymorphism is associated with variation in plasma FVII levels, where Q allele car- ..... and von Willebrand factor: the CHARGE (Cohorts for Heart and Aging Research.

  20. Absence of in vitro Procoagulant Activity in Immunoglobulin Preparations due to Activated Coagulation Factors

    Science.gov (United States)

    Oviedo, Adriana E.; Bernardi, María E.; Guglielmone, Hugo A.; Vitali, María S.

    2015-01-01

    Summary Background Immunoglobulin (IG) products, including intravenous (IVIG) or subcutaneous (SCIG) immunoglobulins are considered safe and effective for medical therapy; however, a sudden and unexpected increase in thromboembolic events (TE) after administration of certain batches of IVIG products has been attributed to the presence of activated coagulation factors, mainly factor XIa. Our aims were to examine the presence of enduring procoagulant activity during the manufacturing process of IGs, with special focus on monitoring factor XIa, and to evaluate the presence of in vitro procoagulant activity attributed to coagulation factors in different lots of IVIG and SCIG. Methods Samples of different steps of IG purification, 19 lots of IVIG and 9 of SCIG were analyzed and compared with 1 commercial preparation of IVIG and 2 of SCIG, respectively. Factors II, VII, IX, XI and XIa and non-activated partial thromboplastin time (NAPTT) were assayed. Results The levels of factors II, VII, IX, X and XI were non-quantifiable once fraction II had been re-dissolved and in all analyzed lots of IVIG and SCIG. The level of factor XIa at that point was under the detection limits of the assay, and NAPTT yielded values greater than the control during the purification process. In SCIG, we detected higher concentrations of factor XIa in the commercial products, which reached values up to 5 times higher than the average amounts found in the 9 batches produced by UNC-Hemoderivados. Factor XIa in commercial IVIG reached levels slightly higher than those of the 19 batches produced by UNC-Hemoderivados. Conclusion IVIG and SCIG manufactured by UNC-Hemoderivados showed a lack of thrombogenic potential, as demonstrated not only by the laboratory data obtained in this study but also by the absence of any reports of TE registered by the post marketing pharmacovigilance department. PMID:26733772

  1. Differential activation of dendritic cells by nerve growth factor and brain-derived neurotrophic factor.

    Science.gov (United States)

    Noga, O; Peiser, M; Altenähr, M; Knieling, H; Wanner, R; Hanf, G; Grosse, R; Suttorp, N

    2007-11-01

    Neurotrophins are involved in inflammatory reactions influencing several cells in health and disease including allergy and asthma. Dendritic cells (DCs) play a major role in the induction of inflammatory processes with an increasing role in allergic diseases as well. The aim of this study was to investigate the influence of neurotrophins on DC function. Monocyte-derived dendritic cells were generated from allergic and non-allergic donors. Neurotrophin receptors were demonstrated by western blotting, flow cytometry and fluorescence microscopy. Activation of small GTPases was evaluated by pull-down assays. DCs were incubated with nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) and supernatants were collected for measurement of IL-4, IL-6, IL-10, IL-12p70, TNF-alpha and TGF-beta. Receptor proteins were detectable by western blot, fluorescence activated cell sorting analysis and fluorescence microscopy. Signalling after neurotrophin stimulation occurred in a ligand-specific pattern. NGF led to decreased RhoA and increased Rac activation, while BDNF affected RhoA and Rac activity in a reciprocal fashion. Cells of allergics released a significantly increased amount of IL-6, while for healthy subjects a significantly higher amount of IL-10 was found. These data indicate that DCs are activated by the neurotrophins NGF and BDNF by different pathways in a receptor-dependant manner. These cells then may initiate inflammatory responses based on allergic sensitization releasing preferred cytokines inducing tolerance or a T-helper type 2 response.

  2. Determinant factors of peak treadmill speed in physically active men.

    Science.gov (United States)

    Alves Pasqua, Leonardo; Damasceno, Mayara V; Bueno, Salomão; Zagatto, Alessandro M; DE Araújo, Gustavo G; Lima-Silva, Adriano E; Bertuzzi, Rômulo

    2016-11-30

    The aim of the present study was to determine whether physiological factors and maximal dynamic strength are able to determine the peak treadmill speed (PTS) in physically active individuals. One hundred and fifty physically active healthy males voluntarily visit the laboratory on three separate occasions and underwent the following activities: first visit: IPAQ (short version), anthropometric measurements, and a maximal incremental test performed for physiological variables (maximal oxygen uptake ( ) and respiratory compensation point (RCP); second visit: constant speed test for running economy (RE) measurement, and familiarization with the maximum dynamic strength (1RM) test in the leg press exercise; third visit: 1RM test. The stepwise multiple regression model selected four independent variables to predict PTS (RCP, , RE, and 1RM). RCP explained 59% (p < 0.001) of variance in PTS, whereas , RE and 1RM accounted for additional 8% (p < 0.001), 4% (p < 0.001), and 1.4% (p = 0.038), respectively. In conclusion, the results of the present study demonstrate that PTS, an important predictor of endurance performance, is determined by both physiological (i.e., RCP, and RE) and muscular (1RM) parameters in healthy active individuals. These results demonstrate that, during a physical evaluation, PTS is able to represent physiological and muscular parameters of physically active individuals. This has the advantage during aerobic fitness evaluations of not requiring expensive equipment and specialized software.

  3. Prevention of leukocyte migration inhibitory factor activity by glucagon.

    Science.gov (United States)

    Pereţianu, D; Deleanu, A; Lotreanu, V; Mogoş, A; Beşliu, C; Tănase, D

    1985-01-01

    Leukocyte migration inhibitory factor (LMIF) activity was tested before and after glucagon administration both in vivo and in vitro. In vivo glucagon 1 mg i.v. vs saline administration inhibited LMIF production by T lymphocytes in 85.21% patients (p less than 0.01). In vitro glucagon in physiologic (125 pg/ml) and pharmacologic (50 ng/ml) doses increased the migration area vs PPD 250 microL (migration index 0.5127 vs 0.3210; p less than 0.05). These results show a significant inhibitory effect of glucagon upon LMIF activity. We suggest that glucagon acts by enhancement of the intralymphocytic cAMP/cGMP ratio (cyclic adenosine monophosphate/cyclic guanosine monophosphate).

  4. Contextual factors influencing leisure physical activity of urbanized indigenous adolescents.

    Science.gov (United States)

    Lo, Feng-En; Tsai, Feng-Chou; Lee, Ming-Been; Tsai, Liang-Ting; Lyu, Shu-Yu; Yang, Chih-Chien

    2015-11-01

    Indigenous populations suffer from disparities in socioeconomic resources and health status. One approach to addressing these disparities is by targeting modifiable risk factors such as leisure physical activity (LPA). This study investigated and compared factors related to LPA among urbanized indigenous and nonindigenous adolescent students. This cross-sectional survey comprised fifth to ninth grade indigenous and nonindigenous students (n = 733). The nonindigenous students were matched with indigenous students on sex and academic achievement and used as a reference group. Data were collected through telephone interviews using structured questionnaires. Major items included: demographic characteristics; average time spent watching television per bout; participation in LPA; and stress and depression experiences. With the exception of the duration of television watching per bout, Chi-square and independent t tests demonstrated that there were no significant differences between indigenous and nonindigenous adolescents in the selected LPA-related factors. Multiple logistic regression analysis including terms investigating interaction between ethnicity and the contextual factors included in this study indicated that the following factors were correlated with LPA participation: age [odds ratio (OR) = 0.82, 95% confidence interval (CI) = 0.71-0.94], male sex (OR = 1.77, 95%CI = 1.19-2.61), total hours spent watching television in the past 2 weeks (OR = 0.79, 95%CI = 0.63-0.99), life satisfaction (OR = 2.25, 95%CI = 1.04-4.90), and exercise enjoyment (OR = 3.40, 95%CI = 1.71-6.74). However, neither indigenous status (OR = 1.03, 95%CI = 0.19-5.79) nor any of the interaction terms reached the significant level. No significant ethnic differences were found in LPA participation. LPA was significantly correlated with age, male sex, total time spent watching television, life satisfaction, and enjoyment of exercise. Copyright © 2014. Published by Elsevier B.V.

  5. Lipopolysaccharide and platelet-activating factor stimulate expression of platelet-activating factor acetylhydrolase via distinct signaling pathways

    Science.gov (United States)

    Abdel-al, Mohammed; Ditmyer, Marcia; Patel, Nipa

    2011-01-01

    Objectives This study was designed to investigate and characterize the ability of platelet-activating factor (PAF) to induce the expression of platelet-activating factor acetylhydrolase (PAF-AH). Methods Ribonuclease protection assays and quantitative real-time PCR were used to investigate the ability of lipopolysaccharide (LPS) and PAF to regulate PAF-AH mRNA expression in human monocyte–macrophage 6 (MM6) cells. Pharmacological inhibitors of mitogen activated protein kinases (MAPK) and PAF receptor antagonists were used to investigate the mechanism of regulation of PAF-AH. Results PAF-AH mRNA levels were increased upon exposure to LPS or PAF in a dose-dependent manner. LPS elicited a more potent and rapid increase in PAF-AH expression than the PAF-stimulated response. However, when administered concomitantly, PAF augmented the LPS-stimulated response. LPS-stimulated PAF-AH expression was susceptible to partial inhibition by a p38 MAPK inhibitor and PAF receptor antagonists. PAF-induced up-regulation of PAF-AH levels was solely mediated via the PAF receptor and was p38 MAPK-independent. Conclusion The proinflammatory mediators, LPS and PAF, increased levels of PAF-AH mRNA via distinct signaling pathways. PMID:21432021

  6. Complement factor C4 activation in patients with hereditary angioedema

    DEFF Research Database (Denmark)

    Åbom, Anne; Bygum, Anette; Koch, Claus

    2017-01-01

    Objectives: Low complement factor C4 is usually considered a valuable screening tool for patients with the potentially life-threatening hereditary angioedema with C1-inhibitor (C1-INH) deficiency (C1-INH-HAE). However, there are patients with C1-INH-HAE presenting with normal C4 levels. This means......, that C1-INH-HAE may potentially be overlooked, if screening is performed only by measurement of C4. It has been suggested that measurement of C4 activation products is better suited to avoid false negative results. Our aim was to investigate whether total antigenic C4 or non-functional C4c is a better...... measure of the increased C4 activation in C1-INH-HAE patients. Design and methods: Two different monoclonal antibodies (mAb) to human C4 were produced: one had specificity for the β-chain of C4 and would thus react with both functional and non-functional C4, and the other was developed against the factor...

  7. Associations between Socio-Motivational Factors, Physical Education Activity Levels and Physical Activity Behavior among Youth

    Science.gov (United States)

    Ning, Weihong; Gao, Zan; Lodewyk, Ken

    2012-01-01

    This study examined the relationships between established socio-motivational factors and children's physical activity levels daily and during physical education classes. A total of 307 middle school students (149 boys, 158 girls) from a suburban public school in the Southern United States participated in this study. Participants completed…

  8. Physical activity and sedentary behaviors associated factors in adolescents

    Directory of Open Access Journals (Sweden)

    Daniel Giordani Vasques

    2009-01-01

    Full Text Available The purpose of this study was to analyze factors associated with physical activity and sedentary behaviors in adolescents. The sample consisted of 1675 students (784 boys and 891 girls ranging in age from 11-17 years from Caxias do Sul, RS. A questionnaire was applied to identify physical activity level (PAL, 3-day recall andweekly hours of sedentary behavior. Low PAL was defined as energy expenditure less than 37 kcal/kg per day, and elevated sedentary behavior (ESB was defined as more than 14 h/week watching TV, playing video games or using a computer. Chi-square testresults indicated a higher prevalence of low PAL among girls (66.8%>43.2%, p84.0%, p=0.001. Using a Poisson hierarchical regression model, low PAL was associated with up to 4 persons living at home (PR=1.21, 95%CI: 1.00-1.46 and low maternal PAL (PR=1.23, 95%CI:1.00-1.53 among boys, and with age 15-17 years (PR=1.30, 95%CI: 1.18-1.44, up to 4 persons living at home (PR=1.17, 95%CI: 1.04-1.31, having a TV in the bedroom (PR=1.13, 95%CI: 1.02-1.25 and passive transport to school (PR=1.10, 95%CI: 1.00-1.22 among girls. In girls, ESB was associated with high parental educational level(PR=1.08, 95%CI: 1.01-1.16 and having a TV in the bedroom (PR=1.15, 95%CI: 1.08-1.22. The results suggest an association between socioeconomic measures and risk behaviors (low PAL and ESB. Knowledge about the factors associated with low PAL and ESB facilitates the implantation of more effective interventions in order to promote a more active lifestyle.

  9. Environmental factors associated with physician's engagement in communication activities.

    Science.gov (United States)

    Mazurenko, Olena; Hearld, Larry R

    2015-01-01

    Communication between patients and providers is a crucial component of effective care coordination and is associated with a number of desired patient and provider outcomes. Despite these benefits, physician-patient and physician-physician communication occurs infrequently. The purpose of this study was to examine the relationship between a medical practice's external environment and physician engagement in communication activities. This was a cross-sectional examination of 4,299 U.S. physicians' self-reported engagement in communication activities. Communication was operationalized as physician's time spent on communication with patients and other providers during a typical work day. The explanatory variables were measures of environmental complexity, dynamism, and munificence. Data sources were the Health Tracking Physician Survey, the Area Resource File database, and the Dartmouth Atlas. Binary logistic regression was used to estimate the association between the environmental factors and physician engagement in communication activities. Several environmental factors, including per capita income (odds ratio range, 1.17-1.38), urban location (odds ratio range, 1.08-1.45), fluctuations in Health Maintenance Organization penetration (odds ratio range, 3.47-13.22), poverty (odds ratio range, 0.80-0.97) and population rates (odds ratio range, 1.01-1.02), and the presence of a malpractice crisis (odds ratio range, 0.22-0.43), were significantly associated with communication. Certain aspects of a physician's external environment are associated with different modes of communication with different recipients (patients and providers). This knowledge can be used by health care managers and policy makers who strive to improve communication between different stakeholders within the health care system (e.g., patient and providers).

  10. Active surveillance and risk factors for leptospirosis in Hawaii.

    Science.gov (United States)

    Sasaki, D M; Pang, L; Minette, H P; Wakida, C K; Fujimoto, W J; Manea, S J; Kunioka, R; Middleton, C R

    1993-01-01

    A clinic-hospital-based leptospirosis surveillance program was conducted to determine the morbidity and risk factors in nonepidemic settings. The study was conducted on two islands, Kauai and Hawaii (Big Island), in the state of Hawaii for one year during 1988 and 1989. An active, more comprehensive case detection system was used on the Big Island that enabled us to determine the incidence of clinical disease. Subjects from both islands were used to conduct a case-control study for risk factors. One hundred seventy-two subjects from the Big Island (who presented with any two of the following symptoms: fever, headache, myalgia, or nausea/vomiting) were enrolled in the study. Twenty cases were diagnosed by culture, serology, or fluorescent antibody tissue staining at autopsy. Six cases required hospitalization and two succumbed to fatal infections. We estimated that these cases represented an annual incidence rate of 128 per 100,000 person-years in our target population. For 33 cases, 77 controls were matched for island, age, sex, and time of onset of illness. Interviews were conducted retrospectively in a double-blinded fashion with cases and controls and evaluated approximately 30 risk factors. Factors that were associated most strongly with development of leptospirosis were household use of rainwater catchment systems (P = 0.003), presence of skin cuts during the incubation period (P = 0.008), contact with cattle or the urine of cattle (P = 0.05 and P = 0.03, respectively), and handling of animal tissues (P = 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Thalidomide for treatment of gastrointestinal bleedings due to angiodysplasia : a case report in acquired von Willebrand syndrome and review of the literature

    NARCIS (Netherlands)

    Engelen, E T; van Galen, K P M; Schutgens, R E G

    INTRODUCTION: Acquired von Willebrand syndrome is a rare bleeding disorder and treatment of the associated gastrointestinal (GI) bleeding due to angiodysplasia is challenging. AIM: The aim of this study was to present a new case on the successful use of thalidomide in a patient with acquired von

  12. Antifibrinolytic therapy for preventing oral bleeding in patients with haemophilia or Von Willebrand disease undergoing minor oral surgery or dental extractions

    NARCIS (Netherlands)

    van Galen, Karin Pm|info:eu-repo/dai/nl/325853886; Engelen, Eveline T; Mauser-Bunschoten, Evelien P|info:eu-repo/dai/nl/074719718; van Es, Robert Jj|info:eu-repo/dai/nl/216460646; Schutgens, Roger Eg|info:eu-repo/dai/nl/258752084

    2015-01-01

    BACKGROUND: Minor oral surgery or dental extractions (oral or dental procedures) are widely performed and can be complicated by hazardous oral bleeding, especially in people with an inherited bleeding disorder such as haemophilia or Von Willebrand disease. The amount and severity of singular

  13. Factors influencing nurses' decisions to activate medical emergency teams.

    Science.gov (United States)

    Pantazopoulos, Ioannis; Tsoni, Aikaterini; Kouskouni, Evangelia; Papadimitriou, Lila; Johnson, Elizabeth O; Xanthos, Theodoros

    2012-09-01

    To evaluate the relationship between nurse demographics and correct identification of clinical situations warranting specific nursing actions, including activation of the medical emergency team. If abnormal physiology is left untreated, the patient may develop cardiac arrest. Nurses in general wards are those who perceive any clinical deterioration in patients. A descriptive, quantitative design was selected. An anonymous survey with 13 multiple choice questions was distributed to 150 randomly selected nurses working in general medical and surgical wards of a large tertiary hospital in Athens, Greece. After explanation of the purposes of the study, 94 nurses (response ratio: 62%) agreed to respond to the questionnaire. Categories with the greatest nursing concern were patients with heart ratemedical emergency team activation in a significantly higher rate and also scored significantly higher in questions concerning clinical evaluation than nurses who had graduated from a two-year educational programme. Activation of the medical emergency team is influenced by factors such as level of education and cardiopulmonary resuscitation courses attendance. Graduating from a four-year educational programme helps nurses identify emergencies. However, irrespective of the educational programme they have followed, undertaking a basic life support or advanced life support provider course is critical as it helps them identify cardiac or respiratory emergencies. © 2012 Blackwell Publishing Ltd.

  14. Vascular endothelial cell function and cardiovascular risk factors in patients with chronic renal failure

    DEFF Research Database (Denmark)

    Haaber, A B; Eidemak, I; Jensen, T

    1995-01-01

    Cardiovascular risk factors and markers of endothelial cell function were studied in nondiabetic patients with mild to moderate chronic renal failure. The transcapillary escape rate of albumin and the plasma concentrations of von Willebrand factor, fibrinogen, and plasma lipids were measured in 29...

  15. Storage and regulated secretion of factor VIII in blood outgrowth endothelial cells

    NARCIS (Netherlands)

    van den Biggelaar, M.; Bouwens, E.A.M.; Kootstra, N.A.; Hebbel, R.P.; Voorberg, J.; Mertens, K.

    2009-01-01

    Background Gene therapy provides an attractive alternative for protein replacement therapy in hemophilia A patients. Recent studies have shown the potential benefit of directing factor (F)VIII gene delivery to cells that also express its natural carrier protein von Willebrand factor (VWF). In this

  16. Modeling of human factor Va inactivation by activated protein C

    Directory of Open Access Journals (Sweden)

    Bravo Maria

    2012-05-01

    Full Text Available Abstract Background Because understanding of the inventory, connectivity and dynamics of the components characterizing the process of coagulation is relatively mature, it has become an attractive target for physiochemical modeling. Such models can potentially improve the design of therapeutics. The prothrombinase complex (composed of the protease factor (FXa and its cofactor FVa plays a central role in this network as the main producer of thrombin, which catalyses both the activation of platelets and the conversion of fibrinogen to fibrin, the main substances of a clot. A key negative feedback loop that prevents clot propagation beyond the site of injury is the thrombin-dependent generation of activated protein C (APC, an enzyme that inactivates FVa, thus neutralizing the prothrombinase complex. APC inactivation of FVa is complex, involving the production of partially active intermediates and “protection” of FVa from APC by both FXa and prothrombin. An empirically validated mathematical model of this process would be useful in advancing the predictive capacity of comprehensive models of coagulation. Results A model of human APC inactivation of prothrombinase was constructed in a stepwise fashion by analyzing time courses of FVa inactivation in empirical reaction systems with increasing number of interacting components and generating corresponding model constructs of each reaction system. Reaction mechanisms, rate constants and equilibrium constants informing these model constructs were initially derived from various research groups reporting on APC inactivation of FVa in isolation, or in the presence of FXa or prothrombin. Model predictions were assessed against empirical data measuring the appearance and disappearance of multiple FVa degradation intermediates as well as prothrombinase activity changes, with plasma proteins derived from multiple preparations. Our work integrates previously published findings and through the cooperative

  17. hypoxia-inducible factors activate CD133 promoter through ETS family transcription factors.

    Directory of Open Access Journals (Sweden)

    Shunsuke Ohnishi

    Full Text Available CD133 is a cellular surface protein that has been reported to be a cancer stem cell marker, and thus it is considered to be a potential target for cancer treatment. However, the mechanism regulating CD133 expression is not yet understood. In this study, we analyzed the activity of five putative promoters (P1-P5 of CD133 in human embryonic kidney (HEK 293 cells and colon cancer cell line WiDr, and found that the activity of promoters, particularly of P5, is elevated by overexpression of hypoxia-inducible factors (HIF-1α and HIF-2α. Deletion and mutation analysis identified one of the two E-twenty six (ETS binding sites (EBSs in the P5 region as being essential for its promoter activity induced by HIF-1α and HIF-2α. In addition, a chromatin imunoprecipitation assay demonstrated that HIF-1α and HIF-2α bind to the proximal P5 promoter at the EBSs. The immunoprecipitation assay showed that HIF-1α physically interacts with Elk1; however, HIF-2α did not bind to Elk1 or ETS1. Furthermore, knockdown of both HIF-1α and HIF-2α resulted in a reduction of CD133 expression in WiDr. Taken together, our results revealed that HIF-1α and HIF-2α activate CD133 promoter through ETS proteins.

  18. Molecular and clinical profile of von Willebrand disease in Spain (PCM-EVW-ES): comprehensive genetic analysis by next-generation sequencing of 480 patients.

    Science.gov (United States)

    Borràs, Nina; Batlle, Javier; Pérez-Rodríguez, Almudena; López-Fernández, María Fernanda; Rodríguez-Trillo, Ángela; Lourés, Esther; Cid, Ana Rosa; Bonanad, Santiago; Cabrera, Noelia; Moret, Andrés; Parra, Rafael; Mingot-Castellano, María Eva; Balda, Ignacia; Altisent, Carme; Pérez-Montes, Rocío; Fisac, Rosa María; Iruín, Gemma; Herrero, Sonia; Soto, Inmaculada; de Rueda, Beatriz; Jiménez-Yuste, Víctor; Alonso, Nieves; Vilariño, Dolores; Arija, Olga; Campos, Rosa; Paloma, María José; Bermejo, Nuria; Berrueco, Rubén; Mateo, José; Arribalzaga, Karmele; Marco, Pascual; Palomo, Ángeles; Sarmiento, Lizheidy; Iñigo, Belén; Nieto, María Del Mar; Vidal, Rosa; Martínez, María Paz; Aguinaco, Reyes; César, Jesús María; Ferreiro, María; García-Frade, Javier; Rodríguez-Huerta, Ana María; Cuesta, Jorge; Rodríguez-González, Ramón; García-Candel, Faustino; Cornudella, Rosa; Aguilar, Carlos; Vidal, Francisco; Corrales, Irene

    2017-12-01

    Molecular diagnosis of patients with von Willebrand disease is pending in most populations due to the complexity and high cost of conventional molecular analyses. The need for molecular and clinical characterization of von Willebrand disease in Spain prompted the creation of a multicenter project (PCM-EVW-ES) that resulted in the largest prospective cohort study of patients with all types of von Willebrand disease. Molecular analysis of relevant regions of the VWF, including intronic and promoter regions, was achieved in the 556 individuals recruited via the development of a simple, innovative, relatively low-cost protocol based on microfluidic technology and next-generation sequencing. A total of 704 variants (237 different) were identified along VWF, 155 of which had not been previously recorded in the international mutation database. The potential pathogenic effect of these variants was assessed by in silico analysis. Furthermore, four short tandem repeats were analyzed in order to evaluate the ancestral origin of recurrent mutations. The outcome of genetic analysis allowed for the reclassification of 110 patients, identification of 37 asymptomatic carriers (important for genetic counseling) and re-inclusion of 43 patients previously excluded by phenotyping results. In total, 480 patients were definitively diagnosed. Candidate mutations were identified in all patients except 13 type 1 von Willebrand disease, yielding a high genotype-phenotype correlation. Our data reinforce the capital importance and usefulness of genetics in von Willebrand disease diagnostics. The progressive implementation of molecular study as the first-line test for routine diagnosis of this condition will lead to increasingly more personalized and effective care for this patient population. Copyright© 2017 Ferrata Storti Foundation.

  19. Comprehensive Behavioral Analysis of Activating Transcription Factor 5-Deficient Mice

    Directory of Open Access Journals (Sweden)

    Mariko Umemura

    2017-07-01

    Full Text Available Activating transcription factor 5 (ATF5 is a member of the CREB/ATF family of basic leucine zipper transcription factors. We previously reported that ATF5-deficient (ATF5-/- mice demonstrated abnormal olfactory bulb development due to impaired interneuron supply. Furthermore, ATF5-/- mice were less aggressive than ATF5+/+ mice. Although ATF5 is widely expressed in the brain, and involved in the regulation of proliferation and development of neurons, the physiological role of ATF5 in the higher brain remains unknown. Our objective was to investigate the physiological role of ATF5 in the higher brain. We performed a comprehensive behavioral analysis using ATF5-/- mice and wild type littermates. ATF5-/- mice exhibited abnormal locomotor activity in the open field test. They also exhibited abnormal anxiety-like behavior in the light/dark transition test and open field test. Furthermore, ATF5-/- mice displayed reduced social interaction in the Crawley’s social interaction test and increased pain sensitivity in the hot plate test compared with wild type. Finally, behavioral flexibility was reduced in the T-maze test in ATF5-/- mice compared with wild type. In addition, we demonstrated that ATF5-/- mice display disturbances of monoamine neurotransmitter levels in several brain regions. These results indicate that ATF5 deficiency elicits abnormal behaviors and the disturbance of monoamine neurotransmitter levels in the brain. The behavioral abnormalities of ATF5-/- mice may be due to the disturbance of monoamine levels. Taken together, these findings suggest that ATF5-/- mice may be a unique animal model of some psychiatric disorders.

  20. Transcription elongation factor GreA has functional chaperone activity.

    Directory of Open Access Journals (Sweden)

    Kun Li

    Full Text Available BACKGROUND: Bacterial GreA is an indispensable factor in the RNA polymerase elongation complex. It plays multiple roles in transcriptional elongation, and may be implicated in resistance to various stresses. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we show that Escherichia coli GreA inhibits aggregation of several substrate proteins under heat shock condition. GreA can also effectively promote the refolding of denatured proteins. These facts reveal that GreA has chaperone activity. Distinct from many molecular chaperones, GreA does not form stable complexes with unfolded substrates. GreA overexpression confers the host cells with enhanced resistance to heat shock and oxidative stress. Moreover, GreA expression in the greA/greB double mutant could suppress the temperature-sensitive phenotype, and dramatically alleviate the in vivo protein aggregation. The results suggest that bacterial GreA may act as chaperone in vivo. CONCLUSIONS/SIGNIFICANCE: These results suggest that GreA, in addition to its function as a transcription factor, is involved in protection of cellular proteins against aggregation.

  1. Transcription factor PIF4 controls the thermosensory activation of flowering

    KAUST Repository

    Kumar, S. Vinod

    2012-03-21

    Plant growth and development are strongly affected by small differences in temperature. Current climate change has already altered global plant phenology and distribution, and projected increases in temperature pose a significant challenge to agriculture. Despite the important role of temperature on plant development, the underlying pathways are unknown. It has previously been shown that thermal acceleration of flowering is dependent on the florigen, FLOWERING LOCUS T (FT). How this occurs is, however, not understood, because the major pathway known to upregulate FT, the photoperiod pathway, is not required for thermal acceleration of flowering. Here we demonstrate a direct mechanism by which increasing temperature causes the bHLH transcription factor PHYTOCHROME INTERACTING FACTOR4 (PIF4) to activate FT. Our findings provide a new understanding of how plants control their timing of reproduction in response to temperature. Flowering time is an important trait in crops as well as affecting the life cycles of pollinator species. A molecular understanding of how temperature affects flowering will be important for mitigating the effects of climate change. © 2012 Macmillan Publishers Limited. All rights reserved.

