How useful is determination of anti-factor Xa activity to guide bridging therapy with enoxaparin? A pilot study.

Science.gov (United States)

Hammerstingl, Christoph; Omran, Heyder; Tripp, Christian; Poetzsch, Bernd

2009-02-01

Low-molecular-weight heparins (LMWH) are commonly used as peri-procedural bridging anticoagulants. The usefulness of measurement of anti-factor Xa activity (anti-Xa) to guide bridging therapy with LMWH is unknown. It was the objective of this study to determine levels of anti-Xa during standard bridging therapy with enoxaparin, and to examine predictors for residual anti-Xa. Consecutive patients receiving enoxaparin at a dosage of 1 mg/kg body weight/12 hours for temporary interruption of phenprocoumon were prospectively enrolled to the study. Blood-samples were obtained 14 hours after LMWH-application immediately pre- procedurally. Procedural details, clinical and demographic data were collected and subsequently analyzed. Seventy patients were included (age 75.2 +/- 10.8 years, Cr Cl 55.7 +/- 21.7ml/min, body mass index [BMI] 27.1 +/- 4.9). LMWH- therapy was for a mean of 4.2 +/- 1.6 days; overall anti-Xa was 0.58 +/- 0.32 U/ml. In 37 (52.8%) of patients anti-Xa was > or U/ml, including 10 (14.3%) patients with anti-Xa > 1U/ml. Linear regression analysis of single variables and logistic multivariable regression analysis failed to prove a correlation between anti-Xa and single or combined factors. No major bleeding, no thromboembolism and four (5.7%) minor haemorrhages were observed. When bridging OAC with therapeutic doses of enoxaparin a high percentage of patients undergo interventions with high residual anti-Xa. The levels of anti-Xa vary largely and are independent of single or combined clinical variables. Since the anti-Xa-related outcome of patients receiving bridging therapy with LMWH is not investigated, no firm recommendation on the usefulness of monitoring of anti-Xa can be given at this stage.

Expressional and Biochemical Characterization of Rice Disease Resistance Gene Xa3/Xa26 Family

Institute of Scientific and Technical Information of China (English)

Songjie Xu; Yinglong Cao; Xianghua Li; Shiping Wang

2007-01-01

The rice (Oryza sativa L.) Xa3/Xa26 gene, conferring race-specific resistance to bacterial blight disease and encoding a leucine-rich repeat (LRR) receptor kinase-like protein, belongs to a multigene family consisting of tandem clustered homologous genes, colocalizing with several uncharacterized genes for resistance to bacterial blight or fungal blast. To provide more information on the expressional and biochemical characteristics of the Xa3/Xa26 family, we analyzed the family members. Four Xa3/Xa26 family members in the indica rice variety Teqing, which carries a bacterial blight resistance gene with a chromosomal location tightly linked to Xa3/Xa26, and five Xa3/Xa26 family members in the japonica rice variety Nipponbare, which carries at least one uncharacterized blast resistance gene, were constitutively expressed in leaf tissue. The result suggests that some of the family members may be candidates of these uncharacterized resistance genes. At least five putative N-glycosylation sites in the LRR domain of XA3/XA26 protein are not glycosylated. The XA3/XA26 and its family members MRKa and MRKc all possess the consensus sequences of paired cysteines, which putatively function in dimerization of the receptor proteins for signal transduction, immediately before the first LRR and immediately after the last LRR. However, no homo-dimer between the XA3/XA26 molecules or hetero-dimer between XA3/XA26 and MRKa or MRKc were formed, indicating that XA3/XA26 protein might function either as a monomer or a hetero-dimer formed with other protein outside of the XA3/XA26 family. These results provide valuable information for further extensive investigation into this multiple protein family.

Ortholog Alleles at Xa3/Xa26 Locus Confer Conserved Race-Specific Resistance against Xanthomonas oryzae in Rice

Institute of Scientific and Technical Information of China (English)

Hong-Jing Li; Xiang-Hua Li; Jing-Hua Xiao; Rod A. Wing; Shi-Ping Wang

2012-01-01

The rice disease resistance (R) gene Xa3/Xa26 (having also been named Xa3 and Xa26) against Xanthomonas oryzae pv.oryzae (Xoo),which causes bacterial blight disease,belongs to a multiple gene family clustered in chromosome 11 and is from an AA genome rice cultivar (Oryza sativa L.).This family encodes leucine-rich repeat (LRR) receptor kinasetype proteins.Here,we show that the orthologs (alleles) of Xa3/Xa26,Xa3/Xa26-2,and Xa3/Xa26-3,from wild Oryza species O.officinalis (CC genome) and O.minuta (BBCC genome),respectively,were also R genes against Xoo.Xa3/Xa26-2 and Xa3/Xa26-3 conferred resistance to 16 of the 18 Xoo strains examined.Comparative sequence analysis of the Xa3/Xa26 families in the two wild Oryza species showed that Xa3/Xa26-3 appeared to have originated from the CC genome of O.minuta.The predicted proteins encoded by Xa3/Xa26,Xa3/Xa26-2,and Xa3/Xa26-3 share 91-99％ sequence identity and 94-99％ sequence similarity.Transgenic plants carrying a single copy of Xa3/Xa26,Xa3/Xa26-2,or Xa3/Xa26-3,in the same genetic background,showed a similar resistance spectrum to a set of Xoo strains,although plants carrying Xa3/Xa26-2 or Xa3/Xa26-3 showed lower resistance levels than the plants carrying Xa3/Xa26.These results suggest that the Xa3/Xa26 locus predates the speciation of A and C genome,which is approximately 7.5 million years ago.Thus,the resistance specificity of this locus has been conserved for a long time.

Clinical Scenarios for Discordant Anti-Xa

Directory of Open Access Journals (Sweden)

Jesus Vera-Aguilera

2016-01-01

Full Text Available Anti-Xa test measures the activity of heparin against the activity of activated coagulation factor X; significant variability of anti-Xa levels in common clinical scenarios has been observed. Objective. To review the most common clinical settings in which anti-Xa results can be bias. Evidence Review. Guidelines and current literature search: we used PubMed, Medline, Embase, and MEDION, from 2000 to October 2013. Results. Anti-Xa test is widely used; however the assay underestimates heparin concentration in the presence of significant AT deficiency, pregnancy, end stage renal disease, and postthrombolysis and in patients with hyperbilirubinemia; limited published data evaluating the safety and effectiveness of anti-Xa assays for managing UH therapy is available. Conclusions and Relevance. To our knowledge this is the first paper that summarizes the most common causes in which this assay can be affected, several “day to day” clinical scenarios can modify the outcomes, and we concur that these rarely recognized scenarios can be affected by negative outcomes in the daily practice.

Exploiting VM/XA

International Nuclear Information System (INIS)

Boeheim, C.

1990-03-01

The Stanford Linear Accelerator Center has recently completed a conversion to IBM's VM/XA SP Release 2 operating system. The primary physics application had been constrained by the previous 16 megabyte memory limit. Work is underway to enable this application to exploit the new features of VM/XA. This paper presents a brief tutorial on how to convert an application to exploit VM/XA and discusses some of the SLAC experiences in doing so. 13 figs

Daboxin P, a Major Phospholipase A2 Enzyme from the Indian Daboia russelii russelii Venom Targets Factor X and Factor Xa for Its Anticoagulant Activity.

Directory of Open Access Journals (Sweden)

Maitreyee Sharma

Full Text Available In the present study a major protein has been purified from the venom of Indian Daboia russelii russelii using gel filtration, ion exchange and Rp-HPLC techniques. The purified protein, named daboxin P accounts for ~24% of the total protein of the crude venom and has a molecular mass of 13.597 kDa. It exhibits strong anticoagulant and phospholipase A2 activity but is devoid of any cytotoxic effect on the tested normal or cancerous cell lines. Its primary structure was deduced by N-terminal sequencing and chemical cleavage using Edman degradation and tandem mass spectrometry. It is composed of 121 amino acids with 14 cysteine residues and catalytically active His48 -Asp49 pair. The secondary structure of daboxin P constitutes 42.73% of α-helix and 12.36% of β-sheet. It is found to be stable at acidic (pH 3.0 and neutral pH (pH 7.0 and has a Tm value of 71.59 ± 0.46°C. Daboxin P exhibits anticoagulant effect under in-vitro and in-vivo conditions. It does not inhibit the catalytic activity of the serine proteases but inhibits the activation of factor X to factor Xa by the tenase complexes both in the presence and absence of phospholipids. It also inhibits the tenase complexes when active site residue (His48 was alkylated suggesting its non-enzymatic mode of anticoagulant activity. Moreover, it also inhibits prothrombinase complex when pre-incubated with factor Xa prior to factor Va addition. Fluorescence emission spectroscopy and affinity chromatography suggest the probable interaction of daboxin P with factor X and factor Xa. Molecular docking analysis reveals the interaction of the Ca+2 binding loop; helix C; anticoagulant region and C-terminal region of daboxin P with the heavy chain of factor Xa. This is the first report of a phospholipase A2 enzyme from Indian viper venom which targets both factor X and factor Xa for its anticoagulant activity.

Silencing of the Rice Gene LRR1 Compromises Rice Xa21 Transcript Accumulation and XA21-Mediated Immunity.

Science.gov (United States)

Caddell, Daniel F; Park, Chang-Jin; Thomas, Nicholas C; Canlas, Patrick E; Ronald, Pamela C

2017-12-01

The rice immune receptor XA21 confers resistance to Xanthomonas oryzae pv. oryzae (Xoo), the causal agent of bacterial leaf blight. We previously demonstrated that an auxilin-like protein, XA21 BINDING PROTEIN 21 (XB21), positively regulates resistance to Xoo. To further investigate the function of XB21, we performed a yeast two-hybrid screen. We identified 22 unique XB21 interacting proteins, including LEUCINE-RICH REPEAT PROTEIN 1 (LRR1), which we selected for further analysis. Silencing of LRR1 in the XA21 genetic background (XA21-LRR1Ri) compromises resistance to Xoo compared with control XA21 plants. XA21-LRR1Ri plants have reduced Xa21 transcript levels and reduced expression of genes that serve as markers of XA21-mediated activation. Overexpression of LRR1 is insufficient to alter resistance to Xoo in rice lines lacking XA21. Taken together, our results indicate that LRR1 is required for wild-type Xa21 transcript expression and XA21-mediated immunity.

Oral direct thrombin inhibitors or oral factor Xa inhibitors for the treatment of deep vein thrombosis.

Science.gov (United States)

Robertson, Lindsay; Kesteven, Patrick; McCaslin, James E

2015-06-30

Deep vein thrombosis (DVT) is a condition in which a clot forms in the deep veins, most commonly of the leg. It occurs in approximately 1 in 1,000 people. If left untreated, the clot can travel up to the lungs and cause a potentially life-threatening pulmonary embolism (PE). Previously, a DVT was treated with the anticoagulants heparin and vitamin K antagonists. However, two forms of novel oral anticoagulants (NOACs) have been developed: oral direct thrombin inhibitors (DTI) and oral factor Xa inhibitors. The new drugs have characteristics that may be favourable over conventional treatment, including oral administration, a predictable effect, lack of frequent monitoring or re-dosing and few known drug interactions. To date, no Cochrane review has measured the effectiveness and safety of these drugs in the treatment of DVT. To assess the effectiveness of oral DTIs and oral factor Xa inhibitors for the treatment of DVT. The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched January 2015) and the Cochrane Register of Studies (last searched January 2015). We searched clinical trials databases for details of ongoing or unpublished studies and the reference lists of relevant articles retrieved by electronic searches for additional citations. We included randomised controlled trials in which people with a DVT confirmed by standard imaging techniques, were allocated to receive an oral DTI or an oral factor Xa inhibitor for the treatment of DVT. Two review authors (LR, JM) independently extracted the data and assessed the risk of bias in the trials. Any disagreements were resolved by discussion with the third review author (PK). We performed meta-analyses when we considered heterogeneity low. The two primary outcomes were recurrent VTE and PE. Other outcomes included all-cause mortality and major bleeding. We calculated all outcomes using an odds ratio (OR) with a 95% confidence interval (CI). We included

Marker-aided Incorporation of Xa38, a Novel Bacterial Blight Resistance Gene, in PB1121 and Comparison of its Resistance Spectrum with xa13 + Xa21.

Science.gov (United States)

Ellur, Ranjith K; Khanna, Apurva; S, Gopala Krishnan; Bhowmick, Prolay K; Vinod, K K; Nagarajan, M; Mondal, Kalyan K; Singh, Nagendra K; Singh, Kuldeep; Prabhu, Kumble Vinod; Singh, Ashok K

2016-07-11

Basmati rice is preferred internationally because of its appealing taste, mouth feel and aroma. Pusa Basmati 1121 (PB1121) is a widely grown variety known for its excellent grain and cooking quality in the international and domestic market. It contributes approximately USD 3 billion to India's forex earning annually by being the most traded variety. However, PB1121 is highly susceptible to bacterial blight (BB) disease. A novel BB resistance gene Xa38 was incorporated in PB1121 from donor parent PR114-Xa38 using a modified marker-assisted backcross breeding (MABB) scheme. Phenotypic selection prior to background selection was instrumental in identifying the novel recombinants with maximum recovery of recurrent parent phenome. The strategy was effective in delimiting the linkage drag to <0.5 mb upstream and <1.9 mb downstream of Xa38 with recurrent parent genome recovery upto 96.9% in the developed NILs. The NILs of PB1121 carrying Xa38 were compared with PB1121 NILs carrying xa13 + Xa21 (developed earlier in our lab) for their resistance to BB. Both NILs showed resistance against the Xoo races 1, 2, 3 and 6. Additionally, Xa38 also resisted Xoo race 5 to which xa13 + Xa21 was susceptible. The PB1121 NILs carrying Xa38 gene will provide effective control of BB in the Basmati growing region.

Marker-aided Incorporation of Xa38, a Novel Bacterial Blight Resistance Gene, in PB1121 and Comparison of its Resistance Spectrum with xa13 + Xa21

Science.gov (United States)

Ellur, Ranjith K.; Khanna, Apurva; S, Gopala Krishnan.; Bhowmick, Prolay K.; Vinod, K. K.; Nagarajan, M.; Mondal, Kalyan K.; Singh, Nagendra K.; Singh, Kuldeep; Prabhu, Kumble Vinod; Singh, Ashok K.

2016-01-01

Basmati rice is preferred internationally because of its appealing taste, mouth feel and aroma. Pusa Basmati 1121 (PB1121) is a widely grown variety known for its excellent grain and cooking quality in the international and domestic market. It contributes approximately USD 3 billion to India’s forex earning annually by being the most traded variety. However, PB1121 is highly susceptible to bacterial blight (BB) disease. A novel BB resistance gene Xa38 was incorporated in PB1121 from donor parent PR114-Xa38 using a modified marker-assisted backcross breeding (MABB) scheme. Phenotypic selection prior to background selection was instrumental in identifying the novel recombinants with maximum recovery of recurrent parent phenome. The strategy was effective in delimiting the linkage drag to <0.5 mb upstream and <1.9 mb downstream of Xa38 with recurrent parent genome recovery upto 96.9% in the developed NILs. The NILs of PB1121 carrying Xa38 were compared with PB1121 NILs carrying xa13 + Xa21 (developed earlier in our lab) for their resistance to BB. Both NILs showed resistance against the Xoo races 1, 2, 3 and 6. Additionally, Xa38 also resisted Xoo race 5 to which xa13 + Xa21 was susceptible. The PB1121 NILs carrying Xa38 gene will provide effective control of BB in the Basmati growing region. PMID:27403778

Oral direct thrombin inhibitors or oral factor Xa inhibitors for the treatment of pulmonary embolism.

Science.gov (United States)

Robertson, Lindsay; Kesteven, Patrick; McCaslin, James E

2015-12-04

Pulmonary embolism is a potentially life-threatening condition in which a clot can travel from the deep veins, most commonly in the leg, up to the lungs. Previously, a pulmonary embolism was treated with the anticoagulants heparin and vitamin K antagonists. Recently, however, two forms of direct oral anticoagulants (DOACs) have been developed: oral direct thrombin inhibitors (DTI) and oral factor Xa inhibitors. The new drugs have characteristics that may be favourable over conventional treatment, including oral administration, a predictable effect, lack of frequent monitoring or re-dosing and few known drug interactions. To date, no Cochrane review has measured the effectiveness and safety of these drugs in the long-term treatment (minimum duration of three months) of pulmonary embolism. To assess the effectiveness of oral DTIs and oral factor Xa inhibitors for the long-term treatment of pulmonary embolism. The Cochrane Vascular Trials Search Co-ordinator searched the Specialised Register (last searched January 2015) and the Cochrane Register of Studies (last searched January 2015). Clinical trials databases were also searched for details of ongoing or unpublished studies. We searched the reference lists of relevant articles retrieved by electronic searches for additional citations. We included randomised controlled trials in which patients with a pulmonary embolism confirmed by standard imaging techniques were allocated to receive an oral DTI or an oral factor Xa inhibitor for the long-term (minimum duration three months) treatment of pulmonary embolism. Two review authors (LR, JM) independently extracted the data and assessed the risk of bias in the trials. Any disagreements were resolved by discussion with the third author (PK). We used meta-analyses when we considered heterogeneity low. The two primary outcomes were recurrent venous thromboembolism and pulmonary embolism. Other outcomes included all-cause mortality and major bleeding. We calculated all outcomes

Assessment of anti-factor Xa activity of heparin in binary parenteral nutrition admixtures for premature neonates.

Science.gov (United States)

Foinard, A; Perez, M; Barthélémy, C; Lannoy, D; Flamein, F; Storme, L; Tournoys, A; Décaudin, B; Odou, P

2015-07-01

An in vitro study was carried out to determine the anti-Xa activity of heparin in binary parenteral nutrition (BPN) admixtures for premature neonates in our neonatal intensive care unit (NICU) after a 24-hour infusion, as well as to assess drug interaction with a 50% glucose solution. Two types of bags were prepared: (1) BPN admixtures (composition defined in the NICU) including sodium heparin at 77 UI/mL and (2) bags containing only G50% with sodium heparin at 193 UI/mL. The anti-Xa activity of heparin was measured in bags at T0, after the 24-hour infusion and in eluates at the outlet of the infusion line after 24hours, using a validated chromogenic anti-Xa method. Comparisons of the mean concentration observed with the theoretical value for anti-Xa activity were performed with the Student t-test. Mean values of anti-Xa activity do not differ significantly from the values expected for all conditions. We found a slight variation in anti-Xa activity when infused over 24hours for both types of bags, with and without in-line filtration, showing that heparin remains stable during this infusion period in both BPN admixtures and G50%. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Andexanet alfa effectively reverses edoxaban anticoagulation effects and associated bleeding in a rabbit acute hemorrhage model

Science.gov (United States)

Lu, Genmin; Pine, Polly; Leeds, Janet M.; DeGuzman, Francis; Pratikhya, Pratikhya; Lin, Joyce; Malinowski, John; Hollenbach, Stanley J.; Curnutte, John T.

2018-01-01

Introduction Increasing use of factor Xa (FXa) inhibitors necessitates effective reversal agents to manage bleeding. Andexanet alfa, a novel modified recombinant human FXa, rapidly reverses the anticoagulation effects of direct and indirect FXa inhibitors. Objective To evaluate the ability of andexanet to reverse anticoagulation in vitro and reduce bleeding in rabbits administered edoxaban. Materials and methods In vitro studies characterized the interaction of andexanet with edoxaban and its ability to reverse edoxaban-mediated anti-FXa activity. In a rabbit model of surgically induced, acute hemorrhage, animals received edoxaban vehicle+andexanet vehicle (control), edoxaban (1 mg/kg)+andexanet vehicle, edoxaban+andexanet (75 mg, 5-minute infusion, 20 minutes after edoxaban), or edoxaban vehicle+andexanet prior to injury. Results Andexanet bound edoxaban with high affinity similar to FXa. Andexanet rapidly and dose-dependently reversed the effects of edoxaban on FXa activity and coagulation pharmacodynamic parameters in vitro. In edoxaban-anticoagulated rabbits, andexanet reduced anti-FXa activity by 82% (from 548±87 to 100±41 ng/ml; P<0.0001), mean unbound edoxaban plasma concentration by ~80% (from 100±10 to 21±6 ng/ml; P<0.0001), and blood loss by 80% vs. vehicle (adjusted for control, 2.6 vs. 12.9 g; P = 0.003). The reduction in blood loss correlated with the decrease in anti-FXa activity (r = 0.6993, P<0.0001) and unbound edoxaban (r = 0.5951, P = 0.0035). Conclusion These data demonstrate that andexanet rapidly reversed the anticoagulant effects of edoxaban, suggesting it could be clinically valuable for the management of acute and surgery-related bleeding. Correlation of blood loss with anti-FXa activity supports the use of anti-FXa activity as a biomarker for assessing anticoagulation reversal in clinical trials. PMID:29590221

The coagulation factor Xa/protease activated receptor-2 axis in the progression of liver fibrosis : a multifaceted paradigm

NARCIS (Netherlands)

Borensztajn, Keren; von der Thusen, Jan H.; Peppelenbosch, Maikel P.; Spek, C. Arnold

2010-01-01

Introduction Activation of the coagulation cascade during liver fibrosis: a puzzling paradox Protease-activated receptors: the link between coagulation cascade activation and liver fibrosis Expression and distribution of human PAR-2 in normal and pathological liver tissue FXa signalling on PAR-2

Measurement of microparticle tissue factor activity in clinical samples: A summary of two tissue factor-dependent FXa generation assays.

Science.gov (United States)

Hisada, Yohei; Alexander, Wyeth; Kasthuri, Raj; Voorhees, Peter; Mobarrez, Fariborz; Taylor, Angela; McNamara, Coleen; Wallen, Hakan; Witkowski, Marco; Key, Nigel S; Rauch, Ursula; Mackman, Nigel

2016-03-01

Thrombosis is a leading cause of morbidity and mortality. Detection of a prothrombotic state using biomarkers would be of great benefit to identify patients at risk of thrombosis that would benefit from thromboprophylaxis. Tissue factor (TF) is a highly procoagulant protein that under normal conditions is not present in the blood. However, increased levels of TF in the blood in the form of microparticles (MPs) (also called extracellular vesicles) are observed under various pathological conditions. In this review, we will discuss studies that have measured MP-TF activity in a variety of diseases using two similar FXa generation assay. One of the most robust signals for MP-TF activity (16-26 fold higher than healthy controls) is observed in pancreatic cancer patients with venous thromboembolism. In this case, the TF+ MPs appear to be derived from the cancer cells. Surprisingly, cirrhosis and acute liver injury are associated with 17-fold and 38-fold increases in MP-TF activity, respectively. Based on mouse models, we speculate that the TF+ MPs are derived from hepatocytes. More modest increases are observed in patients with urinary tract infections (6-fold) and in a human endotoxemia model (9-fold) where monocytes are the likely source of the TF+ MPs. Finally, there is no increase in MP-TF activity in the majority of cardiovascular disease patients. These studies indicate that MP-TF activity may be a useful biomarker to identify patients with particular diseases that have an increased risk of thrombosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

First Steps in the Direction of Synthetic, Allosteric, Direct Inhibitors of Thrombin and Factor Xa

OpenAIRE

Verghese, Jenson; Liang, Aiye; Sidhu, Preet Pal Singh; Hindle, Michael; Zhou, Qibing; Desai, Umesh R.

2009-01-01

Designing non-saccharide functional mimics of heparin is a major challenge. In this work, a library of small, aromatic molecules based on the sulfated DHP scaffold was synthesized and screened against thrombin and factor Xa. The results reveal that i) selected monomeric benzofuran derivatives inhibit the two enzymes, albeit weakly; ii) the two enzymes recognize different structural features in the benzofurans studied suggesting significant selectivity of recognition; and iii) the mechanism of...

Identification of potent orally active factor Xa inhibitors based on conjugation strategy and application of predictable fragment recommender system.

Science.gov (United States)

Ishihara, Tsukasa; Koga, Yuji; Iwatsuki, Yoshiyuki; Hirayama, Fukushi

2015-01-15

Anticoagulant agents have emerged as a promising class of therapeutic drugs for the treatment and prevention of arterial and venous thrombosis. We investigated a series of novel orally active factor Xa inhibitors designed using our previously reported conjugation strategy to boost oral anticoagulant effect. Structural optimization of anthranilamide derivative 3 as a lead compound with installation of phenolic hydroxyl group and extensive exploration of the P1 binding element led to the identification of 5-chloro-N-(5-chloro-2-pyridyl)-3-hydroxy-2-{[4-(4-methyl-1,4-diazepan-1-yl)benzoyl]amino}benzamide (33, AS1468240) as a potent factor Xa inhibitor with significant oral anticoagulant activity. We also reported a newly developed Free-Wilson-like fragment recommender system based on the integration of R-group decomposition with collaborative filtering for the structural optimization process. Copyright © 2014 Elsevier Ltd. All rights reserved.

The role of autolysis loop in determining the specificity of coagulation proteases.

Science.gov (United States)

Yang, L; Manithody, C; Rezaie, A R

2007-08-01

We recently demonstrated that the substitution of the autolysis loop (residues 143 to 154 in the chymotrypsin numbering system) of activated protein C (APC) with the corresponding loop of factor Xa (fXa) renders the APC mutant (APC/fX143-154) susceptible to inhibition by antithrombin (AT) in the presence of pentasaccharide. Our recent results further indicated, that in addition to an improvement in the reactivity of APC/fX143-154 with AT, both the amidolytic and anti-factor Va activities of the mutant APC have also been significantly increased. Since the autolysis loop of APC is five residues longer than the autolysis loop of fXa, it could not be ascertained whether this loop in the mutant APC specifically interacts with the activated conformation of AT or if a shorter autolysis loop is responsible for a global improvement in the catalytic activity of the mutant protease. To answer this question, we prepared another APC mutant in which the autolysis loop of the protease was replaced with the corresponding loop of trypsin (APC/Tryp143-154). Unlike an approximately 500-fold improvement in the reactivity of APC/fX143-154 with AT in the presence of pentasaccharide, the reactivity of APC/Tryp143-154 with the serpin was improved approximately 10-fold. These results suggest that both the length and structure of residues of the autolysis loop are critical for the specificity of the coagulation protease interaction with AT. Further factor Va inactivation studies with the APC mutants revealed a similar role for the autolysis loop of APC in the interaction with its natural substrate.

The role of autolysis loop in determining the specificity of coagulation proteases

Directory of Open Access Journals (Sweden)

L. Yang

2007-08-01

Full Text Available We recently demonstrated that the substitution of the autolysis loop (residues 143 to 154 in the chymotrypsin numbering system of activated protein C (APC with the corresponding loop of factor Xa (fXa renders the APC mutant (APC/fX143-154 susceptible to inhibition by antithrombin (AT in the presence of pentasaccharide. Our recent results further indicated, that in addition to an improvement in the reactivity of APC/fX143-154 with AT, both the amidolytic and anti-factor Va activities of the mutant APC have also been significantly increased. Since the autolysis loop of APC is five residues longer than the autolysis loop of fXa, it could not be ascertained whether this loop in the mutant APC specifically interacts with the activated conformation of AT or if a shorter autolysis loop is responsible for a global improvement in the catalytic activity of the mutant protease. To answer this question, we prepared another APC mutant in which the autolysis loop of the protease was replaced with the corresponding loop of trypsin (APC/Tryp143-154. Unlike an ~500-fold improvement in the reactivity of APC/fX143-154 with AT in the presence of pentasaccharide, the reactivity of APC/Tryp143-154 with the serpin was improved ~10-fold. These results suggest that both the length and structure of residues of the autolysis loop are critical for the specificity of the coagulation protease interaction with AT. Further factor Va inactivation studies with the APC mutants revealed a similar role for the autolysis loop of APC in the interaction with its natural substrate.

Alboserpin, a Factor Xa Inhibitor from the Mosquito Vector of Yellow Fever, Binds Heparin and Membrane Phospholipids and Exhibits Antithrombotic Activity

Czech Academy of Sciences Publication Activity Database

Calvo, E.; Mizurini, D.M.; Sa-Nunes, A.; Ribeiro, J.M.C.; Andersen, J. F.; Mans, B.J.; Monteiro, R.Q.; Kotsyfakis, Michalis; Francischetti, I.M.B.

2011-01-01

Roč. 286, č. 32 (2011), 27998-28010 ISSN 0021-9258 Institutional research plan: CEZ:AV0Z60220518 Keywords : serpin * mosquito * Aedes albopictus * phospholipids * Factor Xa * heparin * binding affinity * coagulation * thrombus * bleeding Subject RIV: GJ - Animal Vermins ; Diseases, Veterinary Medicine Impact factor: 4.773, year: 2011

The rice XA21 ectodomain fused to the Arabidopsis EFR cytoplasmic domain confers resistance to Xanthomonas oryzae pv. oryzae.

Science.gov (United States)

Thomas, Nicholas C; Oksenberg, Nir; Liu, Furong; Caddell, Daniel; Nalyvayko, Alina; Nguyen, Yen; Schwessinger, Benjamin; Ronald, Pamela C

2018-01-01

Rice ( Oryza sativa ) plants expressing the XA21 cell-surface receptor kinase are resistant to Xanthomonas oryzae pv. oryzae (Xoo) infection. We previously demonstrated that expressing a chimeric protein containing the ELONGATION FACTOR Tu RECEPTOR (EFR) ectodomain and the XA21 endodomain (EFR:XA21) in rice does not confer robust resistance to Xoo . To test if the XA21 ectodomain is required for Xoo resistance, we produced transgenic rice lines expressing a chimeric protein consisting of the XA21 ectodomain and EFR endodomain (XA21:EFR) and inoculated these lines with Xoo . We also tested if the XA21:EFR rice plants respond to a synthetic sulfated 21 amino acid derivative (RaxX21-sY) of the activator of XA21-mediated immunity, RaxX. We found that five independently transformed XA21:EFR rice lines displayed resistance to Xoo as measured by lesion length analysis, and showed that five lines share characteristic markers of the XA21 defense response (generation of reactive oxygen species and defense response gene expression) after treatment with RaxX21-sY. Our results indicate that expression of the XA21:EFR chimeric receptor in rice confers resistance to Xoo . These results suggest that the endodomain of the EFR and XA21 immune receptors are interchangeable and the XA21 ectodomain is the key determinant conferring robust resistance to Xoo .

First steps in the direction of synthetic, allosteric, direct inhibitors of thrombin and factor Xa.

Science.gov (United States)

Verghese, Jenson; Liang, Aiye; Sidhu, Preet Pal Singh; Hindle, Michael; Zhou, Qibing; Desai, Umesh R

2009-08-01

Designing non-saccharide functional mimics of heparin is a major challenge. In this work, a library of small, aromatic molecules based on the sulfated DHP scaffold was synthesized and screened against thrombin and factor Xa. The results reveal that (i) selected monomeric benzofuran derivatives inhibit the two enzymes, albeit weakly; (ii) the two enzymes recognize different structural features in the benzofurans studied suggesting significant selectivity of recognition; and (iii) the mechanism of inhibition is allosteric. The molecules represent the first allosteric small molecule inhibitors of the two enzymes.

First Steps in the Direction of Synthetic, Allosteric, Direct Inhibitors of Thrombin and Factor Xa

Science.gov (United States)

Verghese, Jenson; Liang, Aiye; Sidhu, Preet Pal Singh; Hindle, Michael; Zhou, Qibing; Desai, Umesh R.

2009-01-01

Designing non-saccharide functional mimics of heparin is a major challenge. In this work, a library of small, aromatic molecules based on the sulfated DHP scaffold was synthesized and screened against thrombin and factor Xa. The results reveal that i) selected monomeric benzofuran derivatives inhibit the two enzymes, albeit weakly; ii) the two enzymes recognize different structural features in the benzofurans studied suggesting significant selectivity of recognition; and iii) the mechanism of inhibition is allosteric. The molecules represent the first allosteric small molecule inhibitors of the two enzymes. PMID:19540113

Matriptase activation connects tissue factor-dependent coagulation initiation to epithelial proteolysis and signaling.

Science.gov (United States)

Le Gall, Sylvain M; Szabo, Roman; Lee, Melody; Kirchhofer, Daniel; Craik, Charles S; Bugge, Thomas H; Camerer, Eric

2016-06-23

The coagulation cascade is designed to sense tissue injury by physical separation of the membrane-anchored cofactor tissue factor (TF) from inactive precursors of coagulation proteases circulating in plasma. Once TF on epithelial and other extravascular cells is exposed to plasma, sequential activation of coagulation proteases coordinates hemostasis and contributes to host defense and tissue repair. Membrane-anchored serine proteases (MASPs) play critical roles in the development and homeostasis of epithelial barrier tissues; how MASPs are activated in mature epithelia is unknown. We here report that proteases of the extrinsic pathway of blood coagulation transactivate the MASP matriptase, thus connecting coagulation initiation to epithelial proteolysis and signaling. Exposure of TF-expressing cells to factors (F) VIIa and Xa triggered the conversion of latent pro-matriptase to an active protease, which in turn cleaved the pericellular substrates protease-activated receptor-2 (PAR2) and pro-urokinase. An activation pathway-selective PAR2 mutant resistant to direct cleavage by TF:FVIIa and FXa was activated by these proteases when cells co-expressed pro-matriptase, and matriptase transactivation was necessary for efficient cleavage and activation of wild-type PAR2 by physiological concentrations of TF:FVIIa and FXa. The coagulation initiation complex induced rapid and prolonged enhancement of the barrier function of epithelial monolayers that was dependent on matriptase transactivation and PAR2 signaling. These observations suggest that the coagulation cascade engages matriptase to help coordinate epithelial defense and repair programs after injury or infection, and that matriptase may contribute to TF-driven pathogenesis in cancer and inflammation.

Molecular screening of rice ( Oryza sativa L.) germplasm for Xa4 ...

African Journals Online (AJOL)

DNA fingerprinting results indicated the presence of Xa4 gene in 41 entries, while 14 lines were positive for xa5 gene. Only one local line was carrying Xa21 gene along with Xa4. Thus, the present study will not only be helpful for rice breeders to develop new rice varieties carrying disease resistant genes, but will also ...

Maximize x(a - x)

Science.gov (United States)

Lange, L. H.

1974-01-01

Five different methods for determining the maximizing condition for x(a - x) are presented. Included is the ancient Greek version and a method attributed to Fermat. None of the proofs use calculus. (LS)

AVE5026, a new hemisynthetic ultra-low-molecular-weight heparin for the prevention of venous thromboembolism in patients after total knee replacement surgery--TREK: a dose-ranging study

DEFF Research Database (Denmark)

Lassen, M R; Dahl, O E; Mismetti, P

2009-01-01

BACKGROUND: AVE5026 is a new hemisynthetic ultra-low-molecular-weight heparin, with a novel anti-thrombotic profile resulting from high anti-factor (F)Xa activity and residual anti-FIIa activity. AVE5026 is in clinical development for venous thromboembolism (VTE) prevention, a frequent complication....... The primary safety outcome was the incidence of major bleeding. RESULTS: The primary efficacy outcome was assessed in 464 patients. There was a significant dose-response across the five AVE5026 groups for VTE prevention (Pincidence of VTE ranging from 5.3% to 44.1% compared with 35...

AVE5026, a new hemisynthetic ultra-low-molecular-weight heparin for the prevention of venous thromboembolism in patients after total knee replacement surgery

DEFF Research Database (Denmark)

Lassen, Michael Rud; Dahl, O E; Mismetti, P

2009-01-01

BACKGROUND: AVE5026 is a new hemisynthetic ultra-low-molecular-weight heparin, with a novel anti-thrombotic profile resulting from high anti-factor (F)Xa activity and residual anti-FIIa activity. AVE5026 is in clinical development for venous thromboembolism (VTE) prevention, a frequent complication....... The primary safety outcome was the incidence of major bleeding. RESULTS: The primary efficacy outcome was assessed in 464 patients. There was a significant dose-response across the five AVE5026 groups for VTE prevention (Pincidence of VTE ranging from 5.3% to 44.1% compared with 35...

Induction of Xa10-like Genes in Rice Cultivar Nipponbare Confers Disease Resistance to Rice Bacterial Blight.

Science.gov (United States)

Wang, Jun; Tian, Dongsheng; Gu, Keyu; Yang, Xiaobei; Wang, Lanlan; Zeng, Xuan; Yin, Zhongchao

2017-06-01

Bacterial blight of rice, caused by Xanthomonas oryzae pv. oryzae, is one of the most destructive bacterial diseases throughout the major rice-growing regions in the world. The rice disease resistance (R) gene Xa10 confers race-specific disease resistance to X. oryzae pv. oryzae strains that deliver the corresponding transcription activator-like (TAL) effector AvrXa10. Upon bacterial infection, AvrXa10 binds specifically to the effector binding element in the promoter of the R gene and activates its expression. Xa10 encodes an executor R protein that triggers hypersensitive response and activates disease resistance. 'Nipponbare' rice carries two Xa10-like genes in its genome, of which one is the susceptible allele of the Xa23 gene, a Xa10-like TAL effector-dependent executor R gene isolated recently from 'CBB23' rice. However, the function of the two Xa10-like genes in disease resistance to X. oryzae pv. oryzae strains has not been investigated. Here, we designated the two Xa10-like genes as Xa10-Ni and Xa23-Ni and characterized their function for disease resistance to rice bacterial blight. Both Xa10-Ni and Xa23-Ni provided disease resistance to X. oryzae pv. oryzae strains that deliver the matching artificially designed TAL effectors (dTALE). Transgenic rice plants containing Xa10-Ni and Xa23-Ni under the Xa10 promoter provided specific disease resistance to X. oryzae pv. oryzae strains that deliver AvrXa10. Xa10-Ni and Xa23-Ni knock-out mutants abolished dTALE-dependent disease resistance to X. oryzae pv. oryzae. Heterologous expression of Xa10-Ni and Xa23-Ni in Nicotiana benthamiana triggered cell death. The 19-amino-acid residues at the N-terminal regions of XA10 or XA10-Ni are dispensable for their function in inducing cell death in N. benthamiana and the C-terminal regions of XA10, XA10-Ni, and XA23-Ni are interchangeable among each other without affecting their function. Like XA10, both XA10-Ni and XA23-Ni locate to the endoplasmic reticulum (ER) membrane

XA23 is an executor R protein and confers broad-spectrum disease resistance in rice.

Science.gov (United States)

Wang, Chunlian; Zhang, Xiaoping; Fan, Yinglun; Gao, Ying; Zhu, Qinlong; Zheng, Chongke; Qin, Tengfei; Li, Yanqiang; Che, Jinying; Zhang, Mingwei; Yang, Bing; Liu, Yaoguang; Zhao, Kaijun

2014-11-09

The majority of plant disease resistance (R) genes encode proteins that share common structural features. However, the transcription activator-like effector (TALE) associated executor type R genes show no considerable sequence homology to any known R genes. We adopted a map-based cloning approach and TALE-based technology to isolate and characterize Xa23, a new executor R gene derived from the wild rice (Oryza rufipogon) that confers an extremely broad spectrum of resistance to bacterial blight caused by Xanthomonas oryzae pv. oryzae (Xoo). Xa23 encodes a 113-amino acid protein that shares 50% identity to the known executor R protein XA10. The predicted transmembrane helices in XA23 also overlap with those of XA10. Unlike Xa10, however, Xa23 transcription is specifically activated by AvrXa23, a TALE present in all examined Xoo field isolates. Moreover, the susceptible xa23 allele has an identical open reading frame of Xa23, but differs in promoter region by lacking the TALE binding-element (EBE) for AvrXa23. XA23 can trigger strong hypersensitive response in rice, tobacco and tomato. Our results provide the first evidence that plant genomes have an executor R gene family in which members execute their function and spectrum of disease resistance by recognizing the cognate TALEs in pathogen. © The Author 2014. Published by the Molecular Plant Shanghai Editorial Office in association with Oxford University Press on behalf of CSPB and IPPE, SIBS, CAS.

RUBY-1: a randomized, double-blind, placebo-controlled trial of the safety and tolerability of the novel oral factor Xa inhibitor darexaban (YM150) following acute coronary syndrome

DEFF Research Database (Denmark)

Steg, Ph Gabriel; Mehta, Shamir R; Jukema, J Wouter

2011-01-01

To establish the safety, tolerability and most promising regimen of darexaban (YM150), a novel, oral, direct factor Xa inhibitor, for prevention of ischaemic events in acute coronary syndrome (ACS)....

Theoretical calculation of shakeup intensities using Xa--SW wave functions

International Nuclear Information System (INIS)

Tse, J.S.; Loubriel, G.

1981-01-01

The ground and 1s core hole state molecular wave functions of CH 4 , NH 3 , H 2 O, and HF obtained from Xa--SW calculations using the touching spheres (TS) and overlapping spheres (OS) approximations are used to calculate the intensity of shakeup satellites observed in their ls core level photoelectron spectra. The sudden approximation was assumed in the calculation. In case of TS Xa--SW wave functions, the one electron overlap integral inside the intersphere was calculated via Green's theorem. For OS Xa--SW wave functions, the integration over the awkwardly shaped intersphere region was circumvented by distributing the intersphere charge into the atomic spheres according to the charge partition scheme suggested by Case and Karplus. Our results show that there are no significant differences between the shakeup energies calculated from the TS and OS approximations. However, shakeup intensities calculated from TS Xa--SW wave functions are more reliable and in better numerical agreement with experiment

Treatment of proximal deep vein thrombosis with a novel synthetic compound (SR90107A/ORG31540) with pure anti-factor Xa activity - A phase II evaluation

NARCIS (Netherlands)

Buller, HR; Cariou, R; Gallus, A; Gent, M; Ginsberg, J; Prins, MH; Lensing, A; Levi, M; Nurmohammed, N; Hirsh, J; Roberts, R; ten Cate, JW; Decousus, H; Mismetti, P; Buchmuller, A; Charlet, [No Value; Viallon, A; van der Meer, J; Meinardi, [No Value; Meijer, K; Piovella, F; Barone, M; Beltrametti, C; Serafini, S; Kraaijenhagen, RA; Koopman, MMW; Jagt, HHT; Muller, MBR; Kooy, MV; Nauta, S; Gallus, AS; Coghlan, D; Rich, C; Prandoni, P; Scudeller, A; Scarano, L; Girolami, A; Baker, R; Tan, E; Cooney, J; Eikelboom, J; Ninet, J; Dolmazon, C; Madoux, MHG; Coppere, B; Nenci, GG; Agnelli, G; Falcinelli, F; Morini, M; d'Angelo, A

2000-01-01

Background-Patients with venous thromboembolism require initial treatment with an immediate-acting anticoagulant, low-molecular-weight heparin. We evaluated a novel synthetic factor Xa inhibitor (SR90107a/ORG31540) as an alternative treatment. Methods and Results-A randomized-parallel-group, phase

Thrombotic Role of Blood and Endothelial Cells in Uremia through Phosphatidylserine Exposure and Microparticle Release.

Directory of Open Access Journals (Sweden)

Chunyan Gao

Full Text Available The mechanisms contributing to an increased risk of thrombosis in uremia are complex and require clarification. There is scant morphological evidence of membrane-dependent binding of factor Xa (FXa and factor Va (FVa on endothelial cells (EC in vitro. Our objectives were to confirm that exposed phosphatidylserine (PS on microparticle (MP, EC, and peripheral blood cell (PBC has a prothrombotic role in uremic patients and to provide visible and morphological evidence of PS-dependent prothrombinase assembly in vitro. We found that uremic patients had more circulating MP (derived from PBC and EC than controls. Additionally, patients had more exposed PS on their MPs and PBCs, especially in the hemodialysis group. In vitro, EC exposed more PS in uremic toxins or serum. Moreover, reconstitution experiments showed that at the early stages, PS exposure was partially reversible. Using confocal microscopy, we observed that PS-rich membranes of EC and MP provided binding sites for FVa and FXa. Further, exposure of PS in uremia resulted in increased generation of FXa, thrombin, and fibrin and significantly shortened coagulation time. Lactadherin, a protein that blocks PS, reduced 80% of procoagulant activity on PBC, EC, and MP. Our results suggest that PBC and EC in uremic milieu are easily injured or activated, which exposes PS and causes a release of MP, providing abundant procoagulant membrane surfaces and thus facilitating thrombus formation. Blocking PS binding sites could become a new therapeutic target for preventing thrombosis.

Pharmacology of new oral anticoagulants: mechanism of action, pharmacokinetics, pharmacodynamics

Directory of Open Access Journals (Sweden)

Luca Masotti

2013-12-01

Full Text Available Due to their mechanism of action, the new oral anticoagulants are named direct oral anticoagulants (DOACs. Dabigatran is a selective, competitive, direct inhibitor of thrombin (Factor IIa while rivaroxaban, apixaban and edoxaban act by directly inhibiting the activated Factor X (FXa in a selective and competitive manner. DOACs have a relatively short half-life and almost immediate anticoagulant activity, and rapidly reach the plasma peak concentration. Therefore, they do not need a phase of overlapping with parenteral anticoagulants. After their withdrawal, their removal is sufficiently rapid, although influenced by renal function. Dabigatran is the only DOACs to be administered as a pro-drug and becomes active after drug metabolization. The route of elimination of dabigatran is primarily renal, whereas FXa inhibitors are mainly eliminated by the biliary-fecal route. The drug interactions of DOACs are mainly limited to drugs that act on P-glycoprotein for dabigatran and on P-glycoprotein and/or cytochrome P3A4 for anti-Xa. DOACs have no interactions with food. Given their linear pharmacodynamics, with a predictable dose/response relationship and anticoagulant effect, DOACs are administered at a fixed dose and do not require routine laboratory monitoring.

XA readout chip characteristics and CdZnTe spectral measurements

International Nuclear Information System (INIS)

Barbier, L.M.; Birsa, F.; Odom, J.

1999-01-01

The authors report on the performance of a CdZnTe (CZT) array readout by an XA (X-ray imaging chip produced at the AMS foundry) application specific readout chip (ASIC). The array was designed and fabricated at NASA/Goddard Space Flight Center (GSFC) as a prototype for the Burst Arc-Second Imaging and Spectroscopy gamma-ray instrument. The XA ASIC was obtained from Integrated Detector and Electronics (IDE), in Norway. Performance characteristics and spectral data for 241 Am are presented both at room temperature and at -20 C. The measured noise (σ) was 2.5 keV at 60 keV at room temperature. This paper represents a progress report on work with the XA ASIC and CZT detectors. Work is continuing and in particular, larger arrays are planned for future NASA missions

Fine mapping of the rice bacterial blight resistance gene Xa-4 and its co-segregation marker

Institute of Scientific and Technical Information of China (English)

无

2000-01-01

An F2 population developed from the Xa-4 near isogenic lines,IR24 and IRBB4,was used for fine mapping of the rice bacterial blight resistance gene,Xa-4.Some restriction fragment length polymorphism (RFLP) markers on the high-density map constructed by Harushima et al.and the amplified DNA fragments homologous to the conserved domains of plant disease resistance (R) genes were used to construct the genetic linkage map around the gene Xa-4 by scoring susceptible individuals in the population.Xa-4 was mapped between the RFLP marker G181 and the polymerase chain reaction (PCR) marker M55.The R gene homologous fragment marker RS13 was found co-segregating with Xa-4 by analyzing all the plants in the population.This result opened an approach to map-based cloning of this gene,and marker RS13 can be applied to molecular marker-assisted selection of Xa-4 in rice breeding programs.

A ΩXaV motif in the Rift Valley fever virus NSs protein is essential for degrading p62, forming nuclear filaments and virulence.

Science.gov (United States)

Cyr, Normand; de la Fuente, Cynthia; Lecoq, Lauriane; Guendel, Irene; Chabot, Philippe R; Kehn-Hall, Kylene; Omichinski, James G

2015-05-12

Rift Valley fever virus (RVFV) is a single-stranded RNA virus capable of inducing fatal hemorrhagic fever in humans. A key component of RVFV virulence is its ability to form nuclear filaments through interactions between the viral nonstructural protein NSs and the host general transcription factor TFIIH. Here, we identify an interaction between a ΩXaV motif in NSs and the p62 subunit of TFIIH. This motif in NSs is similar to ΩXaV motifs found in nucleotide excision repair (NER) factors and transcription factors known to interact with p62. Structural and biophysical studies demonstrate that NSs binds to p62 in a similar manner as these other factors. Functional studies in RVFV-infected cells show that the ΩXaV motif is required for both nuclear filament formation and degradation of p62. Consistent with the fact that the RVFV can be distinguished from other Bunyaviridae-family viruses due to its ability to form nuclear filaments in infected cells, the motif is absent in the NSs proteins of other Bunyaviridae-family viruses. Taken together, our studies demonstrate that p62 binding to NSs through the ΩXaV motif is essential for degrading p62, forming nuclear filaments and enhancing RVFV virulence. In addition, these results show how the RVFV incorporates a simple motif into the NSs protein that enables it to functionally mimic host cell proteins that bind the p62 subunit of TFIIH.

Rivaroxaban-once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation: rationale and design of the ROCKET AF study

DEFF Research Database (Denmark)

NN, NN

2010-01-01

BACKGROUND: Atrial fibrillation (AF), the most common significant cardiac arrhythmia, increases the risk of stroke, particularly in the elderly. Warfarin is effective in reducing stroke risk but is burdensome to patients and is difficult to control. Rivaroxaban is an oral direct factor Xa inhibit...

Comparative Transcriptome Profiling of Rice Near-Isogenic Line Carrying Xa23 under Infection of Xanthomonas oryzae pv. oryzae.

Science.gov (United States)

Tariq, Rezwan; Wang, Chunlian; Qin, Tengfei; Xu, Feifei; Tang, Yongchao; Gao, Ying; Ji, Zhiyuan; Zhao, Kaijun

2018-03-02

Bacterial blight, caused by Xanthomonas oryzae pv. oryzae ( Xoo ), is an overwhelming disease in rice-growing regions worldwide. Our previous studies revealed that the executor R gene Xa23 confers broad-spectrum disease resistance to all naturally occurring biotypes of Xoo . In this study, comparative transcriptomic profiling of two near-isogenic lines (NILs), CBB23 (harboring Xa23 ) and JG30 (without Xa23 ), before and after infection of the Xoo strain, PXO99 A , was done by RNA sequencing, to identify genes associated with the resistance. After high throughput sequencing, 1645 differentially expressed genes (DEGs) were identified between CBB23 and JG30 at different time points. Gene Ontlogy (GO) analysis categorized the DEGs into biological process, molecular function, and cellular component. KEGG analysis categorized the DEGs into different pathways, and phenylpropanoid biosynthesis was the most prominent pathway, followed by biosynthesis of plant hormones, flavonoid biosynthesis, and glycolysis/gluconeogenesis. Further analysis led to the identification of differentially expressed transcription factors (TFs) and different kinase responsive genes in CBB23, than that in JG30. Besides TFs and kinase responsive genes, DEGs related to ethylene, jasmonic acid, and secondary metabolites were also identified in both genotypes after PXO99 A infection. The data of DEGs are a precious resource for further clarifying the network of Xa23 -mediated resistance.

Cleavage of spike protein of SARS coronavirus by protease factor Xa is associated with viral infectivity

International Nuclear Information System (INIS)

Du, Lanying; Kao, Richard Y.; Zhou, Yusen; He, Yuxian; Zhao, Guangyu; Wong, Charlotte; Jiang, Shibo; Yuen, Kwok-Yung; Jin, Dong-Yan; Zheng, Bo-Jian

2007-01-01

The spike (S) protein of SARS coronavirus (SARS-CoV) has been known to recognize and bind to host receptors, whose conformational changes then facilitate fusion between the viral envelope and host cell membrane, leading to viral entry into target cells. However, other functions of SARS-CoV S protein such as proteolytic cleavage and its implications to viral infection are incompletely understood. In this study, we demonstrated that the infection of SARS-CoV and a pseudovirus bearing the S protein of SARS-CoV was inhibited by a protease inhibitor Ben-HCl. Also, the protease Factor Xa, a target of Ben-HCl abundantly expressed in infected cells, was able to cleave the recombinant and pseudoviral S protein into S1 and S2 subunits, and the cleavage was inhibited by Ben-HCl. Furthermore, this cleavage correlated with the infectivity of the pseudovirus. Taken together, our study suggests a plausible mechanism by which SARS-CoV cleaves its S protein to facilitate viral infection

Tissue factor-dependent activation of tritium-labeled factor IX and factor X in human plasma

International Nuclear Information System (INIS)

Morrison, S.A.; Jesty, J.

1984-01-01

A comparism was made of the tissue factor-dependent activation of tritium-labeled factor IX and factor X in a human plasma system and a study was made of the role of proteases known to stimulate factor VII activity. Plasma was defibrinated by heating and depleted of its factors IX and X by passing it through antibody columns. Addition of human brain thromboplastin, Ca2+, and purified 3H-labeled factor X to the plasma resulted, after a short lag, in burst-like activation of the factor X, measured as the release of radiolabeled activation peptide. The progress of activation was slowed by both heparin and a specific inhibitor of factor Xa but factor X activation could not be completely abolished by such inhibitors. In the case of 3H-factor IX activation, the rate also increased for approximately 3 min after addition of thromboplastin, but was not subsequently curtailed. A survey of proteases implicated as activators of factor VII in other settings showed that both factor Xa and factor IXa could accelerate the activation of factor IX. However, factor Xa was unique in obliterating activation when present at concentrations greater than approximately 1 nM. Heparin inhibited the tissue factor-dependent activation of factor IX almost completely, apparently through the effect of antithrombin on the feedback reactions of factors Xa and IXa on factor VII. These results suggest that a very tight, biphasic control of factor VII activity exists in human plasma, which is modulated mainly by factor Xa. At saturation of factor VIIa/tissue factor, factor IX activation was significantly more rapid than was previously found in bovine plasma under similar conditions. The activation of factor X at saturation was slightly more rapid than in bovine plasma, despite the presence of heparin

Tissue Factor-Expressing Tumor-Derived Extracellular Vesicles Activate Quiescent Endothelial Cells via Protease-Activated Receptor-1

Directory of Open Access Journals (Sweden)

Sara P. Y. Che

2017-11-01

Full Text Available Tissue factor (TF-expressing tumor-derived extracellular vesicles (EVs can promote metastasis and pre-metastatic niche formation, but the mechanisms by which this occurs remain largely unknown. We hypothesized that generation of activated factor X (FXa by TF expressed on tumor-derived EV could activate protease-activated receptors (PARs on non-activated endothelial cells to induce a pro-adhesive and pro-inflammatory phenotype. We obtained EV from TF-expressing breast (MDA-MB-231 and pancreatic (BxPC3 and Capan-1 tumor cell lines. We measured expression of E-selectin and secretion of interleukin-8 (IL-8 in human umbilical vein endothelial cells after exposure to EV and various immunologic and chemical inhibitors of TF, FXa, PAR-1, and PAR-2. After 6 h of exposure to tumor-derived EV (pretreated with factor VIIa and FX in vitro, endothelial cells upregulated E-selectin expression and secreted IL-8. These changes were decreased with an anti-TF antibody, FXa inhibitors (FPRCK and EGRCK, and PAR-1 antagonist (E5555, demonstrating that FXa generated by TF-expressing tumor-derived EV was signaling through endothelial PAR-1. Due to weak constitutive PAR-2 expression, these endothelial responses were not induced by a PAR-2 agonist peptide (SLIGKV and were not inhibited by a PAR-2 antagonist (FSLLRY after exposure to tumor-derived EV. In conclusion, we found that TF-expressing cancer-derived EVs activate quiescent endothelial cells, upregulating E-selectin and inducing IL-8 secretion through generation of FXa and cleavage of PAR-1. Conversion of resting endothelial cells to an activated phenotype by TF-expressing cancer-derived EV could promote cancer metastases.

Introduction of a rice blight resistance gene, Xa21, into five Chinese rice varieties through an Agrobacterium-mediated system

Institute of Scientific and Technical Information of China (English)

无

2000-01-01

A cloned gene, Xa21 was transferred into five widely-used Chinese rice varieties through an Agrobacterium-mediated system, and over 110 independent transgenic lines were obtained. PCR and Southern analysis of transgenic plants revealed the integration of the whole Xa21 gene into the host genomes. The integrated Xa21 gene was stably inherited, and segregated in a 3∶1 ratio in the selfed T1 generation when one copy of the gene was integrated in the transformants. Inoculation tests displayed that transgenic T0 plants and Xa21 PCR-positive T1 plants were highly resistant to bacterial blight disease. The selected Xa21 homozygous resistant transgenic lines with desirable qualities may be propagated as new varieties or utilized in hybrid rice breeding.

Introduction of a rice blight resistance gene, Xa21, into five Chinese rice varieties through an Agrobacterium -mediated system

Institute of Scientific and Technical Information of China (English)

翟文学; 李晓兵; 田文忠; 周永力; 潘学彪; 曹守云; 赵显峰; 赵彬; 章琦; 朱立煌

2000-01-01

A cloned gene, Xa21 was transferred into five widely-used Chinese rice varieties through an Agrobacterium-mediated system, and over 110 independent transgenic lines were obtained. PCR and Southern analysis of transgenic plants revealed the integration of the whole Xa21 gene into the host genomes. The integrated Xa21 gene was stably inherited, and segregated in a 3 : 1 ratio in the selfed T1 generation when one copy of the gene was integrated in the transfor-mants. Inoculation tests displayed that transgenic T0 plants and Xa21 PCR-positive T1 plants were highly resistant to bacterial blight disease. The selected Xa21 homozygous resistant transgenic lines with desirable qualities may be propagated as new varieties or utilized in hybrid rice breeding.

Molecular dynamics characterization of five pathogenic factor X mutants associated with decreased catalytic activity

KAUST Repository

Abdel-Azeim, Safwat; Oliva, Romina M.; Chermak, Edrisse; De Cristofaro, Raimondo; Cavallo, Luigi

2014-01-01

Factor X (FX) is one of the major players in the blood coagulation cascade. Upon activation to FXa, it converts prothrombin to thrombin, which in turn converts fibrinogen into fibrin (blood clots). FXa deficiency causes hemostasis defects, such as intracranial bleeding, hemathrosis, and gastrointestinal blood loss. Herein, we have analyzed a pool of pathogenic mutations, located in the FXa catalytic domain and directly associated with defects in enzyme catalytic activity. Using chymotrypsinogen numbering, they correspond to D102N, T135M, V160A, G184S, and G197D. Molecular dynamics simulations were performed for 1.68 μs on the wild-type and mutated forms of FXa. Overall, our analysis shows that four of the five mutants considered, D102N, T135M, V160A, and G184S, have rigidities higher than those of the wild type, in terms of both overall protein motion and, specifically, subpocket S4 flexibility, while S1 is rather insensitive to the mutation. This acquired rigidity can clearly impact the substrate recognition of the mutants.

Molecular dynamics characterization of five pathogenic factor X mutants associated with decreased catalytic activity

KAUST Repository

Abdel-Azeim, Safwat

2014-11-11

Factor X (FX) is one of the major players in the blood coagulation cascade. Upon activation to FXa, it converts prothrombin to thrombin, which in turn converts fibrinogen into fibrin (blood clots). FXa deficiency causes hemostasis defects, such as intracranial bleeding, hemathrosis, and gastrointestinal blood loss. Herein, we have analyzed a pool of pathogenic mutations, located in the FXa catalytic domain and directly associated with defects in enzyme catalytic activity. Using chymotrypsinogen numbering, they correspond to D102N, T135M, V160A, G184S, and G197D. Molecular dynamics simulations were performed for 1.68 μs on the wild-type and mutated forms of FXa. Overall, our analysis shows that four of the five mutants considered, D102N, T135M, V160A, and G184S, have rigidities higher than those of the wild type, in terms of both overall protein motion and, specifically, subpocket S4 flexibility, while S1 is rather insensitive to the mutation. This acquired rigidity can clearly impact the substrate recognition of the mutants.

Assessment of anti-factor Xa activity of enoxaparin for venous thromboembolism prophylaxis in morbidly obese surgical patients

Directory of Open Access Journals (Sweden)

Nouf Al Otaib

2017-01-01

Conclusions: Weight-based enoxaparin dose led to the anticipated peak anti-Xa levels (0.2–0.6 IU/mL in most of the morbidly obese study patients undergoing surgery without any evidence of major side effects. The weight-based dosing of enoxaparin was also effective in preventing VTE in all patients. Although these results are promising, further comparative trials are needed in the setting of morbidly obese surgical patients.

Tranexamic Acid Failed to Reverse the Anticoagulant Effect and Bleeding by an Oral Direct Factor Xa Inhibitor Edoxaban.

Science.gov (United States)

Honda, Yuko; Furugohri, Taketoshi; Morishima, Yoshiyuki

2018-01-01

Agents to reverse the anticoagulant effect of edoxaban, an oral direct factor Xa inhibitor, would be desirable in emergency situations. The aim of this study is to determine the effect of tranexamic acid, an antifibrinolytic agent, on the anticoagulant activity and bleeding by edoxaban in rats. A supratherapeutic dose of edoxaban (3 mg/kg) was intravenously administered to rats. Three minutes after dosing, tranexamic acid (100 mg/kg) was given intravenously. Bleeding was induced by making an incision with a blade on the planta 8 min after edoxaban injection and bleeding time was measured. Prothrombin time (PT) and clot lysis were examined. A supratherapeutic dose of edoxaban significantly prolonged PT and bleeding time. Tranexamic acid did not affect PT or bleeding time prolonged by edoxaban, although tranexamic acid significantly inhibited clot lysis in rat plasma. An antifibrinolytic agent tranexamic acid failed to reverse the anticoagulant effect and bleeding by edoxaban in rats. © 2017 S. Karger AG, Basel.

3D/3D registration of coronary CTA and biplane XA reconstructions for improved image guidance

Energy Technology Data Exchange (ETDEWEB)

Dibildox, Gerardo, E-mail: g.dibildox@erasmusmc.nl; Baka, Nora; Walsum, Theo van [Biomedical Imaging Group Rotterdam, Departments of Radiology and Medical Informatics, Erasmus Medical Center, 3015 GE Rotterdam (Netherlands); Punt, Mark; Aben, Jean-Paul [Pie Medical Imaging, 6227 AJ Maastricht (Netherlands); Schultz, Carl [Department of Cardiology, Erasmus Medical Center, 3015 GE Rotterdam (Netherlands); Niessen, Wiro [Quantitative Imaging Group, Faculty of Applied Sciences, Delft University of Technology, 2628 CJ Delft, The Netherlands and Biomedical Imaging Group Rotterdam, Departments of Radiology and Medical Informatics, Erasmus Medical Center, 3015 GE Rotterdam (Netherlands)

2014-09-15

Purpose: The authors aim to improve image guidance during percutaneous coronary interventions of chronic total occlusions (CTO) by providing information obtained from computed tomography angiography (CTA) to the cardiac interventionist. To this end, the authors investigate a method to register a 3D CTA model to biplane reconstructions. Methods: The authors developed a method for registering preoperative coronary CTA with intraoperative biplane x-ray angiography (XA) images via 3D models of the coronary arteries. The models are extracted from the CTA and biplane XA images, and are temporally aligned based on CTA reconstruction phase and XA ECG signals. Rigid spatial alignment is achieved with a robust probabilistic point set registration approach using Gaussian mixture models (GMMs). This approach is extended by including orientation in the Gaussian mixtures and by weighting bifurcation points. The method is evaluated on retrospectively acquired coronary CTA datasets of 23 CTO patients for which biplane XA images are available. Results: The Gaussian mixture model approach achieved a median registration accuracy of 1.7 mm. The extended GMM approach including orientation was not significantly different (P > 0.1) but did improve robustness with regards to the initialization of the 3D models. Conclusions: The authors demonstrated that the GMM approach can effectively be applied to register CTA to biplane XA images for the purpose of improving image guidance in percutaneous coronary interventions.

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

Developing an Anti-Xa-Based Anticoagulation Protocol for Patients with Percutaneous Ventricular Assist Devices.

Science.gov (United States)

Sieg, Adam; Mardis, B Andrew; Mardis, Caitlin R; Huber, Michelle R; New, James P; Meadows, Holly B; Cook, Jennifer L; Toole, J Matthew; Uber, Walter E

2015-01-01

Because of the complexities associated with anticoagulation in temporary percutaneous ventricular assist device (pVAD) recipients, a lack of standardization exists in their management. This retrospective analysis evaluates current anticoagulation practices at a single center with the aim of identifying an optimal anticoagulation strategy and protocol. Patients were divided into two cohorts based on pVAD implanted (CentriMag (Thoratec; Pleasanton, CA) / TandemHeart (CardiacAssist; Pittsburgh, PA) or Impella (Abiomed, Danvers, MA)), with each group individually analyzed for bleeding and thrombotic complications. Patients in the CentriMag/TandemHeart cohort were subdivided based on the anticoagulation monitoring strategy (activated partial thromboplastin time (aPTT) or antifactor Xa unfractionated heparin (anti-Xa) values). In the CentriMag/TandemHeart cohort, there were five patients with anticoagulation titrated based on anti-Xa values; one patient developed a device thrombosis and a major bleed, whereas another patient experienced major bleeding. Eight patients received an Impella pVAD. Seven total major bleeds in three patients and no thrombotic events were detected. Based on distinct differences between the devices, anti-Xa values, and outcomes, two protocols were created to guide anticoagulation adjustments. However, anticoagulation in patients who require pVAD support is complex with constantly evolving anticoagulation goals. The ideal level of anticoagulation should be individually determined using several coagulation laboratory parameters in concert with hemodynamic changes in the patient's clinical status, the device, and the device cannulation.

RNA-Seq analysis reveals insight into enhanced rice Xa7-mediated bacterial blight resistance at high temperature.

Directory of Open Access Journals (Sweden)

Stephen P Cohen

Full Text Available Plant disease is a major challenge to agriculture worldwide, and it is exacerbated by abiotic environmental factors. During some plant-pathogen interactions, heat stress allows pathogens to overcome host resistance, a phenomenon which could severely impact crop productivity considering the global warming trends associated with climate change. Despite the importance of this phenomenon, little is known about the underlying molecular mechanisms. To better understand host plant responses during simultaneous heat and pathogen stress, we conducted a transcriptomics experiment for rice plants (cultivar IRBB61 containing Xa7, a bacterial blight disease resistance (R gene, that were infected with Xanthomonas oryzae, the bacterial blight pathogen of rice, during high temperature stress. Xa7-mediated resistance is unusual relative to resistance mediated by other R genes in that it functions better at high temperatures. Using RNA-Seq technology, we identified 8,499 differentially expressed genes as temperature responsive in rice cultivar IRBB61 experiencing susceptible and resistant interactions across three time points. Notably, genes in the plant hormone abscisic acid biosynthesis and response pathways were up-regulated by high temperature in both mock-treated plants and plants experiencing a susceptible interaction and were suppressed by high temperature in plants exhibiting Xa7-mediated resistance. Genes responsive to salicylic acid, an important plant hormone for disease resistance, were down-regulated by high temperature during both the susceptible and resistant interactions, suggesting that enhanced Xa7-mediated resistance at high temperature is not dependent on salicylic acid signaling. A DNA sequence motif similar to known abscisic acid-responsive cis-regulatory elements was identified in the promoter region upstream of genes up-regulated in susceptible but down-regulated in resistant interactions. The results of our study suggest that the plant

Do methodological differences account for the current controversy on tissue factor expression in platelets?

Science.gov (United States)

Brambilla, Marta; Rossetti, Laura; Zara, Chiara; Canzano, Paola; Giesen, Peter L A; Tremoli, Elena; Camera, Marina

2018-06-01

Tissue factor (TF), the key activator of the blood coagulation cascade and of thrombus formation, is also expressed by circulating human platelets. Despite the documented in-depth characterization of platelet TF carried out in the past 15 years, some authors still fail to identify TF in platelets, especially when assessment in platelet-rich plasma (PRP) or washed platelets is carried out. This study aims to extend the characterization of the subset of TF-positive platelets in PRP from healthy subjects and to verify how different centrifugation forces, used to prepare the PRP, could affect the analysis of TF-positive platelets. Data indicate that large-size platelets express significantly higher amount of TF compared to small-size cells, in terms of both TF protein and TF mRNA. Upon stimulation, large platelets readily expose on the cell membrane TF, which is functionally active, i.e., able to generate factor Xa (FXa) as well as thrombin. By contrast, TF activity in small platelets is almost completely quenched by tissue factor pathway inhibitor (TFPI), becoming indeed detectable only after treatment with an anti-TFPI antibody. Our data highlight that particular attention must be paid to the preparation and collection of the PRP since such preanalytical variables may influence the platelet recovery and in turn affect subsequent analysis, whether it is flow cytometry, functional activity tests, proteome, or transcriptome analysis. Indeed, the TF-positive subset of large platelets can easily be lost if centrifugation protocols are not optimized, thus erroneously leading to a false-negative result.

Identification of bacterial blight resistance genes Xa4 in Pakistani ...

African Journals Online (AJOL)

SERVER

2008-03-04

Mar 4, 2008 ... Bacterial blight (BB) caused by Xanthomonas oryzae pv oryzae (Xoo) is a major biotic constraint in the irrigated rice belts. Genetic resistance is the most effective and economical control for bacterial blight. Molecular survey was conducted to identify the rice germplasm/lines for the presence of Xa4, a.

Determination of rivaroxaban in patient’s plasma samples by anti-Xa chromogenic test associated to High Performance Liquid Chromatography tandem Mass Spectrometry (HPLC-MS/MS)

Science.gov (United States)

Derogis, Priscilla Bento Matos; Sanches, Livia Rentas; de Aranda, Valdir Fernandes; Colombini, Marjorie Paris; Mangueira, Cristóvão Luis Pitangueira; Katz, Marcelo; Faulhaber, Adriana Caschera Leme; Mendes, Claudio Ernesto Albers; Ferreira, Carlos Eduardo dos Santos; França, Carolina Nunes; Guerra, João Carlos de Campos

2017-01-01

Rivaroxaban is an oral direct factor Xa inhibitor, therapeutically indicated in the treatment of thromboembolic diseases. As other new oral anticoagulants, routine monitoring of rivaroxaban is not necessary, but important in some clinical circumstances. In our study a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was validated to measure rivaroxaban plasmatic concentration. Our method used a simple sample preparation, protein precipitation, and a fast chromatographic run. It was developed a precise and accurate method, with a linear range from 2 to 500 ng/mL, and a lower limit of quantification of 4 pg on column. The new method was compared to a reference method (anti-factor Xa activity) and both presented a good correlation (r = 0.98, p highly correlated and should be used as clinical tools for drug monitoring. The method was applied successfully in a group of 49 real-life patients, which allowed an accurate determination of rivaroxaban in peak and trough levels. PMID:28170419

Determination of rivaroxaban in patient's plasma samples by anti-Xa chromogenic test associated to High Performance Liquid Chromatography tandem Mass Spectrometry (HPLC-MS/MS).

Science.gov (United States)

Derogis, Priscilla Bento Matos; Sanches, Livia Rentas; de Aranda, Valdir Fernandes; Colombini, Marjorie Paris; Mangueira, Cristóvão Luis Pitangueira; Katz, Marcelo; Faulhaber, Adriana Caschera Leme; Mendes, Claudio Ernesto Albers; Ferreira, Carlos Eduardo Dos Santos; França, Carolina Nunes; Guerra, João Carlos de Campos

2017-01-01

Rivaroxaban is an oral direct factor Xa inhibitor, therapeutically indicated in the treatment of thromboembolic diseases. As other new oral anticoagulants, routine monitoring of rivaroxaban is not necessary, but important in some clinical circumstances. In our study a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was validated to measure rivaroxaban plasmatic concentration. Our method used a simple sample preparation, protein precipitation, and a fast chromatographic run. It was developed a precise and accurate method, with a linear range from 2 to 500 ng/mL, and a lower limit of quantification of 4 pg on column. The new method was compared to a reference method (anti-factor Xa activity) and both presented a good correlation (r = 0.98, p plasma samples for rivaroxaban measurement by HPLC-MS/MS without interferences. The chromogenic and HPLC-MS/MS methods were highly correlated and should be used as clinical tools for drug monitoring. The method was applied successfully in a group of 49 real-life patients, which allowed an accurate determination of rivaroxaban in peak and trough levels.

Possible role of rivaroxaban in attenuating pressure-overload-induced atrial fibrosis and fibrillation.

Science.gov (United States)

Kondo, Hidekazu; Abe, Ichitaro; Fukui, Akira; Saito, Shotaro; Miyoshi, Miho; Aoki, Kohei; Shinohara, Tetsuji; Teshima, Yasushi; Yufu, Kunio; Takahashi, Naohiko

2018-03-01

Coagulation factor Xa (FXa) promotes thrombus formation and exacerbates inflammation via activation of protease-activated receptor (PAR)-2. We tested the hypothesis of whether administration of direct oral anticoagulant, rivaroxaban, would attenuate transverse aortic constriction (TAC)-induced atrial inflammatory fibrosis and vulnerability to atrial fibrillation (AF) in mice. Ten-week-old male CL57/B6 mice were divided into a sham-operation (CNT) group and TAC-surgery group. These two groups were then subdivided into vehicle (VEH) and rivaroxaban (RVX) treatment (30μg/g/day) groups. We assessed PAR-2 expression in response to TAC-related stimulation using rat cultured cells. TAC-induced left atrial thrombus formation was not observed in the TAC-RVX group. Cardiac PAR-2 upregulation was observed in both TAC groups. In the quantitative analysis of mRNA levels, cardiac PAR-2 upregulation was attenuated in the TAC-RVX group compared to TAC-VEH group. In histological evaluation, the TAC-VEH group showed cardiac inhomogeneous interstitial fibrosis and abundant infiltration of macrophages, which were attenuated by RVX administration. Electrophysiological examination revealed that AF duration in the TAC group was shortened by RVX administration. TAC-induced protein overexpression of monocyte chemoattractant protein-1, and mRNA overexpression of tumor necrosis factor-α, interleukin (IL)-1β and IL-6 in the left atrium was suppressed by RVX treatment. In cardiac fibroblasts, persistent intermittent stretch upregulated PAR-2, which was suppressed by RVX pre-incubation. These observations demonstrate that coagulation FXa inhibitor probably has a cardioprotective effect against pressure-overload-induced atrial remodeling. Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Computational investigation of potential dosing schedules for a switch of medication from warfarin to rivaroxaban-an oral, direct Factor Xa inhibitor.

Science.gov (United States)

Burghaus, Rolf; Coboeken, Katrin; Gaub, Thomas; Niederalt, Christoph; Sensse, Anke; Siegmund, Hans-Ulrich; Weiss, Wolfgang; Mueck, Wolfgang; Tanigawa, Takahiko; Lippert, Jörg

2014-01-01

The long-lasting anticoagulant effect of vitamin K antagonists can be problematic in cases of adverse drug reactions or when patients are switched to another anticoagulant therapy. The objective of this study was to examine in silico the anticoagulant effect of rivaroxaban, an oral, direct Factor Xa inhibitor, combined with the residual effect of discontinued warfarin. Our simulations were based on the recommended anticoagulant dosing regimen for stroke prevention in patients with atrial fibrillation. The effects of the combination of discontinued warfarin plus rivaroxaban were simulated using an extended version of a previously validated blood coagulation computer model. A strong synergistic effect of the two distinct mechanisms of action was observed in the first 2-3 days after warfarin discontinuation; thereafter, the effect was close to additive. Nomograms for the introduction of rivaroxaban therapy after warfarin discontinuation were derived for Caucasian and Japanese patients using safety and efficacy criteria described previously, together with the coagulation model. The findings of our study provide a mechanistic pharmacologic rationale for dosing schedules during the therapy switch from warfarin to rivaroxaban and support the switching strategies as outlined in the Summary of Product Characteristics and Prescribing Information for rivaroxaban.

Computational investigation of potential dosing schedules for a switch of medication from warfarin to rivaroxaban—an oral, direct Factor Xa inhibitor

Science.gov (United States)

Burghaus, Rolf; Coboeken, Katrin; Gaub, Thomas; Niederalt, Christoph; Sensse, Anke; Siegmund, Hans-Ulrich; Weiss, Wolfgang; Mueck, Wolfgang; Tanigawa, Takahiko; Lippert, Jörg

2014-01-01

The long-lasting anticoagulant effect of vitamin K antagonists can be problematic in cases of adverse drug reactions or when patients are switched to another anticoagulant therapy. The objective of this study was to examine in silico the anticoagulant effect of rivaroxaban, an oral, direct Factor Xa inhibitor, combined with the residual effect of discontinued warfarin. Our simulations were based on the recommended anticoagulant dosing regimen for stroke prevention in patients with atrial fibrillation. The effects of the combination of discontinued warfarin plus rivaroxaban were simulated using an extended version of a previously validated blood coagulation computer model. A strong synergistic effect of the two distinct mechanisms of action was observed in the first 2–3 days after warfarin discontinuation; thereafter, the effect was close to additive. Nomograms for the introduction of rivaroxaban therapy after warfarin discontinuation were derived for Caucasian and Japanese patients using safety and efficacy criteria described previously, together with the coagulation model. The findings of our study provide a mechanistic pharmacologic rationale for dosing schedules during the therapy switch from warfarin to rivaroxaban and support the switching strategies as outlined in the Summary of Product Characteristics and Prescribing Information for rivaroxaban. PMID:25426077

L2₁ and XA Ordering Competition in Hafnium-Based Full-Heusler Alloys Hf₂VZ (Z = Al, Ga, In, Tl, Si, Ge, Sn, Pb).

Science.gov (United States)

Wang, Xiaotian; Cheng, Zhenxiang; Wang, Wenhong

2017-10-20

For theoretical designing of full-Heusler based spintroinc materials, people have long believed in the so-called Site Preference Rule (SPR). Very recently, according to the SPR, there are several studies on XA-type Hafnium-based Heusler alloys X₂YZ, i.e., Hf₂VAl, Hf₂CoZ (Z = Ga, In) and Hf₂CrZ (Z = Al, Ga, In). In this work, a series of Hf₂-based Heusler alloys, Hf₂VZ (Z = Al, Ga, In, Tl, Si, Ge, Sn, Pb), were selected as targets to study the site preferences of their atoms by first-principle calculations. It has been found that all of them are likely to exhibit the L2₁-type structure instead of the XA one. Furthermore, we reveal that the high values of spin-polarization of XA-type Hf₂VZ (Z = Al, Ga, In, Tl, Si, Ge, Sn, Pb) alloys have dropped dramatically when they form the L2₁-type structure. Also, we prove that the electronic, magnetic, and physics nature of these alloys are quite different, depending on the L2₁-type or XA-type structures.

Marker-Assisted Selection of Xa21 Conferring Resistance to Bacterial Leaf Blight in indica Rice Cultivar LT2

Institute of Scientific and Technical Information of China (English)

Hue Thi NGUYEN; Trung Nguyen DINH; Nakano TOSHITSUGU; Liet Van VU; Quang Hong VU; Tan Van MAI; Thu Thi NGUYEN; Lam Duc VU; Tung Thanh NGUYEN; Long Viet NGUYEN; Hien Thu Thi VU; Hue Thi NONG

2018-01-01

Bacterial leaf blight of rice (BLB), caused by Xanthomonas oryzae pv. oryzae, is one of the most destructive diseases in Asian rice fields. A high-quality rice variety, LT2, was used as the recipient parent. IRBB21, which carries the Xa21 gene, was used as the donor parent. The resistance gene Xa21 was introduced into LT2 by marker-assisted backcrossing. Three Xoo races were used to inoculate the improved lines following the clipping method. Eleven BC3F3lines carrying Xa21 were obtained based on molecular markers and agronomic performance. The 11 lines were then inoculated with the three Xoo races. All the 11 improved lines showed better resistance to BLB than the recipient parent LT2. Based on the level of resistance to BLB and their agronomic performance, five lines (BC3F35.1.5.1, BC3F35.1.5.12, BC3F38.5.6.44, BC3F3 9.5.4.1 and BC3F39.5.4.23) were selected as the most promising for commercial release. These improved lines could contribute to rice production in terms of food security.

Marker-Assisted Selection of Xa21 Conferring Resistance to Bacterial Leaf Blight in indica Rice Cultivar LT2

Directory of Open Access Journals (Sweden)

Hue Thi Nguyen

2018-01-01

Full Text Available Bacterial leaf blight of rice (BLB, caused by Xanthomonas oryzae pv. oryzae, is one of the most destructive diseases in Asian rice fields. A high-quality rice variety, LT2, was used as the recipient parent. IRBB21, which carries the Xa21 gene, was used as the donor parent. The resistance gene Xa21 was introduced into LT2 by marker-assisted backcrossing. Three Xoo races were used to inoculate the improved lines following the clipping method. Eleven BC3F3 lines carrying Xa21 were obtained based on molecular markers and agronomic performance. The 11 lines were then inoculated with the three Xoo races. All the 11 improved lines showed better resistance to BLB than the recipient parent LT2. Based on the level of resistance to BLB and their agronomic performance, five lines (BC3F3 5.1.5.1, BC3F3 5.1.5.12, BC3F3 8.5.6.44, BC3F3 9.5.4.1 and BC3F3 9.5.4.23 were selected as the most promising for commercial release. These improved lines could contribute to rice production in terms of food security.

The Inflammatory Actions of Coagulant and Fibrinolytic Proteases in Disease

Directory of Open Access Journals (Sweden)

Michael Schuliga

2015-01-01

Full Text Available Aside from their role in hemostasis, coagulant and fibrinolytic proteases are important mediators of inflammation in diseases such as asthma, atherosclerosis, rheumatoid arthritis, and cancer. The blood circulating zymogens of these proteases enter damaged tissue as a consequence of vascular leak or rupture to become activated and contribute to extravascular coagulation or fibrinolysis. The coagulants, factor Xa (FXa, factor VIIa (FVIIa, tissue factor, and thrombin, also evoke cell-mediated actions on structural cells (e.g., fibroblasts and smooth muscle cells or inflammatory cells (e.g., macrophages via the proteolytic activation of protease-activated receptors (PARs. Plasmin, the principle enzymatic mediator of fibrinolysis, also forms toll-like receptor-4 (TLR-4 activating fibrin degradation products (FDPs and can release latent-matrix bound growth factors such as transforming growth factor-β (TGF-β. Furthermore, the proteases that convert plasminogen into plasmin (e.g., urokinase plasminogen activator evoke plasmin-independent proinflammatory actions involving coreceptor activation. Selectively targeting the receptor-mediated actions of hemostatic proteases is a strategy that may be used to treat inflammatory disease without the bleeding complications of conventional anticoagulant therapies. The mechanisms by which proteases of the coagulant and fibrinolytic systems contribute to extravascular inflammation in disease will be considered in this review.

Transgenic expression of the rice Xa21 pattern-recognition receptor in banana (Musa sp.) confers resistance to Xanthomonas campestris pv. musacearum.

Science.gov (United States)

Tripathi, Jaindra N; Lorenzen, Jim; Bahar, Ofir; Ronald, Pamela; Tripathi, Leena

2014-08-01

Banana Xanthomonas wilt (BXW), caused by the bacterium Xanthomonas campestris pv. musacearum (Xcm), is the most devastating disease of banana in east and central Africa. The spread of BXW threatens the livelihood of millions of African farmers who depend on banana for food security and income. There are no commercial chemicals, biocontrol agents or resistant cultivars available to control BXW. Here, we take advantage of the robust resistance conferred by the rice pattern-recognition receptor (PRR), XA21, to the rice pathogen Xanthomonas oryzae pv. oryzae (Xoo). We identified a set of genes required for activation of Xa21-mediated immunity (rax) that were conserved in both Xoo and Xcm. Based on the conservation, we hypothesized that intergeneric transfer of Xa21 would confer resistance to Xcm. We evaluated 25 transgenic lines of the banana cultivar 'Gonja manjaya' (AAB) using a rapid bioassay and 12 transgenic lines in the glasshouse for resistance against Xcm. About 50% of the transgenic lines showed complete resistance to Xcm in both assays. In contrast, all of the nontransgenic control plants showed severe symptoms that progressed to complete wilting. These results indicate that the constitutive expression of the rice Xa21 gene in banana results in enhanced resistance against Xcm. Furthermore, this work demonstrates the feasibility of PRR gene transfer between monocotyledonous species and provides a valuable new tool for controlling the BXW pandemic of banana, a staple food for 100 million people in east Africa. © 2014 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

78 FR 24677 - Safety Zone; XA The Experimental Agency Fireworks, Pier 34, East River, NY

Science.gov (United States)

2013-04-26

... Final Rule This rule establishes a temporary safety zone on the navigable waters of the East River, in... Fireworks, Pier 34, East River, NY. (a) Regulated Area. The following area is a temporary safety zone: all... 1625-AA00 Safety Zone; XA The Experimental Agency Fireworks, Pier 34, East River, NY AGENCY: Coast...

Neutralisation of the anti-coagulant effects of heparin by histones in blood plasma and purified systems.

Science.gov (United States)

Longstaff, Colin; Hogwood, John; Gray, Elaine; Komorowicz, Erzsebet; Varjú, Imre; Varga, Zoltán; Kolev, Krasimir

2016-03-01

Neutrophil extracellular traps (NETs) composed primarily of DNA and histones are a link between infection, inflammation and coagulation. NETs promote coagulation and approaches to destabilise NETs have been explored to reduce thrombosis and treat sepsis. Heparinoids bind histones and we report quantitative studies in plasma and purified systems to better understand physiological consequences. Unfractionated heparin (UFH) was investigated by activated partial thromboplastin time (APTT) and alongside low-molecular-weight heparins (LMWH) in purified systems with thrombin or factor Xa (FXa) and antithrombin (AT) to measure the sensitivity of UFH or LMWH to histones. A method was developed to assess the effectiveness of DNA and non-anticoagulant heparinoids as anti-histones. Histones effectively neutralised UFH, the IC50 value for neutralisation of 0.2 IU/ml UFH was 1.8 µg/ml histones in APTT and 4.6 µg/ml against 0.6 IU/ml UFH in a purified system. Histones also inhibited the activities of LMWHs with thrombin (IC50 6.1 and 11.0 µg/ml histones, for different LMWHs) or FXa (IC50 7.8 and 7.0 µg/ml histones). Direct interactions of UFH and LMWH with DNA and histones were explored by surface plasmon resonance, while rheology studies showed complex effects of histones, UFH and LMWH on clot resilience. A conclusion from these studies is that anticoagulation by UFH and LMWH will be compromised by high affinity binding to circulating histones even in the presence of DNA. A complete understanding of the effects of histones, DNA and heparins on the haemostatic system must include an appreciation of direct effects on fibrin and clot structure.

The Factor of Structure and Mechanical Properties in the Production of Critical Fixing Hardware 38XA

Directory of Open Access Journals (Sweden)

G.V. Pachurin

2016-09-01

Full Text Available Fixing hardware made of carbon, high-carbon, and alloyed wires is one of the widespread critical parts in mechanical engineering. The characteristics of fixtures and fasteners and their performance figures are assessed at all stages of steel-making operation, from the choice of burden stock for metal smelting to the method of preparing calibrated rolled metal parts and upsetting end products. Material used for producing long high-duty bolts must be both sufficiently strong and ductile, have homogeneous mechanical properties and chemistry, and no inner or surface defects. When manufacturing fasteners, hot-rolled metal is often plastically deformed by drafting before cold upsetting, and all unacceptable defects are removed by the expensive procedure of lathe-turning. Moreover, this technology of metal processing entails losses of up to 5.5 % in chips. This paper suggests a resource-efficient and environmentally friendlier fabrication method for calibrated rolled metal items made of steel 38XA, 9.65 mm diameter, for cold die-forging of high-duty bolts used in automotive engines, which helps spare expensive lathe-machining processes. Moreover, rolled steel produced using this technology is characterized by high resistance to plastic deformation when cold, which leads to increase n wear-resistance of tools in cold die-forging of bolts.

Interaction of blood coagulation factor Va with phospholipid vesicles examined by using lipophilic photoreagents

International Nuclear Information System (INIS)

Krieg, U.C.; Isaacs, B.S.; Yemul, S.S.; Esmon, C.T.; Bayley, H.; Johnson, A.E.

1987-01-01

Two different lipophilic photoreagents, [ 3 H]adamantane diazirine and 3-(trifluoromethyl)-3-(m-[ 125 I]iodophenyl)diazirine (TID), have been utilized to examine the interactions of blood coagulation factor Va with calcium, prothrombin, factor Xa, and, in particular, phospholipid vesicles. With each of these structurally dissimilar reagents, the extent of photolabeling of factor Va was greater when the protein was bound to a membrane surface than when it was free in solution. Specifically, the covalent photoreaction with Vl, the smaller subunit of factor Va, was 2-fold higher in the presence of phosphatidylcholine/phosphatidylserine (PC/PS, 3:1) vesicles, to which factor Va binds, than in the presence of 100% PC vesicles, to which the protein does not bind. However, the magnitude of the PC/PS-dependent photolabeling was much less than has been observed previously with integral membrane proteins. It therefore appears that the binding of factor Va to the membrane surface exposes Vl to the lipid core of the bilayer, but that only a small portion of the Vl polypeptide is exposed to, or embedded in, the bilayer core. Addition of either prothrombin or active-site-blocked factor Xa to PC/PS-bound factor Va had little effect on the photolabeling of Vl with TID, but reduced substantially the covalent labeling of Vh, the larger subunit of factor Va. This indicates that prothrombin and factor Xa each cover nonpolar surfaces on Vh when the macromolecules associate on the PC/PS surface. It therefore seems likely that the formation of the prothrombinase complex involves a direct interaction between Vh and factor Xa and between Vh and prothrombin.(ABSTRACT TRUNCATED AT 250 WORDS)

XaNSoNS: GPU-accelerated simulator of diffraction patterns of nanoparticles

Directory of Open Access Journals (Sweden)

V.S. Neverov

2017-01-01

Full Text Available XaNSoNS is an open source software with GPU support, which simulates X-ray and neutron 1D (or 2D diffraction patterns and pair-distribution functions (PDF for amorphous or crystalline nanoparticles (up to ∼107 atoms of heterogeneous structural content. Among the multiple parameters of the structure the user may specify atomic displacements, site occupancies, molecular displacements and molecular rotations. The software uses general equations nonspecific to crystalline structures to calculate the scattering intensity. It supports four major standards of parallel computing: MPI, OpenMP, Nvidia CUDA and OpenCL, enabling it to run on various architectures, from CPU-based HPCs to consumer-level GPUs.

XaNSoNS: GPU-accelerated simulator of diffraction patterns of nanoparticles

Science.gov (United States)

Neverov, V. S.

XaNSoNS is an open source software with GPU support, which simulates X-ray and neutron 1D (or 2D) diffraction patterns and pair-distribution functions (PDF) for amorphous or crystalline nanoparticles (up to ∼107 atoms) of heterogeneous structural content. Among the multiple parameters of the structure the user may specify atomic displacements, site occupancies, molecular displacements and molecular rotations. The software uses general equations nonspecific to crystalline structures to calculate the scattering intensity. It supports four major standards of parallel computing: MPI, OpenMP, Nvidia CUDA and OpenCL, enabling it to run on various architectures, from CPU-based HPCs to consumer-level GPUs.

Analysis of nucleotide diversity among alleles of the major bacterial blight resistance gene Xa27 in cultivars of rice (Oryza sativa) and its wild relatives.

Science.gov (United States)

Bimolata, Waikhom; Kumar, Anirudh; Sundaram, Raman Meenakshi; Laha, Gouri Shankar; Qureshi, Insaf Ahmed; Reddy, Gajjala Ashok; Ghazi, Irfan Ahmad

2013-08-01

Xa27 is one of the important R-genes, effective against bacterial blight disease of rice caused by Xanthomonas oryzae pv. oryzae (Xoo). Using natural population of Oryza, we analyzed the sequence variation in the functionally important domains of Xa27 across the Oryza species. DNA sequences of Xa27 alleles from 27 rice accessions revealed higher nucleotide diversity among the reported R-genes of rice. Sequence polymorphism analysis revealed synonymous and non-synonymous mutations in addition to a number of InDels in non-coding regions of the gene. High sequence variation was observed in the promoter region including the 5'UTR with 'π' value 0.00916 and 'θ w ' = 0.01785. Comparative analysis of the identified Xa27 alleles with that of IRBB27 and IR24 indicated the operation of both positive selection (Ka/Ks > 1) and neutral selection (Ka/Ks ≈ 0). The genetic distances of alleles of the gene from Oryza nivara were nearer to IRBB27 as compared to IR24. We also found the presence of conserved and null UPT (upregulated by transcriptional activator) box in the isolated alleles. Considerable amino acid polymorphism was localized in the trans-membrane domain for which the functional significance is yet to be elucidated. However, the absence of functional UPT box in all the alleles except IRBB27 suggests the maintenance of single resistant allele throughout the natural population.

Modeling of human factor Va inactivation by activated protein C

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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

Comparative evaluation of direct thrombin and factor Xa inhibitors with antiplatelet agents under flow and static conditions: an in vitro flow chamber model.

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Kazuya Hosokawa

Full Text Available Dabigatran and rivaroxaban are novel oral anticoagulants that specifically inhibit thrombin and factor Xa, respectively. The aim of this study is to elucidate antithrombotic properties of these anticoagulant agents under arterial and venous shear conditions. Whole blood samples treated with dabigatran or rivaroxaban at 250, 500, and 1000 nM, with/without aspirin and AR-C66096, a P2Y12 antagonist, were perfused over a microchip coated with collagen and tissue thromboplastin at shear rates of 240 and 600 s(-1. Fibrin-rich platelet thrombus formation was quantified by monitoring flow pressure changes. Dabigatran at higher concentrations (500 and 1000 nM potently inhibited thrombus formation at both shear rates, whereas 1000 nM of rivaroxaban delayed, but did not completely inhibit, thrombus formation. Dual antiplatelet agents weakly suppressed thrombus formation at both shear rates, but intensified the anticoagulant effects of dabigatran and rivaroxaban. The anticoagulant effects of dabigatran and rivaroxaban were also evaluated under static conditions using thrombin generation (TG assay. In platelet-poor plasma, dabigatran at 250 and 500 nM efficiently prolonged the lag time (LT and moderately reduce peak height (PH of TG, whereas rivaroxaban at 250 nM efficiently prolonged LT and reduced PH of TG. In platelet-rich plasma, however, both anticoagulants efficiently delayed LT and reduced PH of TG. Our results suggest that dabigatran and rivaroxaban may exert distinct antithrombotic effects under flow conditions, particularly in combination with dual antiplatelet therapy.

Anticoagulant effects of inhaled unfractionated heparin in the dog as determined by partial thromboplastin time and factor Xa activity.

Science.gov (United States)

Manion, Jill S; Thomason, John M; Langston, Vernon C; Claude, Andrew K; Brooks, Marjory B; Mackin, Andrew J; Lunsford, Kari V

2016-01-01

To evaluate the anticoagulant effects of inhaled heparin in dogs. This study was conducted in 3 phases. In phase 1, bronchoalveolar lavage fluid (BALf) was collected to generate an in vitro calibration curve to relate heparin concentration to the activated partial thromboplastin time (aPTT). In phase 2, heparin was administered via nebulization to determine the threshold dose needed to prolong systemic aPTT. In phase 3, the local anticoagulant activity of inhaled heparin was determined by measurement of BALf anti-Xa activity and aPTT. University teaching hospital. Six healthy intact female Walker Hounds were used in this study. Two dogs were used for each phase. Inhaled unfractionated sodium heparin was administered in doses ranging from 50,000 to 200,000 IU. In vitro addition of heparin to BALf caused a prolongation in aPTT. Inhaled heparin at doses as high as 200,000 IU failed to prolong systemic aPTT, and a threshold dose could not be determined. No significant local anticoagulant effects were detected. Even at doses higher than those known to be effective in people, inhaled heparin appears to have no detectable local or systemic anticoagulant effects in dogs with the current delivery method. © Veterinary Emergency and Critical Care Society 2015.

Apixaban Enhances Vasodilatation Mediated by Protease-Activated Receptor 2 in Isolated Rat Arteries

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Ambra Villari

2017-07-01

Full Text Available Apixaban (APX is a direct inhibitor of factor X (FXa approved for prophylaxis and treatment of deep venous thrombosis and atrial fibrillation. Because FXa activates protease-activated receptor 2 (PAR-2 in endothelium and vascular smooth muscle, inhibition of FXa by APX may affect vasomotor function. The effect of APX was assessed in vitro, by wire myography, in rat mesenteric resistance arteries (MRAs and basilar arteries challenged with vasoconstrictors [phenylephrine (PE; 5-hydroxytryptamine (5-HT], vasodilators [acetylcholine (ACh; sodium nitroprusside (SNP] or with the PAR-2 peptide agonist SLIGRL. APX (10 μM reduced the vasoconstriction to PE and 5-HT while did not change the vasodilatation to ACh or SNP. SLIGRL induced concentration-dependent vasodilation in pre-constricted arteries, that was reduced by incubation with the NO inhibitor NG-nitro-L-arginine (L-NNA and abolished by endothelium removal. APX enhanced vasodilation to SLIGRL either in the presence or in the absence of L-NNA, but was ineffective in endothelium-denuded vessels. In preparations from heparin-treated rats (to inhibit FXa APX did not change the vasodilation to SLIGRL. FXa enzymatic activity, detected in mesentery homogenates from controls, was inhibited by APX, whereas APX-sensitive enzymatic activity was undetectable in homogenates from heparin-treated rats. Immunoblot analysis showed that incubation of MRA or aorta with APX increased the abundance of PAR-2, an effect not seen in MRA from heparin-treated rats or in endothelium-denuded aortas. In conclusion, inhibition of FXa by APX increases vasodilatation mediated by PAR-2. APX may act by inhibiting PAR-2 desensitization induced by endogenous FXa. This effect could be useful in the context of endothelial dysfunction associated to cardiovascular diseases.

Fucosylated chondroitin sulfate oligosaccharides exert anticoagulant activity by targeting at intrinsic tenase complex with low FXII activation: Importance of sulfation pattern and molecular size.

Science.gov (United States)

Li, Junhui; Li, Shan; Yan, Lufeng; Ding, Tian; Linhardt, Robert J; Yu, Yanlei; Liu, Xinyue; Liu, Donghong; Ye, Xingqian; Chen, Shiguo

2017-10-20

Fucosylated chondroitin sulfates (fCSs) are structurally unusual glycosaminoglycans isolated from sea cucumbers that exhibit potent anticoagulant activity. These fCSs were isolated from sea cucumber, Isostichopus badionotus and Pearsonothuria graeffei. Fenton reaction followed by gel filtration chromatography afforded fCS oligosaccharides, with different sulfation patterns identified by mass and NMR spectroscopy, and these were used to clarify the relationship between the structures and the anticoagulant activities of fCSs. In vitro activities were measured by activated partial thromboplastin time (APTT), thrombin time (TT), thrombin and factor Xa inhibition, and activation of FXII. The results showed that free radicals preferentially acted on GlcA residues affording oligosaccharides that were purified from both fCSs. The inhibition of thrombin and factor X activities, mediated through antithrombin III and heparin cofactor II of fCSs oligosaccharides were affected by their molecular weight and fucose branches. Oligosaccharides with different sulfation patterns of the fucose branching had a similar ability to inhibit the FXa by the intrinsic factor Xase (factor IXa-VIIIa complex). Oligosaccharides with 2,4-O-sulfo fucose branches from fCS-Ib showed higher activities than ones with 3,4-O-disulfo branches obtained from fCS-Pg. Furthermore, a heptasaccharide is the minimum size oligosaccharide required for anticoagulation and FXII activation. This activity was absent for fCS oligosaccharides smaller than nonasaccharides. Molecular size and fucose branch sulfation are important for anticoagulant activity and reduction of size can reverse the activation of FXII caused by native fCSs. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Análise e identificação das antocianinas de couve rôxa (Brassica spp.)

OpenAIRE

Lopes, Dulce; Jesus, Benvinda; Cabrita, Luís

2004-01-01

A couve rôxa é uma espécie comestível com uma composição em antocianinas rica e complexa. Sabe-se que contem antocianinas poliglicosiladas, aciladas com um ou mesmo dois grupos acilo aromáticos, nomeadamente com ácidos coumárico e caféico. Este padrão de acilação é particularmente interessante, porque confere estabilidade às antocianinas e aumenta o seu potencial de utilização em aplicações famacêuticas, alimentares e cosméticas. Este estudo tem por objectivo determinar a...

Home treatment of patients with low-risk pulmonary embolism with the oral factor Xa inhibitor rivaroxaban. Rationale and design of the HoT-PE Trial.