  2. PSYCHOLOGICAL FACTORS OF LABOR ACTIVITY OF ELDERLY MAN

    Directory of Open Access Journals (Sweden)

    Lyusova O.V.

    2016-04-01

    Full Text Available In modern Russian society occurred deformation traditions of respect and maintain the credibility of the elderly, and the socio-economic situation has deteriorated. An important condition to characterize the elderly is related to labor activity. expressed doubts surrounding their professionalism and high-quality and modern education. In society there are negative stereotypes about the elderly: Edil accusations of conservatism, the inability to take risks, tolerance for young. Old age pensioners perceived themselves as age losses, shrinking circle of social contacts, there is social exclusion, significant interpersonal contacts become strained. The psychological diagnosis of labor socialization of older employees 40 people participated. Conducted an empirical study it possible to identify the factors of labor activity in old age: the age and state of health; desire to raise the level of material well-being, the need to work, enthusiasm labor process, achievement motivation, the need for communication with the team; desire for samooaktualizatsii, positive self-esteem, internal locus of control. Working pensioners have high situational anxiety, adequate to the achievement of the objectives, an adequate assessment of its internal and external quality, high life satisfaction, motivation tends to focus on the process and result, reflexivity, subjectivity, have no fear of being rejected, is well adapted to society. Workers older people have average values of introversion, neuroticism, psychoticism.

  3. Critical success factors for physical activity promotion through community partnerships.

    Science.gov (United States)

    Lucidarme, Steffie; Marlier, Mathieu; Cardon, Greet; De Bourdeaudhuij, Ilse; Willem, Annick

    2014-02-01

    To define key factors of effective evidence-based policy implementation for physical activity promotion by use of a partnership approach. Using Parent and Harvey's model for sport and physical activity community-based partnerships, we defined determinants of implementation based on 13 face-to-face interviews with network organisations and 39 telephone interviews with partner organisations. Furthermore, two quantitative data-sets (n = 991 and n = 965) were used to measure implementation. In total, nine variables were found to influence implementation. Personal contact was the most powerful variable since its presence contributed to success while its absence led to a negative outcome. Four contributed directly to success: political motive, absence of a metropolis, high commitment and more qualified staff. Four others resulted in a less successful implementation: absence of positive merger effects, exposure motive and governance, and dispersed leadership. Community networks are a promising instrument for the implementation of evidence-based policies. However, determinants of both formation and management of partnerships influence the implementation success. During partnership formation, special attention should be given to partnership motives while social skills are of utmost importance for the management.

  4. Bivariate Genomic Footprinting Detects Changes in Transcription Factor Activity

    Directory of Open Access Journals (Sweden)

    Songjoon Baek

    2017-05-01

    Full Text Available In response to activating signals, transcription factors (TFs bind DNA and regulate gene expression. TF binding can be measured by protection of the bound sequence from DNase digestion (i.e., footprint. Here, we report that 80% of TF binding motifs do not show a measurable footprint, partly because of a variable cleavage pattern within the motif sequence. To more faithfully portray the effect of TFs on chromatin, we developed an algorithm that captures two TF-dependent effects on chromatin accessibility: footprinting and motif-flanking accessibility. The algorithm, termed bivariate genomic footprinting (BaGFoot, efficiently detects TF activity. BaGFoot is robust to different accessibility assays (DNase-seq, ATAC-seq, all examined peak-calling programs, and a variety of cut bias correction approaches. BaGFoot reliably predicts TF binding and provides valuable information regarding the TFs affecting chromatin accessibility in various biological systems and following various biological events, including in cases where an absolute footprint cannot be determined.

  5. Bivariate Genomic Footprinting Detects Changes in Transcription Factor Activity.

    Science.gov (United States)

    Baek, Songjoon; Goldstein, Ido; Hager, Gordon L

    2017-05-23

    In response to activating signals, transcription factors (TFs) bind DNA and regulate gene expression. TF binding can be measured by protection of the bound sequence from DNase digestion (i.e., footprint). Here, we report that 80% of TF binding motifs do not show a measurable footprint, partly because of a variable cleavage pattern within the motif sequence. To more faithfully portray the effect of TFs on chromatin, we developed an algorithm that captures two TF-dependent effects on chromatin accessibility: footprinting and motif-flanking accessibility. The algorithm, termed bivariate genomic footprinting (BaGFoot), efficiently detects TF activity. BaGFoot is robust to different accessibility assays (DNase-seq, ATAC-seq), all examined peak-calling programs, and a variety of cut bias correction approaches. BaGFoot reliably predicts TF binding and provides valuable information regarding the TFs affecting chromatin accessibility in various biological systems and following various biological events, including in cases where an absolute footprint cannot be determined. Published by Elsevier Inc.

  6. Platelet factor 4 impairs the anticoagulant activity of activated protein C.

    LENUS (Irish Health Repository)

    Preston, Roger J S

    2009-02-27

    Platelet factor 4 (PF4) is an abundant platelet alpha-granule chemokine released following platelet activation. PF4 interacts with thrombomodulin and the gamma-carboxyglutamic acid (Gla) domain of protein C, thereby enhancing activated protein C (APC) generation by the thrombin-thrombomodulin complex. However, the protein C Gla domain not only mediates protein C activation in vivo, but also plays a critical role in modulating the diverse functional properties of APC once generated. In this study we demonstrate that PF4 significantly inhibits APC anti-coagulant activity. PF4 inhibited both protein S-dependent APC anticoagulant function in plasma and protein S-dependent factor Va (FVa) proteolysis 3- to 5-fold, demonstrating that PF4 impairs protein S cofactor enhancement of APC anticoagulant function. Using recombinant factor Va variants FVa-R506Q\\/R679Q and FVa-R306Q\\/R679Q, PF4 was shown to impair APC proteolysis of FVa at position Arg(306) by 3-fold both in the presence and absence of protein S. These data suggest that PF4 contributes to the poorly understood APC resistance phenotype associated with activated platelets. Finally, despite PF4 binding to the APC Gla domain, we show that APC in the presence of PF4 retains its ability to initiate PAR-1-mediated cytoprotective signaling. In summary, we propose that PF4 acts as a critical regulator of APC generation, but also differentially targets APC toward cytoprotective, rather than anticoagulant function at sites of vascular injury with concurrent platelet activation.

  7. Platelet factor 4 impairs the anticoagulant activity of activated protein C.

    LENUS (Irish Health Repository)

    Preston, Roger J S

    2012-02-01

    Platelet factor 4 (PF4) is an abundant platelet alpha-granule chemokine released following platelet activation. PF4 interacts with thrombomodulin and the gamma-carboxyglutamic acid (Gla) domain of protein C, thereby enhancing activated protein C (APC) generation by the thrombin-thrombomodulin complex. However, the protein C Gla domain not only mediates protein C activation in vivo, but also plays a critical role in modulating the diverse functional properties of APC once generated. In this study we demonstrate that PF4 significantly inhibits APC anti-coagulant activity. PF4 inhibited both protein S-dependent APC anticoagulant function in plasma and protein S-dependent factor Va (FVa) proteolysis 3- to 5-fold, demonstrating that PF4 impairs protein S cofactor enhancement of APC anticoagulant function. Using recombinant factor Va variants FVa-R506Q\\/R679Q and FVa-R306Q\\/R679Q, PF4 was shown to impair APC proteolysis of FVa at position Arg(306) by 3-fold both in the presence and absence of protein S. These data suggest that PF4 contributes to the poorly understood APC resistance phenotype associated with activated platelets. Finally, despite PF4 binding to the APC Gla domain, we show that APC in the presence of PF4 retains its ability to initiate PAR-1-mediated cytoprotective signaling. In summary, we propose that PF4 acts as a critical regulator of APC generation, but also differentially targets APC toward cytoprotective, rather than anticoagulant function at sites of vascular injury with concurrent platelet activation.

  8. Complement factor B activation in patients with preeclampsia.

    Science.gov (United States)

    Velickovic, Ivan; Dalloul, Mudar; Wong, Karen A; Bakare, Olufunke; Schweis, Franz; Garala, Maya; Alam, Amit; Medranda, Giorgio; Lekovic, Jovana; Shuaib, Waqas; Tedjasukmana, Andreas; Little, Perry; Hanono, Daniel; Wijetilaka, Ruvini; Weedon, Jeremy; Lin, Jun; Toledano, Roulhac d'Arby; Zhang, Ming

    2015-06-01

    Preeclampsia is a leading cause of maternal and fetal morbidity and mortality. Bb, the active fragment of complement factor B (fB), has been reported to be a predictor of preeclampsia. However, conflicting results have been found by some investigators. We hypothesized that the disagreement in findings may be due to the racial/ethnic differences among various study groups, and that fB activation is significant in women of an ethnic minority with preeclampsia. We investigated the maternal and fetal levels of Bb (the activated fB fragment) in pregnant women of an ethnic minority with or without preeclampsia. We enrolled 291 pregnant women (96% of an ethnic minority, including 78% African-American). Thirteen percent of these were diagnosed with preeclampsia. Maternal venous blood was collected from all participants together with fetal umbilical cord blood samples from 154 deliveries in the 291 women. The results were analyzed using the Mann-Whitney U test and multivariate analyses. Maternal Bb levels were significantly higher in the preeclamptic group than in the nonpreeclamptic group. Levels of Bb in fetal cord blood were similar in both groups. Subgroup analyses of African-American patients' results confirmed the study hypothesis that there would be a significant increase in Bb in the maternal blood of the preeclamptic group and no increase in Bb in the fetal cord blood of this group. These results suggest that a maternal immune response through complement fB might play a role in the development of preeclampsia, particularly in African-American patients. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. Exploring the plasmatic platelet-activating factor acetylhydrolase activity in patients with anti-phospholipid antibodies

    OpenAIRE

    Fabris, Martina; Cif?, Adriana; Pistis, Cinzia; Siega-Ducaton, Massimo; Fontana, Desr? Ethel; Giacomello, Roberta; Tonutti, Elio; Curcio, Francesco

    2017-01-01

    Purpose To explore the role of plasmatic platelet-activating factor acetylhydrolase (PAF-AH), a marker of cardiovascular risk, in patients with anti-phospholipid antibodies (aPL). Methods PAF-AH activity was assessed in a series of 167 unselected patients screened for aPL in a context of thrombotic events, risk of thrombosis or obstetric complications and in 77 blood donors. Results 116/167 patients showed positive results for at least one aPL among IgG/IgM anti-prothrombin/phosphatidylserine...

  10. Activation of nuclear factor-kappa B via endogenous tumor necrosis factor alpha regulates survival of axotomized adult sensory neurons

    NARCIS (Netherlands)

    Fernyhough, P; Smith, DR; Schapansky, J; Van Der Ploeg, R; Gardiner, NJ; Tweed, CW; Kontos, A; Freeman, L; Purves-Tyson, TD; Glazner, GW

    2005-01-01

    Embryonic dorsal root ganglion (DRG) neurons die after axonal damage in vivo, and cultured embryonic DRG neurons require exogenous neurotrophic factors that activate the neuroprotective transcription factor nuclear factor-kappaB(NF-kappaB) for survival. In contrast, adult DRG neurons survive

  11. Towards determination of the structure of the Saccharomyces cerevisiae a-factor: an acylated pentadecapeptide blocks a-factor activity.

    Science.gov (United States)

    Becker, J M; Marcus, S; Kundu, B; Shenbagamurthi, P; Naider, F

    1987-01-01

    Putative a-factor peptides YIIKGVFWADP, YIIKGVFWANP, YIIKGLFWADP, YIIKGLFWANP, YIIKGVFWDPA, and YIIKGVFWDPACVIA and several peptide derivatives were synthesized and were found to be inactive in growth arrest assays, yet they blocked the activity of biological a-factor. Antagonism was greatest with YIIKGVFWDPAC(palmitoyl)VIA. Thus, the structure of a-factor may be a lipopeptide resembling this palmitoylated pentadecapeptide. Images PMID:3323887

  12. Relationship between platelet activating factor acetylhydrolase activity and apolipoprotein B levels in patients with peanut allergy.

    Science.gov (United States)

    Perelman, Boris; Adil, Areej; Vadas, Peter

    2014-01-01

    Platelet-activating factor (PAF) is a highly potent phospholipid mediator responsible for the life-threatening manifestations of anaphylaxis. PAF acetylhydrolase (PAF-AH) inactivates PAF and protects against severe anaphylaxis whereas deficiency of PAF-AH predisposes to severe or fatal anaphylaxis. Determinants of PAF-AH activity have not been studied in patients with peanut allergy. To determine whether plasma PAF-AH activity in patients with peanut allergy is related to formation of circulating complexes with apolipoprotein B (apoB) the main surface protein on low density lipoprotein particles. Plasma PAF-AH activity and apoB concentrations were measured in 63 peanut allergic patients (35 boys, 28 girls, ages 2 - 19 years). ApoB concentration was measured immunoturbidimetrically using goat anti-human apoB. The correlation between PAF-AH activity and apoB concentration was determined. A positive correlation was found between PAF-AH activity and apoB concentration (r(2) = 0.59, P < 0.0001). In peanut allergic patients, PAF-AH activity strongly correlates with apoB concentration, suggesting the presence of circulating PAF-AH- lipoprotein complexes.

  13. Acquired von Willebrand Syndrome associated to secondary IgM MGUS emerging after Autologous Stem Cell Transplantation for AL Amyloidosis

    Directory of Open Access Journals (Sweden)

    Victor H Jimenez-Zepeda

    2017-05-01

    Full Text Available Acquired von Willebrand syndrome (AVWS is a rare hemorrhagic disorder that occurs in patients with no prior personal or family history of bleeding. Here, we describe a case of AVWS occurring after autologous stem cell transplantation (ASCT. Interestingly, AVWS developed after bortezomib-based induction and conditioning regimens. Recent evidence suggests that the proximity of the bortezomib therapy to the collection of stem cells with consequent depletion of regulatory T cells after the conditioning regimen could explain some of the unusual autoimmune complications reported in patients receiving bortezomib prior to ASCT. In addition, this patient developed a secondary MGUS post-ASCT, which may have also contributed to the AVWS. To the best of our knowledge, this is the first case of post-ASCT AVWS reported. Prospective data is needed to better elucidate the mechanisms by which these unusual complications occur in patients receiving bortezomib prior to ASCT.

  14. Factoring - financial instrument supporting the current activity of an enterprise

    Directory of Open Access Journals (Sweden)

    Dorota Czerwińska-Kayzer

    2009-01-01

    Full Text Available Small and medium enterprises have a difficult access to classic financial sources. Therefore the factoring could be a financial instrument supporting effective management of the liabilities. Factoring improves the financial situation of a company, first of all financial liquidity. Moreover, factoring improves structure of financial statement and creates a possibility of risk transfer of debtor insolvency on factor.

  15. Stimulation of Leishmania tropica protein kinase CK2 activities by platelet-activating factor (PAF).

    Science.gov (United States)

    Dutra, Patricia M L; Vieira, Danielle P; Meyer-Fernandes, Jose R; Silva-Neto, Mario A C; Lopes, Angela H

    2009-09-01

    Leishmania tropica is one of the causative agents of cutaneous leishmaniasis. Platelet-activating factor (PAF) is a phospholipid mediator in diverse biological and pathophysiological processes. Here we show that PAF promoted a three-fold increase on ecto-protein kinase and a three-fold increase on the secreted kinase activity of L. tropica live promastigotes. When casein was added to the reaction medium, along with PAF, there was a four-fold increase on the ecto-kinase activity. When live L. tropica promastigotes were pre-incubated for 30 min in the presence of PAF-plus casein, a six-fold increase on the secreted kinase activity was observed. Also, a protein released from L. tropica promastigotes reacted with polyclonal antibodies for the mammalian CK2 alpha catalytic subunit. Furthermore, in vitro mouse macrophage infection by L. tropica was doubled when promastigotes were pre-treated for 2 h with PAF. Similar results were obtained when the interaction was performed in the presence of purified CK2 or casein. TBB and DRB, CK2 inhibitors, reversed PAF enhancement of macrophage infection by L. tropica. WEB 2086, a competitive PAF antagonist, reversed all PAF effects here described. This study shows for the first time that PAF promotes the activation of two isoforms of CK2, secreted and membrane-bound, correlating these activities to infection of mouse macrophages.

  16. Platelet-activating factor (PAF)-antagonists of natural origin.

    Science.gov (United States)

    Singh, Preeti; Singh, Ishwari Narayan; Mondal, Sambhu Charan; Singh, Lubhan; Garg, Vipin Kumar

    2013-01-01

    Presently herbal medicines are being used by about 80% of the world population for primary health care as they stood the test of time for their safety, efficacy, cultural acceptability and lesser side effects. The discovery of platelet activating factor antagonists (PAF antagonists) during these decades are going on with different framework, but the researchers led their efficiency in studying in vitro test models. Since it is assumed that PAF play a central role in etiology of many diseases in humans such as asthma, neuronal damage, migraine, cardiac diseases, inflammatory, headache etc. Present days instinctively occurring PAF antagonist exists as a specific grade of therapeutic agents for the humans against these and different diseases either laid hold of immunological or non-immunological types. Ginkgolide, cedrol and many other natural PAF antagonists such as andrographolide, α-bulnesene, cinchonine, piperine, kadsurenone, different Piper species' natural products and marine origin plants extracts or even crude drugs having PAF antagonist properties are being used currently against different inflammatory pathologies. This review is an attempt to summarize the data on PAF and action of natural PAF antagonists on it, which were evaluated by in vivo and in vitro assays. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Transcriptional activation of Mina by Sp1/3 factors.

    Science.gov (United States)

    Lian, Shangli; Potula, Hari Hara S K; Pillai, Meenu R; Van Stry, Melanie; Koyanagi, Madoka; Chung, Linda; Watanabe, Makiko; Bix, Mark

    2013-01-01

    Mina is an epigenetic gene regulatory protein known to function in multiple physiological and pathological contexts, including pulmonary inflammation, cell proliferation, cancer and immunity. We showed previously that the level of Mina gene expression is subject to natural genetic variation linked to 21 SNPs occurring in the Mina 5' region. In order to explore the mechanisms regulating Mina gene expression, we set out to molecularly characterize the Mina promoter in the region encompassing these SNPs. We used three kinds of assays--reporter, gel shift and chromatin immunoprecipitation--to analyze a 2 kb genomic fragment spanning the upstream and intron 1 regions flanking exon 1. Here we discovered a pair of Mina promoters (P1 and P2) and a P1-specific enhancer element (E1). Pharmacologic inhibition and siRNA knockdown experiments suggested that Sp1/3 transcription factors trigger Mina expression through additive activity targeted to a cluster of four Sp1/3 binding sites forming the P1 promoter. These results set the stage for comprehensive analysis of Mina gene regulation from the context of tissue specificity, the impact of inherited genetic variation and the nature of upstream signaling pathways.

  18. An activator of blood coagulation factor X from the venom of Bungarus fasciatus.

    Science.gov (United States)

    Zhang, Y; Xiong, Y L; Bon, C

    1995-10-01

    A specific activator of blood coagulation factor X was purified from the venom of Bungarus fasciatus by gel filtration and by ion-exchange chromatography on a Mono-Q column (FPLC). It consisted of a single polypeptide chain, with a mol. wt of 70,000 in reducing and non-reducing conditions. The enzyme had an amidolytic activity towards the chromogenic substrates S-2266 and S-2302 but it did not hydrolyse S-2238, S2251 or S-2222, which are specific substrates for thrombin, plasmin and factor Xa, respectively. The enzyme activated factor X in vitro and the effect was Ca2+ dependent with a Hill coefficient of 7.9. As with physiological activators, the venom activator cleaves the heavy chain of factor X, producing the activated factor Xa alpha. The purified factor X activator from B. fasciatus venom did not activate prothrombin, nor did it cleave or clot purified fibrinogen. The amidolytic activity and the factor X activation activity of the factor X activator from B. fasciatus venom were readily inhibited by serine protease inhibitors such as diisopropyl fluorophosphate (DFP), phenylmethanesulfonyl fluoride (PMSF), benzamidine and by soybean trypsin inhibitor but not by EDTA. These observations suggest that the factor X activator from B. fasciatus venom is a serine protease. It therefore differs from those of activators obtained from Vipera russelli and Bothrops atrox venoms, which are metalloproteinases.

  19. Association of functional thrombin-activatable fibrinolysis inhibitor (TAFI) with conventional cardiovascular risk factors and its correlation with other hemostatic factors in a Spanish population.

    Science.gov (United States)

    Santamaría, Amparo; Borrell, Montserrat; Oliver, Arturo; Ortín, Rosa; Forner, Ruth; Coll, Inmaculada; Mateo, Jose; Souto, Juan Carlos; Fontcuberta, Jordi

    2004-08-01

    Our aim was to determine the associations of functional thrombin-activatable fibrinolysis inhibitor (TAFI) levels in plasma with conventional cardiovascular risk factors, sex and age, and possible correlations with other hemostatic factors in a Spanish population. We included 303 individuals from a Spanish population. Hemostatic factors such as von Willebrand Factor, VII ag, VIIIc, XIc, XIIc, APCR, protein S, protein C, antithrombin, fibrinogen, and t-PA antigen were assayed. The functional TAFI assay was based on the activation of plasma TAFI with thrombin-thrombomodulin, and the measure of TAFIa activity on the hippuryl-Arg substrate. There were no statistical differences in mean values of functional TAFI among the various female age groups or among the different male age groups, with or without cardiovascular risk factors. Only women younger than 30 years of age showed lower levels of functional TAFI compared to older women. No differences were found among men of different ages. Adjusted for sex and age, hemostatic factors did not show a correlation with functional TAFI levels in plasma. Women with hypercholesterolemia showed higher levels of TAFI; other conventional cardiovascular risk factors did not modify functional TAFI levels either in men or in women. We also found no correlation of functional TAFI levels related to any other hemostatic factors. Copyright 2004 Wiley-Liss, Inc.

  20. Decrease of plasma platelet-activating factor acetylhydrolase activity in lipopolysaccharide induced mongolian gerbil sepsis model.

    Directory of Open Access Journals (Sweden)

    Junwei Yang

    Full Text Available Platelet-activating factor (PAF plays an important role in the pathogenesis of sepsis, and the level of plasma PAF acetylhydrolase (pPAF-AH, which inactivates PAF, decreases in sepsis patients except for the sepsis caused by severe leptospirosis. Usually, increase of pPAF-AH activity was observed in lipopolysaccharide (LPS-induced Syrian hamster and rat sepsis models, while contradictory effects were reported for mouse model in different studies. Here, we demonstrated the in vivo effects of LPS upon the change of pPAF-AH activity in C57BL/6 mice and Mongolian gerbils. After LPS-treatment, the clinical manifestations of Mongolian gerbil model were apparently similar to that of C57BL/6 mouse sepsis model. The pPAF-AH activity increased in C57BL/6 mice after LPS induction, but decreased in Mongolian gerbils, which was similar to that of the human sepsis. It thus suggests that among the LPS-induced rodent sepsis models, only Mongolian gerbil could be used for the study of pPAF-AH related to the pathogenesis of human sepsis. Proper application of this model might enable people to clarify the underline mechanism accounted for the contradictory results between the phase II and phase III clinical trials for the administration of recombinant human pPAF-AH in the sepsis therapy.

  1. Endothelial haemostatic factors are associated with progression of urinary albumin excretion in clinically healthy subjects

    DEFF Research Database (Denmark)

    Clausen, P; Feldt-Rasmussen, B; Jensen, G

    1999-01-01

    A slightly elevated urinary albumin excretion rate (UAER), above 5-10 microgram/min, is a predictor of atherosclerotic cardiovascular disease. Endothelial dysfunction is an important early feature of atherosclerosis. The plasma concentration of von Willebrand factor (vWF), a potential marker of e...

  2. Sports Activities as a Factor in Socialization of Deaf Students

    National Research Council Canada - National Science Library

    Radomir Arsic; Slavnic Svetlana; Kovacevic Jasmina

    2012-01-01

    .... In many studies that examined estimates of the level of physical activity among young people with disabilities, deaf or hearing impaired people have the highest level of physical activity in relation...

  3. Contact activation and factor VII after the use of an activated prothrombin complex concentrate (FEIBA) in hemophiliacs with inhibitors.

    Science.gov (United States)

    Mariani, G; Bouma, B N; Mazzucconi, M G; Avvisati, G; Di Nucci, G D; Corrao, D; Mandelli, F

    1983-08-01

    Administration of a brand of activated prothrombin complex concentrate (FEIBA) to hemophiliacs with high-titre inhibitor to factor VIII, induced a shortening of the prothrombin time and thrombotest clotting time. This effect stems partly from the presence in the concentrate of high amounts of activated factor VII (alpha-VII a) which indeed after the infusion, were detected in the plasma of Hemophiliacs. The attained levels of factor alpha-VII a were shown to be proportional to the dose of concentrate administered. This form of activated factor VII was not generated as a result of activation of the contact activation mechanism, since after the infusion of the concentrate no changes were detected in the components of this system. The infused factor VII was indeed present in an activated form and this was further substantiated by the infusion of the concentrate in factor VII deficient patients. These observations suggest that factor alpha-VII a is not generated in vivo and thus is of exogenous origin. The clinical effect may well be due to the presence of this form of activated factor VII; in this context the alternative pathway involving factors IX and X should be implicated.

  4. Response to desmopressin is influenced by the genotype and phenotype in type 1 von Willebrand disease (VWD): results from the European Study MCMDM-1VWD

    DEFF Research Database (Denmark)

    Castaman, G.; Lethagen, S.; Federici, A.B.

    2008-01-01

    We have prospectively evaluated the biologic response to desmopressin in 77 patients with type 1 von Willebrand disease (VWD) enrolled within the Molecular and Clinical Markers for the Diagnosis and Management of type 1 VWD project. Complete response to desmopressin was defined as an increase...... of subtle multimeric abnormalities did not hamper potential clinically useful responses, as in typical type 1 VWD Udgivelsesdato: 2008/4/1...

  5. Physical Activities and Lifestyle Factors Related to Adolescent Idiopathic Scoliosis.

    Science.gov (United States)

    Watanabe, Kota; Michikawa, Takehiro; Yonezawa, Ikuho; Takaso, Masashi; Minami, Shohei; Soshi, Shigeru; Tsuji, Takashi; Okada, Eijiro; Abe, Katsumi; Takahashi, Masamichi; Asakura, Keiko; Nishiwaki, Yuji; Matsumoto, Morio

    2017-02-15

    In addition to genetic factors, environmental and lifestyle factors are thought to play an important role in the onset of adolescent idiopathic scoliosis (AIS). This cross-sectional study was conducted to explore lifestyle factors related to AIS. This study included 2,759 Japanese female junior high school students who planned a secondary screening after an initial moiré topography screening indicated possible scoliosis. The students and their mothers, or guardians, were asked to fill out a questionnaire consisting of 38 questions about demographic factors, lifestyle-related factors, social factors, household environment, participation in sports, health status, and factors related to the mother's pregnancy and delivery. The questionnaire was completed by 2,747 students (a 99.6% response rate). After excluding students with heart disease, neurological disease, or a congenital vertebral anomaly, 2,600 students were eligible for assessment. After undergoing a secondary screening with standing radiographs of the spine, students were assigned to the normal (control) group if radiographs showed a curve of lifestyle-related factor was significantly associated with AIS. However, AIS was associated with classical ballet training (OR, 1.38; 95% confidence interval [CI], 1.09 to 1.75); the odds of AIS developing increased as the child's frequency of training, number of years of experience, and duration of training in ballet increased. The OR for AIS was 1.5 times higher for participants whose mothers had scoliosis. AIS was also associated with a low body mass index (BMI). These associations remained even after mutual adjustment was performed. No association was found between AIS and lifestyle-related factors. However, classical ballet training, a family history of scoliosis, and low BMI may be associated with AIS. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

  6. Effect of montelukast on platelet activating factor- and tachykinin induced mucus secretion in the rat

    Directory of Open Access Journals (Sweden)

    Groneberg David A

    2008-02-01

    Full Text Available Abstract Background Platelet activating factor and tachykinins (substance P, neurokinin A, neurokinin B are important mediators contributing to increased airway secretion in the context of different types of respiratory diseases including acute and chronic asthma. Leukotriene receptor antagonists are recommended as add-on therapy for this disease. The cys-leukotriene-1 receptor antagonist montelukast has been used in clinical asthma therapy during the last years. Besides its inhibitory action on bronchoconstriction, only little is known about its effects on airway secretions. Therefore, the aim of this study was to evaluate the effects of montelukast on platelet activating factor- and tachykinin induced tracheal secretory activity. Methods The effects of montelukast on platelet activating factor- and tachykinin induced tracheal secretory activity in the rat were assessed by quantification of secreted 35SO4 labelled mucus macromolecules using the modified Ussing chamber technique. Results Platelet activating factor potently stimulated airway secretion, which was completely inhibited by the platelet activating factor receptor antagonist WEB 2086 and montelukast. In contrast, montelukast had no effect on tachykinin induced tracheal secretory activity. Conclusion Cys-leukotriene-1 receptor antagonism by montelukast reverses the secretagogue properties of platelet activating factor to the same degree as the specific platelet activating factor antagonist WEB 2086 but has no influence on treacheal secretion elicited by tachykinins. These results suggest a role of montelukast in the signal transduction pathway of platelet activating factor induced secretory activity of the airways and may further explain the beneficial properties of cys-leukotriene-1 receptor antagonists.