Science.gov (United States)

Barco, Stefano; Lankeit, Mareike; Binder, Harald; Schellong, Sebastian; Christ, Michael; Beyer-Westendorf, Jan; Duerschmied, Daniel; Bauersachs, Rupert; Empen, Klaus; Held, Matthias; Schwaiblmair, Martin; Fonseca, Cândida; Jiménez, David; Becattini, Cecilia; Quitzau, Kurt; Konstantinides, Stavros

2016-07-04

Pulmonary embolism (PE) is a potentially life-threatening acute cardiovascular syndrome. However, more than 95 % of patients are haemodynamically stable at presentation, and among them are patients at truly low risk who may qualify for immediate or early discharge. The Home Treatment of Pulmonary Embolism (HoT-PE) study is a prospective international multicentre single-arm phase 4 management (cohort) trial aiming to determine whether home treatment of acute low-risk PE with the oral factor Xa inhibitor rivaroxaban is feasible, effective, and safe. Patients with confirmed PE, who have no right ventricular dysfunction or free floating thrombi in the right atrium or ventricle, are eligible if they meet none of the exclusion criteria indicating haemodynamic instability, serious comorbidity or any condition mandating hospitalisation, or a familial/social environment unable to support home treatment. The first dose of rivaroxaban is given in hospital, and patients are discharged within 48 hours of presentation. Rivaroxaban is taken for at least three months. The primary outcome is symptomatic recurrent venous thromboembolism or PE-related death within three months of enrolment. Secondary outcomes include quality of life and patient satisfaction, and health care resource utilisation compared to existing data on standard-duration hospital treatment. HoT-PE is planned to analyse 1,050 enrolled patients, providing 80 % power to reject the null hypothesis that the recurrence rate of venous thromboembolism is >3 % with α≤0.05. If the hypothesis of HoT-PE is confirmed, early discharge and out-of-hospital treatment may become an attractive, potentially cost-saving option for a significant proportion of patients with acute PE.

Spectrophotometric Methods for the Assay of Fluvoxamine Using Chromogenic Reagents

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V. Annapurna

2010-01-01

Full Text Available Simple, accurate and reproducible UV-Visible spectrophotometric methods were established for the assay of FXA based on the oxidative coupling and condensation reactions. Condensation and coupling of the FXA with Ninhydrin-Ascorbic acid is proposed in method A. Method B includes complexation of FXA with cobalt thiocyanate. The ligating property of FXA with sodium nitro prusside is incorporated in method C. The optical characteristics such as Beers law limits, molar absorptivity and Sandell’s sensitivity for the methods (A-C are given. Regression analysis using the method of least squares was made to evaluate the slope(b, intercept(a and correlation coefficient (r and standard error of estimation (Se for each system. Determination of FXA in bulk form and in pharmaceutical formulations were also incorporated.

Evidence for a saturable mechanism of disappearance of standard heparin in rabbits

International Nuclear Information System (INIS)

Boneu, B.; Caranobe, C.; Gabaig, A.M.; Dupouy, D.; Sie, P.; Buchanan, M.R.; Hirsh, J.

1987-01-01

This work demonstrates that after bolus intravenous injection standard heparin (SH) disappearance results from the combination of a saturable and a non saturable mechanism. Pharmacokinetics and pharmacodynamics of SH were studied by measuring the disappearance of increasing doses (5 - 500 anti-factor Xa U/kg) of 125 I-heparin and of its biological effects. CPM curves allowed the determination of the half lives of heparin according to the dose injected. The half lives were clearly dose dependent and reached a plateau over 100 anti-factor Xa U/kg. The complex curve which describes the amount of heparin cleared per time unit after any given dose has been resolved into its two components reflecting a saturable and a non saturable mechanism of disappearance. For the doses less than 100 anti-factor Xa U/kg the saturable mechanism was preeminent and the anti-factor Xa activity disappearance followed an exponential pattern; for the doses less than 100 anti-factor Xa U/kg the contribution of the non saturable mechanism becomes more important and the anti-factor Xa activity disappearance followed a concave-convex pattern. Further experiments showed that the heparin half life shortened as the circulating anti-factor Xa activity decreased; this phenomenon may explain the concave-convex pattern of the curve of the anticoagulant effect observed after injection of large doses of SH

Trivial topological phase of CaAgP and the topological nodal-line transition in CaAg (P1 -xA sx)

Science.gov (United States)

Xu, N.; Qian, Y. T.; Wu, Q. S.; Autès, G.; Matt, C. E.; Lv, B. Q.; Yao, M. Y.; Strocov, V. N.; Pomjakushina, E.; Conder, K.; Plumb, N. C.; Radovic, M.; Yazyev, O. V.; Qian, T.; Ding, H.; Mesot, J.; Shi, M.

2018-04-01

By performing angle-resolved photoemission spectroscopy and first-principles calculations, we address the topological phase of CaAgP and investigate the topological phase transition in CaAg (P1 -xA sx) . We reveal that in CaAgP, the bulk band gap and surface states with a large bandwidth are topologically trivial, in agreement with hybrid density functional theory calculations. The calculations also indicate that application of "negative" hydrostatic pressure can transform trivial semiconducting CaAgP into an ideal topological nodal-line semimetal phase. The topological transition can be realized by partial isovalent P/As substitution at x =0.38 .

Purification and characterization of Cc-Lec, C-type lactose-binding lectin: A platelet aggregation and blood-clotting inhibitor from Cerastes cerastes venom.

Science.gov (United States)

Samah, Saoud; Fatah, Chérifi; Jean-Marc, Berjeaud; Safia, Kellou-Taîri; Fatima, Laraba-Djebari

2017-09-01

In this study, we reported for the first time the biochemical and structural characterization of Cc-Lec, a C-type lectin purified from Cerastes cerastes venom by affinity chromatography. This lectin was homogeneous by SDS-PAGE, and was shown to be a 34 271.59Da polypeptide by Electrospray mass spectrometry MS-ES-TOF. Its identified sequence of 160 amino acids corresponding to one subunit, revealed a high identity with other related proteins. Cc-Lec modeled 3D structure appeared as homodimer cross-linked by one disulfide bridge. Cc-Lec exhibited a calcium dependent hemagglutinating activity against human group O erythrocytes. Cc-Lec inhibited platelet aggregation induced by ADP, arachidonic acid or fibrinogen suggesting its interaction with their specific receptors namely P2Y1 and/or P2Y12, GPIIb/IIIa and TPα respectively. Cc-Lec was not lethal for mice until 10mg/kg administered by i.p. route. The lectin displayed a lasting anticoagulation on mice plasma even two days post-injection. This anticoagulation seems to be related to its interaction with coagulation factors Xa and IXa. Therefore, Cc-Lec prevented FXa amidolytic activity with Km=4.3310 -4 μg/mL and ki=14.4μg/mL. It seems to interact with these targets through CRD domain which could make it a good target as a pharmacological promising molecule in thrombosis diagnosis and therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Vasorelaxing Action of the Kynurenine Metabolite, Xanthurenic Acid: The Missing Link in Endotoxin-Induced Hypotension?

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Carmine Vecchione

2017-05-01

Full Text Available The kynurenine pathway of tryptophan metabolism is activated by pro-inflammatory cytokines. L-kynurenine, an upstream metabolite of the pathway, acts as a putative endothelium-derived relaxing factor, and has been hypothesized to play a causative role in the pathophysiology of inflammation-induced hypotension. Here, we show that xanthurenic acid (XA, the transamination product of 3-hydroxykynurenine, is more efficacious than L-kynurenine in causing relaxation of a resistance artery, but fails to relax pre-contracted aortic rings. In the mesenteric artery, XA enhanced activating phosphorylation of endothelial nitric oxide synthase (NOS, and the relaxing action of XA was abrogated by pharmacological inhibition of NOS and endothelial-derived hyperpolarizing factor. Systemic injection of XA reduced blood pressure in mice, and serum levels of XA increased by several fold in response to a pulse with the endotoxin, lipopolysaccharide (LPS. LPS-induced hypotension in mice was prevented by pre-treatment with the kynurenine monooxygenase (KMO inhibitor, Ro-618048, which lowered serum levels of XA but enhanced serum levels of L-kynurenine. UPF 648, another KMO inhibitor, could also abrogate LPS-induced hypotension. Our data identify XA as a novel vasoactive compound and suggest that formation of XA is a key event in the pathophysiology of inflammation-induced hypotension.

Rivaroxaban in patients with a recent acute coronary syndrome

DEFF Research Database (Denmark)

Mega, Jessica L; Braunwald, Eugene; Wiviott, Stephen D

2012-01-01

Acute coronary syndromes arise from coronary atherosclerosis with superimposed thrombosis. Since factor Xa plays a central role in thrombosis, the inhibition of factor Xa with low-dose rivaroxaban might improve cardiovascular outcomes in patients with a recent acute coronary syndrome....

Apixaban versus enoxaparin for thromboprophylaxis after hip replacement

DEFF Research Database (Denmark)

Lassen, Michael Rud; Gallus, Alexander; Raskob, Gary E

2010-01-01

There are various regimens for thromboprophylaxis after hip replacement. Low-molecular-weight heparins such as enoxaparin predominantly inhibit factor Xa but also inhibit thrombin to some degree. Orally active, specific factor Xa inhibitors such as apixaban may provide effective thromboprophylaxis...

Edoxaban versus Warfarin for the Treatment of Symptomatic Venous Thromboembolism

DEFF Research Database (Denmark)

Büller, Harry R; Décousus, Hervé; Grosso, Michael A

2013-01-01

Whether the oral factor Xa inhibitor edoxaban can be an alternative to warfarin in patients with venous thromboembolism is unclear.......Whether the oral factor Xa inhibitor edoxaban can be an alternative to warfarin in patients with venous thromboembolism is unclear....

Epitope mapping of functional domains of human factor V with human and mouse monoclonal antibodies

International Nuclear Information System (INIS)

Annamalai, A.E.; Rao, A.K.; Chiu, H.C.; Wang, D.; Dutta-Roy, A.K.; Colman, R.W.

1986-01-01

The authors previously described two human monoclonal antibodies (MAbs) which inactivated factor V. The authors have now purified the predominant antibody (H2) on protein A Sepharose using a pH gradient and typed it as IgG 1 ,. Immunoprecipitation of 125 I-human factor Va with H2 demonstrated specificity for the heavy chain (D), Mr = 105,000. The authors compared using ELISA the competitive binding to factor Va, of H2, H1 and two mouse MAbs, B38 (directed to E) and B10 (to activation peptide, Cl). All four antibodies recognized distinct epitopes in factor V with steric overlap in some cases. Factor Xa showed a concentration dependent competition for binding of H1, H2 and B38 but not B10 to factor V/Va in ELISA. All MAbs bound to factor V/Va in the absence of Ca ++ . However, Ca ++ at 8 mM increased the binding of H1 and H2 to 165% and 360% and did not have any effect on the binding of either mouse MAbs. Prothrombin at a concentration of up to 400 μg/ml did not inhibit binding of any of these antibodies. Thus, both the light (E) and heavy (D) chains of factor Va but not the activation peptide (Cl) interact with factor Xa as defined by the MAbs. In addition, sites on both chains for Ca ++ are recognized by particular MAbs (H1 and H2). These studies increase their knowledge of the interactions of factor V domains in the formation of prothrombinase complex

Single-Molecular Imaging of Anticoagulation Factor I from Snake Venom by Atomic Force Microscopy

Institute of Scientific and Technical Information of China (English)

XU,Xiao-Long(徐小龙); ZHOU,Yun-Shen(周云申); LIU,Qing-Liang(刘清亮); HOU,Jian-Guo(侯建国); YANG,Jing-Long(杨金龙); XIE,Yong-Shu(解永树)

2002-01-01

Anticoagulation factor I (ACF I) from the venom of Agkistrodon acutus is a binding protein to activated coagulation factor X (FXa) and possesses marked anticoagulant activity. Single ACF I molecule has been successfully imaged in air by tapping mode atomic force microscopy (AFM) with high-resolution using glutaraldehyde as a coupling agent. The physical adsorption and covalent binding of ACF I onto the mica show very different surface topographies. The former exhibits the characteristic strand-like structure with much less reproducibility, the latter displays a elliptic granular structure with better reproducibility, which suggests that the stability of ACF I molecules on the mica is enhanced by covalent bonding in the presence of glutaraldehyde. A small-scale AFM amplitude-mode image clearly shows that the covalently bonded ACF I molecule by glutaraldehyde has olive shape structure with an average size of 7.4 nm× 3.6 nm × 3.1 nm, which is very similar to the size determined from the crystal structure of ACF I.

Activation of factor VII bound to tissue factor: A key early step in the tissue factor pathway of blood coagulation

International Nuclear Information System (INIS)

Rao, L.V.M.; Rapaport, S.I.

1988-01-01

Whether the factor VII/tissue factor complex that forms in tissue factor-dependent blood coagulation must be activated to factor VIIa/tissue factor before it can activate its substrates, factor X and IX, has been a difficult question to answer because the substrates, once activated, back-activate factor VII. The earlier studies suggested that human factor VII/tissue factor cannot activate factor IX. Studies have now been extended to the activation of factor X. Reaction mixtures were made with purified factor VII, X, and tissue factor; in some experiments antithrombin III and heparin were added to prevent back-activation of factor VII. Factor X was activated at similar rates in reaction mixtures containing either VII or factor VIIa after an initial 30-sec lag with factor VII. In reaction mixtures with factor VII a linear activation of factor X was established several minutes before cleavage of 125 I-labeled factor VII to the two-chain activated molecule was demonstrable on gel profiles. These data suggest that factor VII/tissue factor cannot activate measurable amounts of factor X over several minutes. Overall, the results support the hypothesis that a rapid preferential activation of factor VII bound to tissue factor by trace amounts of factor Xa is a key early step in tissue factor-dependent blood coagulation

Cerebral Venous Sinus Thrombosis in a Patient with Undiagnosed Factor VII Deficiency.

Science.gov (United States)

Qadir, Hira; Rashid, Anila; Adil, Salman Naseem

2017-09-01

Factor VII (FVII) deficiency is one of the rare inherited bleeding disorders. Thrombosis has been occasionally described in inherited FVII deficiency. Here, we report a young female with undiagnosed FVII deficiency who presented with cerebral venous sinus thrombosis (CVST). Oral contraceptive pill was found to be prothrombotic risk factor. The CVSToccurred in spite of the congenital FVII deficiency indicating that no definitive antithrombotic protection is assured by this defect. Low molecular weight heparin and anti-Xa assay were found to be safe choice of anticoagulation and monitoring, respectively, in this patient.

Hemophilia as a defect of the tissue factor pathway of blood coagulation: Effect of factors VIII and IX on factor X activation in a continuous-flow reactor

International Nuclear Information System (INIS)

Repke, D.; Gemmell, C.H.; Guha, A.; Turitto, V.T.; Nemerson, Y.; Broze, G.J. Jr.

1990-01-01

The effect of factors VIII and IX on the ability of the tissue factor-factor VIIa complex to activate factor X was studied in a continuous-flow tubular enzyme reactor. Tissue factor immobilized in a phospholipid bilayer on the inner surface of the tube was exposed to a perfusate containing factors VIIa, VIII, IX, and X flowing at a wall shear rate of 57, 300, or 1130 sec -1 . The addition of factors VIII and IX at their respective plasma concentrations resulted in a further 2 endash-to 3 endash fold increase. The direct activation of factor X by tissue factor-factor VIIa could be virtually eliminated by the lipoprotein-associated coagulation inhibitor. These results suggest that the tissue factor pathway, mediated through factors VIII and IX, produces significant levels of factor Xa even in the presence of an inhibitor of the tissue factor-factor VIIa complex; moreover, the activation is dependent on local shear conditions. These findings are consistent both with a model of blood coagulation in which initiation of the system results from tissue factor and with the bleeding observed in hemophilia

In vitro evidence of a tissue factor-independent mode of action of recombinant factor VIIa in hemophilia.

Science.gov (United States)

Augustsson, Cecilia; Persson, Egon

2014-11-13

Successful competition of activated factor VII (FVIIa) with zymogen factor VII (FVII) for tissue factor (TF) and loading of the platelet surface with FVIIa are plausible driving forces behind the pharmacological effect of recombinant FVIIa (rFVIIa) in hemophilia patients. Thrombin generation measurements in platelet-rich hemophilia A plasma revealed competition for TF, which potentially could reduce the effective (r)FVIIa:TF complex concentration and thereby attenuate factor Xa production. However, (auto)activation of FVII apparently counteracted the negative effect of zymogen binding; a small impact was observed at endogenous concentrations of FVII and FVIIa but was virtually absent at pharmacological amounts of rFVIIa. Moreover, corrections of the propagation phase in hemophilia A required rFVIIa concentrations above the range where a physiological level of FVII was capable to downregulate thrombin generation. These data strongly suggest that rFVIIa acts independently of TF in hemophilia therapy and that FVII displacement by rFVIIa is a negligible mechanistic component. © 2014 by The American Society of Hematology.

Biodistribution and PET imaging of [18F]-fluoroadenosine derivatives

International Nuclear Information System (INIS)

Alauddin, Mian M.; Shahinian, Antranik; Park, Ryan; Tohme, Michael; Fissekis, John D.; Conti, Peter S.

2007-01-01

Introduction: Many fluorinated analogues of adenosine nucleoside have been synthesized and studied as potential antitumor and antiviral agents. Earlier, we reported radiosynthesis of 2'-deoxy-2'-[ 18 F]fluoro-1-β-D-arabinofuranosyl-adenine ([ 18 F]-FAA) and 3'-deoxy-3'-[ 18 F]fluoro-1-β-D-xylofuranosyl-adenine ([ 18 F]FXA). Now, we report their in vivo studies including blood clearance, biodistribution and micro-PET imaging in tumor-bearing nude mice. Methods: Tumors were grown in 6-week-old athymic nude mice (Harlan, Indianapolis, IN, USA) by inoculation of HT-29 cells, wild-type cells in the left flank and transduced cells with HSV-tk on the right flank. When the tumor was about 1 cm in size, animals were injected with these radiotracers for in vivo studies, including blood clearance, micro-PET imaging and biodistribution. Results: Uptake of [ 18 F]FAA in tumor was 3.3-fold higher than blood, with highest uptake in the spleen. Maximum uptake of [ 18 F]FXA was observed in the heart compared to other organs. There was no tumor uptake of [ 18 F]FXA. Biodistribution results were supported by micro-PET images, which also showed very high uptake of [ 18 F]FAA in spleen and visualization of tumors, and high uptake of [ 18 F]FXA in the heart. Conclusion: These results suggest that [ 18 F]FAA may be useful for tumor imaging, while [ 18 F]FXA may have potential as a heart imaging agent with PET

Malaria infectivity of xanthurenic acid-deficient anopheline mosquitoes produced by TALEN-mediated targeted mutagenesis.

Science.gov (United States)

Yamamoto, Daisuke S; Sumitani, Megumi; Hatakeyama, Masatsugu; Matsuoka, Hiroyuki

2018-02-01

Anopheline mosquitoes are major vectors of malaria parasites. When the gametocytes of the malaria parasite are transferred from a vertebrate to mosquitoes, they differentiate into gametes, and are fertilized in the midguts of mosquitoes. Xanthurenic acid (XA), a waste product of the ommochrome synthesis pathway, has been shown to induce exflagellation during microgametogenesis in vitro; however, it currently remains unclear whether endogenous XA affects the infectivity of anopheline mosquitoes to malaria parasites in vivo due to the lack of appropriate experimental systems such as a XA-deficient line. In the present study, we produced a XA-deficient line in Anopheles stephensi using transcription activator-like effector nuclease (TALEN)-mediated gene targeting (knockout) of the kynurenine 3-monooxygenase (kmo) gene, which encodes an enzyme that participates in the ommochrome synthesis pathway. The knockout of kmo resulted in the absence of XA, and oocyst formation was inhibited in the midguts of these XA-deficient mosquitoes, which, in turn, reduced sporozoite numbers in their salivary glands. These results suggest that endogenous XA stimulates exflagellation, and enhances the infectivity of anopheline mosquitoes to malaria parasites in vivo. The XA-deficient line of the anopheline mosquito provides a useful system for analyzing and understanding the associated factors of malaria gametogenesis in the mosquito midgut.

(Biodegradable Ionomeric Polyurethanes Based on Xanthan: Synthesis, Properties, and Structure

Directory of Open Access Journals (Sweden)

T. V. Travinskaya

2017-01-01

Full Text Available New (biodegradable environmentally friendly film-forming ionomeric polyurethanes (IPU based on renewable biotechnological polysaccharide xanthan (Xa have been obtained. The influence of the component composition on the colloidal-chemical and physic-mechanical properties of IPU/Xa and based films, as well as the change of their properties under the influence of environmental factors, have been studied. The results of IR-, PMS-, DMA-, and X-ray scattering study indicate that incorporation of Xa into the polyurethane chain initiates the formation of a new polymer structure different from the structure of the pure IPU (matrix: an amorphous polymer-polymer microdomain has occurred as a result of the chemical interaction of Xa and IPU. It predetermines the degradation of the IPU/Xa films as a whole, unlike the mixed polymer systems, and plays a key role in the improvement of material performance. The results of acid, alkaline hydrolysis, and incubation into the soil indicate the increase of the intensity of degradation processes occurring in the IPU/Xa in comparison with the pure IPU. It has been shown that the introduction of Xa not only imparts the biodegradability property to polyurethane, but also improves the mechanical properties.

Xanthomonas oryzae pv. oryzae TALE proteins recruit OsTFIIAγ1 to compensate for the absence of OsTFIIAγ5 in bacterial blight in rice.

Science.gov (United States)

Ma, Wenxiu; Zou, Lifang; Ji, Zhiyuan; Xu, Xiameng; Xu, Zhengyin; Yang, Yangyang; Alfano, James R; Chen, Gongyou

2018-04-28

Xanthomonas oryzae pv. oryzae (Xoo), causal agent of bacterial blight (BB) of rice, uses transcription activator-like effectors (TALEs) to interact with the basal transcription factor gama subunit OsTFIIAγ5 (Xa5) and activates transcription of host genes. However, how OsTFIIAγ1, the other OsTFIIAγ protein, functions in the presence of TALEs remains unclear. In this study, we show that OsTFIIAγ1 plays a compensatory role in the absence of Xa5. The expression of OsTFIIAγ1, which is activated by TALE PthXo7, increased the expression of host genes targeted by avirulent and virulent TALEs. Defective OsTFIIAγ1 rice lines showed reduced expression of the TALE-targeted susceptibility (S) genes, OsSWEET11 and OsSWEET14, which resulted in increased BB resistance. Selected TALEs (PthXo1, AvrXa7, and AvrXa27) were evaluated for interactions with OsTFIIAγ1, Xa5 and xa5 (naturally-occurring mutant form of Xa5) using biomolecular fluorescence complementation (BiFC) and microscale thermophoresis (MST). BiFC and MST demonstrated that the three TALEs bind Xa5 and OsTFIIAγ1 with a stronger affinity than xa5. These results provide insight into the complex roles of OsTFIIAγ1 and OsTFIIAγ5 in TALE-mediated host gene transcription. This article is protected by copyright. All rights reserved. © 2018 BSPP and John Wiley & Sons Ltd.

Procoagulant, tissue factor-bearing microparticles in bronchoalveolar lavage of interstitial lung disease patients: an observational study.

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Federica Novelli

Full Text Available Coagulation factor Xa appears involved in the pathogenesis of pulmonary fibrosis. Through its interaction with protease activated receptor-1, this protease signals myofibroblast differentiation in lung fibroblasts. Although fibrogenic stimuli induce factor X synthesis by alveolar cells, the mechanisms of local posttranslational factor X activation are not fully understood. Cell-derived microparticles are submicron vesicles involved in different physiological processes, including blood coagulation; they potentially activate factor X due to the exposure on their outer membrane of both phosphatidylserine and tissue factor. We postulated a role for procoagulant microparticles in the pathogenesis of interstitial lung diseases. Nineteen patients with interstitial lung diseases and 11 controls were studied. All subjects underwent bronchoalveolar lavage; interstitial lung disease patients also underwent pulmonary function tests and high resolution CT scan. Microparticles were enumerated in the bronchoalveolar lavage fluid with a solid-phase assay based on thrombin generation. Microparticles were also tested for tissue factor activity. In vitro shedding of microparticles upon incubation with H₂O₂ was assessed in the human alveolar cell line, A549 and in normal bronchial epithelial cells. Tissue factor synthesis was quantitated by real-time PCR. Total microparticle number and microparticle-associated tissue factor activity were increased in interstitial lung disease patients compared to controls (84±8 vs. 39±3 nM phosphatidylserine; 293±37 vs. 105±21 arbitrary units of tissue factor activity; mean±SEM; p<.05 for both comparisons. Microparticle-bound tissue factor activity was inversely correlated with lung function as assessed by both diffusion capacity and forced vital capacity (r² = .27 and .31, respectively; p<.05 for both correlations. Exposure of lung epithelial cells to H₂O₂ caused an increase in microparticle-bound tissue factor

Bioequivalence of a biosimilar enoxaparin sodium to Clexane® after single 100 mg subcutaneous dose: results of a randomized, double-blind, crossover study in healthy volunteers

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Martínez González J

2018-03-01

Full Text Available Javier Martínez González, Mayte Monreal, Ignacio Ayani Almagia, Jordi Llaudó Garín, Lourdes Ochoa Díaz de Monasterioguren, Ibón Gutierro Adúriz R&D Department, Laboratorios Farmacéuticos Rovi S.A., Madrid, Spain Purpose: To demonstrate the pharmacokinetic/pharmacodynamic (PK/PD equivalence of a biosimilar enoxaparin to the reference drug, and to assess its safety and tolerability in healthy volunteers. Patients and methods: A randomized, double-blind, crossover, 2-sequence, single-dose study was conducted in healthy volunteers of both sexes. Participants were sequentially and randomly administered single subcutaneous injections of enoxaparin 100 mg manufactured by Rovi (test; Madrid, Spain and Clexane® (enoxaparin 100 mg manufactured by Sanofi, reference separated by a 1-week washout period. The primary PK/PD variables were maximum activity (Amax and area under the effect curve from time 0 to the last measured activity (T (AUEC0–T and AUEC from time 0 to infinity (AUEC0–inf of anti-FXa activity, and Amax and AUEC0–T of anti-FIIa activity. Secondary variables were Amax and AUEC0–T, AUEC0–inf of tissue factor pathway inhibitor, and the ratio of AUEC0–T anti-FXa to anti-FIIa activity. Biosimilarity would be shown when the 95% CI of the ratio of geometric least squares means (95% CI RGLSMs of primary PK/PD parameters fell within the standard range of bioequivalence, ie, 80%–125%.Results: The study sample consisted of 46 volunteers (33 males aged 18–44 years and with body mass index ranging from 19.0 to 31.1 kg/m2. Three subjects did not complete the study. The curves of anti-FXa, anti-FIIa and tissue factor pathway inhibitor activities corresponding to administration of the test and reference products were comparable. The 95% CI RGLSMs of Amax, AUEC0–T and AUEC0–inf for anti-FXa activity were 94.6%–105.9%, 99.8%–108.0% and 100.0%–108.6% respectively; Amax and AUEC0–T for anti-FIIa activity were 94.7%–112.6% and

CSAR 2014: A Benchmark Exercise Using Unpublished Data from Pharma.

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Carlson, Heather A; Smith, Richard D; Damm-Ganamet, Kelly L; Stuckey, Jeanne A; Ahmed, Aqeel; Convery, Maire A; Somers, Donald O; Kranz, Michael; Elkins, Patricia A; Cui, Guanglei; Peishoff, Catherine E; Lambert, Millard H; Dunbar, James B

2016-06-27

The 2014 CSAR Benchmark Exercise was the last community-wide exercise that was conducted by the group at the University of Michigan, Ann Arbor. For this event, GlaxoSmithKline (GSK) donated unpublished crystal structures and affinity data from in-house projects. Three targets were used: tRNA (m1G37) methyltransferase (TrmD), Spleen Tyrosine Kinase (SYK), and Factor Xa (FXa). A particularly strong feature of the GSK data is its large size, which lends greater statistical significance to comparisons between different methods. In Phase 1 of the CSAR 2014 Exercise, participants were given several protein-ligand complexes and asked to identify the one near-native pose from among 200 decoys provided by CSAR. Though decoys were requested by the community, we found that they complicated our analysis. We could not discern whether poor predictions were failures of the chosen method or an incompatibility between the participant's method and the setup protocol we used. This problem is inherent to decoys, and we strongly advise against their use. In Phase 2, participants had to dock and rank/score a set of small molecules given only the SMILES strings of the ligands and a protein structure with a different ligand bound. Overall, docking was a success for most participants, much better in Phase 2 than in Phase 1. However, scoring was a greater challenge. No particular approach to docking and scoring had an edge, and successful methods included empirical, knowledge-based, machine-learning, shape-fitting, and even those with solvation and entropy terms. Several groups were successful in ranking TrmD and/or SYK, but ranking FXa ligands was intractable for all participants. Methods that were able to dock well across all submitted systems include MDock,1 Glide-XP,2 PLANTS,3 Wilma,4 Gold,5 SMINA,6 Glide-XP2/PELE,7 FlexX,8 and MedusaDock.9 In fact, the submission based on Glide-XP2/PELE7 cross-docked all ligands to many crystal structures, and it was particularly impressive to see

Two acidic, anticoagulant PLA2 isoenzymes purified from the venom of monocled cobra Naja kaouthia exhibit different potency to inhibit thrombin and factor Xa via phospholipids independent, non-enzymatic mechanism.

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Ashis K Mukherjee

Full Text Available The monocled cobra (Naja kaouthia is responsible for snakebite fatality in Indian subcontinent and in south-western China. Phospholipase A2 (PLA2; EC 3.1.1.4 is one of the toxic components of snake venom. The present study explores the mechanism and rationale(s for the differences in anticoagulant potency of two acidic PLA2 isoenzymes, Nk-PLA2α (13463.91 Da and Nk-PLA2β (13282.38 Da purified from the venom of N. kaouthia.By LC-MS/MS analysis, these PLA2s showed highest similarity (23.5% sequence coverage with PLA2 III isolated from monocled cobra venom. The catalytic activity of Nk-PLA2β exceeds that of Nk-PLA2α. Heparin differentially regulated the catalytic and anticoagulant activities of these Nk-PLA2 isoenzymes. The anticoagulant potency of Nk-PLA2α was comparable to commercial anticoagulants warfarin, and heparin/antithrombin-III albeit Nk-PLA2β demonstrated highest anticoagulant activity. The anticoagulant action of these PLA2s was partially contributed by a small but specific hydrolysis of plasma phospholipids. The strong anticoagulant effect of Nk-PLA2α and Nk-PLA2β was achieved via preferential, non-enzymatic inhibition of FXa (Ki = 43 nM and thrombin (Ki = 8.3 nM, respectively. Kinetics study suggests that the Nk-PLA2 isoenzymes inhibit their "pharmacological target(s" by uncompetitive mechanism without the requirement of phospholipids/Ca(2+. The anticoagulant potency of Nk-PLA2β which is higher than that of Nk-PLA2α is corroborated by its superior catalytic activity, its higher capacity for binding to phosphatidylcholine, and its greater strength of thrombin inhibition. These PLA2 isoenzymes thus have evolved to affect haemostasis by different mechanisms. The Nk-PLA2β partially inhibited the thrombin-induced aggregation of mammalian platelets suggesting its therapeutic application in the prevention of unwanted clot formation.In order to develop peptide-based superior anticoagulant therapeutics, future application of Nk-PLA2

Oral heparin results in the appearance of heparin fragments in the plasma of rats

International Nuclear Information System (INIS)

Larsen, A.K.; Lund, D.P.; Langer, R.; Folkman, J.

1986-01-01

We have previously shown that angiogenesis inhibition and tumor regression can be accomplished by combinations of heparin or heparin fragments with cortisone. Oral heparin was also effective in combination with cortisone. We now show that a single oral dose of [ 35 S]heparin or [ 3 H]heparin (15,000 units/kg) results in continuous release of radioactive material into the bloodstream for at least 12 hr. This is associated with the presence of anti-factor Xa activity at a level of approximately equal to 0.1 unit/ml. The radioactive material is identified as oligo-, di-, and monosaccharides by its behavior in chromatographic systems, its possession of anti-factor Xa activity, and the effect of treatment with bacterial heparinase. The heparin fragments are extensively metabolized to fragments without anti-factor Xa activity that are readily subject to urinary excretion

Low-temperature magnetic ordering in the perovskites Pr 1-xA xCoO 3 (A=Ca, Sr)

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Deac, Iosif G.; Tetean, Romulus; Balasz, Istvan; Burzo, Emil

2010-05-01

The magnetic and electrical properties of polycrystalline Pr 1-xA xCoO 3 cobaltites with A=Ca, Sr and 0≤ x≤0.5 were studied in the temperature range 4 K≤ T≤1000 K and field up to 7 T. The X-ray analyses show the presence of only one phase having monoclinic or orthorhombic symmetry. The magnetic measurements indicate that the Ca-doped samples have at low temperatures, similar properties to the frustrated magnetic materials. PrCoO 3 is a paramagnetic insulator in the range from 4 to 1000 K. The Sr-doped cobaltites exhibit two phase transitions: a paramagnetic-ferromagnetic (or magnetic phase separated state) phase transition at about 240 K and a second one at about 100 K. The magnetic measurements suggest the presence of magnetic clusters and a change in the nature of magnetic coupling between Co ions at low temperatures. A semiconducting type behavior and high negative magnetoresistance was found for the Ca-doped samples, while the Sr-doped ones were metallic and with negligible magnetoresistance. The results are analyzed in the frame of a phase separation scenario in the presence of the spin-state transitions of Co ions.

Sphingosine 1-Phosphate as a Link between Blood Coagulation and Inflammation

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Bernhard Hermann Rauch

2014-06-01

Full Text Available Sphingosine 1-phosphate (S1P is a multifunctional signaling lipid generated from sphingosine by sphingosine kinases. S1P formation has been shown in numerous cells in the circulation, including platelets, vascular endothelial and smooth muscle cells and monocytes. S1P also exerts multiple effects on these cells, i.e. cell proliferation and migration, activation of proinflammatory signaling pathways and release of additional inflammatory mediators. Similar activities and targets have also been identified for activated clotting factors such as thrombin or the activated factor-X (FXa, suggesting a possible involvement of S1P in thrombus-associated cellular signaling and thrombin-induced inflammatory reactions. Several levels of S1P-mediated, thrombin /FXa-induced signaling have already been identified: regulation of sphingosine kinase expression and activity, stimulation of S1P release from platelets and other cells and, possibly regulation of S1P-receptors on target cells. This review summarizes the current state of knowledge about S1P as a clotting factor-regulated molecular link between blood coagulation and inflammation. It is concluded that S1P might represent an until now underestimated lipid mediator of inflammatory reactions following activation of the clotting system and, in this context, also involved in the development and progression of atherosclerosis.

Stroke Prevention: Managing Modifiable Risk Factors

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Silvia Di Legge

2012-01-01

Full Text Available Prevention plays a crucial role in counteracting morbidity and mortality related to ischemic stroke. It has been estimated that 50% of stroke are preventable through control of modifiable risk factors and lifestyle changes. Antihypertensive treatment is recommended for both prevention of recurrent stroke and other vascular events. The use of antiplatelets and statins has been shown to reduce the risk of recurrent stroke and other vascular events. Angiotensin-converting enzyme inhibitors (ACEIs and angiotensin II receptor blockers (ARBs are indicated in stroke prevention because they also promote vascular health. Effective secondary-prevention strategies for selected patients include carotid revascularization for high-grade carotid stenosis and vitamin K antagonist treatment for atrial fibrillation. The results of recent clinical trials investigating new anticoagulants (factor Xa inhibitors and direct thrombin inhibitors clearly indicate alternative strategies in stroke prevention for patients with atrial fibrillation. This paper describes the current landscape and developments in stroke prevention with special reference to medical treatment in secondary prevention of ischemic stroke.

Computationally derived points of fragility of a human cascade are consistent with current therapeutic strategies.

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Deyan Luan

2007-07-01

Full Text Available The role that mechanistic mathematical modeling and systems biology will play in molecular medicine and clinical development remains uncertain. In this study, mathematical modeling and sensitivity analysis were used to explore the working hypothesis that mechanistic models of human cascades, despite model uncertainty, can be computationally screened for points of fragility, and that these sensitive mechanisms could serve as therapeutic targets. We tested our working hypothesis by screening a model of the well-studied coagulation cascade, developed and validated from literature. The predicted sensitive mechanisms were then compared with the treatment literature. The model, composed of 92 proteins and 148 protein-protein interactions, was validated using 21 published datasets generated from two different quiescent in vitro coagulation models. Simulated platelet activation and thrombin generation profiles in the presence and absence of natural anticoagulants were consistent with measured values, with a mean correlation of 0.87 across all trials. Overall state sensitivity coefficients, which measure the robustness or fragility of a given mechanism, were calculated using a Monte Carlo strategy. In the absence of anticoagulants, fluid and surface phase factor X/activated factor X (fX/FXa activity and thrombin-mediated platelet activation were found to be fragile, while fIX/FIXa and fVIII/FVIIIa activation and activity were robust. Both anti-fX/FXa and direct thrombin inhibitors are important classes of anticoagulants; for example, anti-fX/FXa inhibitors have FDA approval for the prevention of venous thromboembolism following surgical intervention and as an initial treatment for deep venous thrombosis and pulmonary embolism. Both in vitro and in vivo experimental evidence is reviewed supporting the prediction that fIX/FIXa activity is robust. When taken together, these results support our working hypothesis that computationally derived points of

Alternative dosing of prophylactic enoxaparin in the trauma patient: is more the answer?

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Kopelman, Tammy R; O'Neill, Patrick J; Pieri, Paola G; Salomone, Jeffrey P; Hall, Scott T; Quan, Asia; Wells, Jordan R; Pressman, Melissa S

2013-12-01

Inadequate anti-factor Xa levels and increased venous thromboembolic events occur in trauma patients receiving standard prophylactic enoxaparin dosing. The aim of this study was to test the hypothesis that higher dosing (40 mg twice daily) would improve peak anti-Xa levels and decrease venous thromboembolism. A retrospective review was performed of trauma patients who received prophylactic enoxaparin and peak anti-Xa levels over 27 months. Patients were divided on the basis of dose: group A received 30 mg twice daily, and group B received 40 mg twice daily. Demographics and rates of venous thromboembolism were compared between dose groups and patients with inadequate or adequate anti-Xa levels. One hundred twenty-four patients were included, 90 in group A and 34 in group B. Demographics were similar, except that patients in group B had a higher mean body weight. Despite this, only 9% of group B patients had inadequate anti-Xa levels, compared with 33% of those in group A (P = .01). Imaging studies were available in 69 patients and revealed 8 venous thromboembolic events (P = NS, group A vs group B) with significantly more venous thromboembolic events occurring in patients with low anti-Xa levels (P = .02). Although higher dosing of enoxaparin led to improved anti-Xa levels, this did not equate to a statistical decrease in venous thromboembolism. Copyright © 2013 Elsevier Inc. All rights reserved.

Use of Enoxaparin in Obese Adolescents During Bariatric Surgery--a Pilot Study.

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Mushtaq, Alvina; Vaughns, Janelle D; Ziesenitz, Victoria C; Nadler, Evan P; van den Anker, John N

2015-10-01

Obese patients have a higher risk of venous thromboembolism when immobilized due to surgery. The objective of this study was to assess anti-factor Xa activity in adolescent bariatric surgical patients receiving prophylactic enoxaparin. Four morbidly obese adolescents undergoing laparoscopic sleeve gastrectomy were enrolled. Enoxaparin was administered (40 mg subcutaneous (SC) if BMI ≤50 kg/m(2) or 60 mg SC if BMI >50 kg/m(2)) for prevention of venous thromboembolism every 12 h starting after induction of anesthesia until discharge. Plasma anti-factor Xa activity was assessed over 12 h after the first dose and used as a surrogate marker for enoxaparin levels. Non-compartmental analysis of anti-factor Xa activity levels was performed and compared with previously published studies. Patients recruited were 16 to 18 years of age with a mean BMI of 52.6 ± 5.8 kg/m(2) (>99th BMI percentile). Peak anti-factor Xa activity ranged from 0.20 to 0.23 IU/mL in our study population, compared to 0.38 to 0.53 IU/mL in the cited lean comparator groups. Our current dosing practice of 40 mg SC for individuals with a BMI ≤50 kg/m(2) and 60 mg for individuals with a BMI ≥50 kg/m(2) resulted in anti-factor Xa activity that was sufficient for adequate thromboprophylaxis in adolescent bariatric surgical patients. Our data also demonstrates lower drug exposures in the obese when compared to lean patients. Therefore, randomized controlled efficacy and safety studies are urgently needed to guide the use of low-molecular-weight heparins in the pediatric and adolescent obese population.

Disappearance of a low molecular weight heparin fraction (CY 216) differs from standard heparin in rabbits

International Nuclear Information System (INIS)

Boneu, B.; Buchanan, M.R.; Caranobe, C.; Gabaig, A.M.; Dupouy, D.; Sie, P.; Hirsh, J.

1987-01-01

In previous studies, we have reported that standard heparin (SH) was cleared by two mechanisms, a saturable mechanism which predominated at low doses (less than 100 anti-factor Xa U/kg) and a non-saturable mechanism which predominated at higher doses, when the first mechanism became saturated. In this study, we examined the importance of these two mechanisms in the disappearance of a low molecular weight heparin fraction (LMWH) (CY 216), by comparing the pharmacokinetics and the pharmacodynamics of a wide range of doses of SH and CY 216 (1.5 to 500 anti-factor Xa U/kg). Pharmacokinetics was measured as the disappearance of 125 I-radiolabelled SH or CY 216. Pharmacodynamics was measured as the disappearance of the anti-factor Xa activity of SH and CY 216. We found that the saturable mechanism contributed little to the disappearance of CY 216 and that it was cleared predominantly by the non-saturable mechanism at all doses tested. Thus, at low doses (less than 100 anti-factor Xa U/kg), SH was cleared more rapidly than CY 216, whereas at higher doses, CY 216 was cleared more rapidly than SH. We conclude that the mechanism of disappearance of LMWH's differ significantly from those of SH, and that this difference may explain the apparent prolonged anticoagulant activity of LMWH's within the therapeutic range doses

Single—Molecular Imaging of Anticoagulation Factor I From Snake Venom by Atomic Force Microscopy

Institute of Scientific and Technical Information of China (English)

徐小龙; 刘清亮; 等

2002-01-01

Anticoagulation factor I( ACF I) from the venom of Agki-strodom acutus is a binding protein to activanted coagulation fac tor X(FXa) and possesses marked anticoagulant acivity,Single ACF I molecule has been successfully imaged in air by tapping mode atomic force microscopy(AFM) with high-resolu-tion using glutaraldehyde as a coupling agent.The physical adsoprtion and covalent binding of ACF I onto the mica show very different surface topographies,The former exhibits the characteristic strand-like structure with much less reproducibility,the latter displays a elliptic granular structure with better repro-ducibility,which sugests that the stability of ACF I molecules on the mica is enhanced by covalent bonding in the presence of glutaraldehyde.A small-scale AFM amplitude -mode impage clearly shows that the covalently bonded ACF I molecule by glutaraldehyde has olive shape structure with an average size of 7.4nm×3.6nm×3.1nm ,which is very similar to the size determined from the crystal structure of ACF I.

The role of apixaban for venous and arterial thromboembolic disease.

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Prom, Rathasen; Spinler, Sarah A

2011-10-01

To provide a comprehensive review of the pharmacology, pharmacokinetics, pharmacodynamics, clinical trial data, adverse effects, and drug interactions of apixaban. An English-language literature search was performed with MEDLINE/PubMed from January 2007 to August 2011 using the search terms apixaban, factor Xa inhibitors, FXa inhibitors, BMS-562247-01, venous thromboembolism, deep vein thrombosis, pulmonary embolism, myocardial infarction, acute coronary syndrome, ACS, atrial fibrillation, atrial arrhythmias, total hip replacement or arthroplasty, total knee replacement or arthroplasty, and orthopedic surgery to identify relevant articles. The references of the retrieved articles, professional society meeting abstracts, and the Web site www.clinicaltrials.gov were reviewed to identify other pertinent articles. Pertinent original studies involving apixaban's pharmacology, pharmacokinetics, drug interactions, and clinical efficacy and safety data were included. Results of 2 large Phase 3 trials suggest that apixaban is superior for stroke and systemic embolism prevention compared to both aspirin and warfarin in patients with atrial fibrillation (AF); rates of major bleeding and intracranial hemorrhage were similar to those of aspirin but significantly reduced compared to warfarin. Completed trials in orthopedic surgery found apixaban to be superior to enoxaparin in total hip replacement (THR) surgery but inferior in total knee replacement (TKR) surgery, with similar rates of major bleeding. A Phase 3 trial of apixaban in acute coronary syndrome was stopped early because of excess bleeding. Future Phase 3 trials will help to determine apixaban's role for treatment of deep vein thrombosis and pulmonary embolism. Currently, apixaban is approved only in Europe for prophylaxis of venous thromboembolism in adults who have undergone elective THR or TKR. A Phase 3 trial in patients with AF revealed apixaban to be superior to warfarin for stroke and systemic embolism

Apixaban or enoxaparin for thromboprophylaxis after knee replacement

DEFF Research Database (Denmark)

Lassen, Michael Rud; Raskob, Gary E; Gallus, Alexander

2009-01-01

BACKGROUND: The optimal strategy for thromboprophylaxis after major joint replacement has not been established. Low-molecular-weight heparins such as enoxaparin predominantly target factor Xa but to some extent also inhibit thrombin. Apixaban, a specific factor Xa inhibitor, may provide effective...... (P=0.03). CONCLUSIONS: As compared with enoxaparin for efficacy of thromboprophylaxis after knee replacement, apixaban did not meet the prespecified statistical criteria for noninferiority, but its use was associated with lower rates of clinically relevant bleeding and it had a similar adverse...

Pathotype profile of Xanthomonas oryzae pv. oryzae isolates from North Sumatera

Science.gov (United States)

Noer, Z.; Hasanuddin; Lisnawita; Suryanto, D.

2018-02-01

The Bacterial blight disease caused by Xanthomonas oryzae pv. oryzae (Xoo) is one of the most important diseases and has caused crop failure in rice crops. This pathogen infects the leaves in all plant growth phases. The purpose of this study is to investigation 10 Xoo isolates pathotype obtained from North Sumatra based on their interactions with 10 near-isogenic rice lines (NIL) of IRRI. The results showed that there are 6 pathotypes of virulence in North Sumatra, they are; pathotype I with incompatible interaction to all Xa genes, pathotype II with compatible interaction to Xa1 and Xa3 genes, while it has incompatible interaction to other genes, pathotype III with compatible interaction to Xa1, Xa5, Xa7, Xa8, Xa10 and Xa11 genes, but it has incompatible interaction to other genes, pathotype IV with compatible interaction to all Xa genes, pathotype V with compatible interaction to Xa1 gene and incompatible interaction to other genes, and pathotype VI with compatible interaction to Xa3 gene and incompatible interaction to other genes. Based on the resistant genes in each individual Xa2, Xa4, and Xa21 genes are the combination of Xa genes which are most suitable for use in the development of rice cultivars in North Sumatra.

Pathology consultation on anticoagulation monitoring: factor X-related assays.

Science.gov (United States)

Wool, Geoffrey D; Lu, Chuanyi M

2013-11-01

To review various anticoagulation therapies and related laboratory monitoring issues, with a focus on factor X-related chromogenic assays. A case-based approach is used to review pertinent published literatures and product inserts of anticoagulation drugs and to look back on clinical use of factor X-related chromogenic assays. The number of anticoagulants available to clinicians has increased greatly in the past decade. Whether and how these anticoagulants should be monitored are areas of uncertainty for clinicians, which can lead to misuse of laboratory assays and suboptimal patient management. Factor X-related assays are of particular concern because of the similar and often confusing test names. Based on a common clinical case scenario and literature review regarding anticoagulant monitoring, an up-to-date discussion and review of the various factor X-related assays are provided, focusing on the differences in test designs and clinical utilities between the chromogenic anti-Xa and chromogenic factor X activity assays. Anticoagulation therapy and related laboratory monitoring are rapidly evolving areas of clinical practices. A good knowledge of relevant laboratory assays and their clinical applications is necessary to help optimize patient care.

Integrated Production of Xylonic Acid and Bioethanol from Acid-Catalyzed Steam-Exploded Corn Stover.

Science.gov (United States)

Zhu, Junjun; Rong, Yayun; Yang, Jinlong; Zhou, Xin; Xu, Yong; Zhang, Lingling; Chen, Jiahui; Yong, Qiang; Yu, Shiyuan

2015-07-01

High-efficiency xylose utilization is one of the restrictive factors of bioethanol industrialization. However, xylonic acid (XA) as a new bio-based platform chemical can be produced by oxidation of xylose with microbial. So, an applicable technology of XA bioconversion was integrated into the process of bioethanol production. After corn stover was pretreated with acid-catalyzed steam-explosion, solid and liquid fractions were obtained. The liquid fraction, also named as acid-catalyzed steam-exploded corn stover (ASC) prehydrolyzate (mainly containing xylose), was catalyzed with Gluconobacter oxydans NL71 to prepare XA. After 72 h of bioconversion of concentrated ASC prehydrolyzate (containing 55.0 g/L of xylose), the XA concentration reached a peak value of 54.97 g/L, the sugar utilization ratio and XA yield were 94.08 and 95.45 %, respectively. The solid fraction was hydrolyzed to produce glucose with cellulase and then fermented with Saccharomyces cerevisiae NL22 to produce ethanol. After 18 h of fermentation of concentrated enzymatic hydrolyzate (containing 86.22 g/L of glucose), the ethanol concentration reached its highest value of 41.48 g/L, the sugar utilization ratio and ethanol yield were 98.72 and 95.25 %, respectively. The mass balance showed that 1 t ethanol and 1.3 t XA were produced from 7.8 t oven dry corn stover.

Assessment of the effects of dalteparin on coagulation variables and determination of a treatment schedule for use in cats.

Science.gov (United States)

Schönig, Jette C; Mischke, Reinhard H

2016-07-01

OBJECTIVE To determine a treatment protocol for SC administration of dalteparin to cats on the basis of currently available detailed pharmacokinetic data and to assess the effect of SC administration of dalteparin to cats on coagulation variables such as activated partial thromboplastin time (aPTT), thrombin time, and results for thromboelastometry, compared with effects on anti-activated coagulation factor X (anti-Xa) activity. ANIMALS 6 healthy domestic shorthair cats. PROCEDURES Cats received 14 injections of dalteparin (75 anti-Xa U/kg, SC) at 6-hour intervals. Blood samples were collected before and 2 hours after the first and second injections on days 1, 2, and 4. Anti-Xa activity was measured by use of a chromogenic substrate assay, aPTT and thrombin time were measured by use of an automated coagulometer, and viscoelastic measurements were obtained with thromboelastrometry. RESULTS 2 hours after the second injection, the target peak anti-Xa activity range of 0.5 to 1.0 U/mL was achieved in all cats, whereas median trough values remained below this range. Peak anti-Xa activity had only minimal effects on coagulation variables; the maximum median ratio for aPTT (in relationship to the value before the first dalteparin injection) was 1.23. CONCLUSIONS AND CLINICAL RELEVANCE Results of this study indicated that this treatment protocol resulted in reproducible anti-Xa activity in cats that was mostly within the targeted peak range of anti-Xa activity recommended for humans. Treatment in accordance with this protocol may not require routine coagulation monitoring of cats, but this must be confirmed in feline patients.