  7. Absence of a desmopressin response after therapeutic expression of factor VIII in hemophilia A dogs with liver-directed neonatal gene therapy

    Science.gov (United States)

    Xu, Lingfei; Nichols, Timothy C.; Sarkar, Rita; McCorquodale, Stephanie; Bellinger, Dwight A.; Ponder, Katherine P.

    2005-01-01

    Hemophilia A (HA) is a bleeding disorder caused by factor VIII (FVIII) deficiency. FVIII replacement therapy can reduce bleeding but is expensive, inconvenient, and complicated by development of antibodies that inhibit FVIII activity in 30% of patients. Neonatal hepatic gene therapy could result in continuous secretion of FVIII into blood and might reduce immunological responses. Newborn HA mice and dogs that were injected i.v. with a retroviral vector (RV) expressing canine B domain-deleted FVIII (cFVIII) achieved plasma cFVIII activity that was 139 ± 22% and 116 ± 5% of values found in normal dogs, respectively, which was stable for 1.5 yr. Coagulation tests were normalized, no bleeding had occurred, and no inhibitors were detected. This is a demonstration of long-term fully therapeutic gene therapy for HA in a large animal model. Desmopressin (DDAVP; 1-deamino-[d-Arg8]vasopressin) is a drug that increases FVIII activity by inducing release of FVIII complexed with von Willebrand factor from endothelial cells. It has been unclear, however, if the FVIII is synthesized by endothelial cells or is taken up from blood. Because the plasma cFVIII in these RV-treated dogs derives primarily from transduced hepatocytes, they provided a unique opportunity to study the biology of the DDAVP response. Here we show that DDAVP did not increase plasma cFVIII levels in the RV-treated dogs, although von Willebrand factor was increased appropriately. This result suggests that the increase in FVIII in normal dogs after DDAVP is due to release of FVIII synthesized by endothelial cells. PMID:15837921

  8. Awareness and habit: important factors in physical activity in children

    NARCIS (Netherlands)

    Kremers, S.P.J.; Dijkman, M.A.M.; de Meij, J.S.B.; Jurg, M.E.; Brug, J.

    2008-01-01

    Purpose - The purpose of this paper is to gain insight into the extent to which Dutch children are aware of their own physical activity level, and to what extent children's physical activity is habitual. Special attention was paid to the potential moderating effect of "awareness" and "habit

  9. Platelet-activating factor (PAF) receptor binding activity of the roots of Enicosanthellum pulchrum.

    Science.gov (United States)

    Nordin, Noraziah; Jalil, Juriyati; Jantan, Ibrahim; Murad, Shahnaz

    2012-03-01

    Enicosanthellum pulchrum (King) Heusden (Annonaceae) is a coniferous tree that is confined to mountain forests. The chemical constituents of this species have been studied previously; however, its biological activity has never been investigated before and is reported here for the first time. The extracts, fractions and compounds from the roots of E. pulchrum were investigated for their inhibitory effects on platelet-activating factor (PAF) receptor binding to rabbit platelets using (3)H-PAF as a ligand. The PAF receptor binding inhibitory effect using rabbit platelets was determined in vitro by measuring the difference between total amount of bound (3)H-PAF in the presence and the absence of excess unlabelled PAF. The compounds were isolated by bioassay-guided fractionation and their structures were elucidated by spectroscopic techniques. Among the extracts tested, the ethyl acetate extract was the most active with 85.6% inhibition, while hexane and methanol extracts showed 40.2 and 42.5% inhibition, respectively. Fractionation of the ethyl acetate extract using vacuum liquid chromatography (VLC) yielded six fractions AEA(I--VI). Chromatography fraction AEA(VI) yielded a new compound, 1-(2',3',4'-trimethoxyphenyl)hexan-1-ol, while fraction AEA(III) afforded three compounds, namely liriodenine, cleistopholine and dehydroanonaine. 1-(2',3',4'-Trimethoxyphenyl)hexan-1-ol, cleistopholine and dehydroanonaine showed relatively strong inhibition with IC(50) values of 26.6, 50.2 and 45.4 µM, respectively. The results suggest that these compounds could be responsible for the PAF antagonistic activity of the ethyl acetate extract of this plant.

  10. Resveratrol enhances antitumor activity of TRAIL in prostate cancer xenografts through activation of FOXO transcription factor.

    Directory of Open Access Journals (Sweden)

    Suthakar Ganapathy

    Full Text Available BACKGROUND: Resveratrol (3, 4', 5 tri-hydroxystilbene, a naturally occurring polyphenol, exhibits anti-inflammatory, antioxidant, cardioprotective and antitumor activities. We have recently shown that resveratrol can enhance the apoptosis-inducing potential of TRAIL in prostate cancer cells through multiple mechanisms in vitro. Therefore, the present study was designed to validate whether resveratrol can enhance the apoptosis-inducing potential of TRAIL in a xenograft model of prostate cancer. METHODOLOGY/PRINCIPAL FINDINGS: Resveratrol and TRAIL alone inhibited growth of PC-3 xenografts in nude mice by inhibiting tumor cell proliferation (PCNA and Ki67 staining and inducing apoptosis (TUNEL staining. The combination of resveratrol and TRAIL was more effective in inhibiting tumor growth than single agent alone. In xenografted tumors, resveratrol upregulated the expressions of TRAIL-R1/DR4, TRAIL-R2/DR5, Bax and p27(/KIP1, and inhibited the expression of Bcl-2 and cyclin D1. Treatment of mice with resveratrol and TRAIL alone inhibited angiogenesis (as demonstrated by reduced number of blood vessels, and VEGF and VEGFR2 positive cells and markers of metastasis (MMP-2 and MMP-9. The combination of resveratrol with TRAIL further inhibited number of blood vessels in tumors, and circulating endothelial growth factor receptor 2-positive endothelial cells than single agent alone. Furthermore, resveratrol inhibited the cytoplasmic phosphorylation of FKHRL1 resulting in its enhanced activation as demonstrated by increased DNA binding activity. CONCLUSIONS/SIGNIFICANCE: These data suggest that resveratrol can enhance the apoptosis-inducing potential of TRAIL by activating FKHRL1 and its target genes. The ability of resveratrol to inhibit tumor growth, metastasis and angiogenesis, and enhance the therapeutic potential of TRAIL suggests that resveratrol alone or in combination with TRAIL can be used for the management of prostate cancer.

  11. [Activity of B and D factors of complement alternative pathway in children with atopic dermatitis].

    Science.gov (United States)

    Gora, N V; Kozlov, L V; Logunov, O V; Bashkina, O A; Rubalskiĭ, O V; Aleshkin, V A

    2014-01-01

    Development of enzyme immunoassay detection of B and D factors of complement alternative pathway functional activity for solving diagnostic and prognostic problems of patient therapy. Study activity of these factors in blood sera of children with atopic dermatitis before and after therapy for elucidation of the role of complement alternative pathway in pathogenesis of this disease. Children aged 6 months to 18 years with atopic dermatitis were examined for functional activity of B and D factors in blood sera before and after therapy by the developed methods. The developed enzyme immunoassay methods for determination of functional activity of B and D complement alternative pathway showed high sensitivity and reliability. In children with atopic dermatitis factor B and D activity was significantly lower than normal before treatment. After treatment these activity increased significantly (p atopic dermatitis in children and the possibility of use of factor B and D functional activity analysis for diagnostic and prognostic purposes.

  12. Demographic factors, workplace factors and active transportation use in the USA: a secondary analysis of 2009 NHTS data.

    Science.gov (United States)

    Quinn, Tyler D; Jakicic, John M; Fertman, Carl I; Barone Gibbs, Bethany

    2017-05-01

    While active transportation has health, economic and environmental benefits, participation within the USA is low. The purpose of this study is to examine relationships of demographic and workplace factors with health-enhancing active transportation and commuting. Participants in the 2009 National Household Travel Survey reported demographics, workplace factors (time/distance to work, flextime availability, option to work from home and work start time) and active transportation (for any purpose) or commuting (to and from work, workers only) as walking or biking (≥10 min bouts only). Multiple logistic regression examined cross-sectional relationships between demographics and workplace factors with active transportation and commuting. Among 152 573 participants, active transportation was reported by 1.11% by biking and 11.74% by walking. Among 111 808 working participants, active commuting was reported by 0.80% by biking and 2.76% by walking. Increased odds (ptransportation were associated with younger age, lower income, urban dwelling, and the highest and lowest education categories. Males had greater odds of commuting and transporting by bike but decreased odds of walk transporting. Inconsistent patterns were observed by race, but whites had greater odds of any biking (ptransportation differed across demographic and workplace factors. These relationships could inform infrastructure policy decisions and workplace wellness programming targeting increased active transportation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  13. Calpain Activator Dibucaine Induces Platelet Apoptosis

    Directory of Open Access Journals (Sweden)

    Jun Liu

    2011-03-01

    Full Text Available Calcium-dependent calpains are a family of cysteine proteases that have been demonstrated to play key roles in both platelet glycoprotein Ibα shedding and platelet activation and altered calpain activity is associated with thrombotic thrombocytopenic purpura. Calpain activators induce apoptosis in several types of nucleated cells. However, it is not clear whether calpain activators induce platelet apoptosis. Here we show that the calpain activator dibucaine induced several platelet apoptotic events including depolarization of the mitochondrial inner transmembrane potential, up-regulation of Bax and Bak, down-regulation of Bcl-2 and Bcl-XL, caspase-3 activation and phosphatidylserine exposure. Platelet apoptosis elicited by dibucaine was not affected by the broad spectrum metalloproteinase inhibitor GM6001. Furthermore, dibucaine did not induce platelet activation as detected by P-selectin expression and PAC-1 binding. However, platelet aggregation induced by ristocetin or α-thrombin, platelet adhesion and spreading on von Willebrand factor were significantly inhibited in platelets treated with dibucaine. Taken together, these data indicate that dibucaine induces platelet apoptosis and platelet dysfunction.

  14. Polyphosphate is a cofactor for the activation of factor XI by thrombin

    Science.gov (United States)

    Choi, Sharon H.; Smith, Stephanie A.

    2011-01-01

    Factor XI deficiency is associated with a bleeding diathesis, but factor XII deficiency is not, indicating that, in normal hemostasis, factor XI must be activated in vivo by a protease other than factor XIIa. Several groups have identified thrombin as the most likely activator of factor XI, although this reaction is slow in solution. Although certain nonphysiologic anionic polymers and surfaces have been shown to enhance factor XI activation by thrombin, the physiologic cofactor for this reaction is uncertain. Activated platelets secrete the highly anionic polymer polyphosphate, and our previous studies have shown that polyphosphate has potent procoagulant activity. We now report that polyphosphate potently accelerates factor XI activation by α-thrombin, β-thrombin, and factor XIa and that these reactions are supported by polyphosphate polymers of the size secreted by activated human platelets. We therefore propose that polyphosphate is a natural cofactor for factor XI activation in plasma that may help explain the role of factor XI in hemostasis and thrombosis. PMID:21976677

  15. Anestesia para septoplastia e turbinectomia em paciente portador de doença de von Willebrand: relato de caso Anestesia para septoplastia y turbinectomia en paciente portador de enfermedad de von Willebrand: relato de caso Anesthesia for septoplasty and turbinectomy in von Willebrand disease patient: case report

    Directory of Open Access Journals (Sweden)

    Múcio Paranhos de Abreu

    2003-06-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Embora a doença de von Willebrand seja o mais comum dos distúrbios hemorrágicos hereditários, as publicações nacionais, relacionando esta doença e a prática anestésica, são escassas. O objetivo deste relato é apresentar um caso de anestesia geral para septoplastia e turbinectomia em paciente portador de doença de von Willebrand - Tipo I, tratado profilaticamente com desmopressina (1-deamino-8-D-arginina vasopressina, DDAVP nos períodos pré e pós-operatório. RELATO DO CASO: Paciente com 19 anos, sexo feminino, 58 kg, portadora de hipotiroidismo, controlado com L-tiroxina (75 mg, e de doença de von Willebrand, que se manifestou há três anos, após extração dentária dos sisos, com sangramento persistente no período pós-operatório. Com o objetivo de se evitar novos episódios hemorrágicos nos períodos per e pós-operatório da cirurgia de septoplastia e turbinectomia a que foi submetida, a paciente foi tratada profilaticamente com desmopressina (0,3 µg.kg-1. A indução anestésica foi realizada com midazolam (2,5 mg, fentanil (150 µg, droperidol (2,5 mg, lidocaína (60 mg, atracúrio (30 mg e metoprolol (4 mg, seguida de intubação traqueal e ventilação sob pressão positiva intermitente. A manutenção da anestesia foi realizada com mistura de oxigênio e óxido nitroso a 50% e sevoflurano a 2%. Esta técnica proporcionou um bom controle da freqüência cardíaca e dos níveis pressóricos durante a cirurgia. A paciente permaneceu com tampão nasal por 24 horas e, quando este foi retirado, não houve sangramento. A paciente recebeu alta hospitalar no dia seguinte ao da cirurgia, sem intercorrências. Não houve episódio hemorrágico no período pós-operatório imediato ou tardio. CONCLUSÕES: O tratamento profilático com DDAVP associado à técnica anestésica utilizada nesse caso, mostrou-se eficaz no controle do sangramento per e pós-operatório.JUSTIFICATIVA Y OBJETIVOS: Aun cuando

  16. Factor VIII C1 domain spikes 2092-2093 and 2158-2159 comprise regions that modulate cofactor function and cellular uptake

    NARCIS (Netherlands)

    Bloem, Esther; van den Biggelaar, Maartje; Wroblewska, Aleksandra; Voorberg, Jan; Faber, Johan H.; Kjalke, Marianne; Stennicke, Henning R.; Mertens, Koen; Meijer, Alexander B.

    2013-01-01

    The C1 domain of factor VIII (FVIII) has been implicated in binding to multiple constituents, including phospholipids, von Willebrand factor, and low-density lipoprotein receptor-related protein (LRP). We have previously described a human monoclonal antibody called KM33 that blocks these

  17. Building gene expression signatures indicative of transcription factor activation to predict AOP modulation

    Science.gov (United States)

    Building gene expression signatures indicative of transcription factor activation to predict AOP modulation Adverse outcome pathways (AOPs) are a framework for predicting quantitative relationships between molecular initiatin...

  18. Behavior change stages related to physical activity in adolescents from Santa Catarina: prevalence and associated factors

    National Research Council Canada - National Science Library

    Silva, Jaqueline Aragoni da; Silva, Kelly Samara da; Lopes, Adair da Silva; Nahas, Markus Vinícius

    2016-01-01

    Abstract Objective: Verify the prevalence and sociodemographic and economic factors associated with behavior change stages for habitual physical activity practice in adolescents from Santa Catarina. Methods...

  19. Implementation of continuous infusion of blood coagulation factors at an academic medical center.

    Science.gov (United States)

    Poppe, Lindsey B; Eckel, Stephen F; Savage, Scott W

    2012-03-15

    A multidisciplinary initiative to promote more cost-effective use of blood factor derivatives and increase pharmacist involvement in associated order verification, dispensing, and monitoring activities is described. After an evaluation of a hospital's procedures for the use of blood factor derivatives identified inconsistencies and opportunities for cost savings, a revised medication-use process promoting continuous infusion of selected products (factors VIII, IX, and VIII/von Willebrand factor) was developed by pharmacy staff with input from physicians and nurse educators. The implementation of the enhanced medication-use procedures included (1) the publication of a compendium of key information on commonly used blood factors, including specific guidance on dosing and administration, (2) the use of Web-based educational modules targeting pharmacists and nurses, (3) greater involvement by pharmacists in blood factor order justification and verification, (4) routine pharmacist assessment of pertinent laboratory values and other determinants of optimal dosing, and (5) refined procedures for changing i.v. tubing. Surveys of pharmacists conducted before and after the practice changes indicated a significant increase in their knowledge of blood factor products and evidence-based best practices for the management of hemophilia. Through a multidisciplinary initiative involving pharmacists, physicians, and nurses, new procedures to promote continuous infusion of selected blood factor products were implemented. Results of a postimplementation survey indicated that educational tools were effective in increasing pharmacists' knowledge of blood factor derivatives and hemophilia management.

  20. Factors influencing nurse participation in continuing professional development activities : Survey results from the Netherlands

    NARCIS (Netherlands)

    Brekelmans, G.A.; Maassen, S.; Poell, R.F.; Weststrate, J.; Geurdes, E.

    2016-01-01

    Background Professionals are individually responsible for planning and carrying out continuing professional development (CPD) activities, ensuring their relevance to current practice and career development. The key factors that encourage nurses to undertake CPD activities are not yet clear. Several

  1. Psychological factors unrelated to activity level in patients with chronic musculoskeletal pain

    NARCIS (Netherlands)

    Helmus, M.; Preuper, H.R.S.; Hof, A.L.; Geertzen, J.H.B.; Reneman, M.F.

    Background: Enhancement of physical activities is an important goal in rehabilitation programmes for patients with chronic musculoskeletal pain (CMP). A relationship between activity level and psychological factors is suggested but studied scarcely. Aim: To explore the relationship between the

  2. Factors affecting teachers' participation in professional learning activities

    NARCIS (Netherlands)

    Kwakman, C.H.E.

    2003-01-01

    This paper describes two studies into teacher workplace learning. The first study aimed at developing a definition of teacher learning at the workplace and at exploring factors that may affect teacher learning at the workplace. Based on a conceptualization of teacher workplace learning as

  3. A MATHEMATICAL MODEL FOR ASSESSING THE FACTORING ACTIVITY

    Directory of Open Access Journals (Sweden)

    Madalina Radoi

    2013-11-01

    Full Text Available Originally–being over 4,000 years old–factoring was first used in the fertile territory of old Mesopotamia at a time when the famous Code of Hammurabi was drawn up. However, many years passed until the British colonists started to use it on a large scale at a time when the metropolis would pay them sums of money for the merchandise that colonists sent to the old continent until they collected the invoices.In Romania factoring started to play a major role in financial operations for it led to the increase of liquidities on the market.According to the Romanian legislation, factoring is a contract concluded between a party known as “the client”, which supplies merchandise or provides services, and a banking institution or specialized financial institution known as “the factor”, whereby the latter ensures the financing source, collects the receivables and protects credit risks, while the client assigns to the factor the receivables resulting from the sale of goods or the provision of services to third parties.

  4. Situational and Personality Factors: Interactive Effects on Attitude - Active Consistency

    Science.gov (United States)

    Albrecht, Stan L.; Warner, Lyle G.

    1975-01-01

    An examination of the combined effect of a situational factor, disclosure, and two personality variables, "need for approval" and "inner-other directedness" on attitude - action relationships with respect to marijuana related attitudes and behavior of college students. Subjects with different personality characteristics were found to respond…

  5. Impact of nonsynonymous mutations of factor X on the functions of factor X and anticoagulant activity of edoxaban.

    Science.gov (United States)

    Noguchi, Kengo; Morishima, Yoshiyuki; Takahashi, Shinichi; Ishihara, Hiroaki; Shibano, Toshiro; Murata, Mitsuru

    2015-03-01

    Edoxaban is an oral direct factor Xa (FXa) inhibitor and its efficacy as an oral anticoagulant is less subject to drug-food and drug-drug interaction than existing vitamin K antagonists. Although this profile of edoxaban suggests it is well suited for clinical use, it is not clear whether genetic variations of factor X influence the activity of edoxaban. Our aim was to investigate a possible impact of single-nucleotide polymorphisms (SNPs) in the factor X gene on the functions of factor X and the activity of edoxaban. Two nonsynonymous SNPs within mature factor X, Ala152Thr and Gly192Arg, were selected as possible candidates that might affect the functions of FXa and the activity of edoxaban. We measured catalytic activities of wild type and mutant FXas in a chromogenic assay using S-2222 and coagulation times including prothrombin time (PT) and activated partial thrombin time (aPTT) of plasma-containing recombinant FXs in the presence and absence of edoxaban. Michaelis-Menten kinetic parameters of FXas, Km and Vmax values, PT and aPTT were not influenced by either mutation indicating these mutations do not affect the FXa catalytic and coagulation activities. The Ki values of edoxaban for the FXas and the concentrations of edoxaban required to double PT and aPTT were not different between wild type and mutated FXas indicating that both mutations have little impact on the activity of edoxaban. In conclusion, these data suggest that edoxaban has little interpatient variability stemming from SNPs in the factor X gene.

  6. Exploring the plasmatic platelet-activating factor acetylhydrolase activity in patients with anti-phospholipid antibodies.

    Science.gov (United States)

    Fabris, Martina; Cifù, Adriana; Pistis, Cinzia; Siega-Ducaton, Massimo; Fontana, Desrè Ethel; Giacomello, Roberta; Tonutti, Elio; Curcio, Francesco

    2017-12-01

    To explore the role of plasmatic platelet-activating factor acetylhydrolase (PAF-AH), a marker of cardiovascular risk, in patients with anti-phospholipid antibodies (aPL). PAF-AH activity was assessed in a series of 167 unselected patients screened for aPL in a context of thrombotic events, risk of thrombosis or obstetric complications and in 77 blood donors. 116/167 patients showed positive results for at least one aPL among IgG/IgM anti-prothrombin/phosphatidylserine (aPS/PT), anti-cardiolipin (aCL), anti-beta2-glycoprotein I (aβ2GPI) or lupus anticoagulant (LAC), while 51/167 patients resulted aPL-negative. LAC+ patients disclosed higher PAF-AH than LAC-negative (22.1 ± 6.4 nmol/min/ml vs. 19.5 ± 4.1 nmol/min/ml; p = 0.0032), and aPL-negative patients (p = 0.03). Patients presenting positive IgG aβ2GPI disclosed higher PAF-AH than patients with only IgM aβ2GPI-positive antibodies (23.1 ± 7.2 nmol/min/ml vs. 20.1 ± 5.3 nmol/min/ml; p = 0.035), as well as than patients showing only isolated LAC, aCL or aPS/PT (16.9 ± 3.8 nmol/min/ml; p = 0.003). PAF-AH plasmatic activity is particularly up-regulated in LAC+ and in aβ2GPI IgG+ patients, possibly representing an alternative prognostic biomarker for the therapeutic management of APS patients.

  7. Differential procoagulant activity of microparticles derived from monocytes, granulocytes, platelets and endothelial cells: impact of active tissue factor.

    Science.gov (United States)

    Shustova, Olga N; Antonova, Olga A; Golubeva, Nina V; Khaspekova, Svetlana G; Yakushkin, Vladimir V; Aksuk, Svetlana A; Alchinova, Irina B; Karganov, Mikhail Y; Mazurov, Alexey V

    2017-07-01

    : Microparticles released by activated/apoptotic cells exhibit coagulation activity as they express phosphatidylserine and some of them - tissue factor. We compared procoagulant properties of microparticles from monocytes, granulocytes, platelets and endothelial cells and assessed the impact of tissue factor in observed differences. Microparticles were sedimented (20 000g, 30 min) from the supernatants of activated monocytes, monocytic THP-1 cells, granulocytes, platelets and endothelial cells. Coagulation activity of microparticles was examined using plasma recalcification assay. The size of microparticles was evaluated by dynamic light scattering. Tissue factor activity was measured by its ability to activate factor X. All microparticles significantly accelerated plasma coagulation with the shortest lag times for microparticles derived from monocytes, intermediate - for microparticles from THP-1 cells and endothelial cells, and the longest - for microparticles from granulocytes and platelets. Average diameters of microparticles ranged within 400-600 nm. The largest microparticles were produced by endothelial cells and granulocytes, smaller - by monocytes, and the smallest - by THP-1 cells and platelets. The highest tissue factor activity was detected in microparticles from monocytes, lower activity - in microparticles from endothelial cells and THP-1 cells, and no activity - in microparticles from platelets and granulocytes. Anti-tissue factor antibodies extended coagulation lag times for microparticles from monocytes, endothelial cells and THP-1 cells and equalized them with those for microparticles from platelets and granulocytes. Higher coagulation activity of microparticles from monocytes, THP-1 cells and endothelial cells in comparison with microparticles from platelets and granulocytes is determined mainly by the presence of active tissue factor.

  8. Structure activity relationship of phenolic diterpenes from Salvia officinalis as activators of the nuclear factor E2-related factor 2 pathway.

    Science.gov (United States)

    Fischedick, Justin T; Standiford, Miranda; Johnson, Delinda A; Johnson, Jeffrey A

    2013-05-01

    Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor known to activate cytoprotective genes which may be useful in the treatment of neurodegenerative disease. In order to better understand the structure activity relationship of phenolic diterpenes from Salvia officinalis L., we isolated carnosic acid, carnosol, epirosmanol, rosmanol, 12-methoxy-carnosic acid, sageone, and carnosaldehyde using polyamide column, centrifugal partition chromatography, and semi-preparative high performance liquid chromatography. Isolated compounds were screened in vitro for their ability to active the Nrf2 and general cellular toxicity using mouse primary cortical cultures. All compounds except 12-methoxy-carnosic acid were able to activate the antioxidant response element. Furthermore both carnosol and carnoasldehyde were able to induce Nrf2-dependent gene expression as well as protect mouse primary cortical neuronal cultures from H(2)O(2) induced cell death. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Centrally active differentiation factors in the nervous system.

    Science.gov (United States)

    Iacovitti, L

    1994-01-01

    The adult mammalian brain is a remarkably heterogeneous structure comprised of more than 50 biochemically distinct types of neurons. This phenotypic diversity is established during development, not only as the result of genetic but also epigenetic influences. It is believed that extracellular proteins, called differentiation factors, both instruct neurons in their original choice of neurotransmitter substance and, in certain situations, revise those biochemical decisions. The first candidate differentiation factor in the brain has only recently been proposed. This muscle-derived substance has the unique ability, in culture, to initiate expression of genes associated with catecholamine transmitter synthesis in non-catecholamine neurons of the brain. Because it also amplifies expression in cultured catecholamine-producing neurons in vitro and in vivo, it may prove to be an important therapeutic agent in diseases involving catecholamine shortages.

  10. Alterations in the coagulation system of active smokers from the Ludwigshafen Risk and Cardiovascular Health (LURIC) study.

    Science.gov (United States)

    Delgado, G; Siekmeier, R; Grammer, T B; Boehm, B O; März, W; Kleber, M E

    2015-01-01

    Smoking is an important and preventable risk factor of cardiovascular diseases with effects on blood coagulation. Our aim was to analyze the influence of smoking on coagulation parameters. Concentrations or activities of blood coagulation factors were compared in 777 active smokers and 1,178 lifetime non-smokers of the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. The association with mortality was examined using Cox regression. The findings show that AS had a tendency toward thrombosis. They displayed significantly higher values for fibrinogen, soluble fibrinogen, factor XIII, and tissue factor pathway inhibitor; whereas FVII, FVIII, FXII, von Willebrand factor (vWF), and thrombomodulin were decreased. The Cox regression analysis showed fibrinogen, FVIII, vWF, thrombomodulin, and tissue factor pathway inhibitor to be independent risk factors for mortality in active smokers with hazard ratios of 1.16 (95% CI: 1.02-1.31), 1.40 (1.22-1.59), 1.37 (1.22-1.56), 1.19 (1.07-1.31), and 1.22 (1.06-1.40) per increase of one standard deviation. We conclude that active smokers have an increased thrombogenic potential associated with significant changes in the coagulation system. Individual parameters of the coagulation system are independent predictors of mortality. Therefore, parameters of the coagulation system, apart from other risk factors for cardiovascular disease (e.g., lipids or life-style) should be determined for risk prediction in active smokers.

  11. THE FACTORS THAT INFLUENCE THE ACTIVITY OF ECONOMIC ENTITIES

    OpenAIRE

    SINTEA (ANGHEL) LUCICA

    2014-01-01

    In the current situation many experts and ordinary people are asking themselves: Where is the economy heading? How can we counteract the disruptive factors? Which strategies must be employed? How should the risks be properly assessed in order to diminish them to the lowest level? What measures should be taken to improve the situation? This requires a necessary economic and financial analysis, based on the data from the financial statements, the discovery and application o...

  12. Relation of physical activity to cardiovascular disease mortality and the influence of cardiometabolic risk factors.

    Science.gov (United States)

    Reddigan, Jacinta I; Ardern, Chris I; Riddell, Michael C; Kuk, Jennifer L

    2011-11-15

    Physical activity can improve several metabolic risk factors associated with cardiovascular disease (CVD) and is associated with a lower risk of CVD mortality. We sought to evaluate the extent to which metabolic risk factors mediate the association between physical activity and CVD mortality and whether physical activity provides protective effects against CVD mortality in healthy adults and those with metabolic risk factors. A sample of 10,261 adults from the Third National Health and Nutrition Examination Survey with public-access mortality data linkage (follow-up 13.4 ± 3.9 years) was used. Physical activity was assessed by questionnaire and classified into inactive, light, and moderate/vigorous activity categories. Metabolic risk factors (dyslipidemia, type 2 diabetes mellitus, obesity, hypertension, inflammation, and insulin resistance) were categorized using clinical thresholds. After adjusting for basic confounders, engaging in light or moderate/vigorous physical activity was associated with a lower risk of CVD mortality (p activity remained at lower risk of CVD mortality. In addition, physical activity provided protective effects for CVD mortality in healthy subjects and those with metabolic risk factors in isolation or in clusters. In conclusion, physical activity was associated with a lower risk of CVD mortality independent of traditional and inflammatory risk factors. Taken together these results suggest that physical activity may protect against CVD mortality regardless of the presence of metabolic risk factors. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Physical activity and cardiovascular risk factors in children

    DEFF Research Database (Denmark)

    Andersen, Lars Bo; Riddoch, Chris; Kriemler, Susi

    2011-01-01

    A number of recent systematic reviews have resulted in changes in international recommendations for children's participation in physical activity (PA) for health. The World Health Authority (WHO) has recently released new recommendations. The WHO still recommends 60 min of moderate to vigorous ph...

  14. Physical activity, mediating factors and risk of colon cancer

    DEFF Research Database (Denmark)

    Aleksandrova, Krasimira; Jenab, Mazda; Leitzmann, Michael

    2017-01-01

    Background: There is convincing evidence that high physical activity lowers the risk of colon cancer; however, the underlying biological mechanisms remain largely unknown. We aimed to determine the extent to which body fatness and biomarkers of various biologically plausible pathways account for ......%; 111%) of the association, respectively. Conclusions: Promoting physical activity, particularly outdoors, and maintaining metabolic health and adequate vitamin D levels could represent a promising strategy for colon cancer prevention.......Background: There is convincing evidence that high physical activity lowers the risk of colon cancer; however, the underlying biological mechanisms remain largely unknown. We aimed to determine the extent to which body fatness and biomarkers of various biologically plausible pathways account...... for the association between physical activity and colon cancer. Methods: We conducted a nested case-control study in a cohort of 519 978 men and women aged 25 to 70 years followed from 1992 to 2003. A total of 713 incident colon cancer cases were matched, using risk-set sampling, to 713 controls on age, sex, study...

  15. Risk factors for teenage pregnancy among sexually active black ...

    African Journals Online (AJOL)

    Motivation. Teenage pregnancy is an important health and social problem in South Africa. So far research on adolescent sexual activity has been almost exclusively descriptive; as a result there is considerable knowledge about practices of adolescents in general and outcomes of their pregnancies, but very limited ...

  16. Factors influencing activity of triazole fungicides towards Botrytis cinerea.

    NARCIS (Netherlands)

    Stehmann, C.; Waard, de M.A.

    1996-01-01

    The activity of triazole fungicides towards Botrytis cinerea was investigated in vitro (radial growth on fungicide-amended agar) and in vivo (foliar-sprayed tomato plants and dip-treated grapes). In both tests the benzimidazoles, benomyl and thiabendazole, and the dicarboximides, iprodione and

  17. Factors influencing beta-amylase activity in sorghum malt

    CSIR Research Space (South Africa)

    Taylor, JRN

    1993-09-01

    Full Text Available isozyme of pI approximately 4.4-4.5, unlike the many isozymes all of higher pI in barley. However, like barley, sorghum beta-amylase was more temperature-labile than its alpha-amylase. Beta-amylase activity in sorghum malt was increased by germination time...

  18. Factors Related to Exclusion of Students from School Activities.

    Science.gov (United States)

    Weber, Larry J.; And Others

    A survey of 130 high school principals in 3 southern states revealed alcohol abuse, insubordination, and other misbehavior as the major causes for excluding students from participation in school activities. The study also indicated that students have to meet disproportionately higher standards to participate in athletics, cheerleading, and student…

  19. WRKY transcription factors involved in activation of SA biosynthesis genes

    NARCIS (Netherlands)

    van Verk, Marcel C; Bol, John F; Linthorst, Huub J M

    2011-01-01

    Increased defense against a variety of pathogens in plants is achieved through activation of a mechanism known as systemic acquired resistance (SAR). The broad-spectrum resistance brought about by SAR is mediated through salicylic acid (SA). An important step in SA biosynthesis in Arabidopsis is the

  20. Functional mapping of factor VIII C2 domain.

    Science.gov (United States)

    Pellequer, Jean-Luc; Chen, Shu-wen W; Saboulard, Didier; Delcourt, Marc; Négrier, Claude; Plantier, Jean-Luc

    2011-07-01

    The factor VIII (FVIII) is a cofactor of the coagulation cascade. The FVIII C2 domain is a critical domain that participates in the interactions with the von Willebrand factor and the phospholipidic surfaces. To assess the importance of each residue of this domain in the maintenance of the structure and the function of FVIII, a number (n=139) of mutants were generated by substituting the original residues, from Ser2173 to Gly2325, by an alanine. Mutants were built within a complete B domain-deleted FVIII and expressed in COS-1 cells. Mutant antigen levels and procoagulant activities were measured. Two in silico analyses, a sliding average procedure and an analysis of the mutation energy cost were conducted in parallel on the FVIII structure. Both results were in agreement with the functional data, and illustrated the benefit of using such strategies prior to targeting specific residues in the aim of generating active recombinant molecules. The functional assays identify the residues that are important to maintaining the structure of the C2 domain, mainly those forming β-sheet, and those that can afford substitution, establishing a detailed functional relation with the available crystallographic data. This study provided a comprehensive functional mapping of the FVIII C2 domain and discussed the implication of specific residues in respect to the maintenance in the activity and structure stability, the efficiency in secretion, the binding to phospholipids and the formation of epitope.

  1. Relevant Factors of Innovative Activities of Small Business in Regions

    Directory of Open Access Journals (Sweden)

    Yelena Davidovna Vaysman

    2015-12-01

    Full Text Available The article discusses the system analysis aimed to identify the key reasons for the low innovation activity in the regions of the Russian Federation. The research is based on the hypothesis according to which the holism and systematic principles need to be applied for analyzing the reasons of the low innovative activity of small business in the regions,. To implement these principles, the authors have used the concept of «minimum number of descriptive levels of socio-economic system». In the research, the spiritual and cultural, cognitive, institutional, material and technological «layers» of the socio-economic system are investigated. The particular attention is paid to the cognitive and institutional segments. The methodological basis of the research is the methods of correlation and regression analysis, maps of positioning, integrated assessment, the author’s method of assessing the development of the knowledge-based economy and clustering. The quality of innovative small firms’ institutional environment is assessed using the resource approach. The authors have obtained the following results. The rate of demand growth for knowledge in the regions exceeded the growth rate of the regional offers of knowledge, including the innovative development of small businesses. A delayed reaction of the suppliers of innovative ideas to the corresponding demand is showed. The trend of differentiation increase of the Russian regions in terms of the knowledge-based economy’s development is revealed. A significant linear correlation of small firms’ innovative activities and the quality of institutional environment haven’t been discovered. It is shown that the regions are almost similar in the quality of basic socio-economic institutions, and more than 60 % of the regions have the intensity of small businesses’ innovation processes below the national average level. The obtained results allow to expand the scientific and methodological basis to

  2. CSF levels of growth factors and plasminogen activators in leptomeningeal metastases.

    NARCIS (Netherlands)

    Langerijt, B. van de; Gijtenbeek, J.M.M.; Reus, H.P.M. de; Sweep, C.G.J.; Geurts-Moespot, A.; Hendriks, J.C.M.; Kappelle, A.C.; Verbeek, M.M.

    2006-01-01

    OBJECTIVE: To investigate the diagnostic value of transforming growth factor beta(1) (TGFbeta(1)), vascular endothelial growth factor (VEGF), urokinase-type plasminogen activator (uPA), and tissue-type plasminogen activator (tPA) in CSF for leptomeningeal metastasis (LM). METHODS: The authors

  3. Moderate to vigorous physical activity and sedentary time and cardiometabolic risk factors in children and adolescents

    DEFF Research Database (Denmark)

    Ekelund, Ulf; Luan, Jian'an; Sherar, Lauren B

    2012-01-01

    Sparse data exist on the combined associations between physical activity and sedentary time with cardiometabolic risk factors in healthy children.......Sparse data exist on the combined associations between physical activity and sedentary time with cardiometabolic risk factors in healthy children....

  4. Predictive factors of unfavorable prostate cancer in patients who underwent prostatectomy but eligible for active surveillance

    Directory of Open Access Journals (Sweden)

    Seol Ho Choo

    2014-06-01

    Conclusions: A significant proportion of patients who were candidates for active surveillance had unfavorable prostate cancer. Age, PSA density, and two positive cores were independent significant predictive factors for unfavorable prostate cancer. These factors should be considered when performing active surveillance.

  5. THE TIME FACTOR IN MARITIME TRANSPORT AND PORT LOGISTICS ACTIVITIES

    Directory of Open Access Journals (Sweden)

    Florin NICOLAE

    2016-06-01

    Full Text Available Execution of the carriage contract requires compliance to all the conditions in it, by all those involved in the transport. Main obligations incumbent upon the vessel, and obviously, to other transporters, who must provide transportation according to deadlines and safety. Contract compliance is certifying transport participants about their seriousness and an appropriate market quotation. Therefore, present work pragmatically sets schematics reference time associated implementation of the carriage contract. Also, are demonstrated relationships established between maritime transport “players” and sequence of activities related to the operation of the vessel in port. The authors propose a set of concepts and terms whose utility is established to solve practical problems in this area of activity.

  6. Dynamic factors and electromyographic activity in a sprint start

    Directory of Open Access Journals (Sweden)

    M Čoh

    2009-07-01

    Full Text Available The aim of the study was to establish the major dynamic parameters as well as the EMG activation of muscles in a sprint start as the first derivative of sprint velocity. The subject of the analysis was block velocity, the production of force in the front and rear starting blocks, the block acceleration in the first two steps and the electromyographic activity (EMG of the following muscles: the erector spinae muscle, gluteus maximus muscle, rectus femoris muscle, vastus medialis muscle, vastus lateralis muscle, biceps femoris muscle and gastrocnemius–medialis muscle. One international-class female sprinter participated in the experiment. She performed eight starts in constant laboratory conditions. The 3-D kinematic analysis was made using a system of nine Smart-e 600 cameras operating at a frame rate of 60 Hz. Dynamic parameters were established by means of two separate force platforms to which the starting blocks were fixed. A 16-channel electromyograph was used to analyse electromyographic activity (EMG. It was established that the block velocity depended on the absolute force produced in the front and rear starting blocks and that it was 2.84±0.21 m.s-1. The maximal force on the rear and front blocks was 628±34 N and 1023±30 N, respectively. In view of the total impulse (210±11 Ns the force production/time ratio in the rear and front blocks was 34%:66%. The erector spinae muscle, vastus lateralis muscle and gastrocnemius–medialis muscle generate the efficiency of the start. The block acceleration in the first two steps primarily depends on the activation of the gluteus maximus muscle, rectus femoris muscle, biceps femoris muscle and gastrocnemius–medialis muscle. A sprint start is a complex motor stereotype requiring a high degree of integration of the processes of central movement regulation and an optimal level of biomotor abilities.

  7. Snoring, sympathetic activity and cardiovascular risk factors in a 70 year old population

    DEFF Research Database (Denmark)

    Jennum, P; Schultz-Larsen, K; Christensen, Niels Juel

    1993-01-01

    In order to describe the relation between snoring, cardiovascular risk factors, metabolic factors and sympathetitic activity, 804 70-year-old males and females were classified according to snoring habits and life-style factors (alcohol and tobacco consumption), blood pressure, body mass index (BMI...

  8. B16-BL6 melanoma cells release inhibitory factor(s) of active pump activity in isolated lymph vessels.

    Science.gov (United States)

    Nakaya, K; Mizuno, R; Ohhashi, T

    2001-12-01

    We investigated whether supernatant cultured with melanoma cell lines B16-BL6 and K1735 or the Lewis lung carcinoma cell line (LLC) can regulate lymphatic pump activity with bioassay preparations isolated from murine iliac lymph vessels. B16-BL6 and LLC supernatants caused significant dilation of lymph microvessels with cessation of pump activity. B16-BL6 supernatant produced dose-related cessation of lymphatic pump activity. There was no significant tachyphylaxis in the supernatant-mediated inhibitory response of lymphatic pump activity. Pretreatment with 3 x 10(-5) M N(omega)-nitro-L-arginine methyl ester (L-NAME) or 10(-7) M or 10(-6) M glibenclamide and 5 x 10(-4) M 5-hydroxydecanoic acid caused significant reduction of supernatant-mediated inhibitory responses. Simultaneous treatment with 10(-3) M L-arginine and 3 x 10(-5) M L-NAME significantly lessened L-NAME-induced inhibition of the supernatant-mediated response, suggesting that endogenous nitric oxide (NO) plays important roles in supernatant-mediated inhibitory responses. Chemical treatment dialyzed substances of heating or digestion with protease had no significant effect on supernatant-mediated response. These findings suggest that B16-BL6 cells may release nonpeptide substance(s) of release of endogenous NO and activation of mitochondrial ATP-sensitive K(+) channels.

  9. [Effects of soil factors on active component content of Chrysanthemum morifolium].

    Science.gov (United States)

    Wang, Yanru; Guo, Qiaosheng; Shao, Qingsong; Zhang, Zhiyuan

    2010-03-01

    To study the effects of soil factors on the active component content of Chrysanthemum morifolium and screen out the leading factors. The active component of water soluble extracts, flavonoids, phenolic compounds and mineral elements were determined and chemical properties and mineral elements of soil were analyzed for studying the effects on Ch. morifolium through correlation, stepwise regression, path and grey correlation analysis. Soil available P and K were the most important factors that affected the active component content of Ch. morifolium, followed by urease, phosphatase and invertase activities and organic matter. The mineral elements in Ch. morifolium and in soil correlated well, P and K were enriched in the plant mostly, followed by Cd, Ca, Zn, Cu. The main leading factors of mineral elements in soil were P and K, followed by Fe, Cu and Zn. Soil was one of the important factors which affected the active component content of Ch. morifolium.

  10. Platelet-Derived Short-Chain Polyphosphates Enhance the Inactivation of Tissue Factor Pathway Inhibitor by Activated Coagulation Factor XI.

    Directory of Open Access Journals (Sweden)

    Cristina Puy

    Full Text Available Factor (F XI supports both normal human hemostasis and pathological thrombosis. Activated FXI (FXIa promotes thrombin generation by enzymatic activation of FXI, FIX, FX, and FV, and inactivation of alpha tissue factor pathway inhibitor (TFPIα, in vitro. Some of these reactions are now known to be enhanced by short-chain polyphosphates (SCP derived from activated platelets. These SCPs act as a cofactor for the activation of FXI and FV by thrombin and FXIa, respectively. Since SCPs have been shown to inhibit the anticoagulant function of TFPIα, we herein investigated whether SCPs could serve as cofactors for the proteolytic inactivation of TFPIα by FXIa, further promoting the efficiency of the extrinsic pathway of coagulation to generate thrombin.Purified soluble SCP was prepared by size-fractionation of sodium polyphosphate. TFPIα proteolysis was analyzed by western blot. TFPIα activity was measured as inhibition of FX activation and activity in coagulation and chromogenic assays. SCPs significantly accelerated the rate of inactivation of TFPIα by FXIa in both purified systems and in recalcified plasma. Moreover, platelet-derived SCP accelerated the rate of inactivation of platelet-derived TFPIα by FXIa. TFPIα activity was not affected by SCP in recalcified FXI-depleted plasma.Our data suggest that SCP is a cofactor for TFPIα inactivation by FXIa, thus, expanding the range of hemostatic FXIa substrates that may be affected by the cofactor functions of platelet-derived SCP.

  11. Rupatadine, a new potent, orally active dual antagonist of histamine and platelet-activating factor (PAF).

    Science.gov (United States)

    Merlos, M; Giral, M; Balsa, D; Ferrando, R; Queralt, M; Puigdemont, A; García-Rafanell, J; Forn, J

    1997-01-01

    Rupatadine (UR-12592, 8-chloro-6, 11-dihydro-11-[1-[(5-methyl3-pyridinyl) methyl]-4-piperidinylidene]-5H-benzo[5,6]-cyclohepta[1,2b]pyridine ) is a novel compound that inhibits both platelet-activating factor (PAF) and histamine (H1) effects through its interaction with specific receptors (Ki(app) values against [3H]WEB-2086 binding to rabbit platelet membranes and [3H]-pyrilamine binding to guinea pig cerebellum membranes were 0.55 and 0.10 microM, respectively). Rupatadine competitively inhibited histamine-induced guinea pig ileum contraction (pA2 = 9.29 +/- 0.06) without affecting contraction induced by ACh, serotonin or leukotriene D4 (LTD4). It also competitively inhibited PAF-induced platelet aggregation in washed rabbit platelets (WRP) (pA2 = 6.68 +/- 0.08) and in human platelet-rich plasma (HPRP) (IC50 = 0.68 microM), while not affecting ADP- or arachidonic acid-induced platelet aggregation. Rupatadine blocked histamine- and PAF-induced effects in vivo, such as hypotension in rats (ID50 = 1.4 and 0.44 mg/kg i.v., respectively) and bronchoconstriction in guinea pigs (ID50 = 113 and 9.6 micrograms/kg i.v.). Moreover, it potently inhibited PAF-induced mortality in mice (ID50 = 0.31 and 3.0 mg/kg i.v. and p.o., respectively) and endotoxin-induced mortality in mice and rats (ID50 = 1.6 and 0.66 mg/kg i.v.). Rupatadine's duration of action was long, as assessed by the histamine- and PAF-induced increase in vascular permeability test in dogs (42 and 34% inhibition at 26 h after 1 mg/kg p.o.). Rupatadine at a dose of 100 mg/kg p.o. neither modified spontaneous motor activity nor prolonged barbiturate-sleeping time in mice, which indicates a lack of sedative effects. Overall, rupatadine combines histamine and PAF antagonist activities in vivo with high potency, the antihistamine properties being similar to or higher than those of loratadine, whereas rupatadine's PAF antagonist effects were near those of WEB-2066. Rupatadine is therefore a good candidate for further

  12. C4b-binding protein inhibits the factor V-dependent but not the factor V-independent cofactor activity of protein S in the activated protein C-mediated inactivation of factor VIIIa

    NARCIS (Netherlands)

    van de Poel, R. H.; Meijers, J. C.; Bouma, B. N.

    2001-01-01

    Activated protein C (APC) is an important inactivator of coagulation factors Va and VIIIa. In the inactivation of factors Va and VIIIa, protein S serves as a cofactor to APC. Protein S can bind to C4b-binding protein (C4BP), and thereby loses its cofactor activity to APC. By modulating free protein

  13. Platelet-activating factor, tumor necrosis factor, hypoxia and necrotizing enterocolitis.

    Science.gov (United States)

    Hsueh, W; Caplan, M S; Sun, X; Tan, X; MacKendrick, W; Gonzalez-Crussi, F

    1994-01-01

    The pathogenesis of necrotizing enterocolitis (NEC) is poorly understood. We have established several animal models of NEC by using a combination of various stimuli and stress, including endotoxin, PAF, TNF, and hypoxia. We discuss the mechanism of their actions and the possible roles of these factors in the pathogenesis of human NEC.

  14. [Risk factors in police activities: operational criticism in surveillance programs].

    Science.gov (United States)

    Ciprani, Fabrizio; Moroni, Maria; Conte, Giovanni

    2014-01-01

    The planning of specific health surveillance programs for police officers is extremely complex due to difficulty in predictability and variety of occupational hazards. Even in the case of conventional occupational risk factors clearly identified by current regulations, particular working conditions may require specific assessment to effectively identify and quantify the risk of occupational exposure. An extensive program of health surveillance, aimed at promoting overall health and effectiveness of the operators, would be really desirable, in order to help better address a number of risks that cannot be easily predicted. The progressive increase in the average age of the working population and the increasing prevalence of chronic degenerative diseases, may also suggest the need for health surveillance procedures designed to verify continued unqualified suitability to police service, providing for the identification of diversified suitability profiles in relation to age and state of health: accordingly, in regard to our field of interest, there is a close link between medico-legal eligibility and occupational medicine.

  15. THE FACTORS THAT INFLUENCE THE ACTIVITY OF ECONOMIC ENTITIES

    Directory of Open Access Journals (Sweden)

    SINTEA(ANGHEL LUCICA

    2014-02-01

    Full Text Available In the current situation many experts and ordinary people are asking themselves: Where is the economy heading? How can we counteract the disruptive factors? Which strategies must be employed? How should the risks be properly assessed in order to diminish them to the lowest level? What measures should be taken to improve the situation? This requires a necessary economic and financial analysis, based on the data from the financial statements, the discovery and application of risk assessment methods and the detection of procedures to mitigate this risk. It is also necessary to draw a comparison between the expected results of a rational and scientific research, and those obtained through empirical processes by means of marketing.

  16. WRKY Transcription Factors Involved in Activation of SA Biosynthesis Genes

    Directory of Open Access Journals (Sweden)

    Bol John F

    2011-05-01

    Full Text Available Abstract Background Increased defense against a variety of pathogens in plants is achieved through activation of a mechanism known as systemic acquired resistance (SAR. The broad-spectrum resistance brought about by SAR is mediated through salicylic acid (SA. An important step in SA biosynthesis in Arabidopsis is the conversion of chorismate to isochorismate through the action of isochorismate synthase, encoded by the ICS1 gene. Also AVRPPHB SUSCEPTIBLE 3 (PBS3 plays an important role in SA metabolism, as pbs3 mutants accumulate drastically reduced levels of SA-glucoside, a putative storage form of SA. Bioinformatics analysis previously performed by us identified WRKY28 and WRKY46 as possible regulators of ICS1 and PBS3. Results Expression studies with ICS1 promoter::β-glucuronidase (GUS genes in Arabidopsis thaliana protoplasts cotransfected with 35S::WRKY28 showed that over expression of WRKY28 resulted in a strong increase in GUS expression. Moreover, qRT-PCR analyses indicated that the endogenous ICS1 and PBS3 genes were highly expressed in protoplasts overexpressing WRKY28 or WRKY46, respectively. Electrophoretic mobility shift assays indentified potential WRKY28 binding sites in the ICS1 promoter, positioned -445 and -460 base pairs upstream of the transcription start site. Mutation of these sites in protoplast transactivation assays showed that these binding sites are functionally important for activation of the ICS1 promoter. Chromatin immunoprecipitation assays with haemagglutinin-epitope-tagged WRKY28 showed that the region of the ICS1 promoter containing the binding sites at -445 and -460 was highly enriched in the immunoprecipitated DNA. Conclusions The results obtained here confirm results from our multiple microarray co-expression analyses indicating that WRKY28 and WRKY46 are transcriptional activators of ICS1 and PBS3, respectively, and support this in silico screening as a powerful tool for identifying new components of stress

  17. Expression and Activation of STAT Transcription Factors in Breast Cancer

    Science.gov (United States)

    1998-05-08

    1993). In brea ~t cancer cells, .p-rolactin activates RAS via recruitment qf signaling proteins SHC, GRB2:apd 50S, in a fashion similar to that observed...BRCA-1 genes. In one study of families with evidence of linkage to BReA -l, the lifetime risk of breast cancer was 87% by age 70. The cumulative risk of...in Breast Cancer , 1996). Early pregnancy and oophorectomy lower the incidence of the disease, whereas late menopause and early menarche increase the

  18. The Drosophila Transcription Factors Tinman and Pannier Activate and Collaborate with Myocyte Enhancer Factor-2 to Promote Heart Cell Fate.

    Directory of Open Access Journals (Sweden)

    TyAnna L Lovato

    Full Text Available Expression of the MADS domain transcription factor Myocyte Enhancer Factor 2 (MEF2 is regulated by numerous and overlapping enhancers which tightly control its transcription in the mesoderm. To understand how Mef2 expression is controlled in the heart, we identified a late stage Mef2 cardiac enhancer that is active in all heart cells beginning at stage 14 of embryonic development. This enhancer is regulated by the NK-homeodomain transcription factor Tinman, and the GATA transcription factor Pannier through both direct and indirect interactions with the enhancer. Since Tinman, Pannier and MEF2 are evolutionarily conserved from Drosophila to vertebrates, and since their vertebrate homologs can convert mouse fibroblast cells to cardiomyocytes in different activator cocktails, we tested whether over-expression of these three factors in vivo could ectopically activate known cardiac marker genes. We found that mesodermal over-expression of Tinman and Pannier resulted in approximately 20% of embryos with ectopic Hand and Sulphonylurea receptor (Sur expression. By adding MEF2 alongside Tinman and Pannier, a dramatic expansion in the expression of Hand and Sur was observed in almost all embryos analyzed. Two additional cardiac markers were also expanded in their expression. Our results demonstrate the ability to initiate ectopic cardiac fate in vivo by the combination of only three members of the conserved Drosophila cardiac transcription network, and provide an opportunity for this genetic model system to be used to dissect the mechanisms of cardiac specification.

  19. Hypoperfusion in severely injured trauma patients is associated with reduced coagulation factor activity.

    Science.gov (United States)

    Jansen, Jan O; Scarpelini, Sandro; Pinto, Ruxandra; Tien, Homer C; Callum, Jeannie; Rizoli, Sandro B

    2011-11-01

    Recent studies have shown that acute traumatic coagulopathy is associated with hypoperfusion, increased plasma levels of soluble thrombomodulin, and decreased levels of protein C but with no change in factor VII activity. These findings led to the hypothesis that acute traumatic coagulopathy is primarily due to systemic anticoagulation, by activated protein C, rather than decreases in serine protease activity. This study was designed to examine the effect of hypoperfusion secondary to traumatic injury on the activity of coagulation factors. Post hoc analysis of prospectively collected data on severely injured adult trauma patients presenting to a single trauma center within 120 minutes of injury. Venous blood was analyzed for activity of factors II, V, VII, VIII, IX, X, and XI. Base deficit from arterial blood samples was used as a marker of hypoperfusion. Seventy-one patients were identified. The activity of factors II, V, VII, IX, X, and XI correlated negatively with base deficit, and after stratification into three groups, based on the severity of hypoperfusion, a statistically significant dose-related reduction in the activity of factors II, VII, IX, X, and XI was observed. Hypoperfusion is also associated with marked reductions in factor V activity levels, but these appear to be relatively independent of the degree of hypoperfusion. The activity of factor VIII did not correlate with base deficit. Hypoperfusion in trauma patients is associated with a moderate, dose-dependent reduction in the activity of coagulation factors II, VII, IX, X, and XI, and a more marked reduction in factor V activity, which is relatively independent of the severity of shock. These findings suggest that the mechanisms underlying decreased factor V activity--which could be due to activated protein C mediated cleavage, thus providing a possible link between the proposed thrombomodulin/thrombin-APC pathway and the serine proteases of the coagulation cascade--and the reductions in factors

  20. Role of hemostatic factors on the risk of venous thrombosis in people with impaired kidney function.

    Science.gov (United States)

    Ocak, Gürbey; Vossen, Carla Y; Lijfering, Willem M; Verduijn, Marion; Dekker, Friedo W; Rosendaal, Frits R; Cannegieter, Suzanne C

    2014-02-11

    Factors explaining the association between impaired kidney function and venous thrombosis have not been identified so far. The aim of our study was to determine whether the association between impaired kidney function and venous thrombosis can be explained by the concurrent presence of genetic or acquired venous thrombosis risk factors. The glomerular filtration rate was estimated (eGFR) in 2473 venous thrombosis patients and 2936 controls from a population-based case-control study. Kidney function was grouped into 6 categories based on percentiles of the eGFR in the controls (>50th [reference], 10th-50th, 5th-10th, 2.5th-5th, 1st-2.5th, and percentile). Several hemostatic factors showed a procoagulant shift with decreasing kidney function in controls, most notably factor VIII and von Willebrand factor. Compared with eGFR >50th percentile, factor VIII levels (adjusted mean difference, 60 IU/dL for the percentile category) and von Willebrand factor levels (adjusted mean difference, 60 IU/dL for the percentile category) increased with each percentile category. The odds ratios for venous thrombosis similarly increased across the categories from 1.1 (95% confidence interval, 0.9-1.3) for the 10th to 50th percentile to 3.7 (95% confidence interval, 2.4-5.7) for the percentile category. Adjustment for factor VIII or von Willebrand factor attenuated these odds ratios, indicating an effect of eGFR on thrombosis through these factors. Adjustments for other risk factors for venous thrombosis did not affect the odds ratios. Impaired kidney function affects venous thrombosis risk via concurrently raised factor VIII and von Willebrand factor levels.