The Role of RaxST, a Prokaryotic Sulfotransferase, and RaxABC, a Putative Type I Secretion System, in Activation of the Rice XA21-Mediated Immune Response

Directory of Open Access Journals (Sweden)

Pamela C. Ronald

2014-01-01

Full Text Available Tyrosine sulfation is an important posttranslational modification that determines the outcome of serious diseases in plants and animals. We have recently demonstrated that the plant pathogen Xanthomonas oryzae pv. oryzae (Xoo carries a functional sulfotransferase (RaxST. raxST is required for activation of rice Xa21-mediated immunity indicating the critical, but unknown, function of raxST in mediating the Xoo/rice interaction. The raxST gene resides in the same operon (raxSTAB as components of a predicted type I secretion and processing system (RaxA and RaxB. These observations suggest a model where RaxST sulfates a molecule that contains a leader peptide, which is cleaved by the peptidase domain of the RaxB protein and secreted outside the bacterial cell by the RaxABC T1SS.

Factor XI and XII as antithrombotic targets.

Science.gov (United States)

Müller, Felicitas; Gailani, David; Renné, Thomas

2011-09-01

Arterial and venous thrombosis are major causes of morbidity and mortality, and the incidence of thromboembolic diseases increases as a population ages. Thrombi are formed by activated platelets and fibrin. The latter is a product of the plasma coagulation system. Currently available anticoagulants such as heparins, vitamin K antagonists and inhibitors of thrombin or factor Xa target enzymes of the coagulation cascade that are critical for fibrin formation. However, fibrin is also necessary for terminating blood loss at sites of vascular injury. As a result, anticoagulants currently in clinical use increase the risk of bleeding, partially offsetting the benefits of reduced thrombosis. This review focuses on new targets for anticoagulation that are associated with minimal or no therapy-associated increased bleeding. Data from experimental models using mice and clinical studies of patients with hereditary deficiencies of coagulation factors XI or XII have shown that both of these clotting factors are important for thrombosis, while having minor or no apparent roles in processes that terminate blood loss (hemostasis). Hereditary deficiency of factor XII (Hageman factor) or factor XI, plasma proteases that initiate the intrinsic pathway of coagulation, impairs thrombus formation and provides protection from vascular occlusive events, while having a minimal impact on hemostasis. As the factor XII-factor XI pathway contributes to thrombus formation to a greater extent than to normal hemostasis, pharmacological inhibition of these coagulation factors may offer the exciting possibility of anticoagulation therapies with minimal or no bleeding risk.

Molecular size is important for the safety and selective inhibition of intrinsic factor Xase for fucosylated chondroitin sulfate.

Science.gov (United States)

Yan, Lufeng; Li, Junhui; Wang, Danli; Ding, Tian; Hu, Yaqin; Ye, Xingqian; Linhardt, Robert J; Chen, Shiguo

2017-12-15

Fucosylated chondroitin sulfate from sea cucumber Isostichopus badionotus (FCS-Ib) showed potent anticoagulant activities without selectivity. The present study focused on developing safe FCS-Ib oligomers showing selective inhibition of intrinsic factor Xase (anti-FXase) prepared through partial N-deacetylation-deaminative cleavage. The N-deacetylation degree was regulated by reaction time, controlling the resulting oligomer distribution. Structure analysis confirmed the selectivity of degradation, and 12 high purity fractions with trisaccharide-repeating units were separated. In vitro anticoagulant assays indicated a decrease in molecular weight (Mw) dramatically reduced activated partial thromboplastin time (APTT), thrombin time (TT), AT-dependent anti-FIIa and anti-FXa activities, while the oligomers retained potent anti-FXase activity until they fell below 3kDa. Meanwhile, human FXII activation and platelet aggregation were markedly reduced with decreasing Mw and were moderate when under 12.0kDa. Thus, fragments of 3-12.0kDa should be safe and effective as selective inhibitors of intrinsic tenase complex for application as clinical anticoagulants. Copyright © 2017 Elsevier Ltd. All rights reserved.

Assessment of Heparin Anticoagulation Measured Using i-STAT and Hemochron Activated Clotting Time.

Science.gov (United States)

Maslow, Andrew; Chambers, Alison; Cheves, Tracey; Sweeney, Joseph

2018-01-31

Adequate anticoagulation, measured using activated clotting time (ACT), is important during vascular and cardiac surgeries. Unfractionated heparin is the most common anticoagulant used. The purpose of this analysis was to compare the i-STAT ACT (iACT) to the Hemochron ACT (hACT), both of which were then compared to anti-factor Xa (anti-Xa) assay, a representation of heparin level and activity. Prospective study. Tertiary care cardiovascular center. Eleven consecutive elective adult cardiac surgical patients. Prior to cardiopulmonary bypass, ACTs were measured using i-STAT and Hemochron technologies and compared to each other and to anti-Xa assay prior to and during a cumulative administration of heparin. Data were compared using bias analyses. Heparin (300 U/kg) was administered in quarterly doses. Coagulation labs were collected prior to and 3 minutes after each quarterly dose of heparin. The baseline ACTs for i-STAT and Hemochron were 147 and 142 seconds, respectively. A significant association was found between iACT and hACT (p = 0.002). The iACT measurements underestimated hACT at ACT levels >180 seconds or anti-Xa levels >0.75 U/mL. No significant difference was found between ACT data at anti-Xa levels 0.75 U/mL. Copyright © 2018 Elsevier Inc. All rights reserved.

Determination of enoxaparin with rotational thrombelastometry using the prothrombinase-induced clotting time reagent.

Science.gov (United States)

Schaden, Eva; Schober, Andreas; Hacker, Stefan; Spiss, Christian; Chiari, Astrid; Kozek-Langenecker, Sibylle

2010-04-01

Drug monitoring of low molecular weight heparin is generally not recommended, but could be reasonable in critically ill patients, whose risk for bleeding or thrombosis shows a high interpatient variability. Anti-Xa assays are not available around the clock even in central hospitals, whereas rotational thrombelastometry (ROTEM) becomes increasingly used at the bedside. Prothrombinase-induced clotting time (PiCT) reagent allows determination of factor Xa-inhibition in plasma. The aim of our study was to evaluate enoxaparin determination in whole blood with the ROTEM using specific test modifications, including PiCT. After ethics committee's approval, citrated whole blood obtained from overall 16 healthy volunteers was incubated with enoxaparin at 16 different anti-Xa concentrations. Main endpoint was the clotting time (CT) in ROTEM representing initial activation of clot formation. CT was determined in the new PiCT-ROTEM test, in a low-tissue factor-activated modification (LowTF-ROTEM) as well as in the commercially available heparin-sensitive ROTEM assays (HEPTEM and INTEM). In the absence of enoxaparin, CT values were 168.6 +/- 6.1 s (PiCT-ROTEM), 247.3 +/- 18.6 s (LowTF-ROTEM), and -6.2 +/- 7.9 s (INTEM-HEPTEM). A linear dependency (P anti-Xa concentration and CT was found for PiCT-ROTEM, LowTF-ROTEM, and for INTEM-HEPTEM with correlation coefficients of 0.93 for PiCT-ROTEM, 0.94 for LowTF-ROTEM, and 0.81 for INTEM-HEPTEM. This in-vitro experiment demonstrates a strong correlation between enoxaparin anti-Xa concentrations and specific ROTEM tests. These promising assays should be further evaluated for monitoring anticoagulation in high-risk patients in clinical studies.

Modeling the reduction of gross lithium erosion observed under high-flux deuterium bombardment

NARCIS (Netherlands)

Abrams, T.; Jaworski, M. A.; Kaita, R.; Nichols, J. H.; Stotler, D. P.; De Temmerman, G.; van den Berg, M. A.; van der Meiden, H. J.; Morgan, T. W.

2015-01-01

Abstract Both thin (<1&#xa0;μm) and thick (∼500&#xa0;μm) lithium films under high-flux deuterium and neon plasma bombardment were studied in the linear plasma device Magnum-PSI at ion fluxes >1024&#xa0;m−2&#xa0;s−1 and surface temperatures <700&#xa0;°C.

Deuterium-induced nanostructure formation on tungsten exposed to high-flux plasma

NARCIS (Netherlands)

Xu, H.Y.; De Temmerman, G.; Luo, G. N.; Jia, Y. Z.; Yuan, Y.; Fu, B. Q.; Godfrey, A.; Liu, W.

2015-01-01

Surface topography of polycrystalline tungsten (W) have been examined after exposure to a low-energy (38&#xa0;eV/D), high-flux (∼1.1–1.5&#xa0;×&#xa0;1024&#xa0;m−2&#xa0;s−1) deuterium plasma in the Pilot-PSI linear plasma device. The methods used were scanning electron microscopy

Paris saponin-induced autophagy promotes breast cancer cell apoptosis via the Akt/mTOR signaling pathway.

Science.gov (United States)

Xie, Zhan-Zhi; Li, Man-Mei; Deng, Peng-Fei; Wang, Sheng; Wang, Lei; Lu, Xue-Ping; Hu, Liu-Bing; Chen, Zui; Jie, Hui-Yang; Wang, Yi-Fei; Liu, Xiao-Xiao; Liu, Zhong

2017-02-25

Paris saponins possess anticancer, anti-inflammatory, and antiviral effects. However, the anticancer effect of Paris saponins has not been well elucidated and the mechanisms underlying the potential function of Paris saponins in cancer therapy are needed to be further identify. In this study, we report that saponin compounds isolated from Paris polyphylla exhibited antitumor activity against breast cancer cell lines, MCF-7 and MDA-MB-231. Paris saponin XA-2 induced apoptosis in both cell lines, as evidenced by the activation of caspases and cleavage of Poly (ADP-ribose) polymerase. The ability of XA-2 to induce autophagy was confirmed by acridine orange staining, accumulation of autophagosome-bound Long chain 3 (LC3)-II, and measurement of autophagic flux. XA-2-induced autophagy was observed to promote apoptosis by the combined treatment of breast cancer cell lines with XA-2 and autophagy inhibitors 3-methyladenine and bafilomycin A1, respectively. Moreover, we report a decrease in the levels of Akt/mTOR signaling pathway proteins, such as the phosphorylated forms of Akt, mTOR, P70S6K, and eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1). Taken together, these results provide important insights explaining the anticancer activity of Paris saponins and the potential development of XA-2 as a new therapeutic agent. Copyright © 2017 Elsevier B.V. All rights reserved.

Nucleotide diversity analysis of three major bacterial blight resistance genes in rice.

Directory of Open Access Journals (Sweden)

Waikhom Bimolata

Full Text Available Nucleotide sequence polymorphisms among R gene alleles influence the process of co-evolutionary interaction between host and pathogen by shaping the response of host plants towards invading pathogens. Here, we present the DNA sequence polymorphisms and diversities present among natural alleles of three rice bacterial blight resistance genes, Xa21, Xa26 and xa5. The diversity was examined across different wild relatives and cultivars of Oryza species. Functional significance of selected alleles was evaluated through semi-quantitative reverse transcription polymerase chain reaction and real time PCR. The greatest nucleotide diversity and singleton variable sites (SVS were present in Xa26 (π = 0.01958; SVS = 182 followed by xa5 and Xa21 alleles. The highest frequency of single nucleotide polymorphisms were observed in Xa21 alleles and least in xa5. Transition bias was observed in all the genes and 'G' to 'A' transitions were more favored than other form of transitions. Neutrality tests failed to show the presence of selection at these loci, though negative Tajima's D values indicate the presence of a rare form of polymorphisms. At the interspecies level, O. nivara exhibited more diversity than O. sativa. We have also identified two nearly identical resistant alleles of xa5 and two sequentially identical alleles of Xa21. The alleles of xa5 showed basal levels of expression while Xa21 alleles were functionally not expressed.

Association of prothrombin complex concentrate administration and hematoma enlargement in non-vitamin K antagonist oral anticoagulant-related intracerebral hemorrhage.

Science.gov (United States)

Gerner, Stefan T; Kuramatsu, Joji B; Sembill, Jochen A; Sprügel, Maximilian I; Endres, Matthias; Haeusler, Karl Georg; Vajkoczy, Peter; Ringleb, Peter A; Purrucker, Jan; Rizos, Timolaos; Erbguth, Frank; Schellinger, Peter D; Fink, Gereon R; Stetefeld, Henning; Schneider, Hauke; Neugebauer, Hermann; Röther, Joachim; Claßen, Joseph; Michalski, Dominik; Dörfler, Arnd; Schwab, Stefan; Huttner, Hagen B

2018-01-01

To investigate parameters associated with hematoma enlargement in non-vitamin K antagonist oral anticoagulant (NOAC)-related intracerebral hemorrhage (ICH). This retrospective cohort study includes individual patient data for 190 patients with NOAC-associated ICH over a 5-year period (2011-2015) at 19 departments of neurology across Germany. Primary outcome was the association of prothrombin complex concentrate (PCC) administration with hematoma enlargement. Subanalyses were calculated for blood pressure management and its association with the primary outcome. Secondary outcomes include associations with in-hospital mortality and functional outcome at 3 months assessed using the modified Rankin Scale. The study population for analysis of primary and secondary outcomes consisted of 146 NOAC-ICH patients with available follow-up imaging. Hematoma enlargement occurred in 49/146 (33.6%) patients with NOAC-related ICH. Parameters associated with hematoma enlargement were blood pressure ≥ 160mmHg within 4 hours and-in the case of factor Xa inhibitor ICH-anti-Xa levels on admission. PCC administration prior to follow-up imaging was not significantly associated with a reduced rate of hematoma enlargement either in overall NOAC-related ICH or in patients with factor Xa inhibitor intake (NOAC: risk ratio [RR] = 1.150, 95% confidence interval [CI] = 0.632-2.090; factor Xa inhibitor: RR = 1.057, 95% CI = 0.565-1.977), regardless of PCC dosage given or time interval until imaging or treatment. Systolic blood pressure levels < 160mmHg within 4 hours after admission were significantly associated with a reduction in the proportion of patients with hematoma enlargement (RR = 0.598, 95% CI = 0.365-0.978). PCC administration had no effect on mortality and functional outcome either at discharge or at 3 months. In contrast to blood pressure control, PCC administration was not associated with a reduced rate of hematoma enlargement in NOAC-related ICH

Free vibration of elastically supported thin cylinders including gyroscopic effects

CSIR Research Space (South Africa)

Loveday, PW

1998-10-29

Full Text Available [ The equations D[R[ 747723 JSV 106:2 "Issue# MS 1560 VIBRATION OF THIN CYLINDERS 442 required for this procedure\\ including the gyroscopic terms\\ are included in Appendix A[ The displacement functions can then be written as follows] W"x# C0 cosh a0xa C1 sinh a0... xa C2 cos g1xa C3 sin g1xa epx:a0C4 cos qxa C5 sin qxa 1 e px:a0C6 cos qxa C7 sin qxa 1 "6a# V"x# A0C0 cosh a0xa A0C1 sinh a0xa A2C2 cos g1xa A2C3 sin g1xa epx:a$"A4C4 A5C5# cos qxa "A4C5 A5C4# sin qxa % e px:a$"A4C6 A5C7# cos...

Xanthium italicum, Xanthium strumarium and Arctium lappa as new hosts for Diaporthe helianthi.

Science.gov (United States)

Vrandecic, Karolina; Jurkovic, Drazenka; Riccioni, Luca; Cosic, Jasenka; Duvnjak, Tomislav

2010-07-01

Sunflower (Helianthus annuus) stem canker caused by Diaporthe helianthi is one of the most important sunflower diseases in Croatia. Until recently, sunflower was the only known host for D. helianthi. In our research carried out in the area of Eastern Croatia, isolates of Diaporthe/Phomospis were collected from Xanthium italicum, X. strumarium and Arctium lappa. Using morphological, cultural and molecular ITS rDNA data, isolates from these weeds were identified as D. helianthi. The following isolates were used in the pathogenicity test: one isolate originated from sunflower (Su5/04), three from X. italicum (Xa2, Xa3 and Xa5), two from X. strumarium (Xa9 and Xa12), one from Xanthium sp. (Xa13) and one from A. lappa (Ar3). According to the results, it was determined that isolate Xa5 (originated from X. italicum) was the most pathogenic to sunflower stems. The average length of the lesion was 11.3 cm. The lowest level of pathogenicity was found in Xa9 (isolated from X. strumarium). The length of the lesion was 0.1 cm.

Protein C inhibitor acts as a procoagulant by inhibiting the thrombomodulin-induced activation of protein C in human plasma

NARCIS (Netherlands)

Elisen, M. G.; von dem Borne, P. A.; Bouma, B. N.; Meijers, J. C.

1998-01-01

Protein C inhibitor (PCI), which was originally identified as an inhibitor of activated protein C, also efficiently inhibits coagulation factors such as factor Xa and thrombin. Recently it was found, using purified proteins, that the anticoagulant thrombin-thrombomodulin complex was also inhibited

The effects of blood feeding and exogenous supply of tryptophan on the quantities of xanthurenic acid in the salivary glands of Anopheles stephensi (Diptera: Culicidae).

Science.gov (United States)

Okech, Bernard; Arai, Meiji; Matsuoka, Hiroyuki

2006-03-24

Xanthurenic acid (XA), produced as a byproduct during the biosynthesis of insect eye pigment (ommochromes), is a strong inducer of Plasmodium gametogenesis at very low concentrations. In previous studies, it was shown that XA is present in Anopheles stephensi (Diptera: Culicidae) mosquito salivary glands and that during blood feeding the mosquitoes ingested their own saliva into the midgut. Considering these two facts together, it is therefore likely that XA is discharged with saliva during blood feeding and is swallowed into the midgut where it exerts its effect on Plasmodium gametocytes. However, the quantities of XA in the salivary glands and midgut are unknown. In this study, we used high performance liquid chromatography with electrochemical detection to detect and quantify XA in the salivary glands and midgut. Based on the results of this study, we found 0.28+/-0.05 ng of XA in the salivary glands of the mosquitoes, accounting for 10% of the total XA content in the mosquito whole body. The amounts of XA in the salivary glands reduced to 0.13+/-0.06 ng after mosquitoes ingested a blood meal. Approximately 0.05+/-0.01 ng of XA was detected in the midgut of nonblood fed An. stephensi mosquitoes. By adding synthetic tryptophan as a source of XA into larval rearing water (2 mM) or in sugar meals (10 mM), we evaluated whether XA levels in the mosquito (salivary glands, midgut, and whole body) were boosted and the subsequent effect on infectivity of Plasmodium berghei in the treated mosquito groups. A female specific increase in XA content was observed in the whole body and in the midgut of mosquito groups where tryptophan was added either in the larval water or sugar meals. However, XA in the salivary glands was not affected by tryptophan addition to larval water, and surprisingly it reduced when tryptophan was added to sugar meals. The P. berghei oocyst loads in the mosquito midguts were lower in mosquitoes fed tryptophan treated sugar meals than in mosquitoes

Functional Marker Assisted Improvement of Stable Cytoplasmic Male Sterile Lines of Rice for Bacterial Blight Resistance

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Jegadeesan Ramalingam

2017-06-01

Full Text Available Bacterial blight (BB, caused by Xanthomonas oryzae pv.oryzae is one among the major diseases in rice, which in severe condition cause losses up to 60% in total yield. Marker assisted pyramiding of three broad spectrum BB resistance genes (xa5, xa13, and Xa21 in prominent rice varieties is the most economical and effective strategy for the management of the BB disease. We report here the pyramiding of three genes (xa5, xa13, and Xa21 in maintainer lines (CO 2B, CO 23B, and CO 24B of three promising wild abortive cytoplasmic male sterile lines (CO 2A, CO 23A, and CO 24A through functional markers assisted back cross breeding. IRBB60 with xa5, xa13, and Xa21 genes is used as a donor parent. BC2F1 and BC2F2 generations from a cross of CO 2B, CO 23B, and CO 24B with IRBB60 were evaluated for bacterial blight and non-fertility restoration. In BC2F1, plants with all three resistance genes (xa5, xa13, and Xa21 and high parent genome recovery was identified. In BC2F2, plants with all resistance genes and without fertility restorer (Rf3 and Rf4 were selected. Based on agronomic traits, BB resistance and maintenance of sterility, two plants each in CO 2B × IRBB60, CO 24B × IRBB60 and one plant in CO 23B × IRBB60 combinations were identified. The identified lines were crossed with respective male sterile lines for conversion of improved B line into CMS line through back-crossing, in addition to selfing. The plants with high recurrent genome and phenotypically similar to parental lines and sterile are being used for the hybrid rice development program. Currently, using these lines (improved CMS line, test crosses were made to develop new rice hybrids. Hybrids combinations viz., CO 23A × AD08009R and CO 24A × IET20898R were found to be stable at different locations with high yield. The R line used in this study has been introgressed with xa5, xa13, and Xa21 genes in a separate breeding program. These new hybrids with resistance against bacterial blight

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.

Development of Coagulation Factor Probes for the Identification of Procoagulant Circulating Tumor Cells

Energy Technology Data Exchange (ETDEWEB)

Tormoen, Garth W.; Cianchetti, Flor A. [Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR (United States); Bock, Paul E. [Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN (United States); McCarty, Owen J. T., E-mail: tormoeng@ohsu.edu [Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR (United States); Department of Cell and Developmental Biology, Oregon Health and Science University, Portland, OR (United States); Division of Hematology and Medical Oncology, Department of Medicine, Oregon Health and Science University, Portland, OR (United States)

2012-09-06

Metastatic cancer is associated with a hypercoagulable state, and pathological venous thromboembolic disease is a significant source of morbidity and the second leading cause of death in patients with cancer. Here we aimed to develop a novel labeling strategy to detect and quantify procoagulant circulating tumor cells (CTCs) from patients with metastatic cancer. We hypothesize that the enumeration of procoagulant CTCs may be prognostic for the development of venous thrombosis in patients with cancer. Our approach is based on the observation that cancer cells are capable of initiating and facilitating cell-mediated coagulation in vitro, whereby activated coagulation factor complexes assemble upon cancer cell membrane surfaces. Binding of fluorescently labeled, active site-inhibited coagulation factors VIIa, Xa, and IIa to the metastatic breast cancer cell line, MDA-MB-231, non-metastatic colorectal cell line, SW480, or metastatic colorectal cell line, SW620, was characterized in a purified system, in anticoagulated blood and plasma, and in plasma under conditions of coagulation. We conclude that a CTC labeling strategy that utilizes coagulation factor-based fluorescent probes may provide a functional assessment of the procoagulant potential of CTCs, and that this strategy is amenable to current CTC detection platforms.

Prolonged Cerebral Circulation Time Is the Best Parameter for Predicting Vasospasm during Initial CT Perfusion in Subarachnoid Hemorrhagic Patients.

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Chun Fu Lin

Full Text Available We sought to imitate angiographic cerebral circulation time (CCT and create a similar index from baseline CT perfusion (CTP to better predict vasospasm in patients with subarachnoid hemorrhage (SAH.Forty-one SAH patients with available DSA and CTP were retrospectively included. The vasospasm group was comprised of patients with deterioration in conscious functioning and newly developed luminal narrowing; remaining cases were classified as the control group. The angiography CCT (XA-CCT was defined as the difference in TTP (time to peak between the selected arterial ROIs and the superior sagittal sinus (SSS. Four arterial ROIs were selected to generate four corresponding XA-CCTs: the right and left anterior cerebral arteries (XA-CCTRA2 and XA-CCTLA2 and right- and left-middle cerebral arteries (XA-CCTRM2 and XA-CCTLM2. The CCTs from CTP (CT-CCT were defined as the differences in TTP from the corresponding arterial ROIs and the SSS. Correlations of the different CCTs were calculated and diagnostic accuracy in predicting vasospasm was evaluated.Intra-class correlations ranged from 0.96 to 0.98. The correlations of XA-CCTRA2, XA-CCTRM2, XA-CCTLA2, and XA-CCTLM2 with the corresponding CT-CCTs were 0.64, 0.65, 0.53, and 0.68, respectively. All CCTs were significantly prolonged in the vasospasm group (5.8-6.4 s except for XA-CCTLA2. CT-CCTA2 of 5.62 was the optimal cut-off value for detecting vasospasm with a sensitivity of 84.2% and specificity 82.4.CT-CCTs can be used to interpret cerebral flow without deconvolution algorithms, and outperform both MTT and TTP in predicting vasospasm risk. This finding may help facilitate management of patients with SAH.

Thrombin induces epithelial-mesenchymal transition and collagen production by retinal pigment epithelial cells via autocrine PDGF-receptor signaling.

Science.gov (United States)

Bastiaans, Jeroen; van Meurs, Jan C; van Holten-Neelen, Conny; Nagtzaam, Nicole M A; van Hagen, P Martin; Chambers, Rachel C; Hooijkaas, Herbert; Dik, Willem A

2013-12-19

De-differentiation of RPE cells into mesenchymal cells (epithelial-mesenchymal transition; EMT) and associated collagen production contributes to development of proliferative vitreoretinopathy (PVR). In patients with PVR, intraocular coagulation cascade activation occurs and may play an important initiating role. Therefore, we examined the effect of the coagulation proteins factor Xa and thrombin on EMT and collagen production by RPE cells. Retinal pigment epithelial cells were stimulated with factor Xa or thrombin and the effect on zonula occludens (ZO)-1, α-smooth muscle actin (α-SMA), collagen, and platelet-derived growth factor (PDGF)-B were determined by real-time quantitative-polymerase chain reaction (RQ-PCR), immunofluorescence microscopy, and HPLC and ELISA for collagen and PDGF-BB in culture supernatants, respectively. PDGF-receptor activation was determined by phosphorylation analysis and inhibition studies using the PDGF-receptor tyrosine kinase inhibitor AG1296. Thrombin reduced ZO-1 gene expression (P production of α-SMA and collagen increased. In contrast to thrombin, factor Xa hardly stimulated EMT by RPE. Thrombin clearly induced PDGF-BB production and PDGF-Rβ chain phosphorylation in RPE. Moreover, AG1296 significantly blocked the effect of thrombin on EMT and collagen production. Our findings demonstrate that thrombin is a potent inducer of EMT by RPE via autocrine activation of PDGF-receptor signaling. Coagulation cascade-induced EMT of RPE may thus contribute to the formation of fibrotic retinal membranes in PVR and should be considered as treatment target in PVR.

Apixaban

Science.gov (United States)

... medications called factor Xa inhibitors. It works by blocking the action of a certain natural substance that ... rash chest pain or tightness swelling of the face or tongue trouble breathing wheezing feeling dizzy or ...

Universal, class-specific and drug-specific reversal agents for the new oral anticoagulants.

Science.gov (United States)

Ansell, Jack E

2016-02-01

Although there is controversy about the absolute need for a reversal agent for the new direct oral anticoagulants (DOACs), the absence of such an agent is a barrier to more widespread use of these agents. For the management of major life-threatening bleeding with the DOACs, most authorities recommend the use of four factor prothrombin complex concentrates, although the evidence to support their use in terms of improving outcomes is meager. At the present time, there are three antidotes in development and poised to enter the market. Idarucizumab is a drug-specific antidote targeted to reverse the direct thrombin inhibitor, dabigatran. Andexanet alfa is a class-specific antidote targeted to reverse the oral direct factor Xa inhibitors as well as the indirect inhibitor, enoxaparin. Ciraparantag is a universal antidote targeted to reverse the direct thrombin and factor Xa inhibitors as well as the indirect inhibitor, enoxaparin.

Simukunin from the Salivary Glands of the Black Fly Simulium vittatum Inhibits Enzymes That Regulate Clotting and Inflammatory Responses

Czech Academy of Sciences Publication Activity Database

Tsujimoto, H.; Kotsyfakis, Michalis; Francischetti, I.M.B.; Eum, J. H.; Strand, M. R.; Champagne, D. E.

2012-01-01

Roč. 7, č. 2 (2012), e29964 E-ISSN 1932-6203 Institutional research plan: CEZ:AV0Z60220518 Keywords : Simulium vittatum * Kunitz-family protein * elastase * cathepsin G * Factor Xa * coagulation * inflammation * serine proteases * BPTI-like inhibitor * Simukunin Subject RIV: EC - Immunology Impact factor: 3.730, year: 2012

Trial design: Rivaroxaban for the prevention of major cardiovascular events after transcatheter aortic valve replacement: Rationale and design of the GALILEO study

NARCIS (Netherlands)

Windecker, Stephan; Tijssen, Jan; Giustino, Gennaro; Guimarães, Ana H. C.; Mehran, Roxana; Valgimigli, Marco; Vranckx, Pascal; Welsh, Robert C.; Baber, Usman; van Es, Gerrit-Anne; Wildgoose, Peter; Volkl, Albert A.; Zazula, Ana; Thomitzek, Karen; Hemmrich, Melanie; Dangas, George D.

2017-01-01

Optimal antithrombotic treatment after transcatheter aortic valve replacement (TAVR) is unknown and determined empirically. The direct factor Xa inhibitor rivaroxaban may potentially reduce TAVR-related thrombotic complications and premature valve failure. GALILEO is an international, randomized,

Metabolite profiles of rice cultivars containing bacterial blight-resistant genes are distinctive from susceptible rice

Institute of Scientific and Technical Information of China (English)

Jiao Wu; Haichuan Yu; Haofu Dai; Wenli Mei; Xin Huang; Shuifang Zhu; Ming Peng

2012-01-01

The metabolic changes of bacterial blight-resistant line C418/Xa23 generated by molecular marker-assisted selection (n =12),transgenic variety C418-Xa21 generated by using the Agrobacterium-mediated system (n =12),and progenitor cultivar C418 (n =12) were monitored using gas chromatography/mass spectrometry.The validation,discrimination,and establishment of correlative relationships between metabolite signals were performed by cluster analysis,principal component analysis,and partial least squares-discriminant analysis.Significant and unintended changes were observed in 154 components in C418/Xa23 and 48 components in C418-Xa21 compared with C418 (P ＜ 0.05,Fold change ＞ 2.0).The most significant decreases detected (P＜ 0.001) in both C418/Xa23 and C418-Xa21 were in three amino acids: glycine,tyrosine,and alanine,and four identified metabolites: malic acid,ferulic acid,succinic acid,and glycerol.Linoleic acid was increased specifically in C418/Xa23 which was derived from traditional breeding.This line,possessing a distinctive metabolite profile as a positive control,shows more differences vs.the parental than the transgenic line.Only succinic acid that falls outside the boundaries of natural variability between the two non-transgenic varieties C418 and C418/Xa23 should be further investigated with respect to safety or nutritional impact.

Coagulation factor VII is regulated by androgen receptor in breast cancer.

Science.gov (United States)

Naderi, Ali

2015-02-01

Androgen receptor (AR) is widely expressed in breast cancer; however, there is limited information on the key molecular functions and gene targets of AR in this disease. In this study, gene expression data from a cohort of 52 breast cancer cell lines was analyzed to identify a network of AR co-expressed genes. A total of 300 genes, which were significantly enriched for cell cycle and metabolic functions, showed absolute correlation coefficients (|CC|) of more than 0.5 with AR expression across the dataset. In this network, a subset of 35 "AR-signature" genes were highly co-expressed with AR (|CC|>0.6) that included transcriptional regulators PATZ1, NFATC4, and SPDEF. Furthermore, gene encoding coagulation factor VII (F7) demonstrated the closest expression pattern with AR (CC=0.716) in the dataset and factor VII protein expression was significantly associated to that of AR in a cohort of 209 breast tumors. Moreover, functional studies demonstrated that AR activation results in the induction of factor VII expression at both transcript and protein levels and AR directly binds to a proximal region of F7 promoter in breast cancer cells. Importantly, AR activation in breast cancer cells induced endogenous factor VII activity to convert factor X to Xa in conjunction with tissue factor. In summary, F7 is a novel AR target gene and AR activation regulates the ectopic expression and activity of factor VII in breast cancer cells. These findings have functional implications in the pathobiology of thromboembolic events and regulation of factor VII/tissue factor signaling in breast cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

Avaliação comparativa das propriedades de xantanas produzidas pelo patovar pruni e clairana com xantana comercial para predição de uso Comparative evaluation of xanthans properties produced by pathovar pruni and clairana with commercial xanthan to predict their uses

Directory of Open Access Journals (Sweden)

Patrícia D. Oliveira

2013-01-01

Full Text Available O presente trabalho teve como objetivo determinar a adequabilidade de três amostras de biopolímero xantana (Xa 06, Xa 82 e Xa 106 e uma clairana como viscosificantes de fluidos de perfuração de poços de petróleo, comparando com uma amostra de xantana comercial, Xanvis®. Foram realizadas análises reológicas, determinados os conteúdos de acetil, piruvato e íons Na+ K+ e Ca2+, e avaliada a capacidade viscosificante segundo norma específica da Petrobras. Os conteúdos de grupos acetil e piruvato para as xantanas e clairana diferiram significativamente entre si, mas foram compatíveis com valores preconizados ou citados na literatura concernente. Com relação ao conteúdo de íons, a xantana comercial apresentou quantidade de cálcio superior, as amostras Xa 06, Xa 82 e Xa 106 tiveram maior teor de potássio e a clairana maior teor de sódio. A viscosidade e a viscoelasticidade da amostra de xantana comercial foram superiores às demais amostras analisadas. Na análise como viscosificante para fluidos de perfuração as amostras de xantana comercial e Xa 106 atingiram os requisitos estabelecidos para os parâmetros n, K e força gel da norma Petrobras N-2605. Com a interpretação conjunta dos resultados obtidos pode-se inferir que apenas as xantanas Xanvis® e Xa 106 apresentam características adequadas à utilização como viscosificante em fluido de perfuração de petróleo. As demais amostras possuem características reológicas adequadas à utilização como espessantes ou estabilizantes em outros segmentos industriais, como em alimentos, tintas e cosméticos.The aim of this study was to determine the suitability of three xanthans (Xa 06, Xa 82 and Xa 106 and a clairana biopolymer for use as drilling fluid thickeners and comparing them against a commercial sample, Xanvis®. Rheological analyses were performed to determine the acetyl, pyruvate and Na+ K+ and Ca2+ ion content and their thickening ability, according to Petrobras

Synthesis of Phosphatidylserine and Its Stereoisomers: Their Role in Activation of Blood Coagulation.

Science.gov (United States)

Mallik, Suman; Prasad, Ramesh; Bhattacharya, Anindita; Sen, Prosenjit

2018-05-10

Natural phosphatidylserine (PS), which contains two chiral centers, enhances blood coagulation. However, the process by which PS enhanced blood coagulation is not completely understood. An efficient and flexible synthetic route has been developed to synthesize all of the possible stereoisomers of PS. In this study, we examined the role of PS chiral centers in modulating the activity of the tissue factor (TF)-factor VIIa coagulation initiation complex. Full length TF was relipidated with phosphatidylcholine, and the synthesized PS isomers were individually used to estimate the procoagulant activity of the TF-FVIIa complex via a FXa generation assay. The results revealed that the initiation complex activity was stereoselective and had increased sensitivity to the configuration of the PS glycerol backbone due to optimal protein-lipid interactions.

Abnormal X : autosome ratio, but normal X chromosome inactivation in human triploid cultures

Directory of Open Access Journals (Sweden)

Norwood Thomas H

2006-07-01

Full Text Available Abstract Background X chromosome inactivation (XCI is that aspect of mammalian dosage compensation that brings about equivalence of X-linked gene expression between females and males by inactivating one of the two X chromosomes (Xi in normal female cells, leaving them with a single active X (Xa as in male cells. In cells with more than two X's, but a diploid autosomal complement, all X's but one, Xa, are inactivated. This phenomenon is commonly thought to suggest 1 that normal development requires a ratio of one Xa per diploid autosomal set, and 2 that an early event in XCI is the marking of one X to be active, with remaining X's becoming inactivated by default. Results Triploids provide a test of these ideas because the ratio of one Xa per diploid autosomal set cannot be achieved, yet this abnormal ratio should not necessarily affect the one-Xa choice mechanism for XCI. Previous studies of XCI patterns in murine triploids support the single-Xa model, but human triploids mostly have two-Xa cells, whether they are XXX or XXY. The XCI patterns we observe in fibroblast cultures from different XXX human triploids suggest that the two-Xa pattern of XCI is selected for, and may have resulted from rare segregation errors or Xi reactivation. Conclusion The initial X inactivation pattern in human triploids, therefore, is likely to resemble the pattern that predominates in murine triploids, i.e., a single Xa, with the remaining X's inactive. Furthermore, our studies of XIST RNA accumulation and promoter methylation suggest that the basic features of XCI are normal in triploids despite the abnormal X:autosome ratio.

Influence of tungsten microstructure and ion flux on deuterium plasma-induced surface modifications and deuterium retention

NARCIS (Netherlands)

Buzi, L.; De Temmerman, G.; Unterberg, B.; M. Reinhart,; Dittmar, T.; Matveev, D.; Linsmeier, C.; Breuer, U.; Kreter, A.; Van Oost, G.

2015-01-01

The influence of surface temperature, particle flux density and material microstructure on the surface morphology and deuterium retention was studied by exposing tungsten targets (20&#xa0;μm and 40&#xa0;μm grain size) to deuterium plasma at the same particle fluence (1026&#xa0;m−2) and

Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism

NARCIS (Netherlands)

Büller, Harry R; Décousus, Hervé; Grosso, Michael A; Mercuri, Michele; Middeldorp, Saskia; Prins, Martin H; Raskob, Gary E; Schellong, Sebastian M; Schwocho, Lee; Segers, Annelise; Shi, Minggao; Verhamme, Peter; Wells, Phil; Kamphuisen, P.W.

2013-01-01

BACKGROUND: Whether the oral factor Xa inhibitor edoxaban can be an alternative to warfarin in patients with venous thromboembolism is unclear. METHODS: In a randomized, double-blind, noninferiority study, we randomly assigned patients with acute venous thromboembolism, who had initially received

Hepatoprotective Effects of Chinese Medicine Herbs Decoction on Liver Cirrhosis in Rats

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Nor Aziyah Mat-Rahim

2017-01-01

Full Text Available Hepatoprotective and curative activities of aqueous extract of decoction containing 10 Chinese medicinal herbs (HPE-XA-08 were evaluated in Sprague–Dawley albino rats with liver damage induced by thioacetamide (TAA. These activities were assessed by investigating the liver enzymes level and also histopathology investigation. Increases in alkaline phosphatase (ALP and gamma-glutamyl transferase (GGT levels were observed in rats with cirrhotic liver. No significant alterations of the liver enzymes were observed following treatment with HPE-XA-08. Histopathology examination of rats treated with HPE-XA-08 at 250 mg/kg body weight, however, exhibited moderate liver protective effects. Reduced extracellular matrix (ECM proteins within the hepatocytes were noted in comparison to the cirrhotic liver. The curative effects of HPE-XA-08 were observed with marked decrease in the level of ALP (more than 3x and level of GGT (more than 2x in cirrhotic rat treated with 600 mg/kg body weight HPE-XA-08 in comparison to cirrhotic rat treated with just water diluent. Reversion of cirrhotic liver to normal liver condition in rats treated with HPE-XA-08 was observed. Results from the present study suggest that HPE-XA-08 treatment assisted in the protection from liver cirrhosis and improved the recovery of cirrhotic liver.

Cross System Extensions (CSE) experience

International Nuclear Information System (INIS)

Johnston, T.Y.

1990-08-01

Cross System Extension (CSE) provides VM/XA systems with the ability to share minidisks and spool in loosely coupled environment. CSE will also cooperate with the VM/HPO Inter System Facility (ISF) in sharing minidisks between VM/XA and VM/HPO to XA, reliability of CSE, and some operational considerations when running with it

New oral anticoagulant-induced bleeding: clinical presentation and management

NARCIS (Netherlands)

Levy, Jerrold H.; Levi, Marcel

2014-01-01

Bleeding is a significant complication of anticoagulant therapy. With the emergence of new oral anticoagulants (NOACs; ie, direct factor IIa or Xa inhibitors), this risk is further compounded by the lack of validated reversal strategies for these agents. Emerging postmarketing evidence suggests that

New oral anticoagulants: their advantages and disadvantages compared with vitamin K antagonists in the prevention and treatment of patients with thromboembolic events.

Science.gov (United States)

Mekaj, Ymer H; Mekaj, Agon Y; Duci, Shkelzen B; Miftari, Ermira I

2015-01-01

Despite the discovery and application of many parenteral (unfractionated and low-molecular-weight heparins) and oral anticoagulant vitamin K antagonist (VKA) drugs, the prevention and treatment of venous and arterial thrombotic phenomena remain major medical challenges. Furthermore, VKAs are the only oral anticoagulants used during the past 60 years. The main objective of this study is to present recent data on non-vitamin K antagonist oral anticoagulants (NOACs) and to analyze their advantages and disadvantages compared with those of VKAs based on a large number of recent studies. NOACs are novel direct-acting medications that are selective for one specific coagulation factor, either thrombin (IIa) or activated factor X (Xa). Several NOACs, such as dabigatran (a direct inhibitor of FIIa) and rivaroxaban, apixaban and edoxaban (direct inhibitors of factor Xa), have been used for at least 5 years but possibly 10 years. Unlike traditional VKAs, which prevent the coagulation process by suppressing the synthesis of vitamin K-dependent factors, NOACs directly inhibit key proteases (factors IIa and Xa). The important indications of these drugs are the prevention and treatment of deep vein thrombosis and pulmonary embolisms, and the prevention of atherothrombotic events in the heart and brain of patients with acute coronary syndrome and atrial fibrillation. They are not fixed, and dose-various strengths are available. Most studies have reported that more advantages than disadvantages for NOACs when compared with VKAs, with the most important advantages of NOACs including safety issues (ie, a lower incidence of major bleeding), convenience of use, minor drug and food interactions, a wide therapeutic window, and no need for laboratory monitoring. Nonetheless, there are some conditions for which VKAs remain the drug of choice. Based on the available data, we can conclude that NOACs have greater advantages and fewer disadvantages compared with VKAs. New studies are required

Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial

DEFF Research Database (Denmark)

Lassen, Michael Rud; Raskob, Gary E; Gallus, Alexander

2010-01-01

BACKGROUND: Low-molecular-weight heparins such as enoxaparin are preferred for prevention of venous thromboembolism after major joint replacement. Apixaban, an orally active factor Xa inhibitor, might be as effective, have lower bleeding risk, and be easier to use than is enoxaparin. We assessed ...

Edoxaban versus warfarin in patients with atrial fibrillation

NARCIS (Netherlands)

Giugliano, R.P.; Ruff, C.T.; Braunwald, E.; Murphy, S.A.; Wiviott, S.D.; Halperin, J.L.; Waldo, A.L.; Ezekowitz, M.D.; Weitz, J.I.; Spinar, J.; Ruzyllo, W.; Ruda, M.; Koretsune, Y.; Betcher, J.; Shi, M.; Grip, L.T.; Patel, S.P.; Patel, I.; Hanyok, J.J.; Mercuri, M.; Antman, E.M.; Verheugt, F.W.A.; et al.,

2013-01-01

BACKGROUND: Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known. METHODS: We conducted a randomized, double-blind, double-dummy trial comparing two

Edoxaban versus Warfarin in Patients with Atrial Fibrillation

NARCIS (Netherlands)

Giugliano, Robert P.; Ruff, Christian T.; Braunwald, Eugene; Murphy, Sabina A.; Wiviott, Stephen D.; Halperin, Jonathan L.; Waldo, Albert L.; Ezekowitz, Michael D.; Weitz, Jeffrey I.; Špinar, Jindřich; Ruzyllo, Witold; Ruda, Mikhail; Koretsune, Yukihiro; Betcher, Joshua; Shi, Minggao; Grip, Laura T.; Patel, Shirali P.; Patel, Indravadan; Hanyok, James J.; Mercuri, Michele; Antman, Elliott M.; Braunwald, E.; Antman, E. M.; Giugliano, R. P.; Ruff, C. T.; Morin, S. E.; Hoffman, E. B.; Murphy, S. A.; Deenadayalu, N.; Grip, L.; Mercuri, M.; Lanz, H.; Patel, I.; Curt, V.; Duggal, A.; Hanyok, J.; Davé, J.; Morgan, D.; Choi, Y.; Shi, M.; Jin, J.; Xie, J.; Crerand, W.; Kappelhof, J.; Maxwell, W.; Zhang, X.; Zhang, Z.; de Groot, J. [=Joris R.; de Vos, R.; Hoekstra, J.

2013-01-01

BackgroundEdoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known. MethodsWe conducted a randomized, double-blind, double-dummy trial comparing two

Apixaban with antiplatelet therapy after acute coronary syndrome

NARCIS (Netherlands)

Alexander, J.H.; Lopes, R.D.; James, S.; Kilaru, R.; He, Y.; Mohan, P.; Bhatt, D.L.; Goodman, S.; Verheugt, F.W.A.; Flather, M.; Huber, K.; Liaw, D.; Husted, S.E.; Lopez-Sendon, J.; De Caterina, R.; Jansky, P.; Darius, H.; Vinereanu, D.; Cornel, J.H.; Cools, F.; Atar, D.; Leiva-Pons, J.L.; Keltai, M.; Ogawa, H.; Pais, P.; Parkhomenko, A.; Ruzyllo, W.; Diaz, R.; White, H.; Ruda, M.; Geraldes, M.; Lawrence, J.; Harrington, R.A.; Wallentin, L.

2011-01-01

BACKGROUND: Apixaban, an oral, direct factor Xa inhibitor, may reduce the risk of recurrent ischemic events when added to antiplatelet therapy after an acute coronary syndrome. METHODS: We conducted a randomized, double-blind, placebo-controlled clinical trial comparing apixaban, at a dose of 5 mg

Risk factors for epistaxis in patients followed in general practices in Germany.

Science.gov (United States)

Seidel, D U; Jacob, L; Kostev, K; Sesterhenn, A M

2017-12-01

The goal of the present study was to analyze the risk factors for epistaxis in patients followed in general practices in Germany. The current study sample included patients aged 18 years or older who received a first epistaxis diagnosis between January 2012 and December 2016 (index date). Epistaxis patients and controls without epistaxis were matched (1:1) on the basis of age, gender, insurance status and physician. A total of 16,801 patients with epistaxis and 16,801 control subjects were included in this study. Of the subjects, 53.2% were men, and the mean age was 59.6 years (SD=21.2 years). Epistaxis was found to be positively associated with hypertension, obesity, chronic sinusitis, other disorders of the nose and nasal sinuses, anxiety disorder, and adjustment disorder (ORs ranging from 1.13 to 1.44). Epistaxis was also associated with the prescription of vitamin K antagonists, preparations from the heparin group, platelet aggregation inhibitors excluding heparin, direct thrombin inhibitors, direct factor Xa inhibitors, other antithrombotic agents, selective serotonin reuptake inhibitors and nasal steroids (ORs ranging from 1.15 to 3.55). Overall, epistaxis risk is increased by multiple medical and psychiatric disorders. Several antithrombotic and nasal steroid therapies are also associated with this risk.

Overexpression of Rice Auxilin-Like Protein, XB21, Induces Necrotic Lesions, up-Regulates Endocytosis-Related Genes, and Confers Enhanced Resistance to Xanthomonas oryzae pv. oryzae.

Science.gov (United States)

Park, Chang-Jin; Wei, Tong; Sharma, Rita; Ronald, Pamela C

2017-12-01

The rice immune receptor XA21 confers resistance to the bacterial pathogen, Xanthomonas oryzae pv. oryzae (Xoo). To elucidate the mechanism of XA21-mediated immunity, we previously performed a yeast two-hybrid screening for XA21 interactors and identified XA21 binding protein 21 (XB21). Here, we report that XB21 is an auxilin-like protein predicted to function in clathrin-mediated endocytosis. We demonstrate an XA21/XB21 in vivo interaction using co-immunoprecipitation in rice. Overexpression of XB21 in rice variety Kitaake and a Kitaake transgenic line expressing XA21 confers a necrotic lesion phenotype and enhances resistance to Xoo. RNA sequencing reveals that XB21 overexpression results in the differential expression of 8735 genes (4939 genes up- and 3846 genes down-regulated) (≥2-folds, FDR ≤0.01). The up-regulated genes include those predicted to be involved in 'cell death' and 'vesicle-mediated transport'. These results indicate that XB21 plays a role in the plant immune response and in regulation of cell death. The up-regulation of genes controlling 'vesicle-mediated transport' in XB21 overexpression lines is consistent with a functional role for XB21 as an auxilin.

Cytological diagnosis of xanthogranulomatous appendicitis

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Rajni Kaushik

2017-01-01

Full Text Available Xanthogranulomatous reaction can occur in any organ but the most common sites are kidney and gallbladder. Xanthogranulomatous appendicitis (XA is a rare clinical entity. There are a few case reports of XA diagnosed on histopathology but none on cytology. Here we report a case of a 47-year-old lady who presented with acute abdomen and was found to have a mass lesion in the right iliac fossa. She was diagnosed with XA intraoperatively on imprint cytology that was subsequently confirmed on histopathological examination. Due to the rarity of XA itself and the use of imprint cytology for intraoperative diagnosis the case is being presented.

Synthesis, purification, and characterization of an Arg152 → Glu site-directed mutant of recombinant human blood clotting factor VII

International Nuclear Information System (INIS)

Wildgoose, P.; Kisiel, W.; Berkner, K.L.

1990-01-01

Coagulation factor VII circulates in blood as a single-chain zymogen of a serine protease and is converted to its activated two-chain form, factor VIIa, by cleavage of an internal peptide bond located at Arg 152 -Ile 153 . Previous studies using serine protease active-site inhibitors suggest that zymogen factor VII may possess sufficient proteolytic activity to initiate the extrinsic pathway of blood coagulation. In order to assess the putative intrinsic proteolytic activity of single-chain factor VII, the authors have constructed a site-specific mutant of recombinant human factor VII in which arginine-152 has been replaced with a glutamic acid residue. Mutant factor VII was purified in a single step from culture supernatants of baby hamster kidney cells transfected with a plasmid containing the sequence for Arg 152 → Glu factor VII using a calcium-dependent, murine anti-factor VII monoclonal antibody column. The clotting activity of mutant factor VII was completely inhibited following incubation with dansyl-Glu-Gly-Arg chloromethyl ketone, suggesting that the apparent clotting activity of mutant factor VII was due to a contaminating serine protease. Immunoblots of mutant factor VII with human factor IXa revealed no cleavage, whereas incubation of mutant factor VII with human factor Xa resulted in cleavage of mutant factor VII and the formation of a lower molecular weight degradation product migrating at M r ∼40 000. The results are consistent with the proposal that zymogen factor VII possesses no intrinsic proteolytic activity toward factor X or factor IX

Oral Rivaroxaban for the Treatment of Symptomatic Pulmonary Embolism

NARCIS (Netherlands)

Büller, Harry R.; Prins, Martin H.; Lensin, Anthonie W. A.; Decousus, Hervé; Jacobson, Barry F.; Minar, Erich; Chlumsky, Jaromir; Verhamme, Peter; Wells, Phil; Agnelli, Giancarlo; Cohen, Alexander; Berkowitz, Scott D.; Bounameaux, Henri; Davidson, Bruce L.; Misselwitz, Frank; Gallus, Alex S.; Raskob, Gary E.; Schellong, Sebastian; Segers, Annelise; Berkowitz, Scott; Gallus, Alexander; Lensing, Anthonie W. A.; Haskell, Lloyd; Raskob, Gary; Bauersachs, Rupert; van Bellen, Bonno; Boda, Zoltán; Borris, Lars; Brenner, Benjamin; Brighton, Tim; Davidson, Bruce; Decousus, Herve; Eriksson, Henry; Jacobson, Barry; Kakkar, Ajay; Kwong, Yok-Lam; Lee, Lai Heng; Meijer, Karina; van der Meer, Jan; Monreal, Manuel; Piovella, Franco; Sandset, Per Morten; Smith, Mark; Tomkowski, Witold; Wang, Yuqi; Brandjes, Dees; Mac Gillavry, Melvin; Otten, Hans-Martin; Carlsson, Anders; Kamphuisen, P.

2012-01-01

BACKGROUND A fixed-dose regimen of rivaroxaban, an oral factor Xa inhibitor, has been shown to be as effective as standard anticoagulant therapy for the treatment of deep-vein thrombosis, without the need for laboratory monitoring. This approach may also simplify the treatment of pulmonary embolism.

Apixaban versus warfarin in patients with atrial fibrillation

NARCIS (Netherlands)

Granger, C.B.; Alexander, J.H.; McMurray, J.J.; Lopes, R.D.; Hylek, E.M.; Hanna, M.; Al-Khalidi, H.R.; Ansell, J.; Atar, D.; Avezum, A.; Bahit, M.C.; Diaz, R.; Easton, J.D.; Ezekowitz, J.A.; Flaker, G.; Garcia, D.; Geraldes, M.; Gersh, B.J.; Golitsyn, S.; Goto, S.; Hermosillo, A.G.; Hohnloser, S.H.; Horowitz, J.; Mohan, P.; Jansky, P.; Lewis, B.S.; Lopez-Sendon, J.L.; Pais, P.; Parkhomenko, A.; Verheugt, F.W.A.; Zhu, J.; Wallentin, L.

2011-01-01

BACKGROUND: Vitamin K antagonists are highly effective in preventing stroke in patients with atrial fibrillation but have several limitations. Apixaban is a novel oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke in a similar population in comparison with aspirin.

Cysteine-dependent immune regulation by TRX and MIF/GIF family proteins.

Science.gov (United States)

Kondo, Norihiko; Ishii, Yasuyuki; Son, Aoi; Sakakura-Nishiyama, Junko; Kwon, Yong-Won; Tanito, Masaki; Nishinaka, Yumiko; Matsuo, Yoshiyuki; Nakayama, Toshinori; Taniguchi, Masaru; Yodoi, Junji

2004-03-29

Thioredoxin (TRX) superfamily proteins that contain a conserved redox-active site -Cys-Xa.a.-Xa.a.-Cys- includes proinflammatory cytokine, macrophage migration inhibiting factor (MIF) and the immune regulatory cytokine, glycosylation inhibiting factor (GIF) in which Cys-60 is cysteinylated. In this report, we have analyzed the functional interaction between TRX and MIF/GIF. The stable Jurkat T cell line transfected with human TRX gene (TRX-transfectant) was highly resistant to hydrogen peroxide-induced apoptosis, but not the cell line transfected with vector (mock-transfectant). The expression level of MIF/GIF protein of TRX-transfectant was lower than that of mock-transfectant. Conversely, the expression level of intracellular TRX protein in CD4(+)-T cells derived from MIF -/- mice were significantly higher than that from background BALB/c mice. These findings collectively suggest that oxidative stress-induced apoptosis on T lymphocytes might be protected by the reciprocal regulation of TRX and MIF/GIF expression.

Purification method for recombinant proteins based on a fusion between the target protein and the C-terminus of calmodulin

Science.gov (United States)

Schauer-Vukasinovic, Vesna; Deo, Sapna K.; Daunert, Sylvia

2002-01-01

Calmodulin (CaM) was used as an affinity tail to facilitate the purification of the green fluorescent protein (GFP), which was used as a model target protein. The protein GFP was fused to the C-terminus of CaM, and a factor Xa cleavage site was introduced between the two proteins. A CaM-GFP fusion protein was expressed in E. coli and purified on a phenothiazine-derivatized silica column. CaM binds to the phenothiazine on the column in a Ca(2+)-dependent fashion and it was, therefore, used as an affinity tail for the purification of GFP. The fusion protein bound to the affinity column was then subjected to a proteolytic digestion with factor Xa. Pure GFP was eluted with a Ca(2+)-containing buffer, while CaM was eluted later with a buffer containing the Ca(2+)-chelating agent EGTA. The purity of the isolated GFP was verified by SDS-PAGE, and the fluorescence properties of the purified GFP were characterized.

Low-molecular-weight heparins: pharmacologic profile and product differentiation.

Science.gov (United States)

Fareed, J; Jeske, W; Hoppensteadt, D; Clarizio, R; Walenga, J M

1998-09-10

The interchangeability of low-molecular-weight heparins (LMWHs) has been the subject of discussion since these products were first introduced for the prophylaxis of deep vein thrombosis. Experimental evidence now exists to show that LMWHs differ from each other in a number of characteristics. Products have been differentiated on the basis of molecular weight and biologic properties, but only limited information derived from the clinical setting is available. Potency has been described on the basis of anti-Factor Xa activity, but at equivalent anti-Xa activities, the anti-Factor IIa activity of different products shows marked variations. At the relatively small doses used for the management of postsurgical deep vein thrombosis, the effect of these interproduct differences may be relatively minor, but as LMWHs are developed for therapeutic use at much higher doses, such differences may become clinically important. Variations in safety and efficacy reported in clinical trials of LMWHs may reflect the known differences in their molecular composition and pharmacologic properties.

Synthesis, purification, and characterization of an Arg sub 152 yields Glu site-directed mutant of recombinant human blood clotting factor VII

Energy Technology Data Exchange (ETDEWEB)

Wildgoose, P.; Kisiel, W. (Univ. of New Mexico, Albuquerque (USA)); Berkner, K.L. (ZymoGenetics, Inc., Seattle, WA (USA))

1990-04-03

Coagulation factor VII circulates in blood as a single-chain zymogen of a serine protease and is converted to its activated two-chain form, factor VIIa, by cleavage of an internal peptide bond located at Arg{sub 152}-Ile{sub 153}. Previous studies using serine protease active-site inhibitors suggest that zymogen factor VII may possess sufficient proteolytic activity to initiate the extrinsic pathway of blood coagulation. In order to assess the putative intrinsic proteolytic activity of single-chain factor VII, the authors have constructed a site-specific mutant of recombinant human factor VII in which arginine-152 has been replaced with a glutamic acid residue. Mutant factor VII was purified in a single step from culture supernatants of baby hamster kidney cells transfected with a plasmid containing the sequence for Arg{sub 152} {yields} Glu factor VII using a calcium-dependent, murine anti-factor VII monoclonal antibody column. The clotting activity of mutant factor VII was completely inhibited following incubation with dansyl-Glu-Gly-Arg chloromethyl ketone, suggesting that the apparent clotting activity of mutant factor VII was due to a contaminating serine protease. Immunoblots of mutant factor VII with human factor IXa revealed no cleavage, whereas incubation of mutant factor VII with human factor Xa resulted in cleavage of mutant factor VII and the formation of a lower molecular weight degradation product migrating at M{sup r}{approx}40 000. The results are consistent with the proposal that zymogen factor VII possesses no intrinsic proteolytic activity toward factor X or factor IX.

Patrón tromboelastográfico en pacientes anticoagulados con rivaroxabán por fibrilación auricular

Directory of Open Access Journals (Sweden)

Susana Pacheco Jaramillo

2016-11-01

Conclusión: El patrón tromboelastográfico obtenido en la mayoría de pacientes del estudio se caracterizó por un tiempo de reacción alto y un índice de coagulación bajo, posiblemente debido al efecto del inhibidor del factor Xa.

Extreme Apprenticeship – Emphasising conceptual understanding in undergraduate mathematics

OpenAIRE

Rämö , Johanna; Oinonen , Lotta; Vikberg , Thomas

2015-01-01

International audience; Extreme Apprenticeship (XA) is an educational method that has been used in teaching undergraduate mathematics in the University of Helsinki. In this paper, we analyse the course assignments and exam questions of a certain lecture course that has recently been reformed to an XA-based course. The results show that the XA method has made it possible to move the emphasis from rote learning towards understanding the concepts behind the procedures.

Tribimaximal neutrino mixing from A4 replication

International Nuclear Information System (INIS)

Carone, Christopher D.; Lebed, Richard F.

2011-01-01

Motivated by dimensional deconstruction, we propose a model of tribimaximal neutrino mixing based on A 4 xA 4 symmetry. In this model, the two triplet symmetry-breaking fields of conventional A 4 models are taken to transform under different A 4 group factors, but are not distinguished by any other quantum numbers. An additional bi-triplet flavor field breaks A 4 xA 4 to its diagonal subgroup. If the bi-triplet transforms under an additional Z 3 symmetry, we show that one can construct a general, renormalizable superpotential that yields the desired pattern of symmetry breaking. We identify the features that this model has in common with a deconstructed 5D theory in which A 4 is a subgroup of a continuous gauged flavor symmetry in the bulk.

Moojenactivase, a novel pro-coagulant PIIId metalloprotease isolated from Bothrops moojeni snake venom, activates coagulation factors II and X and induces tissue factor up-regulation in leukocytes.

Science.gov (United States)

Sartim, Marco A; Costa, Tassia R; Laure, Helen J; Espíndola, Milena S; Frantz, Fabiani G; Sorgi, Carlos A; Cintra, Adélia C O; Arantes, Eliane C; Faccioli, Lucia H; Rosa, José C; Sampaio, Suely V

2016-05-01

Coagulopathies following snakebite are triggered by pro-coagulant venom toxins, in which metalloproteases play a major role in envenomation-induced coagulation disorders by acting on coagulation cascade, platelet function and fibrinolysis. Considering this relevance, here we describe the isolation and biochemical characterization of moojenactivase (MooA), a metalloprotease from Bothrops moojeni snake venom, and investigate its involvement in hemostasis in vitro. MooA is a glycoprotein of 85,746.22 Da, member of the PIIId group of snake venom metalloproteases, composed of three linked disulfide-bonded chains: an N-glycosylated heavy chain, and two light chains. The venom protease induced human plasma clotting in vitro by activating on both blood coagulation factors II (prothrombin) and X, which in turn generated α-thrombin and factor Xa, respectively. Additionally, MooA induced expression of tissue factor (TF) on the membrane surface of peripheral blood mononuclear cells (PBMC), which led these cells to adopt pro-coagulant characteristics. MooA was also shown to be involved with production of the inflammatory mediators TNF-α, IL-8 and MCP-1, suggesting an association between MooA pro-inflammatory stimulation of PBMC and TF up-regulation. We also observed aggregation of washed platelets when in presence of MooA; however, the protease had no effect on fibrinolysis. Our findings show that MooA is a novel hemostatically active metalloprotease, which may lead to the development of coagulopathies during B. moojeni envenomation. Moreover, the metalloprotease may contribute to the development of new diagnostic tools and pharmacological approaches applied to hemostatic disorders.

TAL effectors and the executor R genes.

Science.gov (United States)

Zhang, Junli; Yin, Zhongchao; White, Frank

2015-01-01

Transcription activator-like (TAL) effectors are bacterial type III secretion proteins that function as transcription factors in plants during Xanthomonas/plant interactions, conditioning either host susceptibility and/or host resistance. Three types of TAL effector associated resistance (R) genes have been characterized-recessive, dominant non-transcriptional, and dominant TAL effector-dependent transcriptional based resistance. Here, we discuss the last type of R genes, whose functions are dependent on direct TAL effector binding to discrete effector binding elements in the promoters. Only five of the so-called executor R genes have been cloned, and commonalities are not clear. We have placed the protein products in two groups for conceptual purposes. Group 1 consists solely of the protein from pepper, BS3, which is predicted to have catalytic function on the basis of homology to a large conserved protein family. Group 2 consists of BS4C-R, XA27, XA10, and XA23, all of which are relatively short proteins from pepper or rice with multiple potential transmembrane domains. Group 2 members have low sequence similarity to proteins of unknown function in closely related species. Firm predictions await further experimentation on these interesting new members to the R gene repertoire, which have potential broad application in new strategies for disease resistance.

TAL effectors and the executor R genes

Directory of Open Access Journals (Sweden)

Junli eZhang

2015-08-01

Full Text Available Transcription activation-like (TAL effectors are bacterial type III secretion proteins that function as transcription factors in plants during Xanthomonas/plant interactions, conditioning either host susceptibility and/or host resistance. Three types of TAL effector associated resistance (R genes have been characterized - recessive, dominant non-transcriptional and dominant TAL effector-dependent transcriptional based resistance. Here, we discuss the last type of R genes, whose functions are dependent on direct TAL effector binding to discrete effector binding elements in the promoters. Only five of the so-called executor R genes have been cloned, and commonalities are not clear. We have placed the protein products in two groups for conceptual purposes. Group 1 consists solely of the protein from pepper, BS3, which is predicted to have catalytic function on the basis of homology to a large conserved protein family. Group 2 consists of BS4C-R, XA27, XA10, and XA23, all of which are relatively short proteins from pepper or rice with multiple potential transmembrane domains. Group 2 members have low sequence similarity to proteins of unknown function in closely related species. Firm predictions await further experimentation on these interesting new members to the R gene repertoire, which have potential broad application in new strategies for disease resistance.

In vitro anticoagulation monitoring of low-molecular-weight heparin

Institute of Scientific and Technical Information of China (English)

WANG Jian-qi; SHI Xu-bo; YANG Jin-gang; HU Da-yi

2009-01-01

Background Although low-molecular-weight heparin has replaced unfractionated heparin to become the primary anticoagulation drug for treatment of acute coronary syndrome, there is no convenient bedside monitoring method. We explored the best laboratory monitoring method of low-molecular-weight heparins (enoxapadn, dalteparin, and nadroparin) by use of the Sonoclot coagulation analyzer to monitor the activated clotting time.Methods Atotal of 20 healthy volunteers were selected and 15 ml of fasting venous blood samples were collected and incubated. Four coagulants, kaolin, diatomite, glass bead, and magnetic stick, were used to determine the activated clotting time of the low-molecular-weight heparins at different in vitro anti-Xa factor concentrations. A correlation analysis was made to obtain the regression equation. The activated clotting time of the different low-molecular-weight heparins with the same anti-Xa factor concentration was monitored when the coagulant glass beads were applied. Results The activated clotting time measured using the glass beads, diatomite, kaolin, and magnetic stick showed a linear correlation with the concentration of nadroparin (r= 0.964, 0.966, 0.970, and 0.947, respectively). The regression equation showed that the linear slopes of different coagulants were significantly different (glass beads 230.03 s/IU,diatomite 89.91 s/IU, kaolin 50.87 s/IU, magnetic stick could not be calculated). When the concentration of the anti-Xa factor was the same for different low-molecular-weight heparins, the measured activated clotting time was different after the application of the glass bead coagulant.Conclusions The glass bead coagulant is most feasible for monitoring the in vitro anticoagulation activity of nadroparin.The different effects of different low-molecular-weight heparins on the activated clotting time may be related to the different anti-Ila activities.

Analgesic effects of an ethanol extract of the fruits of Xylopia aethiopica (Dunal A. Rich (Annonaceae and the major constituent, xylopic acid in murine models

Directory of Open Access Journals (Sweden)

Eric Woode

2012-01-01

Full Text Available Background: Fruit extracts of Xylopia aethiopica are used traditionally in the management of pain disorders including rheumatism, headache, colic pain, and neuralgia. Little pharmacological data exists in scientific literature of the effect of the fruit extract and its major diterpene, xylopic acid, on pain. The present study evaluated the analgesic properties of the ethanol extract of X. aethiopica (XAE and xylopic acid (XA, in murine models. Materials and Methods: XAE and XA were assessed in chemical (acetic acid-induced abdominal writhing and formalin tests, thermal (Tail-flick and Hargreaves thermal hyperalgesia tests, and mechanical (Randall-Selitto paw pressure test pain models. Results: XAE and XA exhibited significant analgesic activity in all the pain models used. XAE (30-300 mg kg -1 , p.o. and XA (10-100 mg kg -1 , p.o. inhibited acetic acid-induced visceral nociception, formalin- induced paw pain (both neurogenic and inflammatory, thermal pain as well as carrageenan-induced mechanical and thermal hyperalgesia in animals. Morphine (1-10 mg kg -1 , i.p. and diclofenac (1-10 mg kg -1 , i.p., used as controls, exhibited similar anti-nociceptive activities. XAE and XA did not induce tolerance to their respective anti-nociceptive effects in the formalin test after chronic administration. Morphine tolerance did not also cross-generalize to the analgesic effects of XAE or XA. Conclusions: These findings establish the analgesic properties of the ethanol fruit extract of X. aethiopica and its major diterpene, xylopic acid.

The probability to initiate X chromosome inactivation is determined by the X to autosomal ratio and X chromosome specific allelic properties.

Directory of Open Access Journals (Sweden)

Kim Monkhorst

Full Text Available In female mammalian cells, random X chromosome inactivation (XCI equalizes the dosage of X-encoded gene products to that in male cells. XCI is a stochastic process, in which each X chromosome has a probability to be inactivated. To obtain more insight in the factors setting up this probability, we studied the role of the X to autosome (X ratio A ratio in initiation of XCI, and have used the experimental data in a computer simulation model to study the cellular population dynamics of XCI.To obtain more insight in the role of the XratioA ratio in initiation of XCI, we generated triploid mouse ES cells by fusion of haploid round spermatids with diploid female and male ES cells. These fusion experiments resulted in only XXY triploid ES cells. XYY and XXX ES lines were absent, suggesting cell death related either to insufficient X-chromosomal gene dosage (XYY or to inheritance of an epigenetically modified X chromosome (XXX. Analysis of active (Xa and inactive (Xi X chromosomes in the obtained triploid XXY lines indicated that the initiation frequency of XCI is low, resulting in a mixed population of XaXiY and XaXaY cells, in which the XaXiY cells have a small proliferative advantage. This result, and findings on XCI in diploid and tetraploid ES cell lines with different X ratio A ratios, provides evidence that the X ratio A ratio determines the probability for a given X chromosome to be inactivated. Furthermore, we found that the kinetics of the XCI process can be simulated using a probability for an X chromosome to be inactivated that is proportional to the X ratio A ratio. These simulation studies re-emphasize our hypothesis that the probability is a function of the concentration of an X-encoded activator of XCI, and of X chromosome specific allelic properties determining the threshold for this activator.The present findings reveal that the probability for an X chromosome to be inactivated is proportional to the X ratio A ratio. This finding

Laboratory Assessment of the Anticoagulant Activity of Direct Oral Anticoagulants: A Systematic Review.

Science.gov (United States)

Samuelson, Bethany T; Cuker, Adam; Siegal, Deborah M; Crowther, Mark; Garcia, David A

2017-01-01

Direct oral anticoagulants (DOACs) are the treatment of choice for most patients with atrial fibrillation and/or noncancer-associated venous thromboembolic disease. Although routine monitoring of these agents is not required, assessment of anticoagulant effect may be desirable in special situations. The objective of this review was to summarize systematically evidence regarding laboratory assessment of the anticoagulant effects of dabigatran, rivaroxaban, apixaban, and edoxaban. PubMed, Embase, and Web of Science were searched for studies reporting relationships between drug levels and coagulation assay results. We identified 109 eligible studies: 35 for dabigatran, 50 for rivaroxaban, 11 for apixaban, and 13 for edoxaban. The performance of standard anticoagulation tests varied across DOACs and reagents; most assays, showed insufficient correlation to provide a reliable assessment of DOAC effects. Dilute thrombin time (TT) assays demonstrated linear correlation (r 2  = 0.67-0.99) across a range of expected concentrations of dabigatran, as did ecarin-based assays. Calibrated anti-Xa assays demonstrated linear correlation (r 2  = 0.78-1.00) across a wide range of concentrations for rivaroxaban, apixaban, and edoxaban. An ideal test, offering both accuracy and precision for measurement of any DOAC is not widely available. We recommend a dilute TT or ecarin-based assay for assessment of the anticoagulant effect of dabigatran and anti-Xa assays with drug-specific calibrators for direct Xa inhibitors. In the absence of these tests, TT or APTT is recommended over PT/INR for assessment of dabigatran, and PT/INR is recommended over APTT for detection of factor Xa inhibitors. Time since last dose, the presence or absence of drug interactions, and renal and hepatic function should impact clinical estimates of anticoagulant effect in a patient for whom laboratory test results are not available. Copyright © 2016 American College of Chest Physicians. Published by Elsevier

Reversing the Effect of Oral Anticoagulant Drugs: Established and Newer Options.

Science.gov (United States)

Ansell, Jack E

2016-06-01

The vitamin K antagonists (VKAs) have been the standard (and only) oral anticoagulants used for the long-term treatment or prevention of venous thromboembolism or stroke in patients with atrial fibrillation. The coagulopathy induced by VKAs can be reversed with vitamin K, and in urgent situations, the vitamin K-dependent coagulation factors can be replaced by transfusion. In the last decade, a new class of oral anticoagulants has been developed, direct oral anticoagulants that bind to a specific coagulation factor and neutralize it. These compounds were shown to be effective and safe compared with the VKAs and were licensed for specific indications, but without a specific reversal agent. The absence of a reversal agent is a barrier to more widespread use of these agents. Currently, for the management of major life-threatening bleeding with the direct oral anticoagulants, most authorities recommend the use of four factor prothrombin complex concentrates. There are now three reversal agents in development and poised to enter the market. Idarucizumab is a specific antidote targeted to reverse the direct thrombin inhibitor, dabigatran, which was recently approved for use in the USA. Andexanet alfa is an antidote targeted to reverse the oral direct factor Xa inhibitors as well as the indirect inhibitor enoxaparin. Ciraparantag is an antidote targeted to reverse the direct thrombin and factor Xa inhibitors as well as the indirect inhibitor enoxaparin.

Comparative physical mapping of rice BAC clones linked to resistance genes Glh,Bph-3 and xa-5 in Oryza sativa L.and O.granulata Nees et Am.ex Watt.

Institute of Scientific and Technical Information of China (English)

XIONG Zhiyong; TAN Guangxuan; YOU Aiqing; HE Guangyuan; SHE Chaowen; LI Lijia; SONG Yunchun

2004-01-01

Oryza granulata Nees et Arn. ex Watt. is one of the three wild relatives of rice, which are the most valuable for study and utilization in China. In this study, the homology and physical locations of three rice resistance genes, Glh,Bph-3 and xa-5 are comparatively analyzed between O. sativa and O. granulata by Southern blotting and fluorescence in situ hybridization (FISH). The results of Southern blotting indicate that there exist homologous sequences of the tested RFLP markers in O. granulata. By using three bacterial artificial chromosome (BAC) clones scanned by the tested RFLP as probes, FISH signals are detected on both mitotic and pachytene chromosomes in O. sativa and O. granulata.Dual-color FISH demonstrates that two of the three BAC clones (14E16 and 38J9) are located on the short arm of the same chromosome pair in O. granulata. Additionally, colinearity is shown for the two clones between O. sativa and O.granulata. Another BAC clone 44B4 is located on the end of the short arm of other chromosome pair in these two species.Although the phylogenetic relationship between O. sativa and O. granulata is the most distinct in Oryza and these two species have evidently different biological features and ecological habits, the relative lengths and arm ratios of the detected chromosomes and the relative positions of the tested clone signals on chromosomes in O. granulata are quite similar to those in O. sativa.

Reversal Strategies for NOACs

DEFF Research Database (Denmark)

Husted, Steen; Verheugt, Freek; Comuth, Willemijn

2015-01-01

, coagulation factor concentrates or NOAC-specific antidotes could be used. Coagulation factor concentrates can be used in patients with haemophilia and to reverse the effect of VKAs but, in NOAC-treated patients, results are inconsistent and these agents could potentially have pro-thrombotic effects. Specific...... antidotes for NOACs are expected to be on the market soon. Phase III clinical trials with a humanized antibody fragment directed against dabigatran (idarucizumab) and recombinant, modified factor Xa (andexanet alfa) are ongoing. A molecule (aripazine) with broad activity against various anticoagulants...

fxa ax ax I = + + + ∈ and ) ab I - ∈ . ra I ( ) xf

African Journals Online (AJOL)

Dr. Ahmed

The famous basis theorem of David Hilbert is an important theorem in commutative algebra. In particular the Hilbert's basis theorem is the most important source of Noetherian rings which are by far the most important class of rings in commutative algebra. In this paper we have used Hilbert's theorem to examine their unique ...

Helium effects on tungsten surface morphology and deuterium retention

NARCIS (Netherlands)

Ueda, Y.; H. Y. Peng,; H. T. Lee,; N. Ohno,; S. Kajita,; Yoshida, N.; Doerner, R.; De Temmerman, G.; V. Alimov,; G. Wright,

2013-01-01

Recent experimental results on tungsten surface morphology, especially nano-structure (fuzz), induced by helium plasma exposure at temperatures between 1000&#xa0;K and 2000&#xa0;K are reviewed. This structure was firstly reported in 2006. In this review, most of experimental results reported

The impact of founder events on chromosomal variability in multiply mating species

DEFF Research Database (Denmark)

Pool, John E; Nielsen, Rasmus

2008-01-01

size reductions and recent bottlenecks leading to decreased X/A diversity ratios. Here we use theory and simulation to investigate a separate demographic effect-that of founder events involving multiply mated females-and find that it leads to much stronger reductions in X/A diversity ratios than...

Compression of digital images in radiology. Results of a consensus conference; Kompression digitaler Bilddaten in der Radiologie. Ergebnisse einer Konsensuskonferenz

Energy Technology Data Exchange (ETDEWEB)

Loose, R. [Klinikum Nuernberg-Nord (Germany). Inst. fuer Diagnostische und Interventionelle Radiologie; Braunschweig, R. [BG Kliniken Bergmannstrost, Halle/Saale (Germany). Klinik fuer Bildgebende Diagnostik und Interventionsradiologie; Kotter, E. [Universitaetsklinikum Freiburg (Germany). Abt. Roentgendiagnostik; Mildenberger, P. [Mainz Univ. (Germany). Klinik und Poliklinik fuer Diagnostische und Interventionelle Radiologie; Simmler, R.; Wucherer, M. [Klinikum Nuernberg (Germany). Inst. fuer Medizinische Physik

2009-01-15

Purpose: Recommendations for lossy compression of digital radiological DICOM images in Germany by means of a consensus conference. The compression of digital radiological images was evaluated in many studies. Even though the results demonstrate full diagnostic image quality of modality-dependent compression between 1:5 and 1:200, there are only a few clinical applications. Materials and Methods: A consensus conference with approx. 80 interested participants (radiology, industry, physics, and agencies) without individual invitation was organized by the working groups AGIT and APT of the German Roentgen Society DRG to determine compression factors without loss of diagnostic image quality for different anatomical regions for CT, CR/DR, MR, RF/XA examinations. The consent level was specified as at least 66 %. Results: For individual modalities the following compression factors were recommended: CT (brain) 1:5, CT (all other applications) 1:8, CR/DR (all applications except mammography) 1:10, CR/DR (mammography) 1:15, MR (all applications) 1:7, RF/XA (fluoroscopy, DSA, cardiac angio) 1:6. The recommended compression ratios are valid for JPEG and JPEG 2000 /Wavelet compressions. Conclusion: The results may be understood as recommendations and indicate limits of compression factors with no expected reduction of diagnostic image quality. They are similar to the current national recommendations for Canada and England. (orig.)

Simultaneous and Sequential Feature Negative Discriminations: Elemental Learning and Occasion Setting in Human Pavlovian Conditioning

Science.gov (United States)

Baeyens, Frank; Vervliet, Bram; Vansteenwegen, Debora; Beckers, Tom; Hermans, Dirk; Eelen, Paul

2004-01-01

Using a conditioned suppression task, we investigated simultaneous (XA-/A+) vs. sequential (X [right arrow] A-/A+) Feature Negative (FN) discrimination learning in humans. We expected the simultaneous discrimination to result in X (or alternatively the XA configuration) becoming an inhibitor acting directly on the US, and the sequential…

African Journal of Biotechnology - Vol 11, No 33 (2012)

African Journals Online (AJOL)

Introgression of bacterial blight (BB) resistance genes Xa7 and Xa21 into popular restorer line and their hybrids by molecular marker-assisted backcross (MABC) selection scheme ... Concentration of selected heavy metals in water of the Juru River, Penang, Malaysia · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT

Cavalieri Integration - CSIR Technical report

CSIR Research Space (South Africa)

Grobler, TL

2011-10-01

Full Text Available ] is called a translational function. Two examples of trans- lational functions are shown in Figure 4.A and Figure 4.B, and Figure 4.C presents an example of a linear function a(y) which is not translational with respect to f(x). y f(x) xa b a(y) A. y... f(x) xa b a(y) B. y f(x) xa b a(y) C. Figure 4. Examples of translational, and non-translational functions. De nition 3.2 (Cavalieri region R). Let R be any region (in R2) bounded by a nonnegative function f(x) (which is continuous...

Cavalieri integration

CSIR Research Space (South Africa)

Ackermann, ER

2012-09-01

Full Text Available ; b] is called a translational function. Two examples of translational functions are shown in Figure 4.A and Figure 4.B, and Figure 4.C presents an example of a linear function a(y) which is not translational with respect to f(x). y f(x) xa b a...(y) A. y f(x) xa b a(y) B. y f(x) xa b a(y) C. Figure 4: Examples of translational, and non-translational functions. De nition 3.2 (Cavalieri region R). Let R be any region (in R2) bounded by a nonnegative function f(x) (which is continuous...

Phosphatidylserine-exposing blood and endothelial cells contribute to the hypercoagulable state in essential thrombocythemia patients.

Science.gov (United States)

Tong, Dongxia; Yu, Muxin; Guo, Li; Li, Tao; Li, Jihe; Novakovic, Valerie A; Dong, Zengxiang; Tian, Ye; Kou, Junjie; Bi, Yayan; Wang, Jinghua; Zhou, Jin; Shi, Jialan

2018-04-01

The mechanisms of thrombogenicity in essential thrombocythemia (ET) are complex and not well defined. Our objective was to explore whether phosphatidylserine (PS) exposure on blood cells and endothelial cells (ECs) can account for the increased thrombosis and distinct thrombotic risks among mutational subtypes in ET. Using flow cytometry and confocal microscopy, we found that the levels of PS-exposing erythrocytes, platelets, leukocytes, and serum-cultured ECs were significantly higher in each ET group [JAK2, CALR, and triple-negative (TN) (all P cells and serum-cultured ECs led to markedly shortened coagulation time and dramatically increased levels of FXa, thrombin, and fibrin production. This procoagulant activity could be largely blocked by addition of lactadherin (approx. 70% inhibition). Confocal microscopy showed that the FVa/FXa complex and fibrin fibrils colocalized with PS on ET serum-cultured ECs. Additionally, we found a relationship between D-dimer, prothrombin fragment F1 + 2, and PS exposure. Our study reveals a previously unrecognized link between hypercoagulability and exposed PS on cells, which might also be associated with distinct thrombotic risks among mutational subtypes in ET. Thus, blocking PS-binding sites may represent a new therapeutic target for preventing thrombosis in ET.

Journal of Genetics | Indian Academy of Sciences

Indian Academy of Sciences (India)

... backcross derived line possessing Xa21 + Pi2 and another possessing Xa33 were intercrossed to stack the target resistance genes into the genetic background of RPHR-1005. At ICF4, 10 promising lines possessing three resistance genes in homozygous condition along with fine-grain type, complete fertility restoration, ...

Characterization of a disease susceptibility locus for exploring an efficient way to improve rice resistance against bacterial blight

Institute of Scientific and Technical Information of China (English)

Qi Cheng; Weihua Mao; Wenya Xie; Qinsong Liu; Jianbo Cao; Meng Yuan; Qinglu Zhang; Xianghua Li; Shiping Wang

2017-01-01

Bacterial blight caused by Xanthomonas oryzae pv.oryzae (Xoo) is the most harmful bacterial disease of rice worldwide.Previously,we characterized major disease resistance (MR) gene xa25,which confers race-specific resistance to Xoo strain PXO339.The xa25 is a recessive allele of the SWEET13 locus,but SWEET13's interaction with PXO339 and how efficiently using this locus for rice breeding still need to be defined.Here we show that the SWEET13 allele from rice Zhenshan 97 is a susceptibility gene to PXO339.Using this allele's promoter to regulate xa25 resulted in disease,suggesting that the promoter is a key determinant in SWEET13 caused disease in Zhanshan 97 after PXO339 infection.PXO339 transcriptionally induces SWEET13 to cause disease.Partial suppressing SWEET13 expression leads to a high level of resistance to PXO339.Thus,the transcriptionally suppressed SWEET13 functions as xa25 in resistance to PXO339.Hybrid rice is widely grown in many countries.However,recessive MR genes have not been efficiently used for disease resistance breeding in hybrid rice production for both parents of the hybrid have to carry the same recessive gene.However,the suppressed SWEET13 functions dominantly,which will have advantage to improve the resistance of hybrid rice to xa25-incomptible Xoo.

Rivaroxaban limits complement activation compared with warfarin in antiphospholipid syndrome patients with venous thromboembolism.

Science.gov (United States)

Arachchillage, D R J; Mackie, I J; Efthymiou, M; Chitolie, A; Hunt, B J; Isenberg, D A; Khamashta, M; Machin, S J; Cohen, H

2016-11-01

Essentials Complement activation has a pathogenic role in thrombotic antiphospholipid syndrome (APS). Coagulation proteases such as factor Xa can activate complement proteins. Complement activation markers were elevated in anticoagulated thrombotic APS patients. Complement activation decreased in APS patients switching from warfarin to rivaroxaban. Background Complement activation may play a major role in the pathogenesis of thrombotic antiphospholipid syndrome (APS). Coagulation proteases such as factor Xa can activate complement proteins. Aims To establish whether rivaroxaban, a direct factor Xa inhibitor, limits complement activation compared with warfarin in APS patients with previous venous thromboembolism (VTE). Methods A total of 111 APS patients with previous VTE, on warfarin target INR 2.5, had blood samples taken at baseline and at day 42 after randomization in the RAPS (Rivaroxaban in Antiphospholipid Syndrome) trial. Fifty-six patients remained on warfarin and 55 switched to rivaroxaban. Fifty-five normal controls (NC) were also studied. Markers of complement activation (C3a, C5a, terminal complement complex [SC5b-9] and Bb fragment) were assessed. Results APS patients had significantly higher complement activation markers compared with NC at both time-points irrespective of the anticoagulant. There were no differences between the two patient groups at baseline, or patients remaining on warfarin at day 42. In 55 patients randomized to rivaroxaban, C3a, C5a and SC5b-9 were lower at day 42 (median (ng mL -1 ) [confidence interval] 64 [29-125] vs. 83 [35-147], 9 [2-15] vs. 12 [4-18] and 171 [56-245] vs. 201 [66-350], respectively) but levels of Bb fragment were unchanged. There were no correlations between rivaroxaban levels and complement activation markers. Conclusions APS patients with previous VTE on warfarin exhibit increased complement activation, which is likely to occur via the classical pathway and is decreased by rivaroxaban administration

Inhibition of PAI-1 release from human endothelial cells by Angelica keiskei Koidzumi (Ashitaba chalcones is structure-dependent

Directory of Open Access Journals (Sweden)

Naoki Ohkura

2015-12-01

Full Text Available Angelica keiskei Koidzumi (Ashitaba is a traditional herbal medicine and it is also regarded in Japan as a health food that might have antithrombotic properties. Ashitaba exudate suppresses lipopolysaccharide (LPS-induced plasma plasminogen activator inhibitor 1 (PAI-1, a risk factor for thrombotic diseases in mice. Xanthoangelol (XA and 4-hydroxyderricin (4-HD comprise > 95% of total chalcones from Ashitaba exudates that also contain trace amounts of other chalcone subtypes. The present study aimed to determine the effects of Ashitaba chalcones including xanthoangelols B (XB, D (XD, E (XE, F (XF and XA as well as 4-HD on PAI-1 levels in the medium of stimulated human EA.hy926 endothelial cells. Xanthoangelol (10 and #61549;M inhibited PAI-1 production at a rate of 77.1%, whereas the inhibition rates of XB, XD, XE and 4-HD were not significant. Xanthoangelol F was highly cytotoxic and thus its ability to inhibit PAI-1 production could not be evaluated. The side hydrocarbon chain of XA played an important role in the excretion of inhibitory activity. Small modifications of the hydrocarbon chain or small functional groups on the A ring measurably influenced the inhibitory activity of xanthoangelols. These findings warrant future research towards an understanding of the mechanism of antithrombotic action of Ashitaba as herbal medicine or antithrombotic health food. [J Intercult Ethnopharmacol 2015; 4(4.000: 355-357

Monitoring of unfractionated heparin with rotational thrombelastometry using the prothrombinase-induced clotting time reagent (PiCT®).

Science.gov (United States)

Schaden, E; Jilch, S; Hacker, S; Schober, A; Kozek-Langenecker, S

2012-12-24

To achieve sufficient and safe anticoagulation with unfractionated heparin (UFH) a close and reliable drug monitoring is necessary. In general, the activated partial thromboplastin time (APTT) is used for this purpose. In acute phase response, however, the APTT test procedure might be unreliable e.g. with false low results in the presence of elevated factor VIII. In this so called heparin resistance, measurement of anti-Xa activity is recommended over APTT to avoid potentially harmful dose escalation. A combination of anti-Xa measurement and global hemostatic testing with ROTEM® employing the anti-Xa sensitive PiCT® reagent showed high correlation with enoxaparin levels. This test modification could also be suitable for monitoring UFH. Aim of the study was to evaluate the correlation between PiCT®-ROTEM® and levels of UFH. In this in-vitro study blood samples from healthy volunteers were spiked with UFH and subjected to different ROTEM® tests. There was a linear correlation between UFH level and clotting time (CT) in the PiCT®-ROTEM® test with an excellent correlation coefficient of 0.92. Additional endpoints showed similar results (PiCT®-ROTEM® MaxVel r = -0.85 and PiCT®-ROTEM® t_MaxVel r = 0.88). As a point-of-care applicable tool ROTEM® is immediately at hand. If further clinical studies confirm sensitivity in heparin resistance, PiCT®-ROTEM® could permit rapid UFH dose adjustments especially required in critical illness with acute phase response. Copyright © 2012 Elsevier B.V. All rights reserved.

An ultrasensitive electrochemical sensor for simultaneous determination of xanthine, hypoxanthine and uric acid based on Co doped CeO{sub 2} nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Lavanya, N. [Department of Bioelectronics and Biosensors, Alagappa University, Karaikudi 630003, Tamilnadu (India); Sekar, C., E-mail: Sekar2025@gmail.com [Department of Bioelectronics and Biosensors, Alagappa University, Karaikudi 630003, Tamilnadu (India); Murugan, R.; Ravi, G. [Department of Physics, Alagappa University, Karaikudi 630003, Tamilnadu (India)

2016-08-01

A novel electrochemical sensor has been fabricated using Co doped CeO{sub 2} nanoparticles for selective and simultaneous determination of xanthine (XA), hypoxanthine (HXA) and uric acid (UA) in a phosphate buffer solution (PBS, pH 5.0) for the first time. The Co-CeO{sub 2} NPs have been prepared by microwave irradiation method and characterized by Powder XRD, Raman spectroscopy, HRTEM and VSM measurements. The electrochemical behaviours of XA, HXA and UA at the Co-CeO{sub 2} NPs modified glassy carbon electrode (GCE) were studied by cyclic voltammetry and square wave voltammetry methods. The modified electrode exhibited remarkably well-separated anodic peaks corresponding to the oxidation of XA, HXA and UA over the concentration range of 0.1–1000, 1–600 and 1–2200 μM with detection limits of 0.096, 0.36, and 0.12 μM (S/N = 3), respectively. For simultaneous detection by synchronous change of the concentrations of XA, HXA and UA, the linear responses were in the range of 1–400 μM each with the detection limits of 0.47, 0.26, and 0.43 μM (S/N = 3), respectively. The fabricated sensor was further applied to the detection of XA, HXA and UA in human urine samples with good selectivity and high reproducibility. - Highlights: • A novel electrochemical sensor has been fabricated for simultaneous determination of purine metabolites xanthine, hypoxanthine, and uric acid based on Co doped CeO{sub 2} nanoparticles. • The Co-CeO{sub 2} modified glassy carbon electrode exhibited wide linear range towards the detection of XA, HXA and UA than ever reported in the literature. • The fabricated sensor was successfully applied for the analysis of human urine samples with satisfactory results.

Strategy Of Attrition: Why General Westmoreland Failed In 1967

Science.gov (United States)

2016-05-26

assault on South Vietnamese regulars at Xa Tan Hung resulted in...with forty-six wounded. To complicate the situation, civilian casualties continued to mass. During the attack at Xa Tan Hung, the Viet Cong wounded...Ronald H. Advice And Support: The Early. Years, 1941-1960. Washington, DC: Center of Military History,1985. Taleb, Nassim Nicholas . Antifragile: Things

The effect of a new direct Factor Xa inhibitor on human osteoblasts: an in-vitro study comparing the effect of rivaroxaban with enoxaparin

LENUS (Irish Health Repository)

Solayar, Gandhi N

2011-10-28

Abstract Background Current treatments for the prevention of thromboembolism include heparin and low-molecular weight heparins (LMWHs). A number of studies have suggested that long term administration of these drugs may adversely affect osteoblasts and therefore, bone metabolism. Xarelto™ (Rivaroxaban) is a new anti-thrombotic drug for the prevention of venous thromboembolism in adult patients undergoing elective hip and knee replacement surgery. The aim of this in vitro study was to investigate the possible effects of rivaroxaban on osteoblast viability, function and gene expression compared to enoxaparin, a commonly used LMWH. Methods Primary human osteoblast cultures were treated with varying concentrations of rivaroxaban (0.013, 0.13, 1.3 and 13 μg\\/ml) or enoxaparin (1, 10 and 100 μg\\/ml). The effect of each drug on osteoblast function was evaluated by measuring alkaline phosphatase activity. The MTS assay was used to assess the effect of drug treatments on cell proliferation. Changes in osteocalcin, Runx2 and BMP-2 messenger RNA (mRNA) expression following drug treatments were measured by real-time polymerase chain reaction (PCR). Results Rivaroxaban and enoxaparin treatment did not adversely affect osteoblast viability. However, both drugs caused a significant reduction in osteoblast function, as measured by alkaline phosphatase activity. This reduction in osteoblast function was associated with a reduction in the mRNA expression of the bone marker, osteocalcin, the transcription factor, Runx2, and the osteogenic factor, BMP-2. Conclusions These data show that rivaroxaban treatment may negatively affect bone through a reduction in osteoblast function.

The nonenzymatic subunit of pseutarin C, a prothrombin activator from eastern brown snake (Pseudonaja textilis) venom, shows structural similarity to mammalian coagulation factor V.

Science.gov (United States)

Rao, Veena S; Swarup, Sanjay; Kini, R Manjunatha

2003-08-15

Pseutarin C is a group C prothrombin activator from the venom of the eastern brown snake Pseudonaja textilis. It is a multi-subunit protein complex consisting of catalytic and nonenzymatic subunits similar to coagulation factor Xa and factor Va, respectively. Here we describe the complete sequence of the nonenzymatic subunit. Based on the partial amino acid sequence of the nonenzymatic subunit, degenerate primers were designed. Using a "walking" strategy based on sequentially designed primers, we determined the complete cDNA sequence of the nonenzymatic subunit. The cDNA encodes a protein of 1461 amino acid residues, which includes a 30-residue signal peptide, a mature protein of 1430 amino acid residues, and a stop codon. cDNA blot analysis showed a single transcript of approximately 4.6 kb. The deduced amino acid sequence shows approximately 50% identity to mammalian factor V and by homology has a similar domain structure consisting of domains A1-A2-B-A3-C1-C2. Interestingly, the B domain of pseutarin C is shorter than that of mammalian factor V (FV). Although most of the proteolytic activation sites are conserved, 2 of 3 proteolytic sites cleaved by activated protein C are mutated, and thus activated protein C is not able to inactivate this procoagulant toxin. The predicted posttranslational modifications, including disulfide bonds, N-glycosylation, phosphorylation, and sulfation, in pseutarin C are significantly different compared with bovine factor V. Thus, our data demonstrate that the nonenzymatic subunit of group C prothrombin activators is structurally similar to mammalian FV.

Abscisic acid, xanthoxin and violaxanthin in the caps of gravistimulated maize roots

Science.gov (United States)

Feldman, L. J.; Arroyave, N. J.; Sun, P. S.

1985-01-01

The occurrence and distribution of abscisic acid (ABA), xanthoxin (Xa) and the carotenoid violaxanthin (Va) were investigated in root tips of maize (Zea mays L. cv. Merit). In roots grown in the dark, Va and ABA were present in relatively high amounts in the root cap and in low amounts in the adjacent terminal 1.5 mm of the root. Xanthoxin was present in equal concentrations in both regions. In roots exposed to light, the ABA distribution was reversed, with relatively low levels in the root cap and high levels in the adjacent 1.5-mm segment. Light also caused a decrease in Va in both regions of the root and an increase in Xa, especially in the cap. In the maize cultivar used for this work, light is necessary for gravitropic curving. This response occurs within the same time frame as the light-induced ABA redistribution as well as the changes in the levels of Va and Xa. These data are consistent with a role for ABA in root gravitropism and support the proposal that Xa may arise from the turnover of Va.

Simulating Ru L ₃ -Edge X-ray Absorption Spectroscopy with Time-Dependent Density Functional Theory: Model Complexes and Electron Localization in Mixed-Valence Metal Dimers

Energy Technology Data Exchange (ETDEWEB)

Van Kuiken, Benjamin E.; Valiev, Marat; Daifuku, Stephanie L.; Bannan, Caitlin; Strader, Matthew L.; Cho, Hana; Huse, Nils; Schoenlein, Robert W.; Govind, Niranjan; Khalil, Munira

2013-05-30

Ruthenium L3-edge X-ray absorption (XA) spectroscopy probes unoccupied 4d orbitals of the metal atom and is increasingly being used to investigate the local electronic structure in ground and excited electronic states of Ru complexes. The simultaneous development of computational tools for simulating Ru L3-edge spectra is crucial for interpreting the spectral features at a molecular level. This study demonstrates that time-dependent density functional theory (TDDFT) is a viable and predictive tool for simulating ruthenium L3-edge XA spectroscopy. We systematically investigate the effects of exchange correlation functional and implicit and explicit solvent interactions on a series of RuII and RuIII complexes in their ground and electronic excited states. The TDDFT simulations reproduce all of the experimentally observed features in Ru L3-edge XA spectra within the experimental resolution (0.4 eV). Our simulations identify ligand-specific charge transfer features in complicated Ru L3-edge spectra of [Ru(CN)6]4- and RuII polypyridyl complexes illustrating the advantage of using TDDFT in complex systems. We conclude that the B3LYP functional most accurately predicts the transition energies of charge transfer features in these systems. We use our TDDFT approach to simulate experimental Ru L3-edge XA spectra of transition metal mixed-valence dimers of the form [(NC)5MII-CN-RuIII(NH3)5] (where M = Fe or Ru) dissolved in water. Our study determines the spectral signatures of electron delocalization in Ru L3-edge XA spectra. We find that the inclusion of explicit solvent molecules is necessary for reproducing the spectral features and the experimentally determined valencies in these mixed-valence complexes. This study validates the use of TDDFT for simulating Ru 2p excitations using popular quantum chemistry codes and providing a powerful interpretive tool for equilibrium and ultrafast Ru L3-edge XA spectroscopy.

Transcriptomic Analysis and the Expression of Disease-Resistant Genes in Oryza meyeriana under Native Condition.

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Bin He

Full Text Available Oryza meyeriana (O. meyeriana, with a GG genome type (2n = 24, accumulated plentiful excellent characteristics with respect to resistance to many diseases such as rice shade and blast, even immunity to bacterial blight. It is very important to know if the diseases-resistant genes exist and express in this wild rice under native conditions. However, limited genomic or transcriptomic data of O. meyeriana are currently available. In this study, we present the first comprehensive characterization of the O. meyeriana transcriptome using RNA-seq and obtained 185,323 contigs with an average length of 1,692 bp and an N50 of 2,391 bp. Through differential expression analysis, it was found that there were most tissue-specifically expressed genes in roots, and next to stems and leaves. By similarity search against protein databases, 146,450 had at least a significant alignment to existed gene models. Comparison with the Oryza sativa (japonica-type Nipponbare and indica-type 93-11 genomes revealed that 13% of the O. meyeriana contigs had not been detected in O. sativa. Many diseases-resistant genes, such as bacterial blight resistant, blast resistant, rust resistant, fusarium resistant, cyst nematode resistant and downy mildew gene, were mined from the transcriptomic database. There are two kinds of rice bacterial blight-resistant genes (Xa1 and Xa26 differentially or specifically expressed in O. meyeriana. The 4 Xa1 contigs were all only expressed in root, while three of Xa26 contigs have the highest expression level in leaves, two of Xa26 contigs have the highest expression profile in stems and one of Xa26 contigs was expressed dominantly in roots. The transcriptomic database of O. meyeriana has been constructed and many diseases-resistant genes were found to express under native condition, which provides a foundation for future discovery of a number of novel genes and provides a basis for studying the molecular mechanisms associated with disease

Simulating Ru L3-edge X-ray absorption spectroscopy with time-dependent density functional theory: model complexes and electron localization in mixed-valence metal dimers.