  1. Vascular endothelial growth factor activities on osteoarthritic chondrocytes.

    Science.gov (United States)

    Pulsatelli, L; Dolzani, P; Silvestri, T; Frizziero, L; Facchini, A; Meliconi, R

    2005-01-01

    Evaluation of the role of VEGF in cartilage pathophysiology. VEGF release from chondrocytes in the presence of IL-1beta, TGFbeta and IL-10 was detected by immunoassay. VEGF receptor -1 and -2 expression and VEGF ability to modulate caspase -3 and cathepsin B expression were detected by immunohistochemistry on cartilage biopsies and cartilage explants. VEGF effects on chondrocyte proliferation was analysed by a fluorescent dye that binds nucleic acids. VEGF production by osteoartritis (OA) chondrocytes was significantly reduced by IL-1beta while it was increased in the presence of TGFbeta. Cartilage VEGFR-1 immunostaining was significantly downregulated in 'early' OA patients compared to normal controls (NC). VEGFR-2 expression was negligible both in OA and in NC. VEGF decreased the expression of caspase-3 and cathepsin B, whereas it did not affect proliferation. VEGF is able to down-modulate chondrocyte activities related to catabolic events involved in OA cartilage degradation.

  2. Prebiotic Factors Influencing the Activity of a Ligase Ribozyme

    Directory of Open Access Journals (Sweden)

    Fabrizio Anella

    2017-04-01

    Full Text Available An RNA-lipid origin of life scenario provides a plausible route for compartmentalized replication of an informational polymer and subsequent division of the container. However, a full narrative to form such RNA protocells implies that catalytic RNA molecules, called ribozymes, can operate in the presence of self-assembled vesicles composed of prebiotically relevant constituents, such as fatty acids. Hereby, we subjected a newly engineered truncated variant of the L1 ligase ribozyme, named tL1, to various environmental conditions that may have prevailed on the early Earth with the objective to find a set of control parameters enabling both tL1-catalyzed ligation and formation of stable myristoleic acid (MA vesicles. The separate and concurrent effects of temperature, concentrations of Mg2+, MA, polyethylene glycol and various solutes were investigated. The most favorable condition tested consists of 100 mM NaCl, 1 mM Mg2+, 5 mM MA, and 4 °C temperature, whereas the addition of Mg2+-chelating solutes, such as citrate, tRNAs, aspartic acid, and nucleoside triphosphates severely inhibits the reaction. These results further solidify the RNA-lipid world hypothesis and stress the importance of using a systems chemistry approach whereby a wide range of prebiotic factors interfacing with ribozymes are considered.

  3. Transforming Growth Factor-β Signaling Pathway Activation in Keratoconus

    Science.gov (United States)

    ENGLER, CHRISTOPH; CHAKRAVARTI, SHUKTI; DOYLE, JEFFERSON; EBERHART, CHARLES G.; MENG, HUAN; STARK, WALTER J.; KELLIHER, CLARE; JUN, ALBERT S.

    2011-01-01

    PURPOSE To assess the presence of transforming growth factor-β (TGFβ) pathway markers in the epithelium of keratoconus patient corneas. DESIGN Retrospective, comparative case series of laboratory specimens. METHODS Immunohistochemistry results for TGFβ2, total TGFβ, mothers against decacentaplegic homolog (Smad) 2, and phosphorylated Smad2 was performed on formalin-fixed, paraffin-embedded sections of keratoconus patient corneas and normal corneas from human autopsy eyes. Keratoconus patient corneas were divided in two groups, depending on their severity based on keratometer readings and pachymetry. Autopsy controls were age-matched with the keratoconus cases. Immunohistochemistry signal quantification was performed using automated software. Real-time reverse-transcriptase polymerase chain reaction was performed on total ribonucleic acid of epithelium of keratoconus patient corneas and autopsy control corneas. RESULTS Immunohistochemistry quantification showed a significant increase in mean signal in the group of severe keratoconus cases compared with normal corneas for TGFβ2 and phosphorylated Smad2 (P keratoconus cases versus the autopsy controls. Reverse-transcriptase polymerase chain reaction exhibited elevated messenger ribonucleic acid levels of Smad2 and TGFβ2 in severe keratoconus corneal epithelium. CONCLUSIONS This work shows increased TGFβ pathway markers in severe keratoconus cases and provides the rationale for investigating TGFβ signaling further in the pathophysiology of keratoconus. PMID:21310385

  4. Specific features of domestic banks activity in the factoring services market

    Directory of Open Access Journals (Sweden)

    Trygub Olena V.

    2014-01-01

    Full Text Available The article analyses specific features of formation and development of the domestic factoring market. In the result of the study the article establishes that development of factoring in Ukraine took place due to active participation of banking institutions in this process and nowadays they are leaders in the domestic factoring services market due to possessing significant competitive advantages if compared with non-banking companies that specialise in factoring. The article detects that nowadays the banks are not only offerers of factoring services and finance factoring operations of other market participants, but also take an active part in establishment of factoring branches and are consumers of factoring services. In order to accelerate development of international factoring in Ukraine, the article offers such forms of state support of banks, which render factoring services to domestic exporters. The article recommends to focus banks’ attention, under modern conditions that are characterised with volatility of financial markets, on factoring servicing of those clients, whom they have long business relations with, without jeopardising themselves through provision of factoring services to a big number of small debtors. The article provides schemes of banks’ co-operation in the sphere of “non-classic” factoring with accredited factoring companies.

  5. Coagulation and fibrinolysis activation after single-incision versus standard laparoscopic cholecystectomy: a single-center prospective case-controlled pilot study.

    Science.gov (United States)

    Zezos, Petros; Christoforidou, Anna; Kouklakis, Georgios; Tsalikidis, Christos; Dimakis, Constantinos; Laftsidis, Prodromos; Virgiliou, Andriana; Simopoulos, Constantinos; Pitiakoudis, Michail

    2014-02-01

    Laparoscopic cholecystectomy is associated with attenuated acute-phase response and hypercoagulable state compared with the open procedure. Single-incision laparoscopic cholecystectomy is a new technique aiming to minimize the invasiveness of the procedure. By comparing the degree of coagulation and fibrinolysis activation after conventional multiport (CLC) and single-incision (SILC) laparoscopic cholecystectomy, we aimed to determine whether the reduced incision size induces a lower thrombophilic tendency. Thirty-two adult patients with noncomplicated symptomatic cholelithiasis were nonrandomly assigned to CLC or SILC. Prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin complexes (TAT), D-dimers, fibrinogen, and von Willebrand factor levels were measured at baseline, at 1st, and 24th hour, postoperatively. Twenty-six patients were finally included in the study. Fifteen patients underwent CLC (male/female: 5/10) and 11 underwent SILC (male/female: 1/10). There were no perioperative complications. An almost similar postoperative pattern and degree of activation of coagulation and fibrinolysis pathways was noted in both groups. No statistically significant differences were found between SILC and CLC for F1 + 2, TAT, D-dimers, fibrinogen, and von Willebrand factor levels, duration of surgery, length of hospital stay, and postoperative morbidity. A similar pattern and extent of coagulation and fibrinolysis activation is present in SILC and CLC, and therefore there is no difference in tendency for thrombosis. Thromboembolic prophylaxis should be considered in SILC as recommended for CLC, pharmacologic or mechanical, considering the hemorrhagic risk and the presence of additional thromboembolism risk factors. SILC appears to be a safe, feasible technique that can be recommended for its potential advantages in cosmesis and reduced incisional pain.

  6. Exploring Contextual Factors and Patient Activation: Evidence from a Nationally Representative Sample of Patients with Depression

    Science.gov (United States)

    Chen, Jie; Mortensen, Karoline; Bloodworth, Robin

    2014-01-01

    Patient activation has been considered as a "blockbuster drug of the century." Patients with mental disorders are less activated compared to patients with other chronic diseases. Low activation due to mental disorders can affect the efficiency of treatment of other comorbidities. Contextual factors are significantly associated with…

  7. Factor VII-activating protease in patients with acute deep venous thrombosis

    DEFF Research Database (Denmark)

    Sidelmann, Johannes J; Vitzthum, Frank; Funding, Eva

    2008-01-01

    Factor VII-activating protease (FSAP) is involved in haemostasis and inflammation. FSAP cleaves single chain urokinase-type plasminogen activator (scu-PA). The 1601GA genotype of the 1601G/A polymorphism in the FSAP gene leads to the expression of a FSAP variant with reduced ability to activate scu...

  8. Influences of lifestyle factors on cardiac autonomic nervous system activity over time

    NARCIS (Netherlands)

    Hu, Mandy Xian; Lamers, Femke; de Geus, Eco J C; Penninx, Brenda W J H

    Physical activity, alcohol use and smoking might affect cardiovascular disease through modifying autonomic nervous system (ANS) activity. We investigated: 1) whether there are consistent relationships between lifestyle factors and cardiac ANS activity over time, and 2) whether 2-year changes in

  9. Molecular Basis of Enhanced Activity in Factor VIIa-Trypsin Variants Conveys Insights into Tissue Factor-mediated Allosteric Regulation of Factor VIIa Activity

    DEFF Research Database (Denmark)

    Sorensen, Anders B.; Madsen, Jesper Jonasson; Svensson, L. Anders

    2016-01-01

    -ray crystallography, we show that the introduced 170 loop from trypsin directly interacts with the FVIIa active site, stabilizing segment 215-217 and activation loop 3, leading to enhanced activity. Molecular dynamics simulations and novel fluorescence quenching studies support that segment 215-217 conformation...... is pivotal to the enhanced activity of the FVIIa variants. We speculate that the allosteric regulation of FVIIa activity by TF binding follows a similar path in conjunction with protease domain N terminus insertion, suggesting a more complete molecular basis of TF-mediated allosteric enhancement of FVIIa...

  10. In vitro sensitivity of different activated partial thromboplastin time reagents to mild clotting factor deficiencies.

    Science.gov (United States)

    Toulon, P; Eloit, Y; Smahi, M; Sigaud, C; Jambou, D; Fischer, F; Appert-Flory, A

    2016-08-01

    Activated partial thromboplastin time (aPTT) is a routine clotting assay that is widely used to globally screen for coagulation abnormalities. It is commonly admitted that a prolonged test result, may trigger the need for specific assays to be performed, particularly factor measurement. However, the sensitivity of aPTT reagents to deficiencies of clotting factors varies. We evaluated, according to the recommendation of the CLSI H47-A2 guideline, the responsiveness to single factor levels of five aPTT reagents by using factor-deficient plasmas spiked with a calibration plasma to produce individual factor activities ranging from sensitivity of the tested aPTT reagents to single factor deficiency is highly variable. Moreover, for one given aPTT reagent, its sensitivity was very different depending on the deficient factor. This must be considered when analyzing clinical materials. © 2016 John Wiley & Sons Ltd.

  11. Factor analysis shows association between family activity environment and children's health behaviour.

    Science.gov (United States)

    Hendrie, Gilly A; Coveney, John; Cox, David N

    2011-12-01

    To characterise the family activity environment in a questionnaire format, assess the questionnaire's reliability and describe its predictive ability by examining the relationships between the family activity environment and children's health behaviours - physical activity, screen time and fruit and vegetable intake. This paper describes the creation of a tool, based on previously validated scales, adapted from the food domain. Data are from 106 children and their parents (Adelaide, South Australia). Factor analysis was used to characterise factors within the family activity environment. Pearson-Product Moment correlations between the family environment and child outcomes, controlling for demographic variation, were examined. Three factors described the family activity environment - parental activity involvement, opportunity for role modelling and parental support for physical activity - and explained 37.6% of the variance. Controlling for demographic factors, the scale was significantly correlated with children's health behaviour - physical activity (r=0.27), screen time (r=-0.24) and fruit and vegetable intake (r=0.34). The family activity environment questionnaire shows high internal consistency and moderate predictive ability. This study has built on previous research by taking a more comprehensive approach to measuring the family activity environment. This research suggests the family activity environment should be considered in family-based health promotion interventions. © 2011 The Authors. ANZJPH © 2011 Public Health Association of Australia.

  12. Intrapersonal, Behavioral, and Environmental Factors Associated With Meeting Recommended Physical Activity Among Rural Latino Youth

    Science.gov (United States)

    Perry, Cynthia K.; Saelens, Brian E.; Thompson, Beti

    2013-01-01

    This study aimed to identify intrapersonal, behavioral, and environmental factors associated with engaging in recommended levels of physical activity among rural Latino middle school youth. Data were from an anonymous survey of 773 Latino youth (51% female) about level of and barriers and motivators to physical activity, risk behaviors, and park use. Logistic regression models identified factors correlated with meeting recommended levels of physical activity (5 days or more 360 min/day). Thirty-four percent of girls and 41% of boys reported meeting this physical activity recommendation. Participation in an organized after school activity (p < .001) and in physical education (PE) classes 5 days a week (p < .001) were strongly associated with meeting recommended physical activity level. Making PE available 5 days a week and creating opportunities for organized after school physical activity programs may increase the number of rural Latino middle school youth who meet recommended physical activity level. PMID:22109778

  13. Newly diagnosed congenital factor VII deficiency and utilization of recombinant activated factor VII (NovoSeven®

    Directory of Open Access Journals (Sweden)

    Bartosh NS

    2013-03-01

    Full Text Available Nicole S Bartosh, Tara Tomlin, Christian Cable, Kathleen HalkaDepartment of Internal Medicine, Division of Medical Oncology, Scott and White Healthcare and Texas A and M Health Science Center College of Medicine, Temple, TX, USAAbstract: This case report presents a newly diagnosed congenital factor VII deficiency treated with recombinant activated factor VII (rFVIIa. Congenital factor VII deficiency is a rare autosomal-recessive bleeding disorder that occurs in fewer than 1/500,000 persons. Its presentation can vary from epistaxis to hemarthroses and severe central nervous system bleeding, and correlates poorly with factor VII levels. Our patient had not had a significant hemostatic challenge prior to his presentation and therefore never had any symptomatology suggestive of this disease. He was treated with rFVIIa, and was able to undergo repair of his fractures without bleeding.Case report: A 19-year-old African-American male presented to the emergency room after an altercation that resulted in significant trauma. He sustained bilateral mandibular angle fractures and orbital floor fractures, requiring urgent surgical correction. On initial evaluation, he was noted to have a prolonged prothrombin time of 40.1 seconds, with an International Normalized Ratio of 4.0, a normal activated partial thromboplastin time of 29.9 seconds, and a platelet count of 241. After receiving vitamin K and fresh frozen plasma, he was taken to the operating room for a temporary rigid maxillomandibular fixation. A 1:1 mixing study with normal plasma corrected the prothrombin time (decreasing from 40.7 to 14.7 seconds and a factor VII assay revealed 5% of the normal factor VII level. The patient was diagnosed with congenital factor VII deficiency. Due to his coagulopathy and the extensive surgical correction needed, rFVIIa was administered and surgery was accomplished without hemorrhagic sequelae.Conclusion: This case report and review describes a rare congenital

  14. Phosphoinositide 3-Kinases Upregulate System xc− via Eukaryotic Initiation Factor 2α and Activating Transcription Factor 4 – A Pathway Active in Glioblastomas and Epilepsy

    Science.gov (United States)

    Baxter, Paul; Kassubek, Rebecca; Albrecht, Philipp; Van Liefferinge, Joeri; Westhoff, Mike-Andrew; Halatsch, Marc-Eric; Karpel-Massler, Georg; Meakin, Paul J.; Hayes, John D.; Aronica, Eleonora; Smolders, Ilse; Ludolph, Albert C.; Methner, Axel; Conrad, Marcus; Massie, Ann; Hardingham, Giles E.

    2014-01-01

    Abstract Aims: Phosphoinositide 3-kinases (PI3Ks) relay growth factor signaling and mediate cytoprotection and cell growth. The cystine/glutamate antiporter system xc− imports cystine while exporting glutamate, thereby promoting glutathione synthesis while increasing extracellular cerebral glutamate. The aim of this study was to analyze the pathway through which growth factor and PI3K signaling induce the cystine/glutamate antiporter system xc− and to demonstrate its biological significance for neuroprotection, cell growth, and epilepsy. Results: PI3Ks induce system xc− through glycogen synthase kinase 3β (GSK-3β) inhibition, general control non-derepressible-2-mediated eukaryotic initiation factor 2α phosphorylation, and the subsequent translational up-regulation of activating transcription factor 4. This pathway is essential for PI3Ks to modulate oxidative stress resistance of nerve cells and insulin-induced growth in fibroblasts. Moreover, the pathway is active in human glioblastoma cells. In addition, it is induced in primary cortical neurons in response to robust neuronal activity and in hippocampi from patients with temporal lobe epilepsy. Innovation: Our findings further extend the concepts of how growth factors and PI3Ks induce neuroprotection and cell growth by adding a new branch to the signaling network downstream of GSK-3β, which, ultimately, leads to the induction of the cystine/glutamate antiporter system xc−. Importantly, the induction of this pathway by neuronal activity and in epileptic hippocampi points to a potential role in epilepsy. Conclusion: PI3K-regulated system xc− activity is not only involved in the stress resistance of neuronal cells and in cell growth by increasing the cysteine supply and glutathione synthesis, but also plays a role in the pathophysiology of tumor- and non-tumor-associated epilepsy by up-regulating extracellular cerebral glutamate. Antioxid. Redox Signal. 20: 2907–2922. PMID:24219064

  15. Sex differences in social cognitive factors and physical activity in Korean college students

    OpenAIRE

    Choi, Jin Yi; Chang, Ae Kyung; Choi, Eun-Ju

    2015-01-01

    [Purpose] This study examined sex differences in physical activity and social cognitive theory factors in Korean college students. [Subjects and Methods] A cross-sectional survey of 688 college students (285 men and 403 women) in Korea was conducted using a self-reported questionnaire. [Results] There was a significant difference in the level of physical activity between male and female students. The significant predictors of physical activity for male students were physical activity goals, p...

  16. Multiple factors confer specific Cdc42 and Rac protein activation by dedicator of cytokinesis (DOCK) nucleotide exchange factors.

    Science.gov (United States)

    Kulkarni, Kiran; Yang, Jing; Zhang, Ziguo; Barford, David

    2011-07-15

    DOCK (dedicator of cytokinesis) guanine nucleotide exchange factors (GEFs) activate the Rho-family GTPases Rac and Cdc42 to control cell migration, morphogenesis, and phagocytosis. The DOCK A and B subfamilies activate Rac, whereas the DOCK D subfamily activates Cdc42. Nucleotide exchange is catalyzed by a conserved DHR2 domain (DOCK(DHR2)). Although the molecular basis for DOCK(DHR2)-mediated GTPase activation has been elucidated through structures of a DOCK9(DHR2)-Cdc42 complex, the factors determining recognition of specific GTPases are unknown. To understand the molecular basis for DOCK-GTPase specificity, we have determined the crystal structure of DOCK2(DHR2) in complex with Rac1. DOCK2(DHR2) and DOCK9(DHR2) exhibit similar tertiary structures and homodimer interfaces and share a conserved GTPase-activating mechanism. Multiple structural differences between DOCK2(DHR2) and DOCK9(DHR2) account for their selectivity toward Rac1 and Cdc42. Key determinants of selectivity of Cdc42 and Rac for their cognate DOCK(DHR2) are a Phe or Trp residue within β3 (residue 56) and the ability of DOCK proteins to exploit differences in the GEF-induced conformational changes of switch 1 dependent on a divergent residue at position 27. DOCK proteins, therefore, differ from DH-PH GEFs that select their cognate GTPases through recognition of structural differences within the β2/β3 strands.

  17. High Complement Factor I Activity in the Plasma of Children with Autism Spectrum Disorders

    Directory of Open Access Journals (Sweden)

    Naghi Momeni

    2012-01-01

    Full Text Available Autism spectrum disorders (ASDs are neurodevelopmental and behavioural syndromes affecting social orientation, behaviour, and communication that can be classified as developmental disorders. ASD is also associated with immune system abnormality. Immune system abnormalities may be caused partly by complement system factor I deficiency. Complement factor I is a serine protease present in human plasma that is involved in the degradation of complement protein C3b, which is a major opsonin of the complement system. Deficiency in factor I activity is associated with an increased incidence of infections in humans. In this paper, we show that the mean level of factor I activity in the ASD group is significantly higher than in the control group of typically developed and healthy children, suggesting that high activity of complement factor I might have an impact on the development of ASD.

  18. FACTORS SUCCESS OFF PUPILS OF SECONDARY SCHOOLS IN KOSOVO WITH SPECIAL REFERENCE TO OF PHYSICAL ACTIVITY AND SPORTS ACTIVITIES

    Directory of Open Access Journals (Sweden)

    Abedin Ibrahimi

    2013-07-01

    Full Text Available In this paper are presented the emperical results of verification of factors that affect students success of high schools in Kosova. It’s presented metodology of research and are given all results preliminary of anlalysis to all variables,in which the research is based. In this group of factors entered also physical activity and sport,and neither all circumstancers socio-economic wher live the all tested people.

  19. Stress-vulnerability factors as long-term predictors of disease activity in early rheumatoid arthritis.

    NARCIS (Netherlands)

    Evers, A.W.M.; Kraaimaat, F.W.; Geenen, R.; Jacobs, J.W.; Bijlsma, J.W.J.

    2003-01-01

    OBJECTIVE: Stress-vulnerability factors were studied for their ability to predict long-term disease activity in early rheumatoid arthritis. METHODS: In a prospective study involving 78 recently diagnosed rheumatoid arthritis (RA) patients, the role of personality characteristics (neuroticism,

  20. Review of the role of the plasminogen activator system and vascular endothelial growth factor in subfertility.

    NARCIS (Netherlands)

    Ebisch, I.M.W.; Thomas, C.M.G.; Wetzels, A.M.M.; Willemsen, W.N.P.; Sweep, F.C.; Steegers-Theunissen, R.P.M.

    2008-01-01

    OBJECTIVE: To assess the importance of the plasminogen activator (PA) system and vascular endothelial growth factor (VEGF) in subfertility. DESIGN: Review. SETTING: Two university IVF centers. INTERVENTION(S): Systematic literature search (MEDLINE, Science Direct, and bibliographies of published

  1. Use of recombinant activated factor VII in a case of severe postpartum haemorrhage.

    Science.gov (United States)

    Verre, M; Bossio, F; Mammone, A; Piccirillo, M; Tancioni, F; Varano, M

    2006-02-01

    We describe the case of a 24 year old woman, affected by haemorrhagic shock due to post-partum uterine atony, who underwent an emergency hysterectomy with persistent postoperative bleeding, successfully treated with recombinant activated factor VII (Novoseven).

  2. The Contribution of Home, Neighbourhood and School Environmental Factors in Explaining Physical Activity among Adolescents

    Directory of Open Access Journals (Sweden)

    Leen Haerens

    2009-01-01

    Full Text Available The present study aimed at investigating the influence of home, neighbourhood and school environmental factors on adolescents' engagement in self-reported extracurricular physical activity and leisure time sports and on MVPA objectively measured by accelerometers. Environmental factors were assessed using questionnaires. Gender specific hierarchical regression analyses were conducted, with demographic variables entered in the first block, and environmental, psychosocial factors and interactions terms entered in the second block. Participation in extracurricular activities at school was positively related to the number of organized activities and the provision of supervision. Perceived accessibility of neighborhood facilities was not related to engagement in leisure time sports, whereas the availability of sedentary and physical activity equipment was. Findings were generally supportive of ecological theories stating that behaviors are influenced by personal and environmental factors that are constantly interacting.

  3. Dietary and Physical Activity/Inactivity Factors Associated with Obesity in School-Aged Children123

    OpenAIRE

    Perez-Rodriguez, Marcela; Melendez, Guillermo; Nieto, Claudia; Aranda, Marisol; Pfeffer, Frania

    2012-01-01

    Diet and physical activity (PA) are essential components of nutritional status. Adequate nutrition and an active lifestyle are key factors during childhood, because food habits track into adulthood. Children spend more time in school than in any other environment away from home. Studying the diet factors and patterns of PA that affect obesity risk in children during school hours and the complete school day can help identify opportunities to lower this risk. We directly measured the time child...

  4. An Analysis of the Role of Service Specific Risk Factors in Active Duty Navy Suicides

    Science.gov (United States)

    2014-03-01

    risk among teenagers and older adults); furthermore, the age bracket results coincide with the crude suicide numbers in the dataset (the 17–19 age...ROLE OF SERVICE–SPECIFIC RISK FACTORS IN ACTIVE DUTY NAVY SUICIDES by James D. Golliday March 2014 Thesis Co-Advisors: Yu-Chu Shen...COVERED Master’s Thesis 4. TITLE AND SUBTITLE AN ANALYSIS OF THE ROLE OF SERVICE–SPECIFIC RISK FACTORS IN ACTIVE DUTY NAVY SUICIDES 5. FUNDING

  5. Factors That Influence Exercise Among Adults With Arthritis in Three Activity Levels

    OpenAIRE

    Ananian, Cheryl Der; Wilcox, Sara; Saunders, Ruth; Watkins, Ken; Evans, Alexandra

    2006-01-01

    Introduction Recent public health objectives emphasize the importance of exercise for reducing disability among people with arthritis. Despite the documented benefits of exercise, people with arthritis are less active than those without arthritis. The purpose of this study was to examine the factors that influence exercise participation among insufficiently active individuals with arthritis and to compare these factors with those identified by nonexercisers and regular exercisers with arthrit...

  6. Hypoxia-Inducible Factor 1 Is an Inductor of Transcription Factor Activating Protein 2 Epsilon Expression during Chondrogenic Differentiation

    Directory of Open Access Journals (Sweden)

    Stephan Niebler

    2015-01-01

    Full Text Available The transcription factor AP-2ε (activating enhancer-binding protein epsilon is expressed in cartilage of humans and mice. However, knowledge about regulatory mechanisms influencing AP-2ε expression is limited. Using quantitative real time PCR, we detected a significant increase in AP-2ε mRNA expression comparing initial and late stages of chondrogenic differentiation processes in vitro and in vivo. Interestingly, in these samples the expression pattern of the prominent hypoxia marker gene angiopoietin-like 4 (Angptl4 strongly correlated with that of AP-2ε suggesting that hypoxia might represent an external regulator of AP-2ε expression in mammals. In order to show this, experiments directly targeting the activity of hypoxia-inducible factor-1 (HIF1, the complex mediating responses to oxygen deprivation, were performed. While the HIF1-activating compounds 2,2′-dipyridyl and desferrioxamine resulted in significantly enhanced mRNA concentration of AP-2ε, siRNA against HIF1α led to a significantly reduced expression rate of AP-2ε. Additionally, we detected a significant upregulation of the AP-2ε mRNA level after oxygen deprivation. In sum, these different experimental approaches revealed a novel role for the HIF1 complex in the regulation of the AP-2ε gene in cartilaginous cells and underlined the important role of hypoxia as an important external regulatory stimulus during chondrogenic differentiation modulating the expression of downstream transcription factors.

  7. Sun protection factor persistence on human skin during a day without physical activity or ultraviolet exposure

    DEFF Research Database (Denmark)

    Beyer, Ditte Maria; Faurschou, Annesofie; Philipsen, Peter Alshede

    2010-01-01

    Recently, we showed that the sun protection factor (SPF) decreases by a constant factor to reach 55% during a day with activities. Organic sunscreens but not inorganic ones are absorbed through the skin. We wished to determine the SPF decrease caused by absorption by investigating the difference ...

  8. Misfolded proteins activate Factor XII in humans, leading to kallikrein formation without initiating coagulation

    NARCIS (Netherlands)

    Maas, Coen; Govers-Riemslag, Jos W. P.; Bouma, Barend; Schiks, Bettina; Hazenberg, Bouke P. C.; Lokhorst, Henk M.; Hammarstrom, Per; ten Cate, Hugo; de Groot, Philip G.; Bouma, Bonno N.; Gebbink, Martijn F. B. G.

    When blood is exposed to negatively charged surface materials such as glass, an enzymatic cascade known as the contact system becomes activated. This cascade is initiated by autoactivation of Factor XII and leads to both coagulation (via Factor XI) and an inflammatory response (via the

  9. Sun protection factor persistence on human skin during a day without physical activity or ultraviolet exposure

    DEFF Research Database (Denmark)

    Beyer, Ditte Maria; Faurschou, Annesofie; Philipsen, Peter Alshede

    2010-01-01

    Recently, we showed that the sun protection factor (SPF) decreases by a constant factor to reach 55% during a day with activities. Organic sunscreens but not inorganic ones are absorbed through the skin. We wished to determine the SPF decrease caused by absorption by investigating the difference...

  10. Motivating and Demotivating Factors for Students with Low Emotional Intelligence to Participate in Speaking Activities

    Science.gov (United States)

    Méndez López, Mariza G.; Bautista Tun, Moisés

    2017-01-01

    The study aims to understand what factors may motivate and demotivate students with low emotional intelligence to participate in speaking activities during English class. Participants wrote an emotions journal to identify factors affecting student participation and were then interviewed at the end of the study period in order to elaborate on their…

  11. Identification of type 1 von Willebrand disease patients with reduced von Willebrand factor survival by assay of the VWF propeptide in the European study: molecular and clinical markers for the diagnosis and management of type 1 VWD (MCMDM-1VWD)

    DEFF Research Database (Denmark)

    Haberichter, S.L.; Castaman, G.; Budde, U.

    2008-01-01

    VWF survival. In this study, we report the assay of VWFpp and VWF:Ag in 19 individuals recruited from 6 European centers within the MCMDM-1VWD study. Eight individuals had a VWF:Ag level less than 30 IU/dL. Seven of these patients had a robust desmopressin response and significantly reduced VWF half...

  12. SOME IMPORTANT FACTORS AFFECTING EVOLUTION OF ACTIVITY BASED COSTING (ABC SYSTEM IN EGYPTIAN MANUFACTURING FIRMS

    Directory of Open Access Journals (Sweden)

    Karim MAMDOUH ABBAS

    2014-04-01

    Full Text Available The present investigation aims to determine the factors affecting evolution of Activity Based Costing (ABC system in Egyptian case. The study used the survey method to describe and analyze these factors in some Egyptian firms. The population of the study is Egyptian manufacturing firms. Accordingly, the number of received questionnaires was 392 (23 Egyptian manufacturing firms in the first half of 2013. Finally, the study stated some influencing factors for evolution this system (ABC in Egyptian manufacturing firms.

  13. Growth Factor Midkine Promotes T-Cell Activation through Nuclear Factor of Activated T Cells Signaling and Th1 Cell Differentiation in Lupus Nephritis.

    Science.gov (United States)

    Masuda, Tomohiro; Maeda, Kayaho; Sato, Waichi; Kosugi, Tomoki; Sato, Yuka; Kojima, Hiroshi; Kato, Noritoshi; Ishimoto, Takuji; Tsuboi, Naotake; Uchimura, Kenji; Yuzawa, Yukio; Maruyama, Shoichi; Kadomatsu, Kenji

    2017-04-01

    Activated T cells play crucial roles in the pathogenesis of autoimmune diseases, including lupus nephritis (LN). The activation of calcineurin/nuclear factor of activated T cells (NFAT) and STAT4 signaling is essential for T cells to perform various effector functions. Here, we identified the growth factor midkine (MK; gene name, Mdk) as a novel regulator in the pathogenesis of 2,6,10,14-tetramethylpentadecane-induced LN via activation of NFAT and IL-12/STAT4 signaling. Wild-type (Mdk +/+ ) mice showed more severe glomerular injury than MK-deficient (Mdk -/- ) mice, as demonstrated by mesangial hypercellularity and matrix expansion, and glomerular capillary loops with immune-complex deposition. Compared with Mdk -/- mice, the frequency of splenic CD69 + T cells and T helper (Th) 1 cells, but not of regulatory T cells, was augmented in Mdk +/+ mice in proportion to LN disease activity, and was accompanied by skewed cytokine production. MK expression was also enhanced in activated CD4 + T cells in vivo and in vitro. MK induced activated CD4 + T cells expressing CD69 through nuclear activation of NFAT transcription and selectively increased in vitro differentiation of naive CD4 + T cells into Th1 cells by promoting IL-12/STAT4 signaling. These results suggest that MK serves an indispensable role in the NFAT-regulated activation of CD4 + T cells and Th1 cell differentiation, eventually leading to the exacerbation of LN. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  14. Protective factors for youth considered at risk of criminal behaviour: does participation in extracurricular activities help?

    Science.gov (United States)

    Burton, Jodi M; Marshall, Lisa A

    2005-01-01

    There is a lack of research investigating the potential protective effect of participation in extracurricular activities on youth who are at risk of engaging in delinquent activity. This study examined the potential for participation in extracurricular activities to act as a protective factor for youth deemed at risk of engaging in delinquent activity. One hundred and sixty-nine secondary students from Glasgow, Scotland completed two questionnaires (the Youth Self-Report and an additional information sheet) requesting information about their participation in extracurricular and delinquent activities as well as their possible risk factors. Activities included sports, non-sports (hobbies and games), current activities (youth clubs and other organisations) and previous involvement in activities. Risk factors included residing in a broken home, having four or more siblings, academic failure and lacking a non-parental very important person. Delinquent activities included rule-breaking and aggressive behaviours. Independent samples t-tests found that females participated in significantly more non-sports and previous activities than males and that males participated in significantly more rule-breaking behaviour than females. Hierarchical multiple regression analyses found that gender and participation in sports were strong predictors of rule-breaking behaviour. A significant positive correlation was found between participation in sports and involvement in aggressive behaviour. The results suggest that participation in extracurricular activities does not act as a protective factor for youth, regardless of whether or not they are considered to be at risk of engaging in delinquent activity. The significant correlation found between participation in sports and involvement in aggressive behaviour suggests that youth participation in sports may act as a risk factor.

  15. Thrombin generation by activated factor VII on platelet activated by different agonists. Extending the cell-based model of hemostasis

    Directory of Open Access Journals (Sweden)

    Herrera Maria

    2006-04-01

    Full Text Available Abstract Background Platelet activation is crucial in normal hemostasis. Using a clotting system free of external tissue factor, we investigated whether activated Factor VII in combination with platelet agonists increased thrombin generation (TG in vitro. Methods and results TG was quantified by time parameters: lag time (LT and time to peak (TTP, and by amount of TG: peak of TG (PTG and area under thrombin formation curve after 35 minutes (AUC→35min in plasma from 29 healthy volunteers using the calibrated automated thrombography (CAT technique. TG parameters were measured at basal conditions and after platelet stimulation by sodium arachidonate (AA, ADP, and collagen (Col. In addition, the effects of recombinant activated FVII (rFVIIa alone or combined with the other platelet agonists on TG parameters were investigated. We found that LT and TTP were significantly decreased (p 35min were significantly increased (p 35min (but not PTG when compared to platelet rich plasma activated with agonists in the absence of rFVIIa. Conclusion Platelets activated by AA, ADP, Col or rFVIIa triggered TG. This effect was increased by combining rFVIIa with other agonists. Our intrinsic coagulation system produced a burst in TG independent of external tissue factor activity an apparent hemostatic effect with little thrombotic capacity. Thus we suggest a modification in the cell-based model of hemostasis.

  16. A new automated method for continuous registration of factor VII activation in vitro. Activation is accelerated by the concentration of factor VII and the activity state of the protein

    DEFF Research Database (Denmark)

    Bladbjerg, Else-Marie; Jespersen, J; Gram, J

    1994-01-01

    . In this system, FVII activation follows parabolic kinetic after an initial lag-phase. The slope of the linear phase is a measure of the protein concentration of factor VII (FVIItotal), while the length of the non-linear phase represents the velocity of FVII activation. The time required for complete activation...

  17. Reduced ADAMTS13 activity is associated with thrombotic risk in systemic lupus erythematosus.

    Science.gov (United States)

    Martin-Rodriguez, S; Reverter, J C; Tàssies, D; Espinosa, G; Heras, M; Pino, M; Escolar, G; Diaz-Ricart, M

    2015-10-01

    Severe deficiency of ADAMTS13 activity leads to von Willebrand factor (VWF) ultralarge multimers with high affinity for platelets, causing thrombotic thrombocytopenic purpura. Other pathological conditions with moderate ADAMTS13 activity exhibit a thrombotic risk. We examined the ADAMTS13 activity in systemic lupus erythematosus (SLE) and its value as a thrombotic biomarker. ADAMTS13 activity, VWF antigen and multimeric structure, and vascular cell adhesion molecule 1 (VCAM-1) were measured in plasma samples from 50 SLE patients and 50 healthy donors. Disease activity (systemic lupus erythematosus disease activity index; SLEDAI) and organ damage (systemic lupus international collaborating clinics) scores, thrombotic events, antiphospholipid syndrome (APS) and antiphospholipid antibodies (aPLs) were registered. SLE patients showed decreased ADAMTS13 activity and high VWF levels compared with controls (66 ± 27% vs. 101 ± 8%, P 60%, 60-40% and <40%), comparative analysis showed significant association between ADAMTS13 activity and SLEDAI (P < 0.05), presence of aPLs (P < 0.001), APS (P < 0.01) and thrombotic events (P < 0.01). Reduced ADAMTS13 activity together with increased VWF levels were especially notable in patients with active disease and with aPLs. ADAMTS13 activity, in combination with other laboratory parameters, could constitute a potential prognostic biomarker of thrombotic risk in SLE. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  18. Associated factors of estimated desaturase activity in the EPIC-Potsdam study.

    Science.gov (United States)

    Schiller, K; Jacobs, S; Jansen, E; Weikert, C; di Giuseppe, R; Boeing, H; Schulze, M B; Kröger, J

    2014-05-01

    Altered activity of desaturase enzymes may be involved in the development of metabolic diseases like type 2-diabetes. Desaturase activities might be modifiable by diet and lifestyle-related factors, but no study has systematically investigated such factors so far. We aimed to evaluate the association of demographic, anthropometric, dietary and lifestyle characteristics with estimated Δ5-, Δ6- and Δ9-desaturase activity. A subsample (n = 1782) of the EPIC-Potsdam study was used for a cross-sectional analysis, involving men and women, mainly aged 35-65 years. Fatty acid (FA) product-to-precursor ratios, derived from the FA composition of erythrocyte membrane phospholipids, were used to estimate desaturase activities. Multiple linear regression models were used with estimated Δ5-, Δ6- and Δ9-desaturase activity as outcome and demographic (age, sex), anthropometric (BMI, WHR), dietary intake (FAs, carbohydrates) and lifestyle (physical activity, smoking, alcohol consumption) factors as exposure variables. Alcohol intake was positively associated with estimated Δ6- (explained variance in desaturase activity: 1.52%) and estimated Δ9-desaturase activity (explained variance: 5.53%). BMI and WHR showed a weak inverse association with estimated Δ5-desaturase activity (explained variance: BMI: 1.07%; WHR: 1.02%) and weak positive associations with estimated Δ6-(explained variance: BMI: 1.17%; WHR: 1.19%) and estimated Δ9-desaturase activities (explained variance: BMI: 0.70%; WHR: 0.96%). Age, sex, physical activity, smoking and dietary factors were only weakly associated with the estimated desaturase activities. Our findings suggest that alcohol intake as well as obesity measures are associated with the FA ratios reflecting desaturase activity. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Effect of age, sex, physical activity and meteorological factors on haematological parameters of donkeys (Equus asinus).

    Science.gov (United States)

    Zakari, Friday Ocheja; Ayo, Joseph Olusegun; Rekwot, Peter Ibrahim; Kawu, Mohammed Umar

    2016-01-01

    The review examines the role of blood in homeostasis, diagnosis and treatment of disease as influenced by meteorological stress factors, age, sex and physical activity of the donkeys. Haematological parameters play a crucial role in clinical diagnosis of infectious and parasitic diseases, in assessing the responses of donkeys to treatment and in prevention of diseases. The changes in blood values are important in evaluating the responses of the animals to various physiologic conditions. In conclusion, haematological values of donkeys are largely influenced by age, sex, physical factors of the environment and physical activity, and consideration of the factors will aid accurate diagnosis and therapeutic evaluation of equine diseases.

  20. Muscle Atrophy Reversed by Growth Factor Activation of Satellite Cells in a Mouse Muscle Atrophy Model

    DEFF Research Database (Denmark)

    Hauerslev, Simon; Vissing, John; Krag, Thomas O

    2014-01-01

    Muscular dystrophies comprise a large group of inherited disorders that lead to progressive muscle wasting. We wanted to investigate if targeting satellite cells can enhance muscle regeneration and thus increase muscle mass. We treated mice with hepatocyte growth factor and leukemia inhibitory...... factor under three conditions: normoxia, hypoxia and during myostatin deficiency. We found that hepatocyte growth factor treatment led to activation of the Akt/mTOR/p70S6K protein synthesis pathway, up-regulation of the myognic transcription factors MyoD and myogenin, and subsequently the negative growth...... control factor, myostatin and atrophy markers MAFbx and MuRF1. Hypoxia-induced atrophy was partially restored by hepatocyte growth factor combined with leukemia inhibitory factor treatment. Dividing satellite cells were three-fold increased in the treatment group compared to control. Finally, we...

  1. Mechanism of the Ca2+-induced enhancement of the intrinsic factor VIIa activity

    DEFF Research Database (Denmark)

    Bjelke, Jais R; Olsen, Ole H; Fodje, Michel

    2008-01-01

    The intrinsic activity of coagulation factor VIIa (FVIIa) is dependent on Ca(2+) binding to a loop (residues 210-220) in the protease domain. Structural analysis revealed that Ca(2+) may enhance the activity by attenuating electrostatic repulsion of Glu(296) and/or by facilitating interactions...... by a combination of charge neutralization and loop stabilization....

  2. Factor VII-activating protease : Unraveling the release and regulation of dead cell nuclear damps

    NARCIS (Netherlands)

    Marsman, G.

    2017-01-01

    Upon inflammation, uncleared dying cells are an important source of pro-inflammatory damage-associated molecular patterns (DAMPs). Major DAMPs are histones and double-stranded DNA, which together form chromatin. Factor VII-activating protease (FSAP) is activated upon contact with dead cells, and its

  3. Factors of physical activity among Chinese children and adolescents : A systematic review

    NARCIS (Netherlands)

    Lu, Congchao; Stolk, Ronald P.; Sauer, Pieter J. J.; Sijtsma, Anna; Wiersma, Rikstje; Huang, Guowei; Corpeleijn, Eva

    2017-01-01

    Background: Lack of physical activity is a growing problem in China, due to the fast economic development and changing living environment over the past two decades. The aim of this review is to summarize the factors related to physical activity in Chinese children and adolescents during this

  4. Factors that Limit and Enable Preschool-Aged Children's Physical Activity on Child Care Centre Playgrounds

    Science.gov (United States)

    Coleman, Bianca; Dyment, Janet E.

    2013-01-01

    The incidence of childhood obesity amongst preschool-aged children has increased dramatically in recent years and can be attributed, in part, to a lack of physical activity amongst children in this age group. This study explores the social factors that stand to limit and/or enable children's physical activity opportunities in outdoor settings in…

  5. Factors Associated with Sexual Activity among High-School Students in Nairobi, Kenya

    Science.gov (United States)

    Kabiru, Caroline W.; Orpinas, Pamela

    2009-01-01

    The high level of HIV infection in sub-Saharan Africa has led to an increased interest in understanding the determinants of sexual activity among young people, who are at high risk of sexually transmitted infections. The present study examined sociodemographic, behavioral, and psychosocial factors associated with heterosexual activity among a…

  6. Factors Associated with Leisure Activity among Young Adults with Developmental Disabilities

    Science.gov (United States)

    Van Naarden Braun, Kim; Yeargin-Allsopp, Marshalyn; Lollar, Donald

    2006-01-01

    The framework of the International Classification of Functioning, Disability, and Health (ICF) was applied to examine the factors associated with childhood impairment and leisure activity. Information on leisure activity was obtained using a structured questionnaire from a population-based cohort of young adults with childhood impairment. The…

  7. Exploring Socio-Ecological Factors Influencing Active and Inactive Spanish Students in Years 12 and 13

    Science.gov (United States)

    Devís-Devís, José; Beltrán-Carrillo, Vicente J.; Peiró-Velert, Carmen

    2015-01-01

    This paper explores socio-ecological factors and their interplay that emerge from a qualitative study and influence adolescents' physical activity and sport participation. A total of 13 boys and 7 girls active and inactive adolescents, from years 12 and 13 and different types of school (state and private), participated in semi-structured…

  8. Effects of leisure time physical activity on psycho-emotional factors ...

    African Journals Online (AJOL)

    Burnout, a response to chronic emotional stress, could be influenced by parameters such as healthy lifestyle and physical activity, considered to be important factors in maintaining optimal health and wellness. The objective of this study was to determine the influence of leisure time physical activity participation on the levels ...

  9. Physical and Psychosocial Factors Associated With Physical Activity in Patients With Chronic Obstructive Pulmonary Disease

    NARCIS (Netherlands)

    Hartman, Jorine E.; Boezen, H. Marike; de Greef, Mathieu H.; ten Hacken, Nick H.

    2013-01-01

    Objectives: To assess physical activity and sitting time in patients with chronic obstructive pulmonary disease (COPD) and to investigate which physical and psychosocial factors are associated with physical activity and sitting time. Design: Cross-sectional study. Setting: Patients were recruited at

  10. Systematic review on the effect of glucocorticoid use on procoagulant, anti-coagulant and fibrinolytic factors.

    Science.gov (United States)

    van Zaane, B; Nur, E; Squizzato, A; Gerdes, V E A; Büller, H R; Dekkers, O M; Brandjes, D P M

    2010-11-01

    Whether glucocorticoid use contributes to a hypercoagulable state, and thereby enhances the thrombotic risk, is controversial. We aimed to examine the effects of glucocorticoid use on coagulation and fibrinolysis. MEDLINE and EMBASE databases were searched to identify published studies comparing glucocorticoid treatment with a glucocorticoid-free control situation. Subjects could be either patients or healthy volunteers. Two investigators independently performed study selection and data extraction. Results were expressed as standardized mean difference, if possible; data were pooled with a random-effects model. Of the 1967 identified publications, 36 papers were included. In healthy volunteers, a clear rise in factor (F)VII, VIII and XI activity was observed after glucocorticoid treatment, but these data alone provided insufficient evidence to support hypercoagulability. However, during active inflammation, glucocorticoids significantly increased levels of plasminogen activator inhibitor-1 (PAI-1), whereas levels of von Willebrand factor (VWF) and fibrinogen decreased. Peri-operative use of glucocorticoids inhibited the increase in tissue-type plasminogen activator induced by surgery. The present study showed differential effects of glucocorticoids depending on the clinical situation in which it is given, most likely as a result of their disease modifying properties. Clinical outcome studies are needed to adequately assess the risk-benefit of glucocorticoid use per population when thrombotic complication is the focus. © 2010 International Society on Thrombosis and Haemostasis.

  11. Objectively measured physical activity in Brazilians with visual impairment: description and associated factors.

    Science.gov (United States)

    Barbosa Porcellis da Silva, Rafael; Marques, Alexandre Carriconde; Reichert, Felipe Fossati

    2017-05-19

    Low level of physical activity is a serious health issue in individuals with visual impairment. Few studies have objectively measured physical activity in this population group, particularly outside high-income countries. The aim of this study was to describe physical activity measured by accelerometry and its associated factors in Brazilian adults with visual impairment. In a cross-sectional design, 90 adults (18-95 years old) answered a questionnaire and wore an accelerometer for at least 3 days (including one weekend day) to measure physical activity (min/day). Sixty percent of the individuals practiced at least 30 min/day of moderate-to-vigorous physical activity. Individuals who were blind were less active, spent more time in sedentary activities and spent less time in moderate and vigorous activities than those with low vision. Individuals who walked mainly without any assistance were more active, spent less time in sedentary activities and spent more time in light and moderate activities than those who walked with a long cane or sighted guide. Our data highlight factors associated with lower levels of physical activity in people with visual impairment. These factors, such as being blind and walking without assistance should be tackled in interventions to increase physical activity levels among visual impairment individuals. Implications for Rehabilitation Physical inactivity worldwide is a serious health issue in people with visual impairments and specialized institutions and public policies must work to increase physical activity level of this population. Those with lower visual acuity and walking with any aid are at a higher risk of having low levels of physical activity. The association between visual response profile, living for less than 11 years with visual impairment and PA levels deserves further investigations Findings of the present study provide reliable data to support rehabilitation programs, observing the need of taking special attention to

  12. Peripheral brain-derived neurotrophic factor is related to cardiovascular risk factors in active and inactive elderly men

    Directory of Open Access Journals (Sweden)

    A. Zembron-Lacny

    2016-01-01

    Full Text Available Regular exercise plays an important preventive and therapeutic role in heart and vascular diseases, and beneficially affects brain function. In blood, the effects of exercise appear to be very complex and could include protection of vascular endothelial cells via neurotrophic factors and decreased oxidative stress. The purpose of this study was to identify the age-related changes in peripheral brain-derived neurotrophic factor (BDNF and its relationship to oxidative damage and conventional cardiovascular disease (CVD biomarkers, such as atherogenic index, C-reactive protein (hsCRP and oxidized LDL (oxLDL, in active and inactive men. Seventeen elderly males (61-80 years and 17 young males (20-24 years participated in this study. According to the 6-min Åstrand-Rhyming bike test, the subjects were classified into active and inactive groups. The young and elderly active men had a significantly better lipoprotein profile and antioxidant status, as well as reduced oxidative damage and inflammatory state. The active young and elderly men had significantly higher plasma BDNF levels compared to their inactive peers. BDNF was correlated with VO2max (r=0.765, P<0.001. In addition, we observed a significant inverse correlation of BDNF with atherogenic index (TC/HDL, hsCRP and oxLDL. The findings demonstrate that a high level of cardiorespiratory fitness reflected in VO2max was associated with a higher level of circulating BDNF, which in turn was related to common CVD risk factors and oxidative damage markers in young and elderly men.

  13. The stress signalling pathway nuclear factor E2-related factor 2 is activated in the liver of sows during lactation

    Directory of Open Access Journals (Sweden)

    Rosenbaum Susann

    2012-10-01

    Full Text Available Abstract Background It has recently been shown that the lactation-induced inflammatory state in the liver of dairy cows is accompanied by activation of the nuclear factor E2-related factor 2 (Nrf2 pathway, which regulates the expression of antioxidant and cytoprotective genes and thereby protects tissues from inflammatory mediators and reactive oxygen species (ROS. The present study aimed to study whether the Nrf2 pathway is activated also in the liver of lactating sows. Findings Transcript levels of known Nrf2 target genes, UGT1A1 (encoding glucuronosyltransferase 1 family, polypeptide A1, HO-1 (encoding heme oxygenase 1, NQO1 (encoding NAD(PH dehydrogenase, quinone 1, GPX1 (encoding glutathione peroxidase, PRDX6 (encoding peroxiredoxin 6, TXNRD1 (encoding thioredoxin reductase 1, and SOD (encoding superoxide dismutase, in the liver are significantly elevated (between 1.7 and 3.1 fold in lactating sows compared to non-lactating sows. The inflammatory state in the liver was evidenced by the finding that transcript levels of genes encoding acute phase proteins, namely haptoglobin (HP, fibrinogen γ (FGG, complement factor B (CFB, C-reactive protein (CRP and lipopolysaccharide-binding protein (LBP, were significantly higher (2 to 8.7 fold in lactating compared to non-lactating sows. Conclusions The results of the present study indicate that the Nrf2 pathway in the liver of sows is activated during lactation. The activation of Nrf2 pathway during lactation in sows might be interpreted as a physiologic means to counteract the inflammatory process and to protect the liver against damage induced by inflammatory signals and ROS.

  14. Regulation and kinetics of platelet-activating factor and leukotriene C-4 synthesis by activated human basophils

    NARCIS (Netherlands)

    Lie, W. J.; Homburg, C. H. E.; Kuijpers, T. W.; Knol, E. F.; Mul, F. P. J.; Roos, D.; Tool, A. T. J.

    2003-01-01

    Background Allergic disease is the result of an interplay of many different cell types, including basophils and mast cells, in combination with various inflammatory lipid mediators, such as platelet-activating factor (PAF) and leukotrienes (LT). LTC4 synthesis by human basophils has been studied

  15. Streptococcus pyogenes CAMP factor attenuates phagocytic activity of RAW 264.7 cells.

    Science.gov (United States)

    Kurosawa, Mie; Oda, Masataka; Domon, Hisanori; Saitoh, Issei; Hayasaki, Haruaki; Terao, Yutaka

    2016-02-01

    Streptococcus pyogenes produces molecules that inhibit the function of human immune system, thus allowing the pathogen to grow and spread in tissues. It is known that S. pyogenes CAMP factor increases erythrocytosis induced by Staphylococcus aureus β-hemolysin. However, the effects of CAMP factor for immune cells are unclear. In this study, we investigated the effects of CAMP factor to macrophages. Western blotting analysis demonstrated that all examined strains expressed CAMP factor protein. In the presence of calcium or magnesium ion, CAMP factor was significantly released in the supernatant. In addition, both culture supernatant from S. pyogenes strain SSI-9 and recombinant CAMP factor dose-dependently induced vacuolation in RAW 264.7 cells, but the culture supernatant from Δcfa isogenic mutant strain did not. CAMP factor formed oligomers in RAW 264.7 cells in a time-dependent manner. CAMP factor suppressed cell proliferation via G2 phase cell cycle arrest without inducing cell death. Furthermore, CAMP factor reduced the uptake of S. pyogenes and phagocytic activity indicator by RAW 264.7 cells. These results suggest that CAMP factor works as a macrophage dysfunction factor. Therefore, we conclude that CAMP factor allows S. pyogenes to escape the host immune system, and contribute to the spread of streptococcal infection. Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  16. Exploratory study of burn time, duty factor, and fluence on ITER activation hazards

    Energy Technology Data Exchange (ETDEWEB)

    Piet, S.J.

    1992-08-01

    The safety analyses for the Conceptual Design Activity (CDA) of the International Thermonuclear Experimental Reactor (ITER) were based on the simplifying assumption that the activation of materials occurs continuously. Since the analyses showed a significant hazard, it is appropriate to examine how much hazard reduction might occur if this conservative assumption were relaxed. This report explores how much reduction might be gained by considering non-continuous operation, that is, by considering plasma burn time, duty factor, and integrated fluence. Other factors impacting activation hazards - material choice, flux, and size - are not considered here.

  17. Protamine sulfate down-regulates thrombin generation by inhibiting factor V activation.

    LENUS (Irish Health Repository)

    Ni Ainle, Fionnuala

    2009-08-20

    Protamine sulfate is a positively charged polypeptide widely used to reverse heparin-induced anticoagulation. Paradoxically, prospective randomized trials have shown that protamine administration for heparin neutralization is associated with increased bleeding, particularly after cardiothoracic surgery with cardiopulmonary bypass. The molecular mechanism(s) through which protamine mediates this anticoagulant effect has not been defined. In vivo administration of pharmacologic doses of protamine to BALB\\/c mice significantly reduced plasma thrombin generation and prolonged tail-bleeding time (from 120 to 199 seconds). Similarly, in pooled normal human plasma, protamine caused significant dose-dependent prolongations of both prothrombin time and activated partial thromboplastin time. Protamine also markedly attenuated tissue factor-initiated thrombin generation in human plasma, causing a significant decrease in endogenous thrombin potential (41% +\\/- 7%). As expected, low-dose protamine effectively reversed the anticoagulant activity of unfractionated heparin in plasma. However, elevated protamine concentrations were associated with progressive dose-dependent reduction in thrombin generation. To assess the mechanism by which protamine mediates down-regulation of thrombin generation, the effect of protamine on factor V activation was assessed. Protamine was found to significantly reduce the rate of factor V activation by both thrombin and factor Xa. Protamine mediates its anticoagulant activity in plasma by down-regulation of thrombin generation via a novel mechanism, specifically inhibition of factor V activation.

  18. Activation of transcription factors STAT1 and STAT5 in the mouse median eminence after systemic ciliary neurotrophic factor administration.