Science.gov (United States)

Van Kuiken, Benjamin E; Valiev, Marat; Daifuku, Stephanie L; Bannan, Caitlin; Strader, Matthew L; Cho, Hana; Huse, Nils; Schoenlein, Robert W; Govind, Niranjan; Khalil, Munira

2013-05-30

Ruthenium L3-edge X-ray absorption (XA) spectroscopy probes unoccupied 4d orbitals of the metal atom and is increasingly being used to investigate the local electronic structure in ground and excited electronic states of Ru complexes. The simultaneous development of computational tools for simulating Ru L3-edge spectra is crucial for interpreting the spectral features at a molecular level. This study demonstrates that time-dependent density functional theory (TDDFT) is a viable and predictive tool for simulating ruthenium L3-edge XA spectroscopy. We systematically investigate the effects of exchange correlation functional and implicit and explicit solvent interactions on a series of Ru(II) and Ru(III) complexes in their ground and electronic excited states. The TDDFT simulations reproduce all of the experimentally observed features in Ru L3-edge XA spectra within the experimental resolution (0.4 eV). Our simulations identify ligand-specific charge transfer features in complicated Ru L3-edge spectra of [Ru(CN)6](4-) and Ru(II) polypyridyl complexes illustrating the advantage of using TDDFT in complex systems. We conclude that the B3LYP functional most accurately predicts the transition energies of charge transfer features in these systems. We use our TDDFT approach to simulate experimental Ru L3-edge XA spectra of transition metal mixed-valence dimers of the form [(NC)5M(II)-CN-Ru(III)(NH3)5](-) (where M = Fe or Ru) dissolved in water. Our study determines the spectral signatures of electron delocalization in Ru L3-edge XA spectra. We find that the inclusion of explicit solvent molecules is necessary for reproducing the spectral features and the experimentally determined valencies in these mixed-valence complexes. This study validates the use of TDDFT for simulating Ru 2p excitations using popular quantum chemistry codes and providing a powerful interpretive tool for equilibrium and ultrafast Ru L3-edge XA spectroscopy.

SIRT1 genetic variants associate with the metabolic response of Caucasians to a controlled lifestyle intervention – the TULIP Study

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Stefan Norbert

2008-11-01

Full Text Available Abstract Background Sirtuin1 (SIRT1 regulates gene expression in distinct metabolic pathways and mediates beneficial effects of caloric restriction in animal models. In humans, SIRT1 genetic variants associate with fasting energy expenditure. To investigate the relevance of SIRT1 for human metabolism and caloric restriction, we analyzed SIRT1 genetic variants in respect to the outcome of a controlled lifestyle intervention in Caucasians at risk for type 2 diabetes. Methods A total of 1013 non-diabetic Caucasians from the Tuebingen Family Study (TUEF were genotyped for four tagging SIRT1 SNPs (rs730821, rs12413112, rs7069102, rs2273773 for cross-sectional association analyses with prediabetic traits. SNPs that associated with basal energy expenditure in the TUEF cohort were additionally analyzed in 196 individuals who underwent a controlled lifestyle intervention (Tuebingen Lifestyle Intervention Program; TULIP. Multivariate regressions analyses with adjustment for relevant covariates were performed to detect associations of SIRT1 variants with the changes in anthropometrics, weight, body fat or metabolic characteristics (blood glucose, insulin sensitivity, insulin secretion and liver fat, measured by magnetic resonance techniques after the 9-month follow-up test in the TULIP study. Results Minor allele (X/A carriers of rs12413112 (G/A had a significantly lower basal energy expenditure (p = 0.04 and an increased respiratory quotient (p = 0.02. This group (rs12413112: X/A was resistant against lifestyle-induced improvement of fasting plasma glucose (GG: -2.01%, X/A: 0.53%; p = 0.04, had less increase in insulin sensitivity (GG: 17.3%, X/A: 9.6%; p = 0.05 and an attenuated decline in liver fat (GG: -38.4%, X/A: -7.5%; p = 0.01. Conclusion SIRT1 plays a role for the individual lifestyle intervention response, possibly owing to decreased basal energy expenditure and a lower lipid-oxidation rate in rs12413112 X/A allele carriers. SIRT1 genetic

Use of membrane technology and resins for the separation and purification of polyphenols purple tree tomato (Solanum betaceum Cav

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Elena Beltrán

2016-12-01

Full Text Available The polyphenols fractionation of mesocarp juices, placenta and purple tree tomato peel using the pore size of the membrane as a means of selection was performed using micro and ultrafiltration tangential; tests made with HPLC showed that fractionation of phenolic compounds was not performed. The processes of concentration of the clarified juices of placenta and tree tomato peel by reverse osmosis obtained a volumetric concentration factor of 2 and 2.2 respectively. The polyphenol concentration increased by 1.5 times for placenta and 2.4 times for peel and antioxidant capacity increased by 2.4 times for both juices. The anthocyanins of placenta increased by 2.6 times. The use of the resin XA 5071 FG concentrated phenolic compounds with an increase of antioxidant capacity in a range between 4 and 5.5, and anthocyanins concentration was increased 1.8 times in the placenta juice. In conclusion the process of polyphenols concentration of tree tomato was more efficient using the resin XA 5071 FG than the reverse osmosis applied in this research.

Estimating Crustal Properties Directly from Satellite Tracking Data by Using a Topography-based Constraint

Science.gov (United States)

Goossens, S. J.; Sabaka, T. J.; Genova, A.; Mazarico, E. M.; Nicholas, J. B.; Neumann, G. A.; Lemoine, F. G.

2017-12-01

The crust of a terrestrial planet is formed by differentiation processes in its early history, followed by magmatic evolution of the planetary surface. It is further modified through impact processes. Knowledge of the crustal structure can thus place constraints on the planet's formation and evolution. In particular, the average bulk density of the crust is a fundamental parameter in geophysical studies, such as the determination of crustal thickness, studies of the mechanisms of topography support, and the planet's thermo-chemical evolution. Yet even with in-situ samples available, the crustal density is difficult to determine unambiguously, as exemplified by the results for the Gravity and Recovery Interior Laboratory (GRAIL) mission, which found an average crustal density for the Moon that was lower than generally assumed. The GRAIL results were possible owing to the combination of its high-resolution gravity and high-resolution topography obtained by the Lunar Orbiter Laser Altimeter (LOLA) onboard the Lunar Reconnaissance Orbiter (LRO), and high correlations between the two datasets. The crustal density can be determined by its contribution to the gravity field of a planet, but at long wavelengths flexure effects can dominate. On the other hand, short-wavelength gravity anomalies are difficult to measure, and either not determined well enough (other than at the Moon), or their power is suppressed by the standard `Kaula' regularization constraint applied during inversion of the gravity field from satellite tracking data. We introduce a new constraint that has infinite variance in one direction, called xa . For constraint damping factors that go to infinity, it can be shown that the solution x becomes equal to a scale factor times xa. This scale factor is completely determined by the data, and we call our constraint rank-minus-1 (RM1). If we choose xa to be topography-induced gravity, then we can estimate the average bulk crustal density directly from the data

Allosteric Inhibition of Factor XIIIa. Non-Saccharide Glycosaminoglycan Mimetics, but Not Glycosaminoglycans, Exhibit Promising Inhibition Profile.

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Rami A Al-Horani

Full Text Available Factor XIIIa (FXIIIa is a transglutaminase that catalyzes the last step in the coagulation process. Orthostery is the only approach that has been exploited to design FXIIIa inhibitors. Yet, allosteric inhibition of FXIIIa is a paradigm that may offer a key advantage of controlled inhibition over orthosteric inhibition. Such an approach is likely to lead to novel FXIIIa inhibitors that do not carry bleeding risks. We reasoned that targeting a collection of basic amino acid residues distant from FXIIIa's active site by using sulfated glycosaminoglycans (GAGs or non-saccharide GAG mimetics (NSGMs would lead to the discovery of the first allosteric FXIIIa inhibitors. We tested a library of 22 variably sulfated GAGs and NSGMs against human FXIIIa to discover promising hits. Interestingly, although some GAGs bound to FXIIIa better than NSGMs, no GAG displayed any inhibition. An undecasulfated quercetin analog was found to inhibit FXIIIa with reasonable potency (efficacy of 98%. Michaelis-Menten kinetic studies revealed an allosteric mechanism of inhibition. Fluorescence studies confirmed close correspondence between binding affinity and inhibition potency, as expected for an allosteric process. The inhibitor was reversible and at least 9-fold- and 26-fold selective over two GAG-binding proteins factor Xa (efficacy of 71% and thrombin, respectively, and at least 27-fold selective over a cysteine protease papain. The inhibitor also inhibited the FXIIIa-mediated polymerization of fibrin in vitro. Overall, our work presents the proof-of-principle that FXIIIa can be allosterically modulated by sulfated non-saccharide agents much smaller than GAGs, which should enable the design of selective and safe anticoagulants.

Searching Online Chemical Data Repositories via the ChemAgora Portal.

Science.gov (United States)

Zanzi, Antonella; Wittwehr, Clemens

2017-12-26

ChemAgora, a web application designed and developed in the context of the "Data Infrastructure for Chemical Safety Assessment" (diXa) project, provides search capabilities to chemical data from resources available online, enabling users to cross-reference their search results with both regulatory chemical information and public chemical databases. ChemAgora, through an on-the-fly search, informs whether a chemical is known or not in each of the external data sources and provides clikable links leading to the third-party web site pages containing the information. The original purpose of the ChemAgora application was to correlate studies stored in the diXa data warehouse with available chemical data. Since the end of the diXa project, ChemAgora has evolved into an independent portal, currently accessible directly through the ChemAgora home page, with improved search capabilities of online data sources.

[Atrial fibrillation in elderly].

Science.gov (United States)

Arquizan, Caroline

2012-11-01

Atrial fibrilation (AF) is frequent and a strong risk factor for ischemic stroke in elderly. Ischemic stroke in patients with AF are more severe. Vitamine K antagonist therapy is highly effective for stroke prevention but is associated with hemorrhagic risk. The new oral anticoagulants (direct thrombin inhibitor [dabigatran], and direct factor Xa inhibitors [rivaroxaban and apixaban]) have all shown non inferiority or superiority, with better safety, considering the risk of intracranial haemorrhage. On this basis, it is justified to give them in priority in the vast majority of patients with AF, the choice of the drug and the dose is individual.

Disadvantages of VKA and requirements for novel anticoagulants.

Science.gov (United States)

Shameem, Raji; Ansell, Jack

2013-06-01

Vitamin K antagonists have been in wide use for over 70 years. Warfarin, the most commonly used vitamin K antagonist, has been shown to be highly effective in treating and preventing thrombosis. Despite this, warfarin has many disadvantages, which has led to the development of a new class of oral anticoagulants targeted to specific coagulation factors designated as target-specific oral anticoagulants (TSOAs). TSOAs include the thrombin inhibitors (dabigatran) and factor Xa inhibitors (rivaroxaban, apixaban). This chapter reviews the disadvantages of warfarin and evaluates both the advantages and disadvantages of the new oral anticoagulants. © 2013 Elsevier Ltd. All rights reserved.

Histones Differentially Modulate the Anticoagulant and Profibrinolytic Activities of Heparin, Heparin Derivatives, and Dabigatran.

Science.gov (United States)

Ammollo, Concetta Tiziana; Semeraro, Nicola; Carratù, Maria Rosaria; Colucci, Mario; Semeraro, Fabrizio

2016-02-01

The antithrombin activity of unfractionated heparin (UFH) is offset by extracellular histones, which, along with DNA, represent a novel mediator of thrombosis and a structural component of thrombi. Here, we systematically evaluated the effect of histones, DNA, and histone-DNA complexes on the anticoagulant and profibrinolytic activities of UFH, its derivatives enoxaparin and fondaparinux, and the direct thrombin inhibitor dabigatran. Thrombin generation was assessed by calibrated automated thrombinography, inhibition of factor Xa and thrombin by synthetic substrates, tissue plasminogen activator-mediated clot lysis by turbidimetry, and thrombin-activatable fibrinolysis inhibitor (TAFI) activation by a functional assay. Histones alone delayed coagulation and slightly stimulated fibrinolysis. The anticoagulant activity of UFH and enoxaparin was markedly inhibited by histones, whereas that of fondaparinux was enhanced. Histones neutralized both the anti-Xa and anti-IIa activities of UFH and preferentially blocked the anti-IIa activity of enoxaparin. The anti-Xa activity of fondaparinux was not influenced by histones when analyzed by chromogenic substrates, but was potentiated in a plasma prothrombinase assay. Histones inhibited the profibrinolytic activity of UFH and enoxaparin and enhanced that of fondaparinux by acting on the modulation of TAFI activation by anticoagulants. Histone H1 was mainly responsible for these effects. Histone-DNA complexes, as well as intact neutrophil extracellular traps, impaired the activities of UFH, enoxaparin, and fondaparinux. Dabigatran was not noticeably affected by histones and/or DNA, whatever the assay performed. In conclusion, histones and DNA present in the forming clot may variably influence the antithrombotic activities of anticoagulants, suggesting a potential therapeutic advantage of dabigatran and fondaparinux over heparins. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Chronic kidney disease and anticoagulation

DEFF Research Database (Denmark)

Sciascia, Savino; Radin, Massimo; Schreiber, Karen

2017-01-01

Anticoagulation in patients with impaired kidney function can be challenging since drugs' pharmacokinetics and bioavailability are altered in this setting. Patients with chronic kidney disease (CKD) treated with conventional anticoagulant agents [vitamin K antagonist (VKA), low-molecular weight...... are eliminated via the kidneys pose additional challenges. More recently, two classes of direct oral anticoagulant agents (DOACs) have been investigated for the prevention and management of venous thromboembolic events: the direct factor Xa inhibitors rivaroxaban, apixaban and edoxaban, and the direct thrombin...

Incorporation of Bacterial Blight Resistance Genes Into Lowland Rice Cultivar Through Marker-Assisted Backcross Breeding.

Science.gov (United States)

Pradhan, Sharat Kumar; Nayak, Deepak Kumar; Pandit, Elssa; Behera, Lambodar; Anandan, Annamalai; Mukherjee, Arup Kumar; Lenka, Srikanta; Barik, Durga Prasad

2016-07-01

Bacterial blight (BB) of rice caused by Xanthomonas oryzae pv. oryzae is a major disease of rice in many rice growing countries. Pyramided lines carrying two BB resistance gene combinations (Xa21+xa13 and Xa21+xa5) were developed in a lowland cultivar Jalmagna background through backcross breeding by integrating molecular markers. In each backcross generation, markers closely linked to the disease resistance genes were used to select plants possessing the target genes. Background selection was continued in those plants carrying resistant genes until BC(3) generation. Plants having the maximum contribution from the recurrent parent genome were selected in each generation and hybridized with the recipient parent. The BB-pyramided line having the maximum recipient parent genome recovery of 95% was selected among BC3F1 plants and selfed to isolate homozygous BC(3)F(2) plants with different combinations of BB resistance genes. Twenty pyramided lines with two resistance gene combinations exhibited high levels of tolerance against the BB pathogen. In order to confirm the resistance, the pyramided lines were inoculated with different X. oryzae pv. oryzae strains of Odisha for bioassay. The genotypes with combination of two BB resistance genes conferred high levels of resistance to the predominant X. oryzae pv. oryzae isolates prevalent in the region. The pyramided lines showed similarity with the recipient parent with respect to major agro-morphologic traits.

Normal Female Germ Cell Differentiation Requires the Female X Chromosome to Autosome Ratio and Expression of Sex-Lethal in DROSOPHILA MELANOGASTER

OpenAIRE

Schüpbach, Trudi

1985-01-01

In somatic cells of Drosophila, the ratio of X chromosomes to autosomes (X:A ratio) determines sex and dosage compensation. The present paper addresses the question of whether germ cells also use the X:A ratio for sex determination and dosage compensation. Triploid female embryos were generated which, through the loss of an unstable ring-X chromosome, contained some germ cells of 2X;3A constitution in their ovaries. Such germ cells were shown to differentiate along one of two alternative pat...

A review of antithrombotic therapy and the rationale and design of the randomized edoxaban in patients with peripheral artery disease (ePAD) trial adding edoxaban or clopidogrel to aspirin after femoropopliteal endovascular intervention.

Science.gov (United States)

Tangelder, Marco J D; Nwachuku, Chuke E; Jaff, Michael; Baumgartner, Iris; Duggal, Anil; Adams, George; Ansel, Gary; Grosso, Michael; Mercuri, Michele; Shi, Minggao; Minar, Erich; Moll, Frans L

2015-04-01

Compared with the coronary setting, knowledge about antithrombotic therapies after endovascular treatment (EVT) is inadequate in patients with peripheral artery disease (PAD). Based on a review of trials and guidelines, which is summarized in this article, there is scant evidence that antithrombotic drugs improve outcome after peripheral EVT. To address this knowledge gap, the randomized, open-label, multinational edoxaban in patients with Peripheral Artery Disease (ePAD) study (ClinicalTrials.gov identifier NCT01802775) was designed to explore the safety and efficacy of a combined regimen of antiplatelet therapy with clopidogrel and anticoagulation with edoxaban, a selective and direct factor Xa inhibitor, both combined with aspirin. As of July 2014, 203 patients (144 men; mean age 67 years) from 7 countries have been enrolled. These patients have been allocated to once-daily edoxaban [60 mg for 3 months (or 30 mg in the presence of factors associated with increased exposure)] or clopidogrel (75 mg/d for 3 months). All patients received aspirin (100 mg/d) for the 6-month duration of the study. The primary safety endpoint is major or clinically relevant nonmajor bleeding; the primary efficacy endpoint is restenosis or reocclusion at the treated segment(s) measured at 1, 3, and 6 months using duplex ultrasound scanning. All outcomes will be assessed and adjudicated centrally in a masked fashion. The ePAD study is the first of its kind to investigate a combined regimen of antiplatelet therapy and anticoagulation through factor Xa inhibition with edoxaban. © The Author(s) 2015.

Evaluation of the efficacy and safety of rivaroxaban using a computer model for blood coagulation.

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Rolf Burghaus

Full Text Available Rivaroxaban is an oral, direct Factor Xa inhibitor approved in the European Union and several other countries for the prevention of venous thromboembolism in adult patients undergoing elective hip or knee replacement surgery and is in advanced clinical development for the treatment of thromboembolic disorders. Its mechanism of action is antithrombin independent and differs from that of other anticoagulants, such as warfarin (a vitamin K antagonist, enoxaparin (an indirect thrombin/Factor Xa inhibitor and dabigatran (a direct thrombin inhibitor. A blood coagulation computer model has been developed, based on several published models and preclinical and clinical data. Unlike previous models, the current model takes into account both the intrinsic and extrinsic pathways of the coagulation cascade, and possesses some unique features, including a blood flow component and a portfolio of drug action mechanisms. This study aimed to use the model to compare the mechanism of action of rivaroxaban with that of warfarin, and to evaluate the efficacy and safety of different rivaroxaban doses with other anticoagulants included in the model. Rather than reproducing known standard clinical measurements, such as the prothrombin time and activated partial thromboplastin time clotting tests, the anticoagulant benchmarking was based on a simulation of physiologically plausible clotting scenarios. Compared with warfarin, rivaroxaban showed a favourable sensitivity for tissue factor concentration inducing clotting, and a steep concentration-effect relationship, rapidly flattening towards higher inhibitor concentrations, both suggesting a broad therapeutic window. The predicted dosing window is highly accordant with the final dose recommendation based upon extensive clinical studies.

The Xanthomonas Ax21 protein is processed by the general secretory system and is secreted in association with outer membrane vesicles

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Ofir Bahar

2014-01-01

Full Text Available Pattern recognition receptors (PRRs play an important role in detecting invading pathogens and mounting a robust defense response to restrict infection. In rice, one of the best characterized PRRs is XA21, a leucine rich repeat receptor-like kinase that confers broad-spectrum resistance to multiple strains of the bacterial pathogen Xanthomonas oryzae pv. oryzae (Xoo. In 2009 we reported that an Xoo protein, called Ax21, is secreted by a type I-secretion system and that it serves to activate XA21-mediated immunity. This report has recently been retracted. Here we present data that corrects our previous model. We first show that Ax21 secretion does not depend on the predicted type I secretion system and that it is processed by the general secretion (Sec system. We further show that Ax21 is an outer membrane protein, secreted in association with outer membrane vesicles. Finally, we provide data showing that ax21 knockout strains do not overcome XA21-mediated immunity.

The pro-coagulant fibrinogenolytic serine protease isoenzymes purified from Daboia russelii russelii venom coagulate the blood through factor V activation: role of glycosylation on enzymatic activity.

Directory of Open Access Journals (Sweden)

Ashis K Mukherjee

Full Text Available Proteases from Russell's viper venom (RVV induce a variety of toxic effects in victim. Therefore, four new RVV protease isoenzymes of molecular mass 32901.044 Da, 333631.179 Da, 333571.472 Da, and 34594.776 Da, were characterized in this study. The first 10 N-terminal residues of these serine protease isoenzymes showed significant sequence homology with N-terminal sequences of snake venom thrombin-like and factor V-activating serine proteases, which was reconfirmed by peptide mass fingerprinting analysis. These proteases were found to be different from previously reported factor V activators isolated from snake venoms. These proteases showed significantly different fibrinogenolytic, BAEE-esterase and plasma clotting activities but no fibrinolytic, TAME-esterase or amidolytic activity against the chromogenic substrate for trypsin, thrombin, plasmin and factor Xa. Their Km and Vmax values towards fibrinogen were determined in the range of 6.6 to 10.5 µM and 111.0 to 125.5 units/mg protein, respectively. On the basis of fibrinogen degradation pattern, they may be classified as A/B serine proteases isolated from snake venom. These proteases contain ∼ 42% to 44% of N-linked carbohydrates by mass whereas partially deglycosylated enzymes showed significantly less catalytic activity as compared to native enzymes. In vitro these protease isoenzymes induce blood coagulation through factor V activation, whereas in vivo they provoke dose-dependent defibrinogenation and anticoagulant activity in the mouse model. At a dose of 5 mg/kg, none of these protease isoenzymes were found to be lethal in mice or house geckos, suggesting therapeutic application of these anticoagulant peptides for the prevention of thrombosis.

Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial

DEFF Research Database (Denmark)

Lassen, Michael Rud; Raskob, Gary E; Gallus, Alexander

2010-01-01

efficacy and safety of these drugs after elective total knee replacement. METHODS: In ADVANCE-2, a multicentre, randomised, double-blind phase 3 study, patients undergoing elective unilateral or bilateral total knee replacement were randomly allocated through an interactive central telephone system......BACKGROUND: Low-molecular-weight heparins such as enoxaparin are preferred for prevention of venous thromboembolism after major joint replacement. Apixaban, an orally active factor Xa inhibitor, might be as effective, have lower bleeding risk, and be easier to use than is enoxaparin. We assessed...

New Functional Tools for Antithrombogenic Activity Assessment of Live Surface Glycocalyx.

Science.gov (United States)

Dimitrievska, Sashka; Gui, Liqiong; Weyers, Amanda; Lin, Tylee; Cai, Chao; Wu, Wei; Tuggle, Charles T; Sundaram, Sumati; Balestrini, Jenna L; Slattery, David; Tchouta, Lise; Kyriakides, Themis R; Tarbell, John M; Linhardt, Robert J; Niklason, Laura E

2016-09-01

It is widely accepted that the presence of a glycosaminoglycan-rich glycocalyx is essential for endothelialized vasculature health; in fact, a damaged or impaired glycocalyx has been demonstrated in many vascular diseases. Currently, there are no methods that characterize glycocalyx functionality, thus limiting investigators' ability to assess the role of the glycocalyx in vascular health. We have developed novel, easy-to-use, in vitro assays that directly quantify live endothelialized surface's functional heparin weights and their anticoagulant capacity to inactivate Factor Xa and thrombin. Using our assays, we characterized 2 commonly used vascular models: native rat aorta and cultured human umbilical vein endothelial cell monolayer. We determined heparin contents to be ≈10 000 ng/cm(2) on the native aorta and ≈10-fold lower on cultured human umbilical vein endothelial cells. Interestingly, human umbilical vein endothelial cells demonstrated a 5-fold lower anticoagulation capacity in inactivating both Factor Xa and thrombin relative to native aortas. We verified the validity and accuracy of the novel assays developed in this work using liquid chromatography-mass spectrometry analysis. Our assays are of high relevance in the vascular community because they can be used to establish the antithrombogenic capacity of many different types of surfaces such as vascular grafts and transplants. This work will also advance the capacity for glycocalyx-targeting therapeutics development to treat damaged vasculatures. © 2016 American Heart Association, Inc.

Ultrahigh-efficiency apodized grating coupler using fully etched photonic crystals

DEFF Research Database (Denmark)

Ding, Yunhong; Ou, Haiyan; Peucheret, Christophe

2013-01-01

We present an efficient method to design apodized grating couplers with Gaussian output profiles for efficient coupling between standard single mode fibers and silicon chips. An apodized grating coupler using fully etched photonic crystal holes on the silicon-on-insulator platform is designed......, and fabricated in a single step of lithography and etching. An ultralow coupling loss of x2212;1.74x2009;x2009;dB (67% coupling efficiency) with a 3xA0;dB bandwidth of 60xA0;nm is experimentally measured....

Case report

African Journals Online (AJOL)

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21 sept. 2017 ... XA avait aux deux yeux, une AV à 8/10 et XB, une AV de 3/10 améliorée au trou sténopéïque à 7/10 en faveur d'une amétropie. XA présentait un ptosis bilatéral qui remontait à l'âge de 2 ans avec une action du releveur de la paupière supérieure (RPS) à 7 mm et XB, un ptosis bilatéral remontant à l'âge de ...

Finsler-Geometric Continuum Dynamics and Shock Compression

Science.gov (United States)

2018-01-01

version of Finsler theory is newly applied to shock compression of this ceramic. An order parameter is linked simultaneously to densification and...set of algebraic equations that may be solved simultaneously (albeit, not in closed form) for the shock stress, order param- eter, entropy, and shock...δxa ⊗ dX A = ∂ϕ a(X, D, t) ∂X A δ δxa ⊗ dX A = ∂x(X, D, t) ∂X , FaA = ∂Aϕa = ∂Axa . (2.28) The inverse tangent mapping from spatial to referential

Women Aboard Navy Ships: A Comprehensive Health and Readiness Research Project. Volume 1

Science.gov (United States)

1996-12-31

is a woman [9]. Since screening rates for cervical and breast cancer are considered markers of quality health care, such factors affecting women’s...Urinary tract infection El El j. Hernia (other than hiatal) 1El El]_ 1. Hepatitis (Circle type) A B C El El Page -M4 WA 17. During the past 30 days did...ha y i .l El ............. h. Urinary tract infection El El d. KDnpeysinfcin El El j. Hernia (other than hiatal) El El ... k.~~~ An.xa .r u. i .. l

Atrial fibrillation in the elderly

Science.gov (United States)

Franken, Roberto A.; Rosa, Ronaldo F.; Santos, Silvio CM

2012-01-01

This review discusses atrial fibrillation according to the guidelines of Brazilian Society of Cardiac Arrhythmias and the Brazilian Cardiogeriatrics Guidelines. We stress the thromboembolic burden of atrial fibrillation and discuss how to prevent it as well as the best way to conduct cases of atrial fibrillatios in the elderly, reverting the arrhythmia to sinus rhythm, or the option of heart rate control. The new methods to treat atrial fibrillation, such as radiofrequency ablation, new oral direct thrombin inhibitors and Xa factor inhibitors, as well as new antiarrhythmic drugs, are depicted. PMID:22916053

Molecular mimicry modulates plant host responses to pathogens.

Science.gov (United States)

Ronald, Pamela; Joe, Anna

2018-01-25

Pathogens often secrete molecules that mimic those present in the plant host. Recent studies indicate that some of these molecules mimic plant hormones required for development and immunity. This Viewpoint reviews the literature on microbial molecules produced by plant pathogens that functionally mimic molecules present in the plant host. This article includes examples from nematodes, bacteria and fungi with emphasis on RaxX, a microbial protein produced by the bacterial pathogen Xanthomonas oryzae pv. oryzae. RaxX mimics a plant peptide hormone, PSY (plant peptide containing sulphated tyrosine). The rice immune receptor XA21 detects sulphated RaxX but not the endogenous peptide PSY. Studies of the RaxX/XA21 system have provided insight into both host and pathogen biology and offered a framework for future work directed at understanding how XA21 and the PSY receptor(s) can be differentially activated by RaxX and endogenous PSY peptides. © The Author 2017. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Gametogenesis in malaria parasites is mediated by the cGMP-dependent protein kinase.

Directory of Open Access Journals (Sweden)

Louisa McRobert

2008-06-01

Full Text Available Malaria parasite transmission requires differentiation of male and female gametocytes into gametes within a mosquito following a blood meal. A mosquito-derived molecule, xanthurenic acid (XA, can trigger gametogenesis, but the signalling events controlling this process in the human malaria parasite Plasmodium falciparum remain unknown. A role for cGMP was revealed by our observation that zaprinast (an inhibitor of phosphodiesterases that hydrolyse cGMP stimulates gametogenesis in the absence of XA. Using cGMP-dependent protein kinase (PKG inhibitors in conjunction with transgenic parasites expressing an inhibitor-insensitive mutant PKG enzyme, we demonstrate that PKG is essential for XA- and zaprinast-induced gametogenesis. Furthermore, we show that intracellular calcium (Ca2+ is required for differentiation and acts downstream of or in parallel with PKG activation. This work defines a key role for PKG in gametogenesis, elucidates the hierarchy of signalling events governing this process in P. falciparum, and demonstrates the feasibility of selective inhibition of a crucial regulator of the malaria parasite life cycle.

Rational and efficient preparation of a chimeric protein containing a tandem dimer of thrombopoietin mimetic peptide fused to human growth hormone in Escherichia coli.

Science.gov (United States)

Wang, Song; Shen, Mingqiang; Xu, Yang; Chen, Fang; Chen, Mo; Chen, Shilei; Wang, Aiping; Zhang, Zhou; Ran, Xinze; Cheng, Tianmin; Su, Yongping; Wang, Junping

2013-04-01

The 14-mer thrombopoietin mimetic peptide (TMP), especially in the form of dimer, displayed potent megakaryocytopoiesis activity in vitro. However, it is difficult to prepare such short peptide with high bioactivity through gene-engineering approaches. In this study, a chimeric protein containing a tandem dimer of TMP (dTMP) fused to human growth hormone (hGH), a kind of hematopoietic growth factor that activates the same signal pathways as thrombopoietin, was produced in Escherichia coli by soluble expression. By rational utilization of the XmnI and EcoRV restriction sites, a PCR fragment encoding dTMP-GH was inserted into the plasmid vector pMAL-p2X at the position right after Xa factor cleavage site, in frame with maltose-binding protein (MBP) gene. Under optimized conditions, a high-level expression of soluble MBP-dTMP-GH fusion protein was obtained. By application of amylose resin chromatography, Xa factor digestion, hydrophobic chromatography followed by gel filtration, the dTMP-GH fusion protein was separated. Finally, a relatively high yield of dTMP-GH fusion protein with high purity (>98%) and without redundant amino acid was achieved, as identified by high-performance liquid chromatography, mass spectrometry, and amino acid sequencing. The functional assays showed that dTMP-GH could promote the proliferation of megakaryoblast cells and maturation of murine megakaryocytes derived from bone marrow, in a dose-dependent manner. Moreover, an enhanced effect of dTMP-GH on megakaryocytopoiesis was found as compared with equimolar concentration of dTMP and rhGH. This work provides a new avenue to generate thrombopoietic agents based on TMP.

Magnetic studies of the S=1 Heisenberg chain [Ni(Pr(i)xa)(2)(pyr)](n)

Czech Academy of Sciences Publication Activity Database

Orendáčová, A.; Orendáč, M.; Trávníček, Zdeněk; Meisel, M. W.

2003-01-01

Roč. 196, č. 1 (2003), s. 278-281 ISSN 0031-8965 R&D Projects: GA ČR GA203/00/0152 Institutional research plan: CEZ:AV0Z5038910 Keywords : ANISOTROPY * COMPLEX Subject RIV: CE - Biochemistry Impact factor: 0.950, year: 2003

Evaluation of the coagulometer STA R Max® (Stago) for routine coagulation parameters.

Science.gov (United States)

Brulé, Justine; Sinegre, Thomas; Pereira, Bruno; Berger, Marc G; Serre-Sapin, Anne-Françoise; Lebreton, Aurélien

2018-04-01

The STA R Max ® is a fully automated multiparameter coagulometer using clotting (viscosity-based detection system), chromogenic and immunologic assays. STA R Max ® is equipped with an innovative software (STA Coag Expert ® ) designed to assist laboratory in accreditation. The aim of this study was to evaluate its performances for the certification according to ISO 15189 quality standard in the haemostasis unit of our university hospital. The following tests were evaluated: prothrombin time (PT), activated partial thromboplastin time (aPTT), kaolin cephalin clotting time (KCCT), fibrinogen, anti-Xa assay and D-dimers. In normal and pathological range, the intra-assay coefficients of variation (CV) for PT, aPTT, KCCT and fibrinogen were below 4.0%. Intra-assay CV was of 4.0% for the anti-Xa assay and intra-assay CV was of 7.9% for D-dimers. Inter-assay CV were below 5.0% for PT, aPPT, KCCT and fibrinogen, 14.9% for anti-Xa assay and 8.6% for D-dimers. The interlaboratory comparisons were below 8.7% for PT, aPPT and KCCT, 5.0% for fibrinogen and 15.5% for anti-Xa assay. All results were acceptable according to suitable CV established by GFHT and the provider. The concordance between all coagulometers was excellent, with correlation coefficient close to 1 (0.99 for all parameters except for aPPT which was 0.98) calculated thanks to an intra-class correlation study. In conclusion, the STA R Max ® analyser is suitable for haemostasis laboratories and facilitates certification of a laboratory.

Catch a tiger snake by its tail: Differential toxicity, co-factor dependence and antivenom efficacy in a procoagulant clade of Australian venomous snakes.

Science.gov (United States)

Lister, Callum; Arbuckle, Kevin; Jackson, Timothy N W; Debono, Jordan; Zdenek, Christina N; Dashevsky, Daniel; Dunstan, Nathan; Allen, Luke; Hay, Chris; Bush, Brian; Gillett, Amber; Fry, Bryan G

2017-11-01

A paradigm of venom research is adaptive evolution of toxins as part of a predator-prey chemical arms race. This study examined differential co-factor dependence, variations relative to dietary preference, and the impact upon relative neutralisation by antivenom of the procoagulant toxins in the venoms of a clade of Australian snakes. All genera were characterised by venoms rich in factor Xa which act upon endogenous prothrombin. Examination of toxin sequences revealed an extraordinary level of conservation, which indicates that adaptive evolution is not a feature of this toxin type. Consistent with this, the venoms did not display differences on the plasma of different taxa. Examination of the prothrombin target revealed endogenous blood proteins are under extreme negative selection pressure for diversification, this in turn puts a strong negative selection pressure upon the toxins as sequence diversification could result in a drift away from the target. Thus this study reveals that adaptive evolution is not a consistent feature in toxin evolution in cases where the target is under negative selection pressure for diversification. Consistent with this high level of toxin conservation, the antivenom showed extremely high-levels of cross-reactivity. There was however a strong statistical correlation between relative degree of phospholipid-dependence and clotting time, with the least dependent venoms producing faster clotting times than the other venoms even in the presence of phospholipid. The results of this study are not only of interest to evolutionary and ecological disciplines, but also have implications for clinical toxinology. Copyright © 2017 Elsevier Inc. All rights reserved.

Guidance of Autonomous Aerospace Vehicles for Vertical Soft Landing using Nonlinear Control Theory

Science.gov (United States)

2015-08-11

desired plant (1.4) i.e. goal is to ensure that X → Xd as t →∞. 4 Distribution Code A: Approved for public release, distribution is unlimited 1.1 Philosophy...system to follow Ẋd = fd ( Xd ) (1.4) where Xd ∈ℜn represents the desire state vector. In the actual plant model (1.3) the term d(X ) is unknown, the...Kτ(Xest −Xa) (1.6) 2. Xa → Xd as t →∞: This process is accomplished through control synthesis using online adaptation of DI controller. 1.1.1 Control

Lufaxin, a novel factor Xa inhibitor from the salivary gland of the sand fly lutzomyia longipalpis, blocks protease-activated receptor 2 activation and inhibits inflammation and thrombosis in vivo

Czech Academy of Sciences Publication Activity Database

Collin, N.; Assumpção, T.C.F.; Mizurini, D.M.; Gilmore, D.; Dutra-Oliveira, A.; Kotsyfakis, Michalis; Sa-Nunes, A.; Teixeira, C.; Ribeiro, J.M.C.; Monteiro, R.Q.; Valenzuela, J. G.; Francischetti, I.M.B.

2012-01-01

Roč. 32, č. 9 (2012), s. 2185-2198 ISSN 1079-5642 R&D Projects: GA ČR GAP502/12/2409 Institutional support: RVO:60077344 Keywords : hematophagy * leishmaniasis * microcirculation * thrombosis * vector biology Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.338, year: 2012 http://atvb.ahajournals.org/content/32/9/2185

A high-resolution multimode digital microscope system.

Science.gov (United States)

Salmon, Edward D; Shaw, Sidney L; Waters, Jennifer C; Waterman-Storer, Clare M; Maddox, Paul S; Yeh, Elaine; Bloom, Kerry

2013-01-01

This chapter describes the development of a high-resolution, multimode digital imaging system based on a wide-field epifluorescent and transmitted light microscope, and a cooled charge-coupled device (CCD) camera. The three main parts of this imaging system are Nikon FXA microscope, Hamamatsu C4880 cooled CCD camera, and MetaMorph digital imaging system. This chapter presents various design criteria for the instrument and describes the major features of the microscope components-the cooled CCD camera and the MetaMorph digital imaging system. The Nikon FXA upright microscope can produce high resolution images for both epifluorescent and transmitted light illumination without switching the objective or moving the specimen. The functional aspects of the microscope set-up can be considered in terms of the imaging optics, the epi-illumination optics, the transillumination optics, the focus control, and the vibration isolation table. This instrument is somewhat specialized for microtubule and mitosis studies, and it is also applicable to a variety of problems in cellular imaging, including tracking proteins fused to the green fluorescent protein in live cells. The instrument is also valuable for correlating the assembly dynamics of individual cytoplasmic microtubules (labeled by conjugating X-rhodamine to tubulin) with the dynamics of membranes of the endoplasmic reticulum (labeled with DiOC6) and the dynamics of the cell cortex (by differential interference contrast) in migrating vertebrate epithelial cells. This imaging system also plays an important role in the analysis of mitotic mutants in the powerful yeast genetic system Saccharomyces cerevisiae. Copyright © 1998 Elsevier Inc. All rights reserved.

Spotlight on unmet needs in stroke prevention: The PIONEER AF-PCI, NAVIGATE ESUS and GALILEO trials.

Science.gov (United States)

Hemmrich, Melanie; Peterson, Eric D; Thomitzek, Karen; Weitz, Jeffrey I

2016-09-28

Atrial fibrillation (AF) is a major healthcare concern, being associated with an estimated five-fold risk of ischaemic stroke. In patients with AF, anticoagulants reduce stroke risk to a greater extent than acetylsalicylic acid (ASA) or dual antiplatelet therapy (DAPT) with ASA plus clopidogrel. Non-vitamin K antagonist oral anticoagulants (NOACs) are now a widely-accepted therapeutic option for stroke prevention in non-valvular AF (NVAF). There are particular patient types with NVAF for whom treatment challenges remain, owing to sparse clinical data, their high-risk nature or a need to harmonise anticoagulant and antiplatelet regimens if co-administered. This article focuses on three randomised controlled trials (RCTs) that are investigating the utility of rivaroxaban, a direct, oral, factor Xa inhibitor, in additional areas of stroke prevention where data for anticoagulants are lacking: oPen-label, randomized, controlled, multicentre study explorIng twO treatmeNt stratEgiEs of Rivaroxaban and a dose-adjusted oral vitamin K antagonist treatment (PIONEER AF-PCI); New Approach riVaroxoban Inhibition of factor Xa in a Global trial vs Aspirin to prevenT Embolism in Embolic Stroke of Undetermined Source (NAVIGATE ESUS); and Global study comparing a rivAroxaban-based antithrombotic strategy to an antipLatelet-based strategy after transcatheter aortIc vaLve rEplacement to Optimize clinical outcomes (GALILEO). Data from these studies present collaborative efforts to build upon existing registrational Phase III data for rivaroxaban, driving the need for effective and safe treatment of a wider range of patients for stroke prevention.

Severe jaundice due to intrahepatic cholestasis after initiating anticoagulation with rivaroxaban.

Science.gov (United States)

Aslan, Abdullah N; Sari, Cenk; Baştuğ, Serdal; Sari, Sevil Ö; Akçay, Murat; Durmaz, Tahir; Bozkurt, Engin

2016-03-01

Rivaroxaban, a highly selective direct factor Xa inhibitor, is a new oral anticoagulant approved by the US Food and Drug Administration in November 2011 for stroke prophylaxis in patients with nonvalvular atrial fibrillation. Because of its efficacy and once-a-day dosing, it is commonly preferred in patients with nonvalvular atrial fibrillation and intolerance to warfarin in clinical practice. However, it can result in some adverse effects such as bleeding, rashes and liver injury. Here, we described a very rare adverse reaction of rivaroxaban, jaundice due to intrahepatic cholestasis, appeared in a 71-year-old male patient after taking rivaroxaban.

Direct oral anticoagulants and venous thromboembolism

Directory of Open Access Journals (Sweden)

Massimo Franchini

2016-09-01

Full Text Available Venous thromboembolism (VTE, consisting of deep vein thrombosis and pulmonary embolism, is a major clinical concern associated with significant morbidity and mortality. The cornerstone of management of VTE is anticoagulation, and traditional anticoagulants include parenteral heparins and oral vitamin K antagonists. Recently, new oral anticoagulant drugs have been developed and licensed, including direct factor Xa inhibitors (e.g. rivaroxaban, apixaban and edoxaban and thrombin inhibitors (e.g. dabigatran etexilate. This narrative review focusses on the characteristics of these direct anticoagulants and the main results of published clinical studies on their use in the prevention and treatment of VTE.

Meta-analysis of randomized controlled trials on risk of myocardial infarction from the use of oral direct thrombin inhibitors

DEFF Research Database (Denmark)

Artang, Ramin; Rome, Eric; Nielsen, Jørn Dalsgaard

2013-01-01

. To address these questions, we systematically searched MEDLINE and performed a meta-analysis on randomized trials that compared oral DTIs with warfarin for any indication with end point of MIs after randomization. We furthermore performed a secondary meta-analysis on atrial fibrillation stroke prevention...... to experience an MI than their counterparts treated with warfarin (285 of 23,333 vs 133 of 16,024, odds ratio 1.35, 95% confidence interval 1.10 to 1.66, p = 0.005). For secondary analysis, 8 studies (69,615 patients) were identified that compared warfarin with alternative anticoagulant including factor Xa...

Pig BMSCs Transfected with Human TFPI Combat Species Incompatibility and Regulate the Human TF Pathway in Vitro and in a Rodent Model

Directory of Open Access Journals (Sweden)

Hongchen Ji

2015-05-01

Full Text Available Background: The activation of tissue factor (TF is one of the major reasons for coagulation dysregulation after pig-to-primate xenotransplantation. Tissue factor pathway inhibitor (TFPI is the most important inhibitor of TF. Studies have demonstrated species incompatibility between pig TFPI and human TF. Methods: A pig-to-macaque heterotopic auxiliary liver transplantation model was established to determine the origin of activated TF. Chimeric proteins of human and pig TFPI were constructed to assess the role of Kunitz domains in species incompatibility. Immortalised pig bone marrow mesenchymal stem cells transfected with human TFPI were tested for their ability to inhibit clotting in vitro. Results: TF from recipient was activated early after liver xenotransplantation. Pig TFPI Kunitz domain 2 bound human FXa, but Kunitz domain 1 did not effectively inhibit human TF/FVIIa. Immortalised pig bone marrow mesenchymal cells (BMSCs transfected with human TFPI showed a prolonged recalcification time in vitro and in a rodent model. Conclusion: Recipient TF is relevant to dysregulated coagulation after xenotransplantation. Kunitz domain 1 plays the most important role in species incompatibility between pig TFPI and human TF, and clotting can be inhibited by human TFPI-transfected pig BMSCs. Our study shows a possible way to resolve the incompatibility of pig TFPI.

Effect of Co-Administration of Rivaroxaban and Clopidogrel on Bleeding Time, Pharmacodynamics and Pharmacokinetics: A Phase I Study

Directory of Open Access Journals (Sweden)

Michael Becka

2012-02-01

Full Text Available Dual antiplatelet therapy with acetylsalicylic acid and a thienopyridine, such as clopidogrel, is effective for the secondary prevention of cardiovascular events in patients with acute coronary syndrome, but there is still a substantial residual risk of recurrence. Although anticoagulant therapy with a vitamin K antagonist (e.g. warfarin in conjunction with antiplatelet therapy has been shown to reduce the risk of cardiovascular events, the rates of bleeding were increased with these combination therapies; hence, triple therapy with warfarin is currently only recommended in patients at low risk of bleeding. In addition, there are other limitations associated with vitamin K antagonist therapy, including the need for routine coagulation monitoring and dose adjustment to maintain the treatment within the therapeutic range. Rivaroxaban is an oral, direct Factor Xa inhibitor; in clinical practice, it is likely that rivaroxaban will be given to patients who also receive antiplatelet therapy, such as clopidogrel. This randomized, non-blinded, three-way crossover study investigated the effect of rivaroxaban on bleeding time when co­administered with clopidogrel. In addition, the influence of clopidogrel on the safety, tolerability, pharmacodynamics and pharmacokinetics of rivaroxaban was investigated. Of 27 healthy male subjects who received a single 300 mg dose of clopidogrel, 14 were identified as clopidogrel responders and were then randomized to the following three treatments: (A two doses of clopidogrel on two consecutive days (300 mg on day 1; 75 mg on day 2; (B one dose of rivaroxaban (15 mg; or (C a combination of treatments A and B (rivaroxaban given on day 2. All treatments were well tolerated. Bleeding time with co­administration of rivaroxaban and clopidogrel was significantly prolonged in four subjects, compared with either drug alone: combination treatment increased the overall least squares-means to 3.77 times baseline (90% confidence

DynaGuard: Armoring Canary-Based Protections against Brute-Force Attacks

Science.gov (United States)

2015-12-11

format of the canary check or a function’s prologue and epilogue. Finally, due to the small number of canary-protected frames that (on average) are...sje ng 462 .lib qua ntu m 464 .h2 64r ef 471 .om net pp 473 .as tar 483 .xa lan cbm k Apa che Ng inx Pos tgre SQ L SQ Lite My SQ L Sl ow do w n (n...k 456 .hm me r 458 .sje ng 462 .lib qua ntu m 464 .h2 64r ef 471 .om net pp 473 .as tar 483 .xa lan cbm k Apa che Ng inx

1st review of the status of national air quality: 1994-2004

CSIR Research Space (South Africa)

Taviv, I

2006-10-01

Full Text Available od (WC ) Se ttle rs (KZ N) We ntw or th (KZ N) Wa ter va l (M P) Ta ble Vie w (WC ) Mo the rw ell (EC ) Le itru m (FS ) Ale xa ndr a (GA U) Ora nge Fa rm (GA U) Kh aye lits ha (WC ) Ne...) La ng ve rw ac ht (MP ) Le itru m (FS ) Ale xa nd ra (GA U) At hlo ne (WC ) Bu cc leu ch (GA U) Cit y D ee p(G AU ) Ne wt ow n (GA U) No rth er n Wo rks (GA U) O 3 ( p p b ) Average...

Subcutaneous Administration of Low-Molecular-Weight Heparin to Horses Inhibits Ex Vivo Equine Herpesvirus Type 1-Induced Platelet Activation

Directory of Open Access Journals (Sweden)

Tracy Stokol

2018-05-01

Full Text Available Equine herpesvirus type 1 (EHV-1 is a major cause of infectious respiratory disease, abortion and neurologic disease. Thrombosis in placental and spinal vessels and subsequent ischemic injury in EHV-1-infected horses manifests clinically as abortion and myeloencephalopathy. We have previously shown that addition of heparin anticoagulants to equine platelet-rich plasma (PRP can abolish ex vivo EHV-1-induced platelet activation. The goal of this study was to test whether platelets isolated from horses treated with unfractionated heparin (UFH or low-molecular-weight heparin (LMWH were resistant to ex vivo EHV-1-induced activation. In a masked, block-randomized placebo-controlled cross-over trial, 9 healthy adult horses received 4 subcutaneous injections at q. 12 h intervals of one of the following treatments: UFH (100 U/kg loading dose, 3 maintenance doses of 80 U/kg, 2 doses of LMWH (enoxaparin 80 U/kg 24 h apart with saline at the intervening 12 h intervals, or 4 doses of saline. Blood samples were collected before treatment and after 36 h, 40 h (4 h after the last injection and 60 h (24 h after the last injection. Two strains of EHV-1, Ab4 and RacL11, were added to PRP ex vivo and platelet membrane expression of P selectin was measured as a marker of platelet activation. Drug concentrations were monitored in a Factor Xa inhibition (anti-Xa bioassay. We found that LMWH, but not UFH, inhibited platelet activation induced by low concentrations (1 × 106 plaque forming units/mL of both EHV-1 strains at 40 h. At this time point, all horses had anti-Xa activities above 0.1 U/ml (range 0.15–0.48 U/ml with LMWH, but not UFH. By 60 h, a platelet inhibitory effect was no longer detected and anti-Xa activity had decreased (range 0.03 to 0.07 U/ml in LMWH-treated horses. Neither heparin inhibited platelet activation induced by high concentrations (5 × 106 plaque forming units/mL of the RacL11 strain. We found substantial between horse

Single- and multiple-dose pharmacokinetics, pharmacodynamics, and safety of apixaban in healthy Chinese subjects

Directory of Open Access Journals (Sweden)

Cui Y

2013-12-01

anticoagulant, factor Xa inhibitor, pharmacokinetics, pharmacodynamics

Dissolution of targets for the production of Mo-99: Part 1. Influence of NaOH concentration and the addition of NaNO{sub 3} and NaNO{sub 2} on the dissolution time

Energy Technology Data Exchange (ETDEWEB)

Camilo, Ruth L.; Araujo, Izilda da C.; Mindrisz, Ana C.; Forbicini, Christina A.L.G. de O., E-mail: rcamilo@ipen.br, E-mail: icaraujo@ipen.br, E-mail: acmindri@ipen.br, E-mail: cforbici@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN/SP), Sao Paulo, SP (Brazil)

2011-07-01

Faced with global crisis in the production of radioisotope {sup 99}Mo, which product of decay, {sup 99}mTc, is the tracer element most often used in nuclear medicine and accounts for about 80% of all diagnostic procedures in vivo, since September 2008 Brazil is developing the project called Brazilian Multipurpose Reactor (RMB). Within the Brazilian Nuclear Program (PNB) the construction of the RMB, is seen as a long term solution to meet all domestic demand relative to the supply of radioisotopes and radiopharmaceuticals. In the process to be studied to obtain {sup 99}Mo from irradiated UA1{sub x}-A1 LEU targets employing alkaline dissolution, processing time should be minimized, considering the short half life of {sup 99}Mo and {sup 99}mTc, about 66 h and 6 h, respectively. That makes dissolution time a significant factor in the development of the process. This paper presents the results of alkaline dissolution of scraps of Al, used to simulate the dissolution process of UA1{sub x}-A1 targets. Al corresponds to about 79% of the total weight of the UA1{sub x}-A1 target. The effect of NaOH concentration on dissolution time for the interval of 1 to 3.5 mol.L-1 was studied, keeping the molar ratio in 1Al:2.16NaOH and the initial temperature of 88 degree C. The influence of reagent composition over dissolution time was studied using three different solutions: a) 3 mol.L{sup -1} NaOH, b) 3 mol.L{sup -1} NaOH/NaNO{sub 3} and c) 3 mol.L{sup -1} NaOH/NaNO{sub 2}, keeping the same molar ratio and temperature. The results showed that the dissolution time decreases with increasing NaOH concentration and the addition of NaNO{sub 3} or NaNO{sub 2} in the NaOH solution reduces both dissolution time and volume of gases released. (author)

A direct thrombin inhibitor suppresses protein C activation and factor Va degradation in human plasma: Possible mechanisms of paradoxical enhancement of thrombin generation.

Science.gov (United States)

Kamisato, Chikako; Furugohri, Taketoshi; Morishima, Yoshiyuki

2016-05-01

We have demonstrated that antithrombin (AT)-independent thrombin inhibitors paradoxically increase thrombin generation (TG) in human plasma in a thrombomodulin (TM)- and protein C (PC)-dependent manner. We determined the effects of AT-independent thrombin inhibitors on the negative-feedback system, activation of PC and production and degradation of factor Va (FVa), as possible mechanisms underlying the paradoxical enhancement of TG. TG in human plasma containing 10nM TM was assayed by means of the calibrated automated thrombography. As an index of PC activation, plasma concentration of activated PC-PC inhibitor complex (aPC-PCI) was measured. The amounts of FVa heavy chain and its degradation product (FVa(307-506)) were examined by western blotting. AT-independent thrombin inhibitors, melagatran and dabigatran (both at 25-600nM) and 3-30μg/ml active site-blocked thrombin (IIai), increased peak levels of TG. Melagatran, dabigatran and IIai significantly decreased plasma concentration of aPC-PCI complex at 25nM or more, 75nM or more, and 10 and 30μg/ml, respectively. Melagatran (300nM) significantly increased FVa and decreased FVa(307-506). In contrast, a direct factor Xa inhibitor edoxaban preferentially inhibited thrombin generation (≥25nM), and higher concentrations were required to inhibit PC activation (≥150nM) and FVa degradation (300nM). The present study suggests that the inhibitions of protein C activation and subsequent degradation of FVa and increase in FVa by antithrombin-independent thrombin inhibitors may contribute to the paradoxical TG enhancement, and edoxaban may inhibit PC activation and FVa degradation as a result of TG suppression. Copyright © 2016 Elsevier Ltd. All rights reserved.

Impact of Pre-Pregnancy BMI on B Vitamin and Inflammatory Status in Early Pregnancy: An Observational Cohort Study

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Anne-Lise Bjørke-Monsen

2016-11-01

Full Text Available Maternal nutrition and inflammation have been suggested as mediators in the development of various adverse pregnancy outcomes associated with maternal obesity. We have investigated the relation between pre-pregnancy BMI, B vitamin status, and inflammatory markers in a group of healthy pregnant women. Cobalamin, folate, pyridoxal 5′-phosphate, and riboflavin; and the metabolic markers homocysteine, methylmalonic acid, and 3-hydroxykynurenine/xanthurenic acid ratio (HK/XA; and markers of cellular inflammation, neopterin and kynurenine/tryptophan ratio (KTR were determined in pregnancy week 18 and related to pre-pregnancy body mass index (BMI, in 2797 women from the Norwegian Mother and Child Cohort Study (MoBa. Pre-pregnancy BMI was inversely related to folate, cobalamin, pyridoxal 5′-phosphate (PLP, and riboflavin (p < 0.001, and associated with increased neopterin and KTR levels (p < 0.001. Inflammation seemed to be an independent predictor of low vitamin B6 status, as verified by low PLP and high HK/XA ratio. A high pre-pregnancy BMI is a risk factor for low B vitamin status and increased cellular inflammation. As an optimal micronutrient status is vital for normal fetal development, the observed lower B vitamin levels may contribute to adverse pregnancy outcomes associated with maternal obesity and B vitamin status should be assessed in women with high BMI before they get pregnant.

Report: Ozone Transport Commission Incurred Costs Under EPA Assistance Agreements XA98379901, OT83098301, XA97318101, and OT83264901

Science.gov (United States)

Report #2007-4-00068, July 31, 2007. We questioned $2,723,706 of the $9,042,706 in reported outlays because the recipient claimed unallowable outlays for contractual services, indirect costs, and in-kind costs.

Prolonged Activated Clotting Time after Protamine Administration Does Not Indicate Residual Heparinization after Cardiopulmonary Bypass in Pediatric Open Heart Surgery.

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Yamamoto, Tomohiro; Wolf, Hans-Gerd; Sinzobahamvya, Nicodème; Asfour, Boulos; Hraska, Victor; Schindler, Ehrenfried

2015-08-01

In open heart surgery, heparinization is commonly neutralized using an empirical heparin:protamine ratio ranging between 1:1 and 1:1.5. However, these ratios may result in protamine overdose that should be avoided for its negative side effects on the coagulation system. This study aimed to indicate the appropriate treatment for prolonged activated clotting time (ACT) after protamine administration following cardiopulmonary bypass (CPB) in pediatric open heart surgery by investigating the underlying reasons for it. Twenty-seven children (open heart surgery were included. Heparin was administered only before CPB (400 IU/kg) and in the pump priming volume for CPB (2,000 IU) and was neutralized by 1:1 protamine after CPB. The blood heparin concentration was measured using anti-Xa assay. ACT and blood concentrations of heparin, coagulation factors, thrombin-antithrombin complex, and prothrombin fragment 1 + 2 were assessed. A rotational thromboelastometry (ROTEM; Tem International GmbH, München, Bayern, Germany) was used to confirm the coagulation status and residual heparin after protamine administration. Anti-Xa assay showed that there is no residual heparin in the blood after 1:1 protamine administration. Nevertheless, ACT (128.89 ± 3.09 seconds before heparin administration) remained prolonged (177.14 ± 5.43 seconds at 10 minutes after protamine, 182.00 ± 5.90 seconds at 30 minutes after protamine). The blood concentrations of coagulation factors were significantly lower than those before heparin administration (p < 0.01). The low FIBTEM MCF of ROTEM (4.43 ± 0.32 mm) at 10 minutes after protamine indicated low fibrinogen concentration. Prolonged ACT after heparin neutralization by 1:1 protamine administration does not necessarily indicate residual heparin, but low blood concentrations of coagulation factors should be considered as a reason as well. Accordingly, supply of coagulation factors instead of additional protamine should be

Synthesis and in Vitro and in Vivo Anticoagulant and Antiplatelet Activities of Amidino- and Non-Amidinobenzamides

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Soo Hyun Lee

2016-05-01

Full Text Available Three amidino- and ten non-amidinobenzamides were synthesized as 3-aminobenzoic acid scaffold-based anticoagulant and antiplatelet compounds. The anticoagulant activities of thirteen synthesized compounds 1–13, and 2b and 3b as prodrugs were preliminary evaluated by screening the prolongation of activated partial thromboplastin time (aPTT and prothrombin time (PT in vitro. From the aPTT results obtained, two amidinobenzamides, N-(3′-amidinophenyl-3-(thiophen-2′′-ylcarbonylamino benzamide (1, 33.2 ± 0.7 s and N-(4′-amidinophenyl-3-(thiophen-2′′-ylcarbonylamino benzamide (2, 43.5 ± 0.6 s were selected to investigate the further anticoagulant and antiplatelet activities. The aPTT results of 1 (33.2 ± 0.7 s and 2 (43.5 ± 0.6 s were compared with heparin (62.5 ± 0.8 s in vitro at 30 μM. We investigated the effect of 1 and 2 on blood anticoagulant activity (ex vivo and on tail bleeding time (in vivo on mice. A tail cutting/bleeding time assay revealed that both 1 and 2 prolonged bleeding time in mice at a dose of 24.1 g/mouse and above. Compounds 1 and 2 dose-dependently inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation. In addition, 1 and 2 were evaluated on the inhibitory activities of thrombin and FXa as well as the generation of thrombin and FXa in human umbilical vein endothelial cells (HUVECs. Collectively, 1 and 2 possess some antiplatelet and anticoagulant activities and offer a basis for development of a novel antithrombotic product.

Amblyomma americanum tick calreticulin binds C1q but does not inhibit activation of the classical complement cascade.

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Kim, Tae Kwon; Ibelli, Adriana Mércia Guaratini; Mulenga, Albert

2015-02-01

In this study we characterized Amblyomma americanum (Aam) tick calreticulin (CRT) homolog in tick feeding physiology. In nature, different tick species can be found feeding on the same animal host. This suggests that different tick species found feeding on the same host can modulate the same host anti-tick defense pathways to successfully feed. From this perspective it's plausible that different tick species can utilize universally conserved proteins such as CRT to regulate and facilitate feeding. CRT is a multi-functional protein found in most taxa that is injected into the vertebrate host during tick feeding. Apart from it's current use as a biomarker for human tick bites, role(s) of this protein in tick feeding physiology have not been elucidated. Here we show that annotated functional CRT amino acid motifs are well conserved in tick CRT. However our data show that despite high amino acid identity levels to functionally characterized CRT homologs in other organisms, AamCRT is apparently functionally different. Pichia pastoris expressed recombinant (r) AamCRT bound C1q, the first component of the classical complement system, but it did not inhibit activation of this pathway. This contrast with reports of other parasite CRT that inhibited activation of the classical complement pathway through sequestration of C1q. Furthermore rAamCRT did not bind factor Xa in contrast to reports of parasite CRT binding factor Xa, an important protease in the blood clotting system. Consistent with this observation, rAamCRT did not affect plasma clotting or platelet aggregation. We discuss our findings in the context of tick feeding physiology.

Beyond Stroke Prevention in Atrial Fibrillation: Exploring Further Unmet Needs with Rivaroxaban.

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Gibson, C M; Hankey, G J; Nafee, T; Welsh, R C

2018-03-22

With improved life expectancy and the aging population, the global burden of atrial fibrillation (AF) continues to increase, and with AF comes an estimated fivefold increased risk of ischaemic stroke. Prophylactic anticoagulant therapy is more effective in reducing the risk of ischaemic stroke in AF patients than acetylsalicylic acid or dual-antiplatelet therapy combining ASA with clopidogrel. Non-vitamin K antagonist oral anticoagulants are the standard of care for stroke prevention in patients with non-valvular AF. The optimal anticoagulant strategy to prevent thromboembolism in AF patients who are undergoing percutaneous coronary intervention and stenting, those who have undergone successful transcatheter aortic valve replacement and those with embolic stroke of undetermined source are areas of ongoing research. This article provides an update on three randomized controlled trials of rivaroxaban, a direct, oral factor Xa inhibitor, that are complete or are ongoing, in these unmet areas of stroke prevention: oPen-label, randomized, controlled, multicentre study explorIng twO treatmeNt stratEgiEs of Rivaroxaban and a dose-adjusted oral vitamin K antagonist treatment strategy in patients with Atrial Fibrillation who undergo Percutaneous Coronary Intervention (PIONEER AF-PCI) trial; the New Approach riVaroxaban Inhibition of factor Xa in a Global trial vs Aspirin to prevenT Embolism in Embolic Stroke of Undetermined Source (NAVIGATE ESUS) trial and the Global study comparing a rivAroxaban-based antithrombotic strategy to an antipLatelet-based strategy after transcatheter aortIc vaLve rEplacement to Optimize clinical outcomes (GALILEO) trial. The data from these studies are anticipated to help address continuing challenges for a range of patients at risk of stroke. Schattauer.

Use of anticoagulants in elderly patients: practical recommendations

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Helia Robert-Ebadi

2009-04-01

Full Text Available Helia Robert-Ebadi, Grégoire Le Gal, Marc RighiniDivision of Angiology and Hemostasis (HRE, MR, Department of Internal Medicine, Geneva University Hospital and Faculty of Medicine, Geneva, Switzerland, and Department of Internal Medicine and Chest Diseases, EA 3878 (GETBO, Brest University Hospital, Brest, France (GLGAbstract: Elderly people represent a patient population at high thromboembolic risk, but also at high hemorrhagic risk. There is a general tendency among physicians to underuse anticoagulants in the elderly, probably both because of underestimation of thromboembolic risk and overestimation of bleeding risk. The main indications for anticoagulation are venous thromboembolism (VTE prophylaxis in medical and surgical settings, VTE treatment, atrial fibrillation (AF and valvular heart disease. Available anticoagulants for VTE prophylaxis and initial treatment of VTE are low molecular weight heparins (LMWH, unfractionated heparin (UFH or synthetic anti-factor Xa pentasaccharide fondaparinux. For long-term anticoagulation vitamin K antagonists (VKA are the first choice and only available oral anticoagulants nowadays. Assessing the benefit-risk ratio of anticoagulation is one of the most challenging issues in the individual elderly patient, patients at highest hemorrhagic risk often being those who would have the greatest benefit from anticoagulants. Some specific considerations are of utmost importance when using anticoagulants in the elderly to maximize safety of these treatments, including decreased renal function, co-morbidities and risk of falls, altered pharmacodynamics of anticoagulants especially VKAs, association with antiplatelet agents, patient education. Newer anticoagulants that are currently under study could simplify the management and increase the safety of anticoagulation in the future.Keywords: anticoagulation, elderly patients, venous thromboembolism, hemorrhagic risk, atrial fibrillation, thrombin inhibitors, factor Xa

Why Ser and not Thr brokers catalysis in the trypsin fold.

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Pelc, Leslie A; Chen, Zhiwei; Gohara, David W; Vogt, Austin D; Pozzi, Nicola; Di Cera, Enrico

2015-02-24

Although Thr is equally represented as Ser in the human genome and as a nucleophile is as good as Ser, it is never found in the active site of the large family of trypsin-like proteases that utilize the Asp/His/Ser triad. The molecular basis of the preference of Ser over Thr in the trypsin fold was investigated with X-ray structures of the thrombin mutant S195T free and bound to an irreversible active site inhibitor. In the free form, the methyl group of T195 is oriented toward the incoming substrate in a conformation seemingly incompatible with productive binding. In the bound form, the side chain of T195 is reoriented for efficient substrate acylation without causing steric clash within the active site. Rapid kinetics prove that this change is due to selection of an active conformation from a preexisting ensemble of reactive and unreactive rotamers whose relative distribution determines the level of activity of the protease. Consistent with these observations, the S195T substitution is associated with a weak yet finite activity that allows identification of an unanticipated important role for S195 as the end point of allosteric transduction in the trypsin fold. The S195T mutation abrogates the Na(+)-dependent enhancement of catalytic activity in thrombin, activated protein C, and factor Xa and significantly weakens the physiologically important allosteric effects of thrombomodulin on thrombin and of cofactor Va on factor Xa. The evolutionary selection of Ser over Thr in trypsin-like proteases was therefore driven by the need for high catalytic activity and efficient allosteric regulation.

Polysaccharide rich fractions from barks of Ximenia americana inhibit peripheral inflammatory nociception in mice Antinociceptive effect of Ximenia americana polysaccharide rich fractions

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Kaira E.S. da Silva-Leite

Full Text Available Abstract Ximenia americana L., Olacaceae, barks are utilized in folk medicine as analgesic and anti-inflammatory. The objective was to evaluate the toxicity and antinociceptive effect of polysaccharides rich fractions from X. americana barks. The fractions were obtained by extraction with NaOH, followed by precipitation with ethanol and fractionation by ion exchange chromatography. They were administered i.v. or p.o. before nociception tests (writhing, formalin, carragenan-induced hypernociception, hot plate, or during 14 days for toxicity assay. The total polysaccharides fraction (TPL-Xa: 8.1% yield presented 43% carbohydrate (21% uronic acid and resulted in two main fractions after chromatography (FI: 12%, FII: 22% yield. FII showed better homogeneity/purity, content of 44% carbohydrate, including 39% uronic acid, arabinose and galactose as major monosaccharides, and infrared spectra with peaks in carbohydrate range for COO- groups of uronic acid. TPL-Xa (10 mg/kg and FII (0.1 and 1 mg/kg presented inhibitory effect in behavior tests that evaluate nociception induced by chemical and mechanical, but not thermal stimuli. TPL-Xa did not alter parameters of systemic toxicity. In conclusion, polysaccharides rich fractions of X. americana barks inhibit peripheral inflammatory nociception, being well tolerated by animals.

Russian aluminum-lithium alloys for advanced reusable spacecraft

International Nuclear Information System (INIS)

Charette, Ray O.; Leonard, Bruce G.; Bozich, William F.; Deamer, David A.

1998-01-01

Cryotanks that are cost-affordable, robust, fuel-compatible, and lighter weight than current aluminum design are needed to support next-generation launch system performance and operability goals. The Boeing (McDonnell Douglas Aerospace-MDA) and NASA's Delta Clipper-Experimental Program (DC-XA) flight demonstrator test bed vehicle provided the opportunity for technology transfer of Russia's extensive experience base with weight-efficient, highly weldable aluminum-lithium (Al-Li) alloys for cryogenic tank usage. As part of NASA's overall reusable launch vehicle (RLV) program to help provide technology and operations data for use in advanced RLVs, MDA contracted with the Russian Academy of Sciences (RAS/IMASH) for design, test, and delivery of 1460 Al-Li alloy liquid oxygen (LO 2 ) cryotanks: one for development, one for ground tests, and one for DC-XA flight tests. This paper describes the development of Al-Li 1460 alloy for reusable LO 2 tanks, including alloy composition tailoring, mechanical properties database, forming, welding, chemical milling, dissimilar metal joining, corrosion protection, completed tanks proof, and qualification testing. Mechanical properties of the parent and welded materials exceeded expectations, particularly the fracture toughness, which promise excellent reuse potential. The LO 2 cryotank was successfully demonstrated in DC-XA flight tests

Properties of aqueous nitrate and nitrite from x-ray absorption spectroscopy

Energy Technology Data Exchange (ETDEWEB)

Smith, Jacob W.; Lam, Royce K.; Saykally, Richard J., E-mail: saykally@berkeley.edu [Department of Chemistry, University of California, Berkeley, California 94720 (United States); Chemical Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720 (United States); Shih, Orion [National Synchrotron Radiation Research Center, Hsinchu 30076, Taiwan (China); Rizzuto, Anthony M. [Department of Chemistry, University of California, Berkeley, California 94720 (United States); Prendergast, David [The Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, California 94720 (United States)

2015-08-28

Nitrate and nitrite ions are of considerable interest, both for their widespread use in commercial and research contexts and because of their central role in the global nitrogen cycle. The chemistry of atmospheric aerosols, wherein nitrate is abundant, has been found to depend on the interfacial behavior of ionic species. The interfacial behavior of ions is determined largely by their hydration properties; consequently, the study of the hydration and interfacial behavior of nitrate and nitrite comprises a significant field of study. In this work, we describe the study of aqueous solutions of sodium nitrate and nitrite via X-ray absorption spectroscopy (XAS), interpreted in light of first-principles density functional theory electronic structure calculations. Experimental and calculated spectra of the nitrogen K-edge XA spectra of bulk solutions exhibit a large 3.7 eV shift between the XA spectra of nitrate and nitrite resulting from greater stabilization of the nitrogen 1s energy level in nitrate. A similar shift is not observed in the oxygen K-edge XA spectra of NO{sub 3}{sup −} and NO{sub 2}{sup −}. The hydration properties of nitrate and nitrite are found to be similar, with both anions exhibiting a similar propensity towards ion pairing.

Molecular aspects in clinical hemostasis research at Karolinska Institutet.

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Blombäck, Margareta

2010-05-21

The development of hemostasis research at Karolinska Institutet is described, focusing first on the initial findings of the fibrinogen structure and the hereditary bleeding disorders, hemophilia A and von Willebrand's disease. Basic research has focused on new biomarkers for cardiovascular/thromboembolic disorders, such as myocardial infarction and stroke, including preeclampsia and diabetes, with studies on the importance of decreased fibrinolysis in these disorders. Since long, the structure of the fibrin network has been evaluated, and recently the influence of aspirin and new thrombin and factor Xa inhibitors has been investigated. Research on the contact pathway of coagulation has also started at the Unit. 2010 Elsevier Inc. All rights reserved.

Hartree-fock-slater method for materials science the DV-X alpha method for design and characterization of materials

CERN Document Server

Adachi, H; Kawai, J

2006-01-01

Molecular-orbital calculations for materials design such as alloys, ceramics, and coordination compounds are now possible for experimentalists. Molecuar-orbital calculations for the interpretation of chemical effect of spectra are also possible for experimentalists. The most suitable molecular-orbital calculation method for these purpose is the DV-Xa method, which is robust in such a way that the calculation converges to a result even if the structure of the molecule or solid is impossible in the pressure and temperature ranges on earth. This book specially addresses the methods to design novel materials and to predict the spectralline shape of unknown materials using the DV-Xa molecular-orbital method, but is also useful for those who want to calculate electronic structures of materials using any kind of method.

76 FR 59064 - Fisheries of the Exclusive Economic Zone Off Alaska; Shallow-Water Species by Vessels Using Trawl...

Science.gov (United States)

2011-09-23

.... 101126522-0640-02] RIN 0648-XA722 Fisheries of the Exclusive Economic Zone Off Alaska; Shallow- Water... closure. SUMMARY: NMFS is opening directed fishing for shallow-water species by [[Page 59065

Procoagulant Activity of Blood and Endothelial Cells via Phosphatidylserine Exposure and Microparticle Delivery in Patients with Diabetic Retinopathy

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Ying Su

2018-03-01

Full Text Available Background/Aims: The mechanisms for thrombosis in diabetic retinopathy (DR are complex and need to be further elucidated. The purpose of this study was to test phosphatidylserine (PS exposure on microparticles (MPs and MP-origin cells from the circulation and to analyze cell-/MP-associated procoagulant activity (PCA in DR patients. Methods: PS-positive MPs and cells from healthy controls (n = 20 and diabetic patients (n = 60 were analyzed by flow cytometry and confocal microscopy. Clotting time and purified coagulation complex assays were used to measure PCA. Results: PS exposure on platelets and monocytes was higher in proliferative DR (PDR patients than in non-PDR patients or controls. The highest levels of MPs (derived from platelets [30%], erythrocytes [13%], leukocytes [28%], and endothelial cells [10%] were found in patients with PDR. In addition, PS exposure on blood cells and shed MPs in DR patients led to significantly increased FXa and FIIa generation, fibrin formation, and markedly shortened coagulation time. Moreover, lactadherin reduced 70% of PCA by blocking PS, while an anti-tissue factor antibody had a smaller effect. Conclusion: Our results confirmed that PCA in DR patients may be partly ascribed to PS exposure and MP release from blood and endothelial cells. Lactadherin may act as an efficient anticoagulant factor in this process.

[Juvenile myasthenia gravis in sub-Saharan Africa: a case study of two consanguine sisters born from consanguinity in Togo].

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Maneh, Nidain; Apetse, Kossivi; Diatewa, Bénédicte Marèbe; Domingo, Sidik Abou-Bakr; Agba, Aidé Isabelle; Ayena, Koffi Didier; Balogou, Koffi Agnon; Balo, Komi Patrice

2017-01-01

Myasthenia gravis is a rare acquired autoimmune pathology causing neuromuscular transmission impairment. Juvenile onset of myasthenia gravis is often characterized by ocular involvement. We report two cases of ocular juvenile myasthenia gravis (JMG) in two siblings. They were two young girls, XA and XB, aged 11 and 9 years, of Malian origin, residing in Togo, born from first-degree of consanguinity presenting to Ophthalmology due to progressive decrease in visual acuity. XA showed visual acuity 8/10 on both eyes while XB showed improvement in visual acuity from 3/10 to 7/10 using a pinhole occluder, suggesting ametropia. XA had a 2-year history of bilateral ptosis lifting the upper eyelid of 7 mm, while XB had a 3-year history of bilateral ptosis with no lifting of the upper eyelid. Ice pack test was strongly positive in both patients. They had Cogan's lid twitch with paresis of the oculomotor nerve without diplopia. The dosage of acetylcholine receptor autoantibodies was normal. The diagnosis of JMG associated with ametropia was suspected. Ametropia was corrected by glasses and a specific treatment with pyridostigmine was initiated, but both patients were lost to follow-up. Autoimmune myasthenia gravis with inaugural ophthalmologic manifestation is rare but it can occur among children living in sub-Saharan Africa. Studies should be conducted to establish the features of this disease.

Coutilization of D-Glucose, D-Xylose, and L-Arabinose in Saccharomyces cerevisiae by Coexpressing the Metabolic Pathways and Evolutionary Engineering

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Chengqiang Wang

2017-01-01

Full Text Available Efficient and cost-effective fuel ethanol production from lignocellulosic materials requires simultaneous cofermentation of all hydrolyzed sugars, mainly including D-glucose, D-xylose, and L-arabinose. Saccharomyces cerevisiae is a traditional D-glucose fermenting strain and could utilize D-xylose and L-arabinose after introducing the initial metabolic pathways. The efficiency and simultaneous coutilization of the two pentoses and D-glucose for ethanol production in S. cerevisiae still need to be optimized. Previously, we constructed an L-arabinose-utilizing S. cerevisiae BSW3AP. In this study, we further introduced the XI and XR-XDH metabolic pathways of D-xylose into BSW3AP to obtain D-glucose, D-xylose, and L-arabinose cofermenting strain. Benefits of evolutionary engineering: the resulting strain BSW4XA3 displayed a simultaneous coutilization of D-xylose and L-arabinose with similar consumption rates, and the D-glucose metabolic capacity was not decreased. After 120 h of fermentation on mixed D-glucose, D-xylose, and L-arabinose, BSW4XA3 consumed 24% more amounts of pentoses and the ethanol yield of mixed sugars was increased by 30% than that of BSW3AP. The resulting strain BSW4XA3 was a useful chassis for further enhancing the coutilization efficiency of mixed sugars for bioethanol production.

Expression and characterization of antimicrobial peptides Retrocyclin-101 and Protegrin-1 in chloroplasts to control viral and bacterial infections.

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Lee, Seung-Bum; Li, Baichuan; Jin, Shuangxia; Daniell, Henry

2011-01-01

Retrocyclin-101 (RC101) and Protegrin-1 (PG1) are two important antimicrobial peptides that can be used as therapeutic agents against bacterial and/or viral infections, especially those caused by the HIV-1 or sexually transmitted bacteria. Because of their antimicrobial activity and complex secondary structures, they have not yet been produced in microbial systems and their chemical synthesis is prohibitively expensive. Therefore, we created chloroplast transformation vectors with the RC101 or PG1 coding sequence, fused with GFP to confer stability, furin or Factor Xa cleavage site to liberate the mature peptide from their fusion proteins and a His-tag to aid in their purification. Stable integration of RC101 into the tobacco chloroplast genome and homoplasmy were confirmed by Southern blots. RC101 and PG1 accumulated up to 32%-38% and 17%∼26% of the total soluble protein. Both RC101 and PG1 were cleaved from GFP by corresponding proteases in vitro, and Factor Xa-like protease activity was observed within chloroplasts. Confocal microscopy studies showed location of GFP fluorescence within chloroplasts. Organic extraction resulted in 10.6-fold higher yield of RC101 than purification by affinity chromatography using His-tag. In planta bioassays with Erwinia carotovora confirmed the antibacterial activity of RC101 and PG1 expressed in chloroplasts. RC101 transplastomic plants were resistant to tobacco mosaic virus infections, confirming antiviral activity. Because RC101 and PG1 have not yet been produced in other cell culture or microbial systems, chloroplasts can be used as bioreactors for producing these proteins. Adequate yield of purified antimicrobial peptides from transplastomic plants should facilitate further preclinical studies. © 2010 The Authors. Plant Biotechnology Journal © 2010 Society for Experimental Biology and Blackwell Publishing Ltd.

Pharmacokinetics of heparin and related polysaccharides

International Nuclear Information System (INIS)

Boneu, B.; Dol, F.; Caranobe, C.; Sie, P.; Houin, G.

1989-01-01

The pharmacodynamic profile of standard heparin (SH), a low molecular weight derivative (CY 216) and of dermatan sulfate (DS), a new potential antithrombotic drug, was investigated in the rabbit over a large range of doses. After bolus i.v. injection of low doses, the biological activity of SH disappeared exponentially; however, its half-life was prolonged when the dose injected increased, and over 158 micrograms/kg (100 anti-factor Xa U/kg) the biological activity disappeared as a concave-convex curve. CY 216 disappeared more slowly than SH at low doses but faster than SH at higher doses. More than 90% of the DS biological activity present 1 minute after the i.v. injection disappeared exponentially without dose-dependent effects. Increasing doses of the three drugs were then delivered for 5 h under continuous infusions. Below 500 micrograms/kg/h the DS and CY 216 plateau concentrations were higher than that of SH while above this dose the SH concentration was higher than that of DS and CY 216. These observations may be explained by the results of pharmacokinetics experiments where 125 I-labeled compounds were delivered by bolus i.v. injection in association with increasing doses of their unlabeled counterparts. For SH there was a 10-fold difference between the half-life of the lower dose (32 micrograms/kg or 5 anti-factor Xa U/kg) and that of the higher dose (3200 micrograms/kg); it was demonstrated that the half-life of SH continuously shortened as its plasma concentration decreased. In contrast the CY 216 and DS half-lives were very close, independent of the dose delivered, and therefore longer than that of SH at low doses and shorter than that of SH at higher doses

Deep vein thrombosis: a clinical review

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Kesieme EB

2011-04-01

Full Text Available Emeka Kesieme1, Chinenye Kesieme2, Nze Jebbin3, Eshiobo Irekpita1, Andrew Dongo11Department of Surgery, Irrua Specialist Teaching Hospital, Irrua, Nigeria; 2Department of Paediatrics, Irrua Specialist Teaching Hospital, Irrua, Nigeria; 3Department of Surgery, University of Port Harcourt Teaching Hospital, Port-Harcourt, NigeriaBackground: Deep vein thrombosis (DVT is the formation of blood clots (thrombi in the deep veins. It commonly affects the deep leg veins (such as the calf veins, femoral vein, or popliteal vein or the deep veins of the pelvis. It is a potentially dangerous condition that can lead to preventable morbidity and mortality.Aim: To present an update on the causes and management of DVT.Methods: A review of publications obtained from Medline search, medical libraries, and Google.Results: DVT affects 0.1% of persons per year. It is predominantly a disease of the elderly and has a slight male preponderance. The approach to making a diagnosis currently involves an algorithm combining pretest probability, D-dimer testing, and compression ultrasonography. This will guide further investigations if necessary. Prophylaxis is both mechanical and pharmacological. The goals of treatment are to prevent extension of thrombi, pulmonary embolism, recurrence of thrombi, and the development of complications such as pulmonary hypertension and post-thrombotic syndrome.Conclusion: DVT is a potentially dangerous condition with a myriad of risk factors. Prophylaxis is very important and can be mechanical and pharmacological. The mainstay of treatment is anticoagulant therapy. Low-molecular-weight heparin, unfractionated heparin, and vitamin K antagonists have been the treatment of choice. Currently anticoagulants specifically targeting components of the common pathway have been recommended for prophylaxis. These include fondaparinux, a selective indirect factor Xa inhibitor and the new oral selective direct thrombin inhibitors (dabigatran and selective

Swift BAT Thermal Recovery After Loop Heat Pipe #0 Secondary Heater Controller Failure in October 2015

Science.gov (United States)

Choi, Michael K.

2016-01-01

The Swift BAT LHP #0 primary heater controller failed on March 31, 2010. It has been disabled. On October 31, 2015, the secondary heater controller of this LHP failed. On November 1, 2015, the LHP #0 CC temperature increased to as 18.6 C, despite that the secondary heater controller set point was 8.8 C. It caused the average DM XA1 temperature to increase to 25.9 C, which was 5 C warmer than nominal. As a result, the detectors became noisy. To solve this problem, the LHP #1 secondary heater controller set point was decreased in 0.5 C decrements to 2.2 C. The set-point decrease restored the average DM XA1 temperature to a nominal value of 19.7 C on November 21.

Direct Oral Anticoagulants: An Overview for the Interventional Radiologist

Energy Technology Data Exchange (ETDEWEB)

Kumar, Pradesh, E-mail: pradeshkumar@doctors.org.uk; Ravi, Rajeev, E-mail: rajeev.ravi@aintree.nhs.uk; Sundar, Gaurav, E-mail: gaurav.sundar@aintree.nhs.uk [Aintree University Hospitals NHS Foundation Trust, Radiology Department (United Kingdom); Shiach, Caroline, E-mail: caroline.shiach@aintree.nhs.uk [Aintree University Hospitals NHS Foundation Trust, Haematology Department (United Kingdom)

2017-03-15

The direct oral anticoagulants (DOACs) have emerged as a good alternative for the treatment of thromboembolic diseases, and their use in clinical practice is increasing rapidly. The DOACs act by blocking the activity of one single step in the coagulation cascade. These drugs act downstream in the common pathway of the coagulation cascade by directly antagonising the action of thrombin or factor Xa. The development of DOACs represents a paradigm shift from the oral vitamin K antagonists such as warfarin. This article aims to describe the properties of the currently available DOACs including pharmacology and dosing. We also address the strategies for periprocedural management and reversal of anticoagulation of patients treated with these agents.

Rivaroxaban-Induced Nontraumatic Spinal Subdural Hematoma: An Uncommon Yet Life-Threatening Complication

Directory of Open Access Journals (Sweden)

Mazen Zaarour

2015-01-01

Full Text Available In the last decade, the desire for safer oral anticoagulants (OACs led to the emergence of newer drugs. Available clinical trials demonstrated a lower risk of OACs-associated life-threatening bleeding events, including intracranial hemorrhage, compared to warfarin. Nontraumatic spinal hematoma is an uncommon yet life-threatening neurosurgical emergency that can be associated with the use of these agents. Rivaroxaban, one of the newly approved OACs, is a direct factor Xa inhibitor. To the best of our knowledge, to date, only two published cases report the incidence of rivaroxaban-induced nontraumatic spinal subdural hematoma (SSDH. Our case is the third one described and the first one to involve the cervicothoracic spine.

Direct Oral Anticoagulants: An Overview for the Interventional Radiologist

International Nuclear Information System (INIS)

Kumar, Pradesh; Ravi, Rajeev; Sundar, Gaurav; Shiach, Caroline

2017-01-01

The direct oral anticoagulants (DOACs) have emerged as a good alternative for the treatment of thromboembolic diseases, and their use in clinical practice is increasing rapidly. The DOACs act by blocking the activity of one single step in the coagulation cascade. These drugs act downstream in the common pathway of the coagulation cascade by directly antagonising the action of thrombin or factor Xa. The development of DOACs represents a paradigm shift from the oral vitamin K antagonists such as warfarin. This article aims to describe the properties of the currently available DOACs including pharmacology and dosing. We also address the strategies for periprocedural management and reversal of anticoagulation of patients treated with these agents.

Blind Pose Prediction, Scoring, and Affinity Ranking of the CSAR 2014 Dataset.

Science.gov (United States)

Martiny, Virginie Y; Martz, François; Selwa, Edithe; Iorga, Bogdan I

2016-06-27

The 2014 CSAR Benchmark Exercise was focused on three protein targets: coagulation factor Xa, spleen tyrosine kinase, and bacterial tRNA methyltransferase. Our protocol involved a preliminary analysis of the structural information available in the Protein Data Bank for the protein targets, which allowed the identification of the most appropriate docking software and scoring functions to be used for the rescoring of several docking conformations datasets, as well as for pose prediction and affinity ranking. The two key points of this study were (i) the prior evaluation of molecular modeling tools that are most adapted for each target and (ii) the increased search efficiency during the docking process to better explore the conformational space of big and flexible ligands.

Dgroup: DG01195 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available man serum albumin (JP17) ... D02796 ... Albumin iodinated I 131 serum (USAN) ... ATC code: V09XA03 Radioactive diagnostic... agents for Cardiovascular system, Radioactive diagnostic agents for blood volume determination ...

Drug: D10849 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available D10849 Mixture ... Drug Methoxy polyethylene glycol - epoetin beta mixt; Mircera (TN...) Polyethylene glycol monomethyl ester [DR:D05554], Epoetin beta [DR:D03232] ... ATC code: B03XA03 ... PubChem: 319902649 ...

Comparison of transgenic plant production for bacterial blight ...

African Journals Online (AJOL)

USER

2010-03-29

Mar 29, 2010 ... DR - 82 with calli exposed to 300 µM acetosyringone for 2 min. ... provided by the Xa 21 gene. Key words: Transformation efficiency, selection, regeneration, resistance evaluation. ...... Shrawat AK, Becker D, Lorz H (2006).

Drug: D08251 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available D08251 Drug Nandrolone laurate; Nandrolone dodecanoate; Laurabolin [veterinary] (T...14AB01 S01XA11 Chemical group: DG00142 ... Estren derivative veterinary medicine NR3C4 (AR) [HSA:367] [KO:K085

76 FR 25308 - Marine Mammals

Science.gov (United States)

2011-05-04

...-XA165 Marine Mammals AGENCY: National Marine Fisheries Service (NMFS), National Oceanic and Atmospheric... Jennifer Burns, Ph.D., University of Alaska Anchorage, Biology Department, 3101 Science Circle, Anchorage, AK, has been issued a permit to conduct [[Page 25309

On the revision of action laws: an algorithmic approach

CSIR Research Space (South Africa)

Varzinczak, JJ

2009-07-01

Full Text Available that buying can be executed whenever the agent has a token. The set of executability laws of a domain is denoted by X . Given a, Ea (resp. Xa) will denote the set of only those effect (resp. executability) laws about a. Action Theories T = S ∪ E ∪ X...(pi ∧ ϕA) → ⊥ then if T |=Kn(pi∧ϕA) → 〈a〉> and S ′, E ′,X 6|=Kn¬(pi∧ϕA) then Xa′:= {(ϕi∧ pi∧ϕA) → 〈a〉> : ϕi → 〈a〉> ∈ Xa} /* preserve executability law in state not removed */ else E ′:= E ′ ∪ {(pi ∧ ϕA) → [a]⊥} T?ϕ:= S ′ ∪ E ′ ∪ X ′ 4.2 Revising a...

Threshold equalization algorithm for the XAA1.2 ASICs and its application to SuperAGILE X-ray imager

International Nuclear Information System (INIS)

Pacciani, Luigi; Uberti, Olga; Del Monte, Ettore; Argan, Andrea; Feroci, Marco; Soffitta, Paolo; Trois, Alessio; Costa, Enrico; Donnarumma, Immacolata; Evangelista, Yuri; Lazzarotto, Francesco; Rapisarda, Massimo; Morelli, Ennio; Mastropietro, Marcello; Rubini, Alda

2008-01-01

In this paper we report the procedure developed and the results achieved for the equalization of threshold levels for the 6144 discriminator units of XAA1.2 ASICs chosen for the SuperAGILE X-ray imager onboard the AGILE satellite. For these kinds of imager, we will show that the threshold equalization is a critical issue. For each XAA1.2 we reduced the threshold dispersion by a factor of 3-4, and a factor of ∼2 for daisy chains of ASICs. Despite the method being developed for XAA1.2, the discriminator units and threshold fine-adjustment circuits are common to other chips of XA and VA-TA family, so that the algorithm and results can be extended to these two families of ASICs. This work may be useful for the design of electronic boards where the threshold equalization is a crucial issue

Threshold equalization algorithm for the XAA1.2 ASICs and its application to SuperAGILE X-ray imager

Energy Technology Data Exchange (ETDEWEB)

Pacciani, Luigi [Istituto di Fisica Spaziale e Fisica Cosmica, INAF, Roma, via Fosso del Cavaliere, 100-I-00133 Roma (Italy)], E-mail: luigi.pacciani@iasf-roma.inaf.it; Uberti, Olga; Del Monte, Ettore; Argan, Andrea; Feroci, Marco; Soffitta, Paolo; Trois, Alessio; Costa, Enrico; Donnarumma, Immacolata; Evangelista, Yuri; Lazzarotto, Francesco [Istituto di Fisica Spaziale e Fisica Cosmica, INAF, Roma, via Fosso del Cavaliere, 100-I-00133 Roma (Italy); Rapisarda, Massimo [ENEA C.R. Frascati, via Enrico Fermi, 45, I-00044 Frascati (RM) (Italy); Morelli, Ennio [Istituto di Fisica Spaziale e Fisica Cosmica, INAF, Bologna, via P. Gobetti, 101-I-40129 Bologna (Italy); Mastropietro, Marcello [Istituto dei Sistemi Complessi, CNR, Roma, via Salaria, km 29300, I-00016 Monterotondo Scalo (RM) c.p. 10 (Italy); Rubini, Alda [Istituto di Fisica Spaziale e Fisica Cosmica, INAF, Roma, via Fosso del Cavaliere, 100-I-00133 Roma (Italy)

2008-08-11

In this paper we report the procedure developed and the results achieved for the equalization of threshold levels for the 6144 discriminator units of XAA1.2 ASICs chosen for the SuperAGILE X-ray imager onboard the AGILE satellite. For these kinds of imager, we will show that the threshold equalization is a critical issue. For each XAA1.2 we reduced the threshold dispersion by a factor of 3-4, and a factor of {approx}2 for daisy chains of ASICs. Despite the method being developed for XAA1.2, the discriminator units and threshold fine-adjustment circuits are common to other chips of XA and VA-TA family, so that the algorithm and results can be extended to these two families of ASICs. This work may be useful for the design of electronic boards where the threshold equalization is a crucial issue.

76 FR 49735 - Endangered and Threatened Species; Take of Anadromous Fish

Science.gov (United States)

2011-08-11

... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA631 Endangered and Threatened Species; Take of Anadromous Fish AGENCY: National Marine Fisheries Service (NMFS.... Therese Conant, Acting Chief, Endangered Species Division, Office of Protected Resources, National Marine...

76 FR 4551 - Hawaii Crustacean Fisheries; 2011 Northwestern Hawaiian Islands Lobster Harvest Guideline

Science.gov (United States)

2011-01-26

... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration 50 CFR Part 665 RIN 0648-XA159 Hawaii Crustacean Fisheries; 2011 Northwestern Hawaiian Islands Lobster Harvest Guideline AGENCY: National Marine Fisheries Service (NMFS), National Oceanic and Atmospheric Administration (NOAA), Commerce...

Ubiquitin-fusion as a strategy to modulate protein half-life: A3G antiviral activity revisited

International Nuclear Information System (INIS)

Cadima-Couto, Iris; Freitas-Vieira, Acilino; Nowarski, Roni; Britan-Rosich, Elena; Kotler, Moshe; Goncalves, Joao

2009-01-01

The human APOBEC3G (A3G) is a potent inhibitor of HIV-1 replication and its activity is suppressed by HIV-1 virion infectivity factor (Vif). Vif neutralizes A3G mainly by inducing its degradation in the proteasome and blocking its incorporation into HIV-1 virions. Assessing the time needed for A3G incorporation into virions is, therefore, important to determine how quickly Vif must act to induce its degradation. We show that modelling the intracellular half-life of A3G can induce its Vif-independent targeting to the ubiquitin-proteasome system. By using various amino acids (X) in a cleavable ubiquitin-X-A3G fusion, we demonstrate that the half-life (t1/2) of X-A3G can be manipulated. We show that A3G molecules with a half-life of 13 min are incorporated into virions, whereas those with a half-life shorter than 5 min were not. The amount of X-A3G incorporated into virions increases from 13 min (Phe-A3G) to 85 min (Asn-A3G) and remains constant after this time period. Interestingly, despite the presence of similar levels of Arg-A3G (t1/2 = 28 min) and Asp-A3G (t1/2 = 65 min) into HIV-1 Δvif virions, inhibition of viral infectivity was only evident in the presence of A3G proteins with a longer half-life (t1/2 ≥ 65 min).

Changes in heparin dose response slope during cardiac surgery: possible result in inaccuracy in predicting heparin bolus dose requirement to achieve target ACT.

Science.gov (United States)

Ichikawa, Junko; Mori, Tetsu; Kodaka, Mitsuharu; Nishiyama, Keiko; Ozaki, Makoto; Komori, Makiko

2017-09-01

The substantial interpatient variability in heparin requirement has led to the use of a heparin dose response (HDR) technique. The accuracy of Hepcon-based heparin administration in achieving a target activated clotting time (ACT) using an HDR slope remains controversial. We prospectively studied 86 adult patients scheduled for cardiac surgery requiring cardiopulmonary bypass. The total dose of calculated heparin required for patient and pump priming was administered simultaneously to achieve a target ACT of 450 s for HDR on the Hepcon HMS system. Blood samples were obtained after the induction of anesthesia, at 3 min after heparin administration and after the initiation of CPB to measure kaolin ACT, HDR slope, whole-blood heparin concentration based on the HDR slope and anti-Xa heparin concentration, antithrombin and complete blood count. The target ACT of 450 s was not achieved in 68.6% of patients. Compared with patients who achieved the target ACT, those who failed to achieve their target ACT had a significantly higher platelet count at baseline. Correlation between the HDR slope and heparin sensitivity was poor. Projected heparin concentration and anti-Xa heparin concentration are not interchangeable based on the Bland-Altman analysis. It can be hypothesized that the wide discrepancy in HDR slope versus heparin sensitivity may be explained by an inaccurate prediction of the plasma heparin level and/or the change in HDR of individual patients, depending on in vivo factors such as extravascular sequestration of heparin, decreased intrinsic antithrombin activity level and platelet count and/or activity.

Dgroup: DG00137 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available DG00137 Chemical ... DGroup Calcium chloride ... C08130 ... Calcium chloride anhydrous D02256 ... Calcium... chloride (USP); Calcium chloride hydrate (JP17) ... ATC code: A12AA07 B05XA07 G04BA03 Calcium supplement ...

76 FR 26253 - Marine Fisheries Advisory Committee Meeting

Science.gov (United States)

2011-05-06

...; National Ocean Policy, coastal and marine spatial planning, ocean energy and climate change adaptation... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA412 Marine Fisheries Advisory Committee Meeting AGENCY: National Marine Fisheries Service (NMFS), National Oceanic and...

76 FR 5338 - Endangered and Threatened Species; Take of Anadromous Fish

Science.gov (United States)

2011-01-31

... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA183 Endangered and Threatened Species; Take of Anadromous Fish AGENCY: National Marine Fisheries Service (NMFS... regulations (50 CFR parts 222-226) governing listed fish and wildlife permits. [[Page 5339

76 FR 6401 - Endangered and Threatened Species; Take of Anadromous Fish

Science.gov (United States)

2011-02-04

... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA110 Endangered and Threatened Species; Take of Anadromous Fish AGENCY: National Marine Fisheries Service (NMFS... and the Washington Department of Fish and Wildlife submitted to NMFS, pursuant to the protective...

76 FR 65700 - Atlantic Highly Migratory Species; Advisory Panel for Atlantic Highly Migratory Species Southeast...

Science.gov (United States)

2011-10-24

.... Virgin Islands and Puerto Rico, and each of the constituent interstate commissions: the Atlantic States... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA776 Atlantic Highly Migratory Species; Advisory Panel for Atlantic Highly Migratory Species Southeast Data, Assessment...

Incisors as digging tools in molerats (Bathyergidae)

African Journals Online (AJOL)

1998-03-26

Xa and Vb) at which the upper and lower incisors (lines a- ..... JARVIS. JU.M., BENNETT. N.C. 1991. Introducing the Alriean mole-rats (family Bathyergidae). In: The biology of the naked mole-rat: 66 - 96. (Eds) Sherman. R. W ..

77 FR 5775 - Caribbean Fishery Management Council; Public Meeting

Science.gov (United States)

2012-02-06

... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN: 0648-XA981 Caribbean... Oceanic and Atmospheric Administration (NOAA), Commerce. ACTION: Notice of public meeting. SUMMARY: The... --Bulletin/Newsletter --Social Network Pages --Streaming of Council Meetings --Other Business The meeting is...

76 FR 9553 - Mid-Atlantic Fishery Management Council; Public Meeting

Science.gov (United States)

2011-02-18

... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA226 Mid-Atlantic... Oceanic and Atmospheric Administration (NOAA), Commerce. ACTION: Notice of public meeting. SUMMARY: The Social and Economic Sub-Committee of the Mid-Atlantic Fishery Management Council's (Council) Scientific...

76 FR 16620 - Mid-Atlantic Fishery Management Council (MAFMC); Meeting

Science.gov (United States)

2011-03-24

... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA316 Mid-Atlantic... Oceanic and Atmospheric Administration (NOAA), Commerce. ACTION: Notice of public meeting. SUMMARY: The Social and Economic Sub-Committee of the Mid-Atlantic Fishery Management Council's (Council) Scientific...

77 FR 1671 - Endangered Species; File No. 16194

Science.gov (United States)

2012-01-11

... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA925 Endangered... olivacea), leatherback (Dermochelys coriacea), and unidentified hardshell sea turtles for the purposes of..., leatherback, Kemp's ridley, olive ridley, and unidentified hardshell sea turtles had been submitted by the...

77 FR 8776 - Fisheries of the Northeastern United States; Atlantic Bluefish Fishery; 2012 Atlantic Bluefish...

Science.gov (United States)

2012-02-15

.... 120201086-2085-01] RIN 0648-XA904 Fisheries of the Northeastern United States; Atlantic Bluefish Fishery; 2012 Atlantic Bluefish Specifications AGENCY: National Marine Fisheries Service (NMFS), National... comments. SUMMARY: NMFS proposes specifications for the 2012 Atlantic bluefish fishery, including an annual...