    Science.gov (United States)

    Severi, Ilenia; Senzacqua, Martina; Mondini, Eleonora; Fazioli, Francesca; Cinti, Saverio; Giordano, Antonio

    2015-10-05

    Exogenously administered ciliary neurotrophic factor (CNTF) causes weight loss in obese rodents and humans through leptin-like activation of the Jak-STAT3 signaling pathway in hypothalamic arcuate neurons. Here we report for the first time that 40min after acute systemic treatment, rat recombinant CNTF (intraperitoneal injection of 0.3mg/kg of body weight) induced nuclear translocation of the tyrosine-phosphorylated forms of STAT1 and STAT5 in the mouse median eminence and other circumventricular organs, including the vascular organ of the lamina terminalis and the subfornical organ. In the tuberal hypothalamus of treated mice, specific nuclear immunostaining for phospo-STAT1 and phospho-STAT5 was detected in ependymal cells bordering the third ventricle floor and lateral recesses, and in median eminence cells. Co-localization studies documented STAT1 and STAT5 activation in median eminence β-tanycytes and underlying radial glia-like cells. A few astrocytes in the arcuate nucleus responded to CNTF by STAT5 activation. The vast majority of median eminence tanycytes and radial glia-like cells showing phospho-STAT1 and phospho-STAT5 immunoreactivity were also positive for phospho-STAT3. In contrast, STAT3 was the sole STAT isoform activated by CNTF in arcuate nucleus and median eminence neurons. Finally, immunohistochemical evaluation of STAT activation 20, 40, 80, and 120min from the injection demonstrated that cell activation was accompanied by c-Fos expression. Collectively, our findings show that CNTF activates STAT3, STAT1, and STAT5 in vivo. The distinctive activation pattern of these STAT isoforms in the median eminence may disclose novel targets and pathways through which CNTF regulates food intake. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Krüppel-like factor 4, a novel transcription factor regulates microglial activation and subsequent neuroinflammation

    Directory of Open Access Journals (Sweden)

    Das Sulagna

    2010-10-01

    Full Text Available Abstract Background Activation of microglia, the resident macrophages of the central nervous system (CNS, is the hallmark of neuroinflammation in neurodegenerative diseases and other pathological conditions associated with CNS infection. The activation of microglia is often associated with bystander neuronal death. Nuclear factor-κB (NF-κB is one of the important transcription factors known to be associated with microglial activation which upregulates the expression of inducible nitric oxide synthase (iNOS, cyclooxygenase-2 (Cox-2 and other pro-inflammatory cytokines. Recent studies have focused on the role of Krüppel-like factor 4 (Klf4, one of the zinc-finger transcription factors, in mediating inflammation. However, these studies were limited to peripheral system and its role in CNS is not understood. Our studies focused on the possible role of Klf4 in mediating CNS inflammation. Methods For in vitro studies, mouse microglial BV-2 cell lines were treated with 500 ng/ml Salmonella enterica lipopolysacchride (LPS. Brain tissues were isolated from BALB/c mice administered with 5 mg/kg body weight of LPS. Expressions of Klf4, Cox-2, iNOS and pNF-κB were evaluated using western blotting, quantitative real time PCR, and reverse transcriptase polymerase chain reactions (RT-PCRs. Klf4 knockdown was carried out using SiRNA specific for Klf4 mRNA and luciferase assays and electromobility shift assay (EMSA were performed to study the interaction of Klf4 to iNOS promoter elements in vitro. Co-immunoprecipitation of Klf4 and pNF-κB was done in order to study a possible interaction between the two transcription factors. Results LPS stimulation increased Klf4 expression in microglial cells in a time- and dose-dependent manner. Knockdown of Klf4 resulted in decreased levels of the pro-inflammatory cytokines TNF-α, MCP-1 and IL-6, along with a significant decrease in iNOS and Cox-2 expression. NO production also decreased as a result of Klf4 knockdown

  20. Athlete and Coach Relationship as a Factor of the Success in Sports Activities

    OpenAIRE

    Svetlova A.A.,

    2014-01-01

    We present the results of a theoretical analysis of the psychological bases of success of athletes. We provide an overview of studies of the factors influencing the success of the activities in the sport. Sports activities are considered as a joint activity of athlete and coach, the success of which is affected by the personal qualities and characteristics of the relationship of its members. We summarize the main approaches to the study of personality and social psychological aspects of succe...

  1. Hematopoietic and nonhematopoietic cell tissue factor activates the coagulation cascade in endotoxemic mice

    OpenAIRE

    Pawlinski, Rafal; Wang, Jian-Guo; Owens, A. Phillip; Williams, Julie; Antoniak, Silvio; Tencati, Michael; Luther, Thomas; Rowley, Jesse W.; Low, Elizabeth N.; Weyrich, Andrew S.; Mackman, Nigel

    2010-01-01

    Tissue factor (TF) is the primary activator of the coagulation cascade. During endotoxemia, TF expression leads to disseminated intravascular coagulation. However, the relative contribution of TF expression by different cell types to the activation of coagulation has not been defined. In this study, we investigated the effect of either a selective inhibition of TF expression or cell type-specific deletion of the TF gene (F3) on activation of coagulation in a mouse model of endotoxemia. We fou...

  2. THE EXTERNAL FACTORS OF STUDENTS’ INVOLVEMENT IN SPEAKING ACTIVITY AT SMP PROGRESIF BUMI SHALAWAT

    Directory of Open Access Journals (Sweden)

    M.A. Nurul Haikal

    2016-07-01

    Full Text Available This research is conducted to know what factors that influence the students’ involvement in speaking activity in order to practice their speaking skill and what strategies that the teacher used to encourage those external factors. This research uses descriptive qualitative method. There are two instruments used for this research, namely, class observation and interview. Based on the results of class observation and interview, the researcher concludes that teacher factor gives the greatest impact on students’ involvement and the appropriate strategies can support those external factors.

  3. Cellular Transcription Factor YY1 Mediates the Varicella-Zoster Virus (VZV) IE62 Transcriptional Activation

    Science.gov (United States)

    Khalil, Mohamed I.; Sommer, Marvin; Arvin, Ann; Hay, John; Ruyechan, William T.

    2014-01-01

    Several cellular transcription factors have been shown to be involved in IE62-mediated activation. The YY1 cellular transcription factor has activating and repressive effects on gene transcription. Analysis of the VZV genome revealed 19 postulated YY1 binding sites located within putative promoters of 16 VZV genes. Electrophoretic mobility shift assays (EMSA) confirmed the binding of YY1 to ORF10, ORF28/29 and gI promoters and the mutation of these binding sites inhibited YY1 binding and the promoter activation by IE62 alone or following VZV infection. Mutation of the ORF28/29 YY1 site in the VZV genome displayed insignificant influence on virus growth in melanoma cells; but it inhibited the virus replication significantly at day 5 and 6 post infection in HELF cells. This work suggests a novel role for the cellular factor YY1 in VZV replication through the mediation of IE62 activation of viral gene expression. PMID:24418559

  4. Glycosylated human oxyhaemoglobin activates nuclear factor-kappaB and activator protein-1 in cultured human aortic smooth muscle.

    Science.gov (United States)

    Peiro, Concepcion; Matesanz, Nuria; Nevado, Julian; Lafuente, Nuria; Cercas, Elena; Azcutia, Veronica; Vallejo, Susana; Rodriguez-Manas, Leocadio; Sanchez-Ferrer, Carlos F

    2003-10-01

    Diabetic vessels undergo structural changes that are linked to a high incidence of cardiovascular diseases. Reactive oxygen species (ROS) mediate cell signalling in the vasculature, where they can promote cell growth and activate redox-regulated transcription factors, like activator protein-1 (AP-1) or nuclear factor-kappaB (NF-kappaB), which are involved in remodelling and inflammation processes. Amadori adducts, formed through nonenzymatic glycosylation, can contribute to ROS formation in diabetes. In this study, we analysed whether Amadori-modified human oxyhaemoglobin, glycosylated at either normal (N-Hb) or elevated (E-Hb) levels, can induce cell growth and activate AP-1 and NF-kappaB in cultured human aortic smooth muscle cells (HASMC). E-Hb (1 nm-1 x microm), but not N-Hb, promoted a concentration-dependent increase in cell size from nanomolar concentrations, although it failed to stimulate HASMC proliferation. At 10 nm, E-Hb stimulated both AP-1 and NF-kappaB activity, as assessed by transient transfection, electromobility shift assays or immunofluorescence staining. The effects of E-Hb resembled those of the proinflammatory cytokine tumour necrosis factor-alpha (TNF-alpha). E-Hb enhanced intracellular superoxide anions content and its effects on HASMC were abolished by different ROS scavengers. In conclusion, E-Hb stimulates growth and activates AP-1 and NF-kappaB in human vascular smooth muscle by redox-sensitive pathways, thus suggesting a possible direct role for Amadori adducts in diabetic vasculopathy.

  5. Active transportation and cardiovascular disease risk factors in U.S. adults.

    Science.gov (United States)

    Furie, Gregg L; Desai, Mayur M

    2012-12-01

    Evidence of associations between active transportation (walking and bicycling for transportation) and health outcomes is limited. Better understanding of this relationship would inform efforts to increase physical activity by promoting active transportation. This study examined associations between active transportation and cardiovascular disease risk factors in U.S. adults. Using the 2007-2008 and 2009-2010 cycles of the National Health and Nutrition Examination Survey (NHANES), adults (N=9933) were classified by level of active transportation. Multivariable linear and logistic regression analyses controlled for sociodemographic characteristics, smoking status, and minutes/week of non-active transportation physical activity. Analyses were conducted in 2011. Overall, 76% reported no active transportation. Compared with no active transportation, mean BMI was lower among individuals with low (-0.9, 95% CI= -1.4, -0.5) and high (-1.2, 95% CI= -1.7, -0.8) levels of active transportation. Mean waist circumference was lower in the low (-2.2 cm, 95% CI= -3.2, -1.2) and high (-3.1 cm, 95% CI= -4.3, -1.9) active transportation groups. The odds of hypertension were 24% lower (AOR=0.76, 95% CI=0.61, 0.94) and 31% lower (AOR=0.69, 95% CI=0.58, 0.83) among individuals with low and high levels of active transportation, respectively, compared with no active transportation. High active transportation was associated with 31% lower odds of diabetes (AOR=0.69, 95% CI=0.54, 0.88). Active transportation was not associated with high-density lipoprotein level. Active transportation was associated with more-favorable cardiovascular risk factor profiles, providing additional justification for infrastructure and policies that permit and encourage active transportation. Published by Elsevier Inc.

  6. Girls' perception of physical environmental factors and transportation: reliability and association with physical activity and active transport to school

    Directory of Open Access Journals (Sweden)

    Ring Kimberly

    2006-09-01

    Full Text Available Abstract Background Preliminary evidence suggests that the physical environment and transportation are associated with youth physical activity levels. Only a few studies have examined the association of physical environmental factors on walking and bicycling to school. Therefore, the purpose of this study was (1 to examine the test-retest reliability of a survey designed for youth to assess perceptions of physical environmental factors (e.g. safety, aesthetics, facilities near the home and transportation, and (2 to describe the associations of these perceptions with both physical activity and active transport to school. Methods Test and retest surveys, administered a median of 12 days later, were conducted with 480 sixth- and eighth-grade girls in or near six U.S. communities. The instrument consisted of 24 questions on safety and aesthetics of the perceived environment and transportation and related facilities. Additionally, girls were asked if they were aware of 14 different recreational facilities offering structured and unstructured activities, and if so, whether they would visit these facilities and the ease with which they could access them. Test-retest reliability was determined using kappa coefficients, overall and separately by grade. Associations with physical activity and active transport to school were examined using mixed model logistic regression (n = 610, adjusting for grade, race/ethnicity, and site. Results Item-specific reliabilities for questions assessing perceived safety and aesthetics of the neighborhood ranged from 0.31 to 0.52. Reliabilities of items assessing awareness of and interest in going to the 14 recreational facilities ranged from 0.47 to 0.64. Reliabilities of items assessing transportation ranged from 0.34 to 0.58. Some items on girls' perceptions of perceived safety, aesthetics of the environment, facilities, and transportation were important correlates of physical activity and, in some cases, active transport

  7. Sex differences in social cognitive factors and physical activity in Korean college students

    Science.gov (United States)

    Choi, Jin Yi; Chang, Ae Kyung; Choi, Eun-Ju

    2015-01-01

    [Purpose] This study examined sex differences in physical activity and social cognitive theory factors in Korean college students. [Subjects and Methods] A cross-sectional survey of 688 college students (285 men and 403 women) in Korea was conducted using a self-reported questionnaire. [Results] There was a significant difference in the level of physical activity between male and female students. The significant predictors of physical activity for male students were physical activity goals, physical activity self-efficacy, and sitting time. Meanwhile, those for female students were perceived weight, physical activity goal, physical activity outcome expectations, and sitting time. [Conclusion] Sex differences should be considered when developing interventions to increase physical activity. PMID:26180293

  8. Vascular Endothelial Growth Factor Receptor 3 Controls Neural Stem Cell Activation in Mice and Humans

    Directory of Open Access Journals (Sweden)

    Jinah Han

    2015-02-01

    Full Text Available Neural stem cells (NSCs continuously produce new neurons within the adult mammalian hippocampus. NSCs are typically quiescent but activated to self-renew or differentiate into neural progenitor cells. The molecular mechanisms of NSC activation remain poorly understood. Here, we show that adult hippocampal NSCs express vascular endothelial growth factor receptor (VEGFR 3 and its ligand VEGF-C, which activates quiescent NSCs to enter the cell cycle and generate progenitor cells. Hippocampal NSC activation and neurogenesis are impaired by conditional deletion of Vegfr3 in NSCs. Functionally, this is associated with compromised NSC activation in response to VEGF-C and physical activity. In NSCs derived from human embryonic stem cells (hESCs, VEGF-C/VEGFR3 mediates intracellular activation of AKT and ERK pathways that control cell fate and proliferation. These findings identify VEGF-C/VEGFR3 signaling as a specific regulator of NSC activation and neurogenesis in mammals.

  9. Using avian radar to examine relationships among avian activity, bird strikes, and meteorological factors

    Science.gov (United States)

    Coates, Peter S.; Casazza, Michael L.; Halstead, Brian J.; Fleskes, Joseph P.; Laughlin, James A.

    2011-01-01

    Radar systems designed to detect avian activity at airfields are useful in understanding factors that influence the risk of bird and aircraft collisions (bird strikes). We used an avian radar system to measure avian activity at Beale Air Force Base, California, USA, during 2008 and 2009. We conducted a 2-part analysis to examine relationships among avian activity, bird strikes, and meteorological and time-dependent factors. We found that avian activity around the airfield was greater at times when bird strikes occurred than on average using a permutation resampling technique. Second, we developed generalized linear mixed models of an avian activity index (AAI). Variation in AAI was first explained by seasons that were based on average migration dates of birds at the study area. We then modeled AAI by those seasons to further explain variation by meteorological factors and daily light levels within a 24-hour period. In general, avian activity increased with decreased temperature, wind, visibility, precipitation, and increased humidity and cloud cover. These effects differed by season. For example, during the spring bird migration period, most avian activity occurred before sunrise at twilight hours on clear days with low winds, whereas during fall migration, substantial activity occurred after sunrise, and birds generally were more active at lower temperatures. We report parameter estimates (i.e., constants and coefficients) averaged across models and a relatively simple calculation for safety officers and wildlife managers to predict AAI and the relative risk of bird strike based on time, date, and meteorological values. We validated model predictability and assessed model fit. These analyses will be useful for general inference of avian activity and risk assessment efforts. Further investigation and ongoing data collection will refine these inference models and improve our understanding of factors that influence avian activity, which is necessary to inform

  10. Levels of haemostatic factors, arteriosclerosis and cardiovascular disease.

    Science.gov (United States)

    Haverkate, F

    2002-08-01

    Plasma levels of haemostasis factors (HFs) such as fibrinogen, tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) and D-dimer may be markers of arteriosclerosis for the following reasons: There seems to be no difference in levels of HFs between patients with longstanding stable angina and those with an isolated myocardial infarction. HF levels are generally positively associated with subclinical arteriosclerosis as determined by ankle-arm index and carotid ultrasonography in asymptomatic individuals. Levels of most HFs are positively associated with inflammation, which is an essential part of the initiation and progression of the disease. A rough classification is assigned to the associations found in under (2) and (3). Fibrinogen is strongly associated with subclinical arteriosclerosis and with inflammation; Factor VII is not, while an intermediate group is formed by, for instance, von Willebrand Factor (vWF), Factor VIII (F VIII), t-PA, PAI-1, and D-dimer. Also, the associations of HFs with cardiovascular events follow a similar pattern. Fibrinogen is a strong and consistent risk factor in several studies, Factor VII is not, and a similar intermediate group as mentioned under (2) and (3) exists. It suggests that the risk of cardiovascular events in relation to HF levels is explained by their identity as markers of arteriosclerosis. A causal association between HF levels and the disease is not proven. Out of the HF, the markers of coagulation such as thrombin-antithrombin complex and of fibrinolysis such as D-dimer are more likely to act causally. Increased levels indicate that they are markers of arteriosclerosis, but in addition, they may reflect a low-grade, continuous formation and subsequent lysis of fibrin in the disease. As the latter reflects an increased tendency to thrombosis, a causal association of levels of markers of coagulation and fibrinolysis with arteriosclerosis, although not yet proven, seems likely.

  11. The neuropeptide head activator induces activation and translocation of the growth-factor-regulated Ca(2+)-permeable channel GRC.

    Science.gov (United States)

    Boels, K; Glassmeier, G; Herrmann, D; Riedel, I B; Hampe, W; Kojima, I; Schwarz, J R; Schaller, H C

    2001-10-01

    The neuropeptide head activator stimulates cell proliferation of neuronal precursor and neuroendocrine cells. The mitogenic signaling cascade requires Ca(2+) influx for which, as we show in this paper, the growth-factor-regulated Ca(2+)-permeable cation channel, GRC, is responsible. GRC is a member of the transient receptor potential channel family. In uninduced cells only low amounts of GRC are present on the plasma membrane but, upon stimulation with head activator, GRC translocates from an intracellular compartment to the cell surface. Head activator functions as an inducer of GRC translocation in neuronal and neuroendocrine cells, which express GRC endogenously, and also in COS-7 cells after transfection with GRC. Head activator is no direct ligand for GRC, but its action requires the presence of a receptor coupled to a pertussis-toxin inhibitable G-protein. Heterologously expressed GRC becomes activated by head activator, which results in opening of the channel and Ca(2+) influx. SK&F 96365, an inhibitor specific for TRP-like channels, blocks Ca(2+) entry and, consequently, translocation of GRC is prevented. Head activator-induced GRC activation and translocation are also inhibited by wortmannin and KN-93, blockers of the phosphatidylinositol 3-kinase and of the Ca(2+)/calmodulin-dependent kinase, respectively, which implies a role for both kinases in head-activator signaling to GRC.

  12. Inactivation of staphylococcal virulence factors using a light-activated antimicrobial agent

    Directory of Open Access Journals (Sweden)

    Wilson Michael

    2009-10-01

    Full Text Available Abstract Background One of the limitations of antibiotic therapy is that even after successful killing of the infecting microorganism, virulence factors may still be present and cause significant damage to the host. Light-activated antimicrobials show potential for the treatment of topical infections; therefore if these agents can also inactivate microbial virulence factors, this would represent an advantage over conventional antibiotic therapy. Staphylococcus aureus produces a wide range of virulence factors that contribute to its success as a pathogen by facilitating colonisation and destruction of host tissues. Results In this study, the ability of the light-activated antimicrobial agent methylene blue in combination with laser light of 665 nm to inactivate staphylococcal virulence factors was assessed. A number of proteinaceous virulence factors were exposed to laser light in the presence of methylene blue and their biological activities re-determined. The activities of V8 protease, α-haemolysin and sphingomyelinase were shown to be inhibited in a dose-dependent manner by exposure to laser light in the presence of methylene blue. Conclusion These results suggest that photodynamic therapy could reduce the harmful impact of preformed virulence factors on the host.

  13. Ability of physical activity to predict cardiovascular disease beyond commonly evaluated cardiometabolic risk factors.

    Science.gov (United States)

    McGuire, K Ashlee; Janssen, Ian; Ross, Robert

    2009-12-01

    It is well-established that increasing physical activity (PA) is important for the prevention and management of cardiovascular disease (CVD). Although it has been demonstrated that PA predicts CVD independent of commonly measured cardiometabolic risk factors in women, it is unclear whether this association is true in men. The study participants consisted of 5,882 adults (age >or=18 years) from the 1999 to 2004 United States National Health and Nutrition Examination Survey. Blood pressure, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, glucose, and waist circumference were categorized using standard clinical thresholds. The participants were divided into the following groups according to the volume of their moderate-to-vigorous intensity PA: active (>or=150 min/wk), somewhat active (30 to 149 min/wk), and inactive (active participants to have CVD. Additional adjustment for cardiometabolic risk factors did not change the odds ratio for CVD in the inactive group. To further delineate the effects of PA on CVD, the participants were cross-classified according to their PA level and their number of cardiometabolic risk factors. Both PA and cardiometabolic risk factors were independent predictors of CVD (P(trend) <0.0001). The results were not modified by gender. In conclusion, PA was associated with CVD, independent of the common cardiometabolic risk factors, in men and women. The association between PA and CVD risk was not mediated by the measured cardiometabolic risk factors.

  14. Muscle atrophy reversed by growth factor activation of satellite cells in a mouse muscle atrophy model.

    Directory of Open Access Journals (Sweden)

    Simon Hauerslev

    Full Text Available Muscular dystrophies comprise a large group of inherited disorders that lead to progressive muscle wasting. We wanted to investigate if targeting satellite cells can enhance muscle regeneration and thus increase muscle mass. We treated mice with hepatocyte growth factor and leukemia inhibitory factor under three conditions: normoxia, hypoxia and during myostatin deficiency. We found that hepatocyte growth factor treatment led to activation of the Akt/mTOR/p70S6K protein synthesis pathway, up-regulation of the myognic transcription factors MyoD and myogenin, and subsequently the negative growth control factor, myostatin and atrophy markers MAFbx and MuRF1. Hypoxia-induced atrophy was partially restored by hepatocyte growth factor combined with leukemia inhibitory factor treatment. Dividing satellite cells were three-fold increased in the treatment group compared to control. Finally, we demonstrated that myostatin regulates satellite cell activation and myogenesis in vivo following treatment, consistent with previous findings in vitro. Our results suggest, not only a novel in vivo pharmacological treatment directed specifically at activating the satellite cells, but also a myostatin dependent mechanism that may contribute to the progressive muscle wasting seen in severely affected patients with muscular dystrophy and significant on-going regeneration. This treatment could potentially be applied to many conditions that feature muscle wasting to increase muscle bulk and strength.

  15. Athlete and Coach Relationship as a Factor of the Success in Sports Activities

    Directory of Open Access Journals (Sweden)

    Svetlova A.A.,

    2014-11-01

    Full Text Available We present the results of a theoretical analysis of the psychological bases of success of athletes. We provide an overview of studies of the factors influencing the success of the activities in the sport. Sports activities are considered as a joint activity of athlete and coach, the success of which is affected by the personal qualities and characteristics of the relationship of its members. We summarize the main approaches to the study of personality and social psychological aspects of successful athletes and coaches. As the main factors in the success of sports activities, we considered individual psychological characteristics of athletes (motives, attitudes, modes of behavior and response, and socio-psychological characteristics of the interaction of coach and athlete (leadership style, the nature of interpersonal relationships and role expectations. We emphasize the importance of mutual role expectations of athlete and coach to achieve high results of sports activity.

  16. Allograft Inflammatory Factor-1 Links T-Cell Activation, Interferon Response, and Macrophage Activation in Chronic Kawasaki Disease Arteritis.

    Science.gov (United States)

    Rowley, Anne H; Baker, Susan C; Kim, Kwang-Youn A; Shulman, Stanford T; Yang, Amy; Arrollo, David; DeBerge, Matthew; Han, Shuling; Sibinga, Nicholas E S; Pink, Adam J; Thorp, Edward B

    2017-09-01

    Kawasaki disease (KD) is widely viewed as an acute arteritis. However, our pathologic studies show that chronic coronary arteritis can persist long after disease onset and is closely linked with arterial stenosis. Transcriptome profiling of acute KD arteritis tissues revealed upregulation of T lymphocyte, type I interferon, and allograft inflammatory factor-1 (AIF1) genes. We determined whether these immune responses persist in chronic KD arteritis, and we investigated the role of AIF1 in these responses. Gene expression in chronic KD and childhood control arteries was determined by real-time reverse-transcriptase polymerase chain reaction, and arterial protein expression was determined by immunohistochemistry and immunofluorescence. Allograft inflammatory factor-1 small-interfering ribonucleic acid macrophage treatment was performed to investigate the role of AIF1 in macrophage and T lymphocyte activation. Allograft inflammatory factor-1 protein was highly expressed in stenotic KD arteries and colocalized with the macrophage marker CD68. T lymphocyte and interferon pathway genes were significantly upregulated in chronic KD coronary artery tissues. Alpha interferon-induced macrophage expression of CD80 and major histocompatibility complex class II was dependent on AIF1, and macrophage expression of AIF1 was required for antigen-specific T lymphocyte activation. Allograft inflammatory factor-1, originally identified in posttransplant arterial stenosis, is markedly upregulated in KD stenotic arterial tissues. T lymphocyte and type I interferon responses persist in chronic KD arteritis. Allograft inflammatory factor-1 may play multiple roles linking type I interferon response, macrophage activation, and antigen-specific T lymphocyte activation. These results suggest the likely importance of lymphocyte-myeloid cell cross-talk in the pathogenesis of KD arteritis and can inform selection of new immunotherapies for clinical trials in high-risk KD children.

  17. Activated factor X signaling via protease-activated receptor 2 suppresses pro-inflammatory cytokine production from LPS-stimulated myeloid cells.

    LENUS (Irish Health Repository)

    Gleeson, Eimear M

    2013-07-19

    Vitamin K-dependent proteases generated in response to vascular injury and infection enable fibrin clot formation, but also trigger distinct immuno-regulatory signaling pathways on myeloid cells. Factor Xa, a protease crucial for blood coagulation, also induces protease-activated receptor-dependent cell signaling. Factor Xa can bind both monocytes and macrophages, but whether factor Xa-dependent signaling stimulates or suppresses myeloid cell cytokine production in response to Toll-like receptor activation is not known. In this study, exposure to factor Xa significantly impaired pro-inflammatory cytokine production from lipopolysaccharide-treated peripheral blood mononuclear cells, THP-1 monocytic cells and murine macrophages. Furthermore, factor Xa inhibited nuclear factor-kappa B activation in THP-1 reporter cells, requiring phosphatidylinositide 3-kinase activity for its anti-inflammatory effect. Active-site blockade, γ-carboxyglutamic acid domain truncation and a peptide mimic of the factor Xa inter-epidermal growth factor-like region prevented factor Xa inhibition of lipopolysaccharide-induced tumour necrosis factor-α release. In addition, factor Xa anti-inflammatory activity was markedly attenuated by the presence of an antagonist of protease-activated receptor 2, but not protease-activated receptor 1. The key role of protease-activated receptor 2 in eliciting factor Xa-dependent anti-inflammatory signaling on macrophages was further underscored by the inability of factor Xa to mediate inhibition of tumour necrosis factor-α and interleukin-6 release from murine bone marrow-derived protease-activated receptor 2-deficient macrophages. We also show for the first time that, in addition to protease-activated receptor 2, factor Xa requires a receptor-associated protein-sensitive low-density lipoprotein receptor to inhibit lipopolysaccharide-induced cytokine production. Collectively, this study supports a novel function for factor Xa as an endogenous, receptor

  18. Adherence to physical activity recommendations and its associated factors: an interregional population-based study

    Directory of Open Access Journals (Sweden)

    Ala'a Alkerwi

    2015-03-01

    Full Text Available Background. Though the influence of physical activity in preventing cardiovascular diseases is well documented, only a few comparative studies have determined the degree of adherence to physical activity recommendations among populations and identified the demographic, socioeconomic, behavioural and health-related factors associated with good compliance. Design and methods. Cross-sectional interregional NESCaV survey of 3133 subjects compared three populations, Luxembourg, Lorraine (France and Wallonia (Belgium, by using the International Physical Activity Questionnaire. Age and gender prevalence rates of physical activity were standardized to the European population. Results. The likelihood to meet the recommendations was higher in Luxembourg, after adjustment for age, gender, education, employment, weight status, morbidity score, health perception and level of importance attributed to the practice of physical activity (P<0.0001. The odds for meeting the recommendations were significantly higher among those with secondary than tertiary education. Compared to good self-health perception, subjects with poor or fair self-perceived health were less likely to meet the recommendations; this also applied to those attributing little or enough importance to physical activity compared with great importance. Conclusions. Region, education, self-perceived health and perception of importance of physical activity were emerged as independent determinants of meeting the recommendations. Awareness of the positive health effects of physical activity might thus be crucial for motivating the people to become more active. Further research is needed to explore potential region-specific factors which might explain the difference in population behaviours with respect to physical activity.