Estudo parcial da validação do Atlas do Rorschach Sistema Compreensivo em amostra de pacientes psiquiátricos de São Paulo Estudio parcial de la validación del Atlas del Rorschach Sistema Comprensivo en muestra de pacientes psiquiátricos de São Paulo Partial validation study of the Rorschach Comprehensive System atlas on a sample of psychiatric patients of São Paulo

Directory of Open Access Journals (Sweden)

Thaís Cristina Marques

2012-12-01

Full Text Available Este trabalho é parte do estudo de validação do atlas de localização e da lista de qualidade formal brasileiros do Rorschach Sistema Compreensivo em amostra de pacientes psiquiátricos da cidade de São Paulo, comparando as variáveis X+%, XA%, WDA%, X-% e Xu% dos pacientes com os valores encontrados na amostra normativa brasileira. Foram avaliados 45 pacientes, e os instrumentos de seleção foram a entrevista clínica estruturada para diagnóstico do DSM-IV (SCID-I e a Escala das Síndromes Positiva e Negativa (PANSS. 23 pacientes preencheram critério pela SCID-I para transtornos psicóticos e, destes, 19 foram considerados psicóticos pela PANSS. Todos os protocolos foram classificados segundo as classificações norte-americanas e brasileiras. Foi realizada ANOVA, comparando amostras normativas e o grupo de pacientes. As variáveis XA% e X-% mostraram-se sensíveis para detectar as nuances perceptivas entre as pessoas. As áreas de localização e lista de qualidade formal brasileiras se mostraram válidas para discriminar graus de comprometimento perceptivo.Este trabajo es parte del estudio de validación del atlas de localización y de la lista de calidad formal brasileña del Rorschach Sistema Comprensivo en muestra de pacientes psiquiátricos de la ciudad de São Paulo-Brasil, comparando las variables X+%, XA%, WDA%, X-% y Xu% de los pacientes con los valores encontrados en la muestra normativa brasileña. Fueron evaluados 45 pacientes, los instrumentos de selección fueron la Entrevista clínica estructurada para diagnóstico del DSM-IV (SCID-I y la Escala de las Síndromes Positiva y Negativa (PANSS. 23 pacientes lograron criterio por la SCID-I para trastornos psicóticos y de estos 19 fueron considerados psicóticos por la PANSS. Todos los protocolos fueron clasificados según las clasificaciones norteamericanas y brasileñas. Fue realizada ANOVA, comparando muestras normativas y el grupo de pacientes. Las variables XA% y X-% se

Blocking of platelets or intrinsic coagulation pathway-driven thrombosis does not prevent cerebral infarctions induced by photothrombosis.

Science.gov (United States)

Kleinschnitz, Christoph; Braeuninger, Stefan; Pham, Mirko; Austinat, Madeleine; Nölte, Ingo; Renné, Thomas; Nieswandt, Bernhard; Bendszus, Martin; Stoll, Guido

2008-04-01

Models of photochemically-induced thrombosis are widely used in cerebrovascular research. Photothrombotic brain infarctions can be induced by systemic application of photosensitizing dyes followed by focal illumination of the cerebral cortex. Although the ensuing activation of platelets is well established, their contribution for thrombosis and tissue damage has not formally been proved. Infarction to the cerebral cortex was induced in mice by Rose Bengal and a cold light source. To assess the functional role of platelets, animals were platelet-depleted by anti-GPIbalpha antibodies or treated with GPIIb/IIIa-blocking F(ab)(2) fragments. The significance of the plasmatic coagulation cascade was determined by using blood coagulation factor XII (FXII)-deficient mice or heparin. Infarct development and infarct volumes were determined by serial MRI and conventional and electron microscopy. There was no difference in development and final size of photothrombotic infarctions in mice with impaired platelet function. Moreover, deficiency of FXII, which initiates the intrinsic pathway of coagulation and is essential for thrombus formation, or blockade of FXa, the key protease during the waterfall cascade of plasmatic coagulation, by heparin likewise did not affect lesion development. Our data demonstrate that platelet activation, factor XII-driven thrombus formation, and plasmatic coagulation pathways downstream of FX are not a prerequisite for ensuing tissue damage in models of photothrombotic vessel injury indicating that other pathomechanisms are involved. We suggest that this widely used model does not depend on platelet- or plasmatic coagulation-derived thrombosis.

Reversal of target-specific oral anticoagulants

Science.gov (United States)

Siegal, D.M.; Cuker, Adam

2014-01-01

Target-specific oral anticoagulants (TSOACs) provide safe and effective anticoagulation for the prevention and treatment of thrombosis in a variety of clinical settings by interfering with the activity of thrombin (dabigatran) or factor Xa (rivaroxaban, apixaban, edoxaban, betrixaban). Although TSOACs have practical advantages over vitamin K antagonists (VKAs), there are currently no antidotes to reverse their anticoagulant effect. Herein we summarize the available evidence for TSOAC reversal using nonspecific and specific reversal agents. We discuss important limitations of existing evidence, which is derived from studies in human volunteers, animal models and in vitro experiments. Studies evaluating the safety and efficacy of reversal agents on clinical outcomes such as bleeding and mortality in patients with TSOAC-associated bleeding are needed. PMID:24880102

Random Forests Are Able to Identify Differences in Clotting Dynamics from Kinetic Models of Thrombin Generation.

Science.gov (United States)

Arumugam, Jayavel; Bukkapatnam, Satish T S; Narayanan, Krishna R; Srinivasa, Arun R

2016-01-01

Current methods for distinguishing acute coronary syndromes such as heart attack from stable coronary artery disease, based on the kinetics of thrombin formation, have been limited to evaluating sensitivity of well-established chemical species (e.g., thrombin) using simple quantifiers of their concentration profiles (e.g., maximum level of thrombin concentration, area under the thrombin concentration versus time curve). In order to get an improved classifier, we use a 34-protein factor clotting cascade model and convert the simulation data into a high-dimensional representation (about 19000 features) using a piecewise cubic polynomial fit. Then, we systematically find plausible assays to effectively gauge changes in acute coronary syndrome/coronary artery disease populations by introducing a statistical learning technique called Random Forests. We find that differences associated with acute coronary syndromes emerge in combinations of a handful of features. For instance, concentrations of 3 chemical species, namely, active alpha-thrombin, tissue factor-factor VIIa-factor Xa ternary complex, and intrinsic tenase complex with factor X, at specific time windows, could be used to classify acute coronary syndromes to an accuracy of about 87.2%. Such a combination could be used to efficiently assay the coagulation system.

Random Forests Are Able to Identify Differences in Clotting Dynamics from Kinetic Models of Thrombin Generation.

Directory of Open Access Journals (Sweden)

Jayavel Arumugam

Full Text Available Current methods for distinguishing acute coronary syndromes such as heart attack from stable coronary artery disease, based on the kinetics of thrombin formation, have been limited to evaluating sensitivity of well-established chemical species (e.g., thrombin using simple quantifiers of their concentration profiles (e.g., maximum level of thrombin concentration, area under the thrombin concentration versus time curve. In order to get an improved classifier, we use a 34-protein factor clotting cascade model and convert the simulation data into a high-dimensional representation (about 19000 features using a piecewise cubic polynomial fit. Then, we systematically find plausible assays to effectively gauge changes in acute coronary syndrome/coronary artery disease populations by introducing a statistical learning technique called Random Forests. We find that differences associated with acute coronary syndromes emerge in combinations of a handful of features. For instance, concentrations of 3 chemical species, namely, active alpha-thrombin, tissue factor-factor VIIa-factor Xa ternary complex, and intrinsic tenase complex with factor X, at specific time windows, could be used to classify acute coronary syndromes to an accuracy of about 87.2%. Such a combination could be used to efficiently assay the coagulation system.

Identification of Bacterial Plant Pathogens Using Multilocus Polymerase Chain Reaction/Electrospray Ionization-Mass Spectrometry

Science.gov (United States)

2008-01-01

pathogens also have been detected and identified by numerous nucleic acid-based techniques, including Southern blot hybridization and direct nucleotide...Xanthomonas axonopodis pv. vitians FB-1309; ATCC19320 Lettuce ; USA 1 Xanthomonas axonopodis sp. alfalfae XA129; Med. 2 Alfalfa; Sudan 1 Xanthomonas

76 FR 5339 - Endangered and Threatened Species; Take of Anadromous Fish

Science.gov (United States)

2011-01-31

... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA182 Endangered and Threatened Species; Take of Anadromous Fish AGENCY: National Marine Fisheries Service (NMFS... are issued in accordance with and are subject to the ESA and NMFS regulations governing listed fish...

78 FR 36550 - Proposed Data Collections Submitted for Public Comment and Recommendations

Science.gov (United States)

2013-06-18

... barriers to program implementation, solutions to those barriers, and documentation of client health... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention [60Day-13-13XA... prescription filling patterns and timing of refills, checking for medication interactions, patient education...

76 FR 56742 - Mid-Atlantic Fishery Management Council; Workshop

Science.gov (United States)

2011-09-14

... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA700 Mid-Atlantic... and Atmospheric Administration (NOAA), Commerce. ACTION: Notice of a workshop. SUMMARY: The Eight..., economic and social perspectives. DATES: The workshop will be held Tuesday, October 4 through Thursday...

76 FR 71939 - New England Fishery Management Council; Public Meeting

Science.gov (United States)

2011-11-21

... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA837 New England... Oceanic and Atmospheric Administration (NOAA), Commerce. ACTION: Notice; public meeting. SUMMARY: The New... Scientific and Statistical Committee (SSC) will discuss the 2012 SSC calendar and tasks, social science...

77 FR 2961 - Mid-Atlantic Fishery Management Council (MAFMC); Public Meeting

Science.gov (United States)

2012-01-20

... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA943 Mid-Atlantic...), National Oceanic and Atmospheric Administration (NOAA), Commerce. ACTION: Notice of a public meeting... with the Council's Social and Economic Sub-committee of the Scientific and Statistical Committee (SSC...

76 FR 78242 - Endangered and Threatened Species; Take of Anadromous Fish

Science.gov (United States)

2011-12-16

... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA866 Endangered and Threatened Species; Take of Anadromous Fish AGENCY: National Marine Fisheries Service (NMFS... Endangered Species Act (ESA) and to help guide management and conservation efforts. The application may be...

75 FR 71670 - Endangered Species; File No. 15606

Science.gov (United States)

2010-11-24

... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA054 Endangered... (Lepidochelys kempii), loggerhead (Caretta caretta), and hawksbill (Eretmochelys imbricata) sea turtles for... INFORMATION: The subject permit is requested under the authority of the Endangered Species Act of 1973, as...

76 FR 22877 - Endangered Species; File No. 15566

Science.gov (United States)

2011-04-25

... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA387 Endangered...), leatherback (Dermochelys coriacea), and hawksbill (Eretmochelys imbricata) sea turtles for purposes of... Federal Register (75 FR 67682) that a request for a scientific research permit to take sea turtles had...

76 FR 33245 - Endangered Species; File No. 15135

Science.gov (United States)

2011-06-08

... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA466 Endangered..., 132 Conch Court, Emerald Isle, NC 28594, has been issued a permit to take threatened and endangered sea turtles for purposes scientific research. ADDRESSES: The permit and related documents are...

76 FR 20324 - Endangered Species; File No. 15606

Science.gov (United States)

2011-04-12

... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA354 Endangered...), loggerhead (Caretta caretta), and hawksbill (Eretmochelys imbricata) sea turtles for purposes of scientific..., loggerhead, and hawksbill sea turtles had been submitted by the above-named individual. The requested permit...

77 FR 25100 - Fisheries of the Northeastern United States; Atlantic Bluefish Fishery; 2012 Atlantic Bluefish...

Science.gov (United States)

2012-04-27

.... 120201086-2418-02] RIN 0648-XA904 Fisheries of the Northeastern United States; Atlantic Bluefish Fishery; 2012 Atlantic Bluefish Specifications AGENCY: National Marine Fisheries Service (NMFS), National... specifications for the 2012 Atlantic bluefish fishery, including an annual catch limit, total allowable landings...

Long-term outcome of FFR-guided PCI for stable coronary artery disease in daily clinical practice

DEFF Research Database (Denmark)

De Backer, Ole; Biasco, Luigi; Lønborg, Jacob

2016-01-01

AIMS: Our aim was to investigate the strength of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) for stable coronary artery disease (CAD) in daily practice. METHODS AND RESULTS: For this study, 3,512 patients with stable CAD and at least one 50-89% coronary stenosis...... were identified; those patients thought to require PCI (n=1,716) were selected. Of these, 962 (56%) were treated based on angiography (XA) alone, whereas 754 patients (44%) had an FFR-guided treatment. In the latter group, 321 patients (43%) were reallocated to another treatment, predominantly medical...... treatment. After propensity score matching, the number of indicated lesions was 957 in the XA-guided group and 947 in the FFR-guided group. FFR guidance resulted in PCI deferral in 462 lesions (48.8%). In a seven-day landmark analysis, the rate of periprocedural myocardial infarction (MI) was less than half...

76 FR 41764 - Fisheries of the Caribbean, Gulf of Mexico, and South Atlantic; Coral and Coral Reefs off the...

Science.gov (United States)

2011-07-15

... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration [RIN 0648-XA491] Fisheries of the Caribbean, Gulf of Mexico, and South Atlantic; Coral and Coral Reefs off the Southern Atlantic... sanctuaries, special management zones, or artificial reefs without additional authorization. A report on the...

77 FR 2037 - Marine Mammals; Photography Permit File No. 17032

Science.gov (United States)

2012-01-13

... filmmaker hopes to document the behavior of marine animals in the presence of a gray whale carcass. Filming... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA929 Marine Mammals; Photography Permit File No. 17032 AGENCY: National Marine Fisheries Service (NMFS), National...

77 FR 24470 - Marine Mammals; Photography Permit File No. 17032

Science.gov (United States)

2012-04-24

... behavior of marine animals in the presence of a gray whale carcass. Filming will occur between April and... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA929 Marine Mammals; Photography Permit File No. 17032 AGENCY: National Marine Fisheries Service (NMFS), National...

77 FR 2037 - Endangered and Threatened Species; Take of Anadromous Fish

Science.gov (United States)

2012-01-13

... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA928 Endangered and Threatened Species; Take of Anadromous Fish AGENCY: National Marine Fisheries Service (NMFS... advises the public that a direct take permit has been issued to the Washington Department of Fish and...

76 FR 53343 - Atlantic Highly Migratory Species; Commercial Porbeagle Shark Fishery Closure

Science.gov (United States)

2011-08-26

...-XA658 Atlantic Highly Migratory Species; Commercial Porbeagle Shark Fishery Closure AGENCY: National...: Temporary rule; fishery closure. SUMMARY: NMFS is closing the commercial fishery for porbeagle sharks. This... available quota. DATES: The commercial porbeagle shark fishery is closed effective 11:30 p.m. local time...

75 FR 74004 - Atlantic Highly Migratory Species; Advisory Panel

Science.gov (United States)

2010-11-30

... Atlantic Regional Fishery Management Councils, each of the 18 constituent states, both the U.S. Virgin... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA059 Atlantic... nominations for the Advisory Panel (AP) for Atlantic Highly Migratory Species (HMS) Southeast Data, Assessment...

76 FR 57958 - Fisheries of the South Atlantic and Gulf of Mexico; South Atlantic Fishery Management Council...

Science.gov (United States)

2011-09-19

... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN: 0648-XA708 Fisheries...), Commerce. ACTION: Notice of public meetings. SUMMARY: The South Atlantic Fishery Management Council (SAFMC...-pane reviews social and economic information and reports its findings to the SSC. The SEP will discuss...

76 FR 61284 - Accountability Measures and Reduced Season for the South Atlantic Recreational Sector of Golden...

Science.gov (United States)

2011-10-04

... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration 50 CFR Part 622 [Docket No. 0907271173-0629-03] RIN 0648-XA701 Accountability Measures and Reduced Season for the South Atlantic.... SUMMARY: NMFS implements accountability measures (AMs) for the recreational sector of golden tilefish in...

77 FR 24686 - Endangered Species; File No. 15634

Science.gov (United States)

2012-04-25

... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA714 Endangered... Ballance, Ph.D.] has been issued a permit to take leatherback sea turtles (Dermochelys coriacea) for... permit to take leatherback sea turtles had been submitted by the above-named organization. The requested...

77 FR 1062 - Endangered Species; File No. 16146

Science.gov (United States)

2012-01-09

... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA900 Endangered... (Eretmochelys imbricata) sea turtles for the purposes of scientific research. ADDRESSES: The permit and related... take loggerhead, green, and hawksbill sea turtles had been submitted by the above-named individual. The...

76 FR 37327 - Endangered Species; File No. 16253

Science.gov (United States)

2011-06-27

... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA518 Endangered... loggerhead (Caretta caretta) sea turtles for scientific research. DATES: Written, telefaxed, or e-mail... INFORMATION: The subject permit is requested under the authority of the Endangered Species Act of 1973, as...

76 FR 19052 - Endangered Species; File No. 14344

Science.gov (United States)

2011-04-06

...-named organization. The requested permit has been issued under the authority of the Endangered Species..., importing, and exporting of endangered and threatened species (50 CFR parts 222-226). The permit authorizes... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA340 Endangered...

76 FR 51945 - Endangered Species; File No. 16548

Science.gov (United States)

2011-08-19

.... SUPPLEMENTARY INFORMATION: The subject permit is requested under the authority of the Endangered Species Act of... exporting of endangered and threatened species (50 CFR parts 222-226). The Springfield Science Museum is... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA648 Endangered...

76 FR 45230 - Endangered Species; File No. 15802

Science.gov (United States)

2011-07-28

... INFORMATION: The subject permit is requested under the authority of the Endangered Species Act of 1973, as... of endangered and threatened species (50 CFR 222-226). The applicant proposes to monitor smalltooth... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA603 Endangered...

77 FR 30261 - Endangered Species; File No. 16306

Science.gov (United States)

2012-05-22

..., importing, and exporting of endangered and threatened species (50 CFR parts 222-226). The Maine Department... to the disadvantage of such endangered or threatened species, and (3) is consistent with the purposes... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA712 Endangered...

77 FR 47356 - North Pacific Fishery Management Council; Essential Fish Habitat Amendments

Science.gov (United States)

2012-08-08

...-XA500 North Pacific Fishery Management Council; Essential Fish Habitat Amendments AGENCY: National... Pacific Fishery Management Council submitted the following essential fish habitat (EFH) amendments to NMFS... Scallop Fishery off Alaska; and Amendment 1 to the FMP for Fish Resources of the Arctic Management Area...

76 FR 18416 - Atlantic Highly Migratory Species; Atlantic Bluefin Tuna Fisheries

Science.gov (United States)

2011-04-04

... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration 50 CFR Part 635 [Docket No. 100317152-0176-01] RIN 0648-XA327 Atlantic Highly Migratory Species; Atlantic Bluefin Tuna Fisheries AGENCY... ability to attract customers. In addition, recent Large Pelagics Survey estimates indicate that charter...

77 FR 25145 - Marine Mammals; File No. 978-1857

Science.gov (United States)

2012-04-27

... mammals at the Hawaii Institute of Marine Biology through May 31, 2012. The minor amendment (No. 978-1857... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA37 Marine Mammals; File No. 978-1857 AGENCY: National Marine Fisheries Service (NMFS), National Oceanic and...

76 FR 28422 - Marine Mammals; File No. 16053

Science.gov (United States)

2011-05-17

... Paul E. Nachtigall, PhD, Marine Mammal Research Program Hawaii Institute of Marine Biology, P.O. Box... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA384 Marine Mammals; File No. 16053 AGENCY: National Marine Fisheries Service (NMFS), National Oceanic and Atmospheric...

Sex determining signal in Drosophila melanogaster

Indian Academy of Sciences (India)

Administrator

Addition of almost any segment of the X chromosome pro- duced a shift towards ... It is now well established that the X/A signal acts to set the functional state ... tionally related because a defect in one of them can be partly. COMMENTARY ON ...

Managing cancer-related venous thromboembolic disease: low-molecular-weight heparins and beyond.

Science.gov (United States)

O'Connell, Casey L; Liebman, Howard A

2008-12-01

Venous thromboembolism is a major contributor to the morbidity and mortality of patients with cancer. For patients undergoing cancer surgery, several trials support the safety and efficacy of unfractionated heparin and of low-molecular-weight heparin for the prevention of venous thromboembolism, while data regarding the efficacy and safety of these agents in the setting of medical hospitalization is less definitive and must be extracted from trials including noncancer patients with different thrombotic risk factors. Randomized clinical studies confirm that patients with cancer who develop venous thromboembolism have superior outcomes when treated with long-term low-molecular-weight heparin as compared with warfarin. Novel anticoagulants that are orally bioavailable and function by directly inhibiting factor Xa or thrombin are entering the market. To date, data regarding the efficacy and safety of these novel anticoagulants as venous thromboembolism prophylaxis and treatment in cancer patients are not available and must be extracted from larger trials with heterogeneous patient populations.

Anti-leishmanial evaluation of fraxinus xanthoxyloides (G. don) DC. collected from district Islamabad

International Nuclear Information System (INIS)

Younis, T.; Khan, M.R.; Zai, J.A.; Khan, H.; Shah, N.A.

2016-01-01

In this study, we have investigated phytochemical classes, antileishmanial and cytotoxic activity of Fraxinus xanthoxyloides (Oleaceae) leaves. Powder of F. xanthoxyloides leaves was extracted with methanol to obtain the crude extract (FXM) and the resultant was fractionated with solvents in escalating polarity; n-hexane (FXH), chloroform (FXC), ethyl acetate (FXE), n-butanol (FXB) and the residual aqueous (FXA) fraction. Quantitative estimation of terpenoids, coumarins, flavonoids, phenolics and tannins was conducted. Anti-leishmanial activity was performed against Leishmania tropica promastigote stage parasite while insecticidal activity was assessed through brine shrimps lethality assay. Our results showed the maximum concentration of terpenoids in FXC while the highest quantity of coumarins, flavonoids, phenolics and tannins was recorded in FXE. Presence of terpenoids was not detected in FXB and in FXA. Among the extract/fractions, FXC exhibited the highest anti-leishmanial activity with LD/sub 50/ of 15.239+-0.9 mu g/ml to that of glucantime (LD/sub 50/ = 5.6+-2.4 mu g/ml) a reference drug. FXH exhibited the anti-leishmanial activity of LD/sub 50/ = 40.68+-1.9 mu g/ml followed by FXE (LD/sub 50/ = 102.9+-3.1 mu g/ml). Similarly potent insecticidal activity was recorded (LD/sub 50/ = 28.15+-1.8 mu g/ml) for FXC followed by FXH (LD/sub 50/ = 67.59+-2.3 mu g/ml). However, other fractions exhibited low level of anti-leishmanial and insecticidal activity. Correlation analysis exhibited a strong association (p 0.05) with the insecticidal activity. The coumarins established a medium association with the insecticidal activity. Other chemical classes exhibited a moderate to low level of association with the anti-leishmanial and the insecticidal activity. On the basis of these results we can conclude that chloroform fraction of F. xanthoxyloides is a potential source for anti-leishmanial and insecticidal activities and further studies are required to isolate the active

Classifying and scoring of molecules with the NGN: new datasets, significance tests, and generalization

Directory of Open Access Journals (Sweden)

Cameron Christopher JF

2010-10-01

Full Text Available Abstract This paper demonstrates how a Neural Grammar Network learns to classify and score molecules for a variety of tasks in chemistry and toxicology. In addition to a more detailed analysis on datasets previously studied, we introduce three new datasets (BBB, FXa, and toxicology to show the generality of the approach. A new experimental methodology is developed and applied to both the new datasets as well as previously studied datasets. This methodology is rigorous and statistically grounded, and ultimately culminates in a Wilcoxon significance test that proves the effectiveness of the system. We further include a complete generalization of the specific technique to arbitrary grammars and datasets using a mathematical abstraction that allows researchers in different domains to apply the method to their own work. Background Our work can be viewed as an alternative to existing methods to solve the quantitative structure-activity relationship (QSAR problem. To this end, we review a number approaches both from a methodological and also a performance perspective. In addition to these approaches, we also examined a number of chemical properties that can be used by generic classifier systems, such as feed-forward artificial neural networks. In studying these approaches, we identified a set of interesting benchmark problem sets to which many of the above approaches had been applied. These included: ACE, AChE, AR, BBB, BZR, Cox2, DHFR, ER, FXa, GPB, Therm, and Thr. Finally, we developed our own benchmark set by collecting data on toxicology. Results Our results show that our system performs better than, or comparatively to, the existing methods over a broad range of problem types. Our method does not require the expert knowledge that is necessary to apply the other methods to novel problems. Conclusions We conclude that our success is due to the ability of our system to: 1 encode molecules losslessly before presentation to the learning system, and 2

Sen char nsory, acteris pequ physi stics o i (Cary coche of Gree ...

African Journals Online (AJOL)

SAM

purchase in. 1), 1% pequ .... xa Postal 66, s II da UFG, .... the exposure of consumers to high risks of contamination by a ... After the addition of the culture, the milk was kept at 42°C in .... and Robinson (1999), who studied the behavior of starter.

African Journal of Biotechnology - Vol 8, No 21 (2009)

African Journals Online (AJOL)

Analyses of karyotypes and comparative physical locations of the resistance gene, Xa-5, between Oryza sativa and Oryza,/i> officinalis · EMAIL FREE FULL .... Phytochemical constituents and effects of aqueous root-bark extract of Ficus sycomorus L. (Moracaea) on muscular relaxation, anaesthetic and sleeping time on ...

77 FR 32572 - Fisheries of the Caribbean, Gulf of Mexico, and South Atlantic; Coral and Coral Reefs Off the...

Science.gov (United States)

2012-06-01

... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA935 Fisheries of the Caribbean, Gulf of Mexico, and South Atlantic; Coral and Coral Reefs Off the Southern Atlantic... conditions, various species of reef fish, crabs, and lobsters in Federal waters off South Carolina and North...

76 FR 17434 - Receipt of Application for an Endangered Species Act Incidental Take Permit

Science.gov (United States)

2011-03-29

... Atmospheric Administration RIN 0648-XA020 Receipt of Application for an Endangered Species Act Incidental Take..., the Services) for incidental take permits (ITPs) under the Endangered Species Act of 1973, as amended...) and implementing regulations prohibit the taking of animal species listed as endangered or threatened...

77 FR 35355 - User Fee Schedule for Trade Promotion Services

Science.gov (United States)

2012-06-13

...-XA17 User Fee Schedule for Trade Promotion Services AGENCY: U.S. & Foreign Commercial Service... promotion services under the current fee structure. ITA provides a wide range of trade promotion information... these more intensive trade promotion services. The fee revenue is expected to continue to contribute to...

76 FR 71515 - Endangered Species; File No. 16174

Science.gov (United States)

2011-11-18

... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA826 Endangered... issued a permit to take green sea turtles (Chelonia mydas) for the purposes of scientific research... request for a scientific research permit to take green sea turtles had been submitted by the above-named...

75 FR 67682 - Endangered Species; File No. 15566

Science.gov (United States)

2010-11-03

... permit is requested under the authority of the Endangered Species Act of 1973, as amended (ESA; 16 U.S.C... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA013 Endangered Species; File No. 15566 AGENCY: National Marine Fisheries Service (NMFS), National Oceanic and Atmospheric...

75 FR 78974 - Endangered Species

Science.gov (United States)

2010-12-17

...-XA086 Endangered Species AGENCY: National Marine Fisheries Service (NMFS), National Oceanic and... the Endangered Species Act of 1973, as amended (16 U.S.C. 1531 et seq.) and the regulations governing the taking, importing, and exporting of endangered and threatened species (50 CFR 222-226). Permit...

76 FR 40699 - Endangered Species; File No. 16229

Science.gov (United States)

2011-07-11

.... SUPPLEMENTARY INFORMATION: The subject permit is requested under the authority of the Endangered Species Act of... exporting of endangered and threatened species (50 CFR 222-226). The North Carolina Zoo [File No. 16229] is... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA516 Endangered...

75 FR 82295 - Fisheries of the Northeastern United States; Atlantic Bluefish Fishery; Quota Transfer

Science.gov (United States)

2010-12-30

.... 100204079-0199-02] RIN 0648-XA084 Fisheries of the Northeastern United States; Atlantic Bluefish Fishery... the Commonwealth of Virginia is transferring commercial bluefish quota to the State of North Carolina... INFORMATION: Regulations governing the Atlantic bluefish fishery are found at 50 CFR part 648. The regulations...

76 FR 74009 - Fisheries of the Northeastern United States; Bluefish Fishery; Quota Transfer

Science.gov (United States)

2011-11-30

.... 101228634-1149-02] RIN 0648-XA825 Fisheries of the Northeastern United States; Bluefish Fishery; Quota... a portion of its 2011 commercial bluefish quota to New York State. By this action, NMFS adjusts the... Specialist, (978) 281-9224. SUPPLEMENTARY INFORMATION: Regulations governing the bluefish fishery are found...

77 FR 2512 - Marine Mammals

Science.gov (United States)

2012-01-18

...-XA905 Marine Mammals AGENCY: National Marine Fisheries Service (NMFS), National Oceanic and Atmospheric... Dorian Houser, Ph.D., National Marine Mammal Foundation, 2240 Shelter Island Drive, 200, San Diego, CA... subject permit is requested under the authority of the Marine Mammal Protection Act of 1972, as amended...

76 FR 47527 - Retrospective Regulatory Review Under E.O. 13563

Science.gov (United States)

2011-08-05

... DEPARTMENT OF COMMERCE Bureau of Industry and Security 15 CFR Chapter VII [Docket No. 110711380-1379-01] RIN 0694-XA37 Retrospective Regulatory Review Under E.O. 13563 AGENCY: Bureau of Industry and Security, Commerce. ACTION: Notice of inquiry. SUMMARY: The Bureau of Industry and Security (BIS...

77 FR 66564 - North Pacific Fishery Management Council; Essential Fish Habitat Amendments

Science.gov (United States)

2012-11-06

...-XA500 North Pacific Fishery Management Council; Essential Fish Habitat Amendments AGENCY: National... Scallop Fishery off Alaska (Scallop FMP); and Amendment 1 to the FMP for Fish Resources of the Arctic Management Area (Arctic FMP). These amendments update the existing essential fish habitat (EFH) provisions in...

Drug: D01016 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available ne glycerin [DR:D04412], Dental iodine glycerin [DR:D04880], Elemenmic (TN), Iodine...ssified ... DG02017 ... Potassium Same as: C08219 Therapeutic category: 3221 ATC code: R05CA02 S01XA04 V03AB21 ... Component of Compound iodi

76 FR 55276 - Fisheries of the Economic Exclusive Zone Off Alaska; Shallow-Water Species Fishery by Vessels...

Science.gov (United States)

2011-09-07

.... 101126522-0640-02] RIN 0648-XA680 Fisheries of the Economic Exclusive Zone Off Alaska; Shallow- Water...; closure. SUMMARY: NMFS is prohibiting directed fishing for species that comprise the shallow-water species... fourth seasonal apportionment of the Pacific halibut bycatch allowance specified for the shallow-water...

76 FR 39794 - Fisheries of the Economic Exclusive Zone Off Alaska; Shallow-Water Species Fishery by Catcher...

Science.gov (United States)

2011-07-07

.... 101126522-0640-02] RIN 0648-XA539 Fisheries of the Economic Exclusive Zone Off Alaska; Shallow- Water...; closure. SUMMARY: NMFS is prohibiting directed fishing for species that comprise the shallow-water species... species catch (PSC) sideboard limit specified for the shallow-water species fishery for catcher/processors...

System 800xA - a control system for the next generation of power plants; System 800xA - Das Leitsystem der naechsten Kraftwerksgeneration

Energy Technology Data Exchange (ETDEWEB)

Bruns, H. [ABB AG, Mannheim (Germany); Lauxtermann, S. [ABB AG, Minden (Germany)

2006-07-01

The system 800 x A developed by ABB is a power plant control system that is capable of combining the latest technologies in this field with best-practice solutions and integrating the I and C equipment already installed in a plant. System 800 x A offers plant owners a future-oriented integration platform for process control and sub-station control systems on the basis of the new IEC 61850 standard. Through optimised integration and networking of information in combination with direct and context-sensitive information access, decision-taking processes and the analysis of disturbances are speeded up considerably. Consistent data structures, ranging from field data to plant management data, and a simplified system configuration can reliably lower the system operating costs and increase operational reliability for a long time. This consistent technology can integrate turbine automation, unit automation, and all sorts of control functions and thus create single-source automation solutions that are highly harmonised and easy to handle. (orig.)

Methods of etching a substrate

International Nuclear Information System (INIS)

Cosmo, J.J.; Gambino, R.J.; Harper, J.M.E.

1979-01-01

The invention relates to a method of etching a substrate. The substrate is located opposite a target electrode in a vacuum chamber, and the surface of the target electrode is bombarded with energetic particles of atomic dimensions. The target electrode is an intermetallic composition (compound, alloy or finely divided homogeneous mixture) of two metals A and B such that upon bombardment the electrode emits negative ions of metal B which have sufficient energy to produce etching of the substrate. Many target materials are exemplified. Typically the metal A has an electronegativity XA and metal B has an electronegativity XB such that Xb - Xa is greater than about 2.55 electron volts, with the exception of combinations of metals having a fractional ionicity Q less than about 0.314. The source of the energetic particles may be an ionised gas in the vacuum chamber. The apparatus and its mode of operation are described in detail. (U.K.)

Methods of etching a substrate

Energy Technology Data Exchange (ETDEWEB)

Cosmo, J J; Gambino, R J; Harper, J M.E.

1979-05-16

The invention relates to a method of etching a substrate. The substrate is located opposite a target electrode in a vacuum chamber, and the surface of the target electrode is bombarded with energetic particles of atomic dimensions. The target electrode is an intermetallic composition (compound, alloy or finely divided homogeneous mixture) of two metals A and B such that upon bombardment the electrode emits negative ions of metal B which have sufficient energy to produce etching of the substrate. Many target materials are exemplified. Typically the metal A has an electronegativity XA and metal B has an electronegativity XB such that Xb - Xa is greater than about 2.55 electron volts, with the exception of combinations of metals having a fractional ionicity Q less than about 0.314. The source of the energetic particles may be an ionised gas in the vacuum chamber. The apparatus and its mode of operation are described in detail.

Evaluation of the current practices of noise-induced hearing loss (NIHL) awareness training in the South African mining industry

CSIR Research Space (South Africa)

Edwards, AL

2015-01-01

Full Text Available e of h ow w or ke rs a re e du ca te d on th e S pe ci fi c e xa m pl e E ffe ct s of n oi se o n he ar in g, p er m an en ce o f N IH L, u nd er st an di ng th e re su lts o f a nn ua l s ur ve ill an ce , u nd er st an di ng... h ow to h az ar d of n oi se to h ea rin g he al th . pr ot ec t h ea rin g. S ee a ns w er s to Q ue st io n 23 to o. 8 P le as e gi ve a n ex am pl e of h ow w or ke rs a re m ot iv at ed to S pe ci fi c e xa m pl...

Isotopic orientational order in acetyl salicylic acid

International Nuclear Information System (INIS)

Schiebel, P.; Prandl, W.

1999-01-01

Complete text of publication follows. Isotopically mixed methyl groups CD x H 3-x with zero averaged deuteron/hydrogen scattering length 0 = = xa D + (3 - x)a H (a D = 0.667 x 10 -12 ; a H = -0.374 x 10 -12 ) are expected to be invisible in a neutron diffraction experiment. Indeed, in aspirin-CD x H 3-x with an experimentally determined = -0.03 x 10 -12 cm at room temperature only three very week minima have been found. At 10 K, however, one positive and two negative extrema are visible: unique evidence for orientational isotopic order. From a combination of 1-d-Fourier and algebraic methods has been deconvoluted and the orientational distribution function f(φ) has been derived which has three equivalent maxima/minima at 300 K and loses this 3φ periodicity at 10 K. f(φ) is the basis for the determination of the hindrance potential with cos(φ) as the leading term. (author)

Comparison of established and novel purity tests for the quality control of heparin by means of a set of 177 heparin samples.

Science.gov (United States)

Alban, Susanne; Lühn, Susanne; Schiemann, Simone; Beyer, Tanja; Norwig, Jochen; Schilling, Claudia; Rädler, Oliver; Wolf, Bernhard; Matz, Magnus; Baumann, Knut; Holzgrabe, Ulrike

2011-01-01

The widespread occurrence of heparin contaminated with oversulfated chrondroitin sulfate (OSCS) in 2008 initiated a comprehensive revision process of the Pharmacopoeial heparin monographs and stimulated research in analytical techniques for the quality control of heparin. Here, a set of 177 heparin samples from the market in 2008 as well as pure heparin sodium spiked with defined amounts of OSCS and DS were used to evaluate established and novel methods for the quality control of heparin. Besides (1)H nuclear magnetic resonance spectroscopy (NMR), the assessment included two further spectroscopic methods, i.e., attenuated total reflection-infrared spectroscopy (ATR-IR) and Raman spectroscopy, three coagulation assays, i.e., activated partial thromboplastin time (aPTT) performed with both sheep and human plasma and the prothrombin time (PT), and finally two novel purity assays, each consisting of an incubation step with heparinase I followed by either a fluorescence measurement (Inc-PolyH-assay) or by a chromogenic aXa-assay (Inc-aXa-assay). NMR was shown to allow not only sensitive detection, but also quantification of OSCS by using the peak-height method and a response factor determined by calibration. Chemometric evaluation of the NMR, ATR-IR, and Raman spectra by statistical classification techniques turned out to be best with NMR spectra concerning the detection of OSCS. The validity of the aPTT, the current EP assay, could be considerably improved by replacing the sheep plasma by human plasma. In this way, most of the contaminated heparin samples did not meet the novel potency limit of 180 IU/mg. However, also more than 50% of the uncontaminated samples had interpretation of the results.

Gas-phase infrared spectrum of the anionic GFP-chromophore

NARCIS (Netherlands)

Almasian, M.; Grzetic, J.; G. Berden,; Bakker, B.; Buma, W. J.; Oomens, J.

2012-01-01

The gas-phase IR spectrum of the anionic chromophore of the green fluorescent protein (p-hydroxy-benzylidene-2,3-dimethylimidazolidinone, HBDI) is recorded in the 800–1800&#xa0;cm−1 frequency range using the free electron laser FELIX in combination with an electrospray ionization (ESI) Fourier

Ramjets and Ramrockets for Military Applications

Science.gov (United States)

1982-03-01

or auni)from multiple platforms and other operational considerations e-posed in recent XA1(o/nf~ studies should not invalidate the above claim. of...thereby obviating the need for any evaporation time. To ascertain the degree of pre- wix , carbon dioxide (selected because of its denasity similarit7

76 FR 58471 - Endangered Species; File No. 15634

Science.gov (United States)

2011-09-21

... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA714 Endangered..., [Responsible Party: Lisa Ballance, Ph.D.], has applied in due form for a permit to take leatherback sea turtles.... SUPPLEMENTARY INFORMATION: The subject permit is requested under the authority of the Endangered Species Act of...

77 FR 2513 - Draft Environmental Impact Statement for Effects of Oil and Gas Activities in the Arctic Ocean

Science.gov (United States)

2012-01-18

... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA934 Draft Environmental Impact Statement for Effects of Oil and Gas Activities in the Arctic Ocean AGENCY: National Marine... Environmental Impact Statement (DEIS) for the Effects of Oil and Gas Activities in the Arctic Ocean.'' Based on...

77 FR 17460 - Multistakeholder Process To Develop Consumer Data Privacy Codes of Conduct

Science.gov (United States)

2012-03-26

..., 2012, NTIA requested public comments on (1) which consumer data privacy issues should be the focus of.... 120214135-2203-02] RIN 0660-XA27 Multistakeholder Process To Develop Consumer Data Privacy Codes of Conduct... request for public comments on the multistakeholder process to develop consumer data privacy codes of...

76 FR 77781 - Endangered Species; File No. 15802

Science.gov (United States)

2011-12-14

.... SUPPLEMENTARY INFORMATION: The subject permit is requested under the authority of the Endangered Species Act of... exporting of endangered and threatened species (50 CFR 222-226). On July 28, 2011 (76 FR 45230), notice was... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA603 Endangered...

76 FR 48146 - Endangered Species; File No. 1551

Science.gov (United States)

2011-08-08

... subject modification to Permit No. 1551- 02 is requested under the authority of the Endangered Species Act... exporting of endangered and threatened species (50 CFR 222-226). Permit No. 1551, issued on July 24, 2008... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA620 Endangered...

78 FR 38013 - Endangered Species; File No. 15661

Science.gov (United States)

2013-06-25

... authority of the Endangered Species Act of 1973, as amended (16 U.S.C. 1531 et seq.) and the regulations governing the taking, importing, and exporting of endangered and threatened species (50 CFR 222-226). Permit... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA425 Endangered...

76 FR 18725 - Endangered Species; File No. 16174

Science.gov (United States)

2011-04-05

... the authority of the Endangered Species Act of 1973, as amended (ESA; 16 U.S.C. 1531 et seq.) and the regulations governing the taking, importing, and exporting of endangered and threatened species (50 CFR 222... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA348 Endangered...

76 FR 45781 - Endangered Species; File No. 15552

Science.gov (United States)

2011-08-01

... Endangered Species Act of 1973, as amended (ESA; 16 U.S.C. 1531 et seq.) and the regulations governing the taking, importing, and exporting of endangered and threatened species (50 CFR parts 222-226). The five... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA601 Endangered...

76 FR 58471 - Endangered Species; File No. 16306

Science.gov (United States)

2011-09-21

... requested under the authority of the Endangered Species Act of 1973, as amended (ESA; 16 U.S.C. 1531 et seq... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA712 Endangered Species; File No. 16306 AGENCY: National Marine Fisheries Service (NMFS), National Oceanic and Atmospheric...

75 FR 32372 - Information Privacy and Innovation in the Internet Economy

Science.gov (United States)

2010-06-08

.... 100402174-0238-02] RIN 0660-XA12 Information Privacy and Innovation in the Internet Economy AGENCY: National... Internet economy.\\1\\ In addition, the Department announced the formation of a Commerce-wide Internet Policy... Internet Economy, Launches Internet Policy Task Force, Department of Commerce Press Release (April 21, 2010...

76 FR 72643 - Western Pacific Pelagic Fisheries; Closure of the Hawaii Shallow-Set Pelagic Longline Fishery Due...

Science.gov (United States)

2011-11-25

.... 080225267-91393-03] RIN 0648-XA370 Western Pacific Pelagic Fisheries; Closure of the Hawaii Shallow- Set...: Temporary rule; fishery closure. SUMMARY: NMFS closes the shallow-set pelagic longline fishery north of the Equator for all vessels registered under the Hawaii longline limited access program. The shallow-set...

76 FR 57679 - Fisheries of the Exclusive Economic Zone Off Alaska; Shallow-Water Species by Vessels Using Trawl...

Science.gov (United States)

2011-09-16

.... 101126522-0640-02] RIN 0648-XA704 Fisheries of the Exclusive Economic Zone Off Alaska; Shallow- Water... closure. SUMMARY: NMFS is opening directed fishing for shallow-water species by vessels using trawl gear... apportionment of the 2011 Pacific halibut bycatch allowance specified for the trawl shallow-water species...

Karakterisasi Morfometrik dan Jarak Genetik Rumpun-Rumpun Kelinci di Jawa Barat (MORPHOMETRIC CHARACTERIZATION AND GENETIC DISTANCE OF RABBIT BREEDS IN WEST JAVA

Directory of Open Access Journals (Sweden)

Rudi Dedi Iskandar

2017-01-01

Full Text Available The objectives of this study were to assess morphometric characteristics, breeds relationship andvariables that distinguished among breeds of rabbits raised in West Java. This research used 419 rabbitsconsisted of Angora (AG, Dutch (DT, Flemish Giant (FG, Lop (LP, Netherland Dwarf (ND, Composite(PX, Rex (RX, Satin (ST, Reza (XA and New Zealand White (ZW. Head length (PK, head width (LK, earlength (PTL, ear width (LTL, chest width (LD, chest depth (DD, chest circumference (LKD, body length(PB , hips width (LP, length of the scapula bone (PS, humerus length (PH, radius-ulna length (PRU,femur length (PF and tibia length (PT were observed. Data were analyzed with analysis of variance,discriminant and canonical analysis using SAS program ver. 9.1.3 and MEGA5 program to get theconstruction of phenogram tree. FG and ST rabbits were generally larger in size and shape than the otherrabbits breeds, while ND rabbit had the smallest morphological size than other rabbits breeds, except forLK, LD and DD. Results of discriminant analysis showed that LP, RX, ND and XA had a high similarityvalue, otherwise DT, FG, ST, PX, AG and ZW had no the value. The closest genetic distance matrix valueindicated by PX-ZW breeds (1,53 and the farthest genetic distance indicated by FG-ND breeds (6,62.Phenogram tree construction showed that the breeds rabbits divided into five clusters, namely cluster ND,DT; ST clusters; FG cluster; cluster LP, PX, ZW and cluster AG, XA, RX. Phenotypic size that had stronginfluence on the differentiation of rabbit breeds were PTL, LTL, PRU, PH and PF on the canonical 1 alsoPT and PS on canonical 2.

78 FR 20317 - Application for Final Commitment for a Long-Term Loan or Financial Guarantee in Excess of $100...

Science.gov (United States)

2013-04-04

... supplying information that competitors could use to compete with companies in the United States. DATES... or Financial Guarantee in Excess of $100 Million: AP087223XX and AP087223XA AGENCY: Export-Import...''), that Ex-Im Bank has received an application for final commitment for a long-term loan or financial...

76 FR 56167 - Marine Mammals; Pinniped Removal Authority

Science.gov (United States)

2011-09-12

... problem interactions. See http://www.nwr.noaa.gov/Marine-Mammals/Seals-and-Sea-Lions/Sec-120-Authority.cfm... to the pinniped predation problem at Bonneville Dam and is not a na[iuml]ve animal that can be driven... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA681 Marine...

75 FR 70714 - Global Free Flow of Information on the Internet

Science.gov (United States)

2010-11-18

.... 100921457-0561-02] RIN 0660-XA20 Global Free Flow of Information on the Internet AGENCY: National... of comment period. SUMMARY: The Department of Commerce's Internet Policy Task Force announces that... on the global free flow of information on the Internet has been reopened and will extend until 5 p.m...

76 FR 77780 - Endangered Species; File No. 10022

Science.gov (United States)

2011-12-14

... been granted under the authority of the Endangered Species Act of 1973, as amended (ESA; 16 U.S.C. 1531... endangered or threatened species, and (3) is consistent with the purposes and policies set forth in section 2... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA867 Endangered...

The Dramaturgy of Fact: The Testament of History in Two Anti-War Plays.

Science.gov (United States)

Shafer, George

1978-01-01

The dramaturgical dimensions of the "theater of fact" as found in two anti-war plays, "Discourse on Viet Nam" by Peter Weiss and "Xa: A Vietnam Primer" by the ProVisional Theatre are examined. In these plays the author finds that Vietnamese history becomes rhetorical testament in arguments against United States…

Computation of the modified Bessel function of the third kind of imaginary orders: uniform Airy-type asymptotic expansion

NARCIS (Netherlands)

A. Gil (Amparo); J. Segura (Javier); N.M. Temme (Nico)

2002-01-01

textabstractThe use of a uniform Airy-type asymptotic expansion for the computation of the modified Bessel functions of the third kind of imaginary orders ($K_{ia}(x)$) near the transition point $x=a$, is discussed. In [2], an algorithm for the evaluation of $K_{ia}(x)$ was presented, which made use

76 FR 55276 - Fisheries of the Exclusive Economic Zone Off Alaska; Octopus in the Bering Sea and Aleutian Islands

Science.gov (United States)

2011-09-07

.... 101126521-0640-02] RIN 0648-XA683 Fisheries of the Exclusive Economic Zone Off Alaska; Octopus in the Bering... retention of octopus in the Bering Sea and Aleutian Islands (BSAI). This action is necessary because the 2011 total allowable catch of octopus in the BSAI has been reached. DATES: Effective 1200 hrs, Alaska...

Reflection and Non-Reflection of Particle Wavepackets

Science.gov (United States)

Cox, Timothy; Lekner, John

2008-01-01

Exact closed-form solutions of the time-dependent Schrodinger equation are obtained, describing the propagation of wavepackets in the neighbourhood of a potential. Examples given include zero reflection, total reflection and partial reflection of the wavepacket, for the sech[superscript 2]x/a, 1/x[superscript 2] and delta(x) potentials,…

76 FR 66042 - Endangered Species; File No. 1551

Science.gov (United States)

2011-10-25

... granted under the authority of the Endangered Species Act of 1973, as amended (ESA; 16 U.S.C. 1531 et seq... endangered or threatened species, and (3) is consistent with the purposes and policies set forth in section 2... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA785 Endangered...

76 FR 59924 - Fisheries of the Exclusive Economic Zone Off Alaska; Sharks in the Bering Sea and Aleutian...

Science.gov (United States)

2011-09-28

.... 101126521-0640-2] RIN 0648-XA733 Fisheries of the Exclusive Economic Zone Off Alaska; Sharks in the Bering... prohibiting retention of sharks in the Bering Sea and Aleutian Islands management area (BSAI). This action is necessary because the 2011 total allowable catch (TAC) of sharks in the BSAI has been reached. DATES...

Tinzaparin is safe and effective in the management of hemodialysis catheter thrombosis.

LENUS (Irish Health Repository)

Quinlan, Catherine

2012-08-27

Children on hemodialysis are at increased risk of thrombosis, especially when dialyzed via a central venous catheter (CVC); there are limited published data regarding the safety and efficacy of tinzaparin in this group. We conducted a retrospective chart review of all children in the National Pediatric Hemodialysis Centre for Ireland diagnosed with a CVC thrombus and treated with subcutaneous tinzaparin over a 10 year period. Seven children were treated with subcutaneous tinzaparin for 10 CVC thrombi. Tinzaparin was commenced at 175 IU\\/kg\\/day and the dose was titrated by measuring anti-factor Xa levels, aiming for levels of 0.3-1.0 IU\\/ml. Treatment was continued until resolution of the CVC thrombus. Restoration of normal flows during dialysis occurred within 3 days in all patients. There were no episodes of bleeding and all children tolerated the treatment well.

ARC2D - EFFICIENT SOLUTION METHODS FOR THE NAVIER-STOKES EQUATIONS (DEC RISC ULTRIX VERSION)

Science.gov (United States)

Biyabani, S. R.

1994-01-01

ARC2D is a computational fluid dynamics program developed at the NASA Ames Research Center specifically for airfoil computations. The program uses implicit finite-difference techniques to solve two-dimensional Euler equations and thin layer Navier-Stokes equations. It is based on the Beam and Warming implicit approximate factorization algorithm in generalized coordinates. The methods are either time accurate or accelerated non-time accurate steady state schemes. The evolution of the solution through time is physically