  19. Lapses and psychosocial factors related to physical activity in early postmenopause.

    Science.gov (United States)

    Conroy, Molly B; Simkin-Silverman, Laurey R; Pettee, Kelley K; Hess, Rachel; Kuller, Lewis H; Kriska, Andrea M

    2007-10-01

    After menopause, leisure physical activity (PA) levels seem to decline for reasons that are not completely understood. This study examines the associations between PA, lapses in PA, and psychosocial factors in early postmenopausal women. This cross-sectional analysis included 497 women from the Women on the Move through Activity and Nutrition study. PA was assessed with a past-year, interviewer-administered Modifiable Activity Questionnaire. Measures of activity lapses of >or= 2 wk in the past 6 months, exercise decision making, processes of change, and self-efficacy were collected along with Beck Depression Inventory, State-Trait Anxiety Inventory, Cohen Perceived Stress Scale, and Short Form-36. Mean age of participants was 56.9 yr. Compared with less active women, women with significantly higher activity levels reported greater exercise self-efficacy (r = 0.31), more frequent use of behavioral exercise processes of change (r = 0.31), greater perceived benefits for PA (r = 0.22), and better physical quality of life (r = 0.16) (all P activity lapses had higher reported activity levels than regularly active women with lapses or occasionally active women with lapses (P anxiety and depressive symptoms, and less frequent use of behavioral exercise processes of change, were associated with relapse to inactivity. Future interventions for early postmenopausal women should consider psychosocial factors when attempting to encourage and maintain higher levels of PA. Addressing and preventing PA lapses may help to achieve PA goals in this population.

  20. Factors Influencing Entering Teacher Candidates' Preferences for Instructional Activities: A glimpse into their orientations towards teaching

    Science.gov (United States)

    Talanquer, Vicente; Novodvorsky, Ingrid; Tomanek, Debra

    2010-07-01

    The present study was designed to identify and characterize the major factors that influence entering science teacher candidates' preferences for different types of instructional activities, and to analyze what these factors suggest about teacher candidates' orientations towards science teaching. The study involved prospective teachers enrolled in the introductory science teaching course in an undergraduate science teacher preparation program. Our analysis was based on data collected using a teaching and learning beliefs questionnaire, together with structured interviews. Our results indicate that entering science teacher candidates have strong preferences for a few activity types. The most influential factors driving entering science teacher candidates' selections were the potential of the instructional activities to motivate students, be relevant to students' personal lives, result in transfer of skills to non-science situations, actively involve students in goal-directed learning, and implement curriculum that represents what students need to know. This set of influencing factors suggests that entering science teacher candidates' orientations towards teaching are likely driven by one or more of these three central teaching goals: (1) motivating students, (2) developing science process skills, and (3) engaging students in structured science activities. These goals, and the associated beliefs about students, teaching, and learning, can be expected to favor the development or enactment of three major orientations towards teaching in this population of future science teachers: "motivating students," "process," and "activity-driven."

  1. Tourist activity of young people as a factor contributing to their health and proper development.

    Science.gov (United States)

    Biernat, Elżbieta; Tomaszewski, Paweł

    2013-01-01

    The aim of this paper is to assess the level of tourist activity of pupils and students from schools in Warsaw, as well as factors influencing this level of activity. A two-part questionnaire was used that included questions related to participation in tourist trips (day, long, short, and trips abroad) and the International Physical Activity Questionnaire (IPAQ). Among the analyzed factors (gender, level of school, level of physical activity), only the level of school turned out to be the factor which significantly (p=0.000) influenced the physical activity of the respondents. It was observed that tourist activity among pupils and students decreased with age. There is an urgent need for a systematic approach towards promoting and supporting the participation of children and young people in tourism. as well as setting examples of how to travel and rest. Carrying out intervention programmes demands the further identification of factors determining them (e.g. influence of parents' leisure time behaviour), as well as the application of standardized research tools.

  2. The relationship between postnatal depression, sociodemographic factors, levels of partner support, and levels of physical activity.

    Science.gov (United States)

    Saligheh, Maryam; Rooney, Rosanna M; McNamara, Beverley; Kane, Robert T

    2014-01-01

    postnatal depression (PND) is defined as a psychological mood disorder that occurs in a mother within 6 weeks of her giving birth. It refers to an episode that causes mood disturbance and it could begin in, or extend into, the postpartum period. It is thought to have a high impact upon the mother's health as well as the family's functioning and the child's development. Socio-demographic, psych-social, and physical activity factors may all contribute to postpartum mood and ability to cope with responsibilities. The primary aim of this study was to determine which of these factors predicted PND in postpartum women. A secondary aim was to identify the socio-demographic and psycho-social predictors of physical activity in postpartum women. The study used a cross-sectional correlational design. A sample of 150 postpartum women was sent a package of six standardized questionnaires. There was no association between physical activity and PND; however, older mothers, mothers of younger children, mothers who are less reluctant to ask for help, and mothers who are more satisfied with the help they get experience lower levels of PND. Mothers of older babies, mothers with more children, and less educated mothers are more likely to engage in caregiving activities, whereas mothers with fewer children and higher levels of partner support are more likely to engage in occupational activities. None of the socio-demographic factors or any of the parenting factors predicted levels of sporting activity.

  3. Factors Associated with Nursing Activities in Humanitarian Aid and Disaster Relief

    Science.gov (United States)

    Noguchi, Norihito; Inoue, Satoshi; Shimanoe, Chisato; Shibayama, Kaoru; Shinchi, Koichi

    2016-01-01

    Background Although nurses play an important role in humanitarian aid and disaster relief (HA/DR), little is known about the nursing activities that are performed in HA/DR. We aimed to clarify the nursing activities performed by Japanese nurses in HA/DR and to examine the factors associated with the frequency of nursing activities. Methods A self-administered questionnaire survey was completed by 147 nurses with HA/DR experience. The survey extracted information on demographic characteristics, past experience (e.g., disaster medical training experience, HA/DR experience), circumstances surrounding their dispatched to HA/DR (e.g., team size, disaster type, post-disaster phase, mission term), and the frequency of nursing activities performed under HA/DR. The frequency of nursing activities was rated on a 5-point Likert scale. Evaluation of nursing activities was conducted based on the “nursing activity score”, which represents the frequency of each nursing activity. Factors related to the nursing activity score were evaluated by multiple logistic regression analysis. Results Nurses were involved in 27 nursing activities in HA/DR, 10 of which were performed frequently. On analysis, factors significantly associated with nursing activity score were nursing license as a registered nurse (OR 7.79, 95% CI 2.95–20.57), two or more experiences with disaster medical training (OR 2.90 95%, CI 1.12–7.49) and a post-disaster phase of three weeks or longer (OR 8.77, 95% CI 2.59–29.67). Conclusions These results will contribute to the design of evidence-based disaster medical training that improves the quality of nursing activities. PMID:26959351

  4. Prevalence of factors related to active reproductive health behavior: a cross-sectional study Indonesian adolescent.

    Science.gov (United States)

    Susanto, Tantut; Rahmawati, Iis; Wuryaningsih, Emi Wuri; Saito, Ruka; Syahrul; Kimura, Rumiko; Tsuda, Akiko; Tabuchi, Noriko; Sugama, Junko

    2016-01-01

    Complex and diverse factors are related to reproductive health (RH) behavior among adolescents according to the social and cultural context of each countries. This study examined the prevalence of active RH and factors related to active RH behavior among Indonesian adolescents. A cross-sectional study was conducted among 1,040 of students who were selected through a multi-stage random sampling technique. A self-administered questionnaire was developed, including the World Health Organization Illustrative Questionnaire for Interview-Surveys with Young People, pubertal development scale, and sexual activity scale, modified in accordance to the Indonesian context. The data were analyzed using descriptive and comparative statistics, as well as logistic regression analyses. The prevalence of active RH behavior were more higher in boys (56.6%; 95% confidence interval [CI], 50.6% to 62.6%) than in girls (43.7%; 95% CI, 37.6% to 49.8%). Negative attitudes towards RH were a factor related to active RH behavior in both boys and girls. Smoking and kind relationship envisioned before marriage (pacaran [courtship] and nikah siri [non-registered marriage]) were factors related to active RH behavior in boys; whereas the absence of access to information on substance abuse was an additional factor in girls. Moreover, an interaction was found between access to information on development and smoking (boys) and attitudes on RH (girls) as independent variables associated with active RH behavior. Sex education for adolescents in Indonesia, particularly in the context of a health promotion program, should be developed based on prevalent social, cultural, and religious values to prevent active RH behavior. Such programs should focus on the kind of relationship envisioned before marriage and smoking for boys and access to information on subtance abuse for girls.

  5. Norepinephrine activates NF-κB transcription factor in cultured rat pineal gland.

    Science.gov (United States)

    Villela, Darine; de Sá Lima, Larissa; Peres, Rafael; Peliciari-Garcia, Rodrigo Antonio; do Amaral, Fernanda Gaspar; Cipolla-Neto, José; Scavone, Cristóforo; Afeche, Solange Castro

    2014-01-17

    The circadian rhythm in mammalian pineal melatonin secretion is modulated by norepinephrine (NE) released at night. NE interaction with β1-adrenoceptors activates PKA that phosphorylates the transcription factor CREB, leading to the transcription and translation of the arylalkylamine-N-acetyltransferase (AANAT) enzyme. Several studies have reported the interplay between CREB and the nuclear factor-κB (NF-κB) and a circadian rhythm for this transcription factor was recently described in the rat pineal gland. In this work we studied a direct effect of NE on NF-κB activation and the role played by this factor on melatonin synthesis and Aanat transcription and activity. Cultured rat pineal glands were incubated in the presence of two different NF-κB inhibitors, pyrrolidine-dithiocarbamate or sodium salicylate, and stimulated with NE. Melatonin content was quantified by HPLC with electrochemical detection. AANAT activity was measured by a radiometric assay and the expression of Aanat mRNA was analyzed by real-time PCR. Gel shift assay was performed to study the NF-κB activation in cultured rat pineal glands stimulated by NE. Our results showed that the p50/p50 homodimer of NF-κB is activated by NE and that it has a role in melatonin synthesis, acting on Aanat transcription and activity. Here we present evidence that NF-κB is an important transcription factor that acts, directly or indirectly, on Aanat transcription and activity leading to a modulation of melatonin synthesis. NE plays a role in the translocation of NF-κB p50/p50 homodimer to the nucleus of pinealocytes, thus probably influencing the nocturnal pineal melatonin synthesis. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Optimisation of the Factor VIII yield in mammalian cell cultures by reducing the membrane bound fraction

    DEFF Research Database (Denmark)

    Kolind, Mille Petersen; Nørby, Peder Lisby; Berchtold, Martin Werner

    2011-01-01

    of active membrane bound rFVIII to the culture medium. Moreover, the attachment of rFVIII to cell membranes of un-transfected HEK293 cells was studied in the presence of compounds that competes for interactions between rFVIII and PS. Competitive assays between iodinated rFVIII (¹²5I-rFVIII) and annexin V......In vivo, clotting Factor VIII (FVIII) circulates in plasma bound to von Willebrand factor (vWF), and the vWF:FVIII complex prevents binding of FVIII to phosphatidylserine (PS). Activation of FVIII by thrombin releases FVIII from vWF, and subsequently FVIII binds to PS exposed on activated platelets...... of the production cells. Recently, we showed that as much as 90% of secreted rFVIII is bound to transiently transfected production cells during serum free conditions. In this study, we investigated the effect of including vWF in the serum free medium, and demonstrate that addition of vWF results in release...

  7. Physical activity and cardiovascular risk factors among elderly men in Finland, Italy, and the Netherlands.

    Science.gov (United States)

    Bijnen, F C; Feskens, E J; Caspersen, C J; Giampaoli, S; Nissinen, A M; Menotti, A; Mosterd, W L; Kromhout, D

    1996-03-15

    Physical activity pattern and its relation with cardiovascular risk factors was investigated in 1,402 men aged 69-90 years who participated in the 30-year follow-up survey of the Finnish (Eastern and Western Finland), Italian (Montegiorgio and Crevalcore), and Dutch (Zutphen) cohorts of the Seven Countries Study. Physical activity was assessed with a validated self-administered questionnaire designed for retired men. Total physical activity varied largely within cohorts. Median total reported physical activity ranged from 50 minutes/day in Montegiorgio to 89 minutes/day in Crevalcore. Walking, gardening, and bicycling together contributed more than 70% of total physical activity in all cohorts. Depending on the definition of physical inactivity, the estimated prevalence of inactivity varied between 5% and 33% in Zutphen and between 18% and 68% in Montegiorgio. Total physical activity was inversely associated with resting heart rate (r= -0.11, p physical activity pattern.

  8. Low muscle mass in older men: the role of lifestyle, diet and cardiovascular risk factors.

    Science.gov (United States)

    Atkins, J L; Whincup, P H; Morris, R W; Wannamethee, S G

    2014-01-01

    To explore associations between low muscle mass and a wide range of lifestyle, dietary and cardiovascular risk factors in older men including metabolic risk factors, markers of inflammation, endothelial dysfunction and coagulation. Cross-sectional study. British Regional Heart Study. 4252 men aged 60-79 years. PARTICIPANTS attended a physical examination in 1998-2000, and completed a general questionnaire and a food frequency questionnaire. Low muscle mass was assessed by two measures: midarm muscle circumference (MAMC) and fat-free mass index (FFMI). Associations between risk factors and low muscle mass were analysed using logistic regression. Physical inactivity, insulin resistance, C-reactive protein, von Willebrand factor and fibrinogen were associated with significantly increased odds of low MAMC and FFMI after adjustment for body mass index, lifestyle characteristics and morbidity. Those with higher percent energy intake from carbohydrates showed decreased odds of low MAMC (OR: 0.73, 95% CI: 0.55-0.96) and FFMI (OR: 0.76, 95% CI: 0.58-0.99). Other dietary variables, smoking, alcohol intake, D-dimer, interleukin 6 and homocysteine showed no important associations with MAMC and FFMI. Increasing physical activity, consuming a diet with a high proportion of energy from carbohydrates, and taking steps to prevent insulin resistance and reduce inflammation and endothelial dysfunction may help to reduce the risk of low muscle mass in older men.

  9. Factors Influencing Physicians' Selection of Continuous Professional Development Activities: A Cross-Specialty National Survey.

    Science.gov (United States)

    Cook, David A; Price, David W; Wittich, Christopher M; West, Colin P; Blachman, Morris J

    2017-01-01

    We sought to understand what influences physicians' decisions about participation in continuous professional development (CPD) activities, and how often physicians engage in specific CPD activities. From September 2015 to April 2016, we administered a survey to 4648 randomly sampled licensed US physicians. Survey items addressed perceived barriers to CPD, factors that might influence participation in four prototypical CPD activities (reading an article, or completing a local activity, online course, or far-away course), and frequency of CPD engagement. Nine hundred eighty-eight (21.6%) physicians responded. The most important barriers were time (mean [SD] 3.5 [1.3], 1 = not important, 5 = extremely important) and cost (2.9 [1.3]). In prioritizing factors influencing participation in four prototypical CPD activities, topical relevance consistently had the highest average rank. Quality of content and time to complete the activity were also frequently selected. Over the past 3 years, most physicians reported having participated in patient-focused learning and self-directed learning on a weekly basis; quality improvement and local continuing medical education (CME) activities several times per year; online learning, on-site courses, and national board-related activities a few times per year; and interprofessional learning less than once per year. Physicians believed that they ought to engage more often in all of these activities except board-related activities. They would like CME credit for these activities much more often than currently obtained. The reasons physicians select a given CPD activity vary by activity, but invariably include topic and quality of content. Physicians want CME credit for the CPD activities they are already doing.

  10. von Willebrand Disease

    Science.gov (United States)

    ... or increase the risk of bleeding. Examples include aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), clopidogrel, warfarin, or heparin. Any history of liver or kidney disease, blood or bone ...

  11. Motivating and Demotivating Factors for Students With Low Emotional Intelligence to Participate in Speaking Activities

    OpenAIRE

    Mariza G. Méndez López; Moisés Bautista Tun

    2017-01-01

    The study aims to understand what factors may motivate and demotivate students with low emotional intelligence to participate in speaking activities during English class. Participants wrote an emotions journal to identify factors affecting student participation and were then interviewed at the end of the study period in order to elaborate on their experiences. Results showed that male participants experienced a wide range of negative emotions while females experienced a reduced number. Howeve...

  12. Cigarette smoke?induced urothelial cell damage: potential role of platelet?activating factor

    OpenAIRE

    Kispert, Shannon E.; Marentette, John; Campian, E. Cristian; Isbell, T. Scott; Kuenzel, Hannah; McHowat, Jane

    2017-01-01

    Abstract Cigarette smoking is an environmental risk factor associated with a variety of pathologies including cardiovascular disease, inflammation, and cancer development. Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic inflammatory bladder disease with multiple etiological contributors and risk factors associated with its development, including cigarette smoking. Previously, we determined that cigarette smoking was associated with bladder wall accumulation of platelet activ...

  13. [Conception for permanent activation of nuclear factor kbeta as molecular basis for metabolic syndrom pathogenesis].

    Science.gov (United States)

    Kaidashev, I P

    2013-01-01

    The analysis of new data concerning the development of pathology due to the community of evolutionary new pathological factors was done. Author provides the comparison of well-known and new definition for "metabolic syndrome" and diagnostic criteria of this pathology. The conception for permanent activation of nuclear factor kbeta as possible typic pathological process was discussed. Suppose that NF-kbeta is the possible key molecule in the initiation and formation of "vicious circle"--insulinresistance--inflammation--atherosclerosis.

  14. Membrane-to-nucleus signaling links insulin-like growth factor-1- and stem cell factor-activated pathways.

    Directory of Open Access Journals (Sweden)

    Yujiro Hayashi

    Full Text Available Stem cell factor (mouse: Kitl, human: KITLG and insulin-like growth factor-1 (IGF1, acting via KIT and IGF1 receptor (IGF1R, respectively, are critical for the development and integrity of several tissues. Autocrine/paracrine KITLG-KIT and IGF1-IGF1R signaling are also activated in several cancers including gastrointestinal stromal tumors (GIST, the most common sarcoma. In murine gastric muscles, IGF1 promotes Kitl-dependent development of interstitial cells of Cajal (ICC, the non-neoplastic counterpart of GIST, suggesting cooperation between these pathways. Here, we report a novel mechanism linking IGF1-IGF1R and KITLG-KIT signaling in both normal and neoplastic cells. In murine gastric muscles, the microenvironment for ICC and GIST, human hepatic stellate cells (LX-2, a model for cancer niches, and GIST cells, IGF1 stimulated Kitl/KITLG protein and mRNA expression and promoter activity by activating several signaling pathways including AKT-mediated glycogen synthase kinase-3β inhibition (GSK3i. GSK3i alone also stimulated Kitl/KITLG expression without activating mitogenic pathways. Both IGF1 and GSK3i induced chromatin-level changes favoring transcriptional activation at the Kitl promoter including increased histone H3/H4 acetylation and H3 lysine (K 4 methylation, reduced H3K9 and H3K27 methylation and reduced occupancy by the H3K27 methyltransferase EZH2. By pharmacological or RNA interference-mediated inhibition of chromatin modifiers we demonstrated that these changes have the predicted impact on KITLG expression. KITLG knock-down and immunoneutralization inhibited the proliferation of GIST cells expressing wild-type KIT, signifying oncogenic autocrine/paracrine KITLG-KIT signaling. We conclude that membrane-to-nucleus signaling involving GSK3i establishes a previously unrecognized link between the IGF1-IGF1R and KITLG-KIT pathways, which is active in both physiologic and oncogenic contexts and can be exploited for therapeutic purposes.

  15. Human memory manipulated: dissociating factors contributing to MTL activity, an fMRI study.

    Science.gov (United States)

    Pustina, Dorian; Gizewski, Elke; Forsting, Michael; Daum, Irene; Suchan, Boris

    2012-04-01

    Memory processes are mainly studied with subjective rating procedures. We used a morphing procedure to objectively manipulate the similarity of target stimuli. While undergoing functional magnetic resonance imaging, nineteen subjects performed a encoding and recognition task on face and scene stimuli, varying the degree of manipulation of previously studied targets at 0%, 20%, 40% or 60%. Analyses were performed with parametric modulations for objective stimulus status (morphing level), subjective memory (confidence rating), and reaction times (RTs). Results showed that medial temporal lobe (MTL) activity can be best explained by a combination of subjective and objective factors. Memory success is associated with activity modulation in the hippocampus both for faces and for scenes. Memory failures correlated with lower hippocampal activity for scenes, but not for faces. Activity changed during retrieval on similar areas activated during encoding. There was a considerable impact of RTs on memory-related areas. Objective perceptual identity correlated with activity in the left MTL, while subjective memory experience correlated with activity in the right MTL for both types of material. Overall, the results indicate that MTL activity is heterogeneous, showing both linear and non-linear activity, depending on the factor analyzed. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Combined influence of healthy diet and active lifestyle on cardiovascular disease risk factors in adolescents.

    Science.gov (United States)

    Cuenca-García, M; Ortega, F B; Ruiz, J R; González-Gross, M; Labayen, I; Jago, R; Martínez-Gómez, D; Dallongeville, J; Bel-Serrat, S; Marcos, A; Manios, Y; Breidenassel, C; Widhalm, K; Gottrand, F; Ferrari, M; Kafatos, A; Molnár, D; Moreno, L A; De Henauw, S; Castillo, M J; Sjöström, M

    2014-06-01

    To investigate the combined influence of diet quality and physical activity on cardiovascular disease (CVD) risk factors in adolescents, adolescents (n = 1513; 12.5-17.5 years) participating in the Healthy Lifestyle in Europe by Nutrition in Adolescence study were studied. Dietary intake was registered using a 24-h recall and a diet quality index was calculated. Physical activity was assessed by accelerometry. Lifestyle groups were computed as: healthy diet and active, unhealthy diet but active, healthy diet but inactive, and unhealthy diet and inactive. CVD risk factor measurements included cardiorespiratory fitness, adiposity indicators, blood lipid profile, blood pressure, and insulin resistance. A CVD risk score was computed. The healthy diet and active group had a healthier cardiorespiratory profile, fat mass index (FMI), triglycerides, and high-density lipoprotein cholesterol (HDL-C) levels and total cholesterol (TC)/HDL-C ratio (all P ≤ 0.05). Overall, active adolescents showed higher cardiorespiratory fitness, lower FMI, TC/HDL-C ratio, and homeostasis model assessment index and healthier blood pressure than their inactive peers with either healthy or unhealthy diet (all P ≤ 0.05). Healthy diet and active group had healthier CVD risk score compared with the inactive groups (all P ≤ 0.02). Thus, a combination of healthy diet and active lifestyle is associated with decreased CVD risk in adolescents. Moreover, an active lifestyle may reduce the adverse consequences of an unhealthy diet. © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. [Higher physical activity levels are associated with lower prevalence of cardiovascular risk factors in Chile].

    Science.gov (United States)

    Celis-Morales, Carlos; Salas, Carlos; Álvarez, Cristian; Aguilar Farías, Nicolás; Ramírez Campillos, Rodrigo; Leppe, Jaime; Cristi-Montero, Carlos; Díaz Martínez, Ximena; Duran, Eliana; Labraña, Ana María; Martínez, María Adela; Leiva, Ana María; Willis, Naomi

    2015-11-01

    Little is known about the relationship between physical activity (PA) and cardiovascular risk factors in the Chilean population. To investigate the association between different levels and intensities of PA and the prevalence of cardiovascular (CV) risk factors in Chilean adults. Data from the National Health Survey 2009-10 including 5157 participants, provided by the Epidemiology Department of the Ministry of Health, was analyzed in this study. The prevalence of type 2 diabetes mellitus, hypertension, metabolic syndrome and dyslipidemia were determined using international criteria. PA levels were determined using the Global Physical Activity Questionnaire (GPAQ v2) and different levels of PA were derived from it (transport-related, moderate and vigorous PA). Quartiles of PA were determined to investigate the association between PA and cardiovascular risk factors. Twenty three percent of women and 17.1% of men did not meet the PA recommendation (≥ 600 METs.min.week-1). When prevalence of CV risk factors were compared between inactive individuals (active individuals (≥ 9500 METs.min.week-1) a significantly lower prevalence of diabetes mellitus (6.2% and 10%), hypertension (18.0% and 12.4%) and metabolic syndrome (8.9% and 12.1%) for women and men, respectively, was found in the active participants. Similar results were found for high versus low transport-related PA. Increasing levels of PA are associated with a significantly lower frequency of cardiovascular risk factors in Chilean adults.

  18. Platelet activation using electric pulse stimulation: growth factor profile and clinical implications.

    Science.gov (United States)

    Torres, Andrew S; Caiafa, Antonio; Garner, Allen L; Klopman, Steve; LaPlante, Nicole; Morton, Christine; Conway, Kenneth; Michelson, Alan D; Frelinger, Andrew L; Neculaes, V Bogdan

    2014-09-01

    Autologous platelet gel therapy using platelet-rich plasma has emerged as a promising alternative for chronic wound healing, hemostasis, and wound infection control. A critical step for this therapeutic approach is platelet activation, typically performed using bovine thrombin (BT) and calcium chloride. However, exposure of humans to BT can stimulate antibody formation, potentially resulting in severe hemorrhagic or thrombotic complications. Electric pulse stimulation using nanosecond PEFs (pulse electric fields) is an alternative, nonbiochemical platelet activation method, thereby avoiding exposure to xenogeneic thrombin and associated risks. In this study, we identified specific requirements for a clinically relevant activator instrument by dynamically measuring current, voltage, and electric impedance for platelet-rich plasma samples. From these samples, we investigated the profile of growth factors released from human platelets with electric pulse stimulation versus BT, specifically platelet-derived growth factor, transforming growth factor β, and epidermal growth factor, using commercial enzyme-linked immunosorbent assay kits. Electric pulse stimulation triggers growth factor release from platelet α-granules at the same or higher level compared with BT. Electric pulse stimulation is a fast, inexpensive, easy-to-use platelet activation method for autologous platelet gel therapy.

  19. Synthesis and characterization of 18F-labeled active site inhibited factor VII (ASIS)

    DEFF Research Database (Denmark)

    Erlandsson, Maria; Nielsen, Carsten Haagen; Jeppesen, Troels Elmer

    2015-01-01

    Activated factor VII blocked in the active site with Phe-Phe-Arg-chloromethyl ketone (active site inhibited factor VII (ASIS)) is a 50-kDa protein that binds with high affinity to its receptor, tissue factor (TF). TF is a transmembrane glycoprotein that plays an important role in, for example......, thrombosis, metastasis, tumor growth, and tumor angiogenesis. The aim of this study was to develop an 18F-labeled ASIS derivative to assess TF expression in tumors. Active site inhibited factor VII was labeled using N-succinimidyl-4-[18F]fluorobenzoate, and the [18F]ASIS was purified on a PD-10 desalting...... column. The radiochemical yield was 25 ± 6%, the radiochemical purity was >97%, and the pseudospecific radioactivity was 35 ± 9 GBq/µmol. The binding efficacy was evaluated in pull-down experiments, which monitored the binding of unlabeled ASIS and [18F]ASIS to TF and to a specific anti-factor VII...

  20. Peroxisome proliferator-activated receptor gamma recruits the positive transcription elongation factor b complex to activate transcription and promote adipogenesis

    DEFF Research Database (Denmark)

    Iankova, Irena; Petersen, Rasmus K; Annicotte, Jean-Sébastien

    2006-01-01

    Positive transcription elongation factor b (P-TEFb) phosphorylates the C-terminal domain of RNA polymerase II, facilitating transcriptional elongation. In addition to its participation in general transcription, P-TEFb is recruited to specific promoters by some transcription factors such as c...... with and phosphorylation of peroxisome proliferator-activated receptor gamma (PPARgamma), which is the master regulator of this process, on the promoter of PPARgamma target genes. PPARgamma-cdk9 interaction results in increased transcriptional activity of PPARgamma and therefore increased adipogenesis.......-Myc or MyoD. The P-TEFb complex is composed of a cyclin-dependent kinase (cdk9) subunit and a regulatory partner (cyclin T1, cyclin T2, or cyclin K). Because cdk9 has been shown to participate in differentiation processes, such as muscle cell differentiation, we studied a possible role of cdk9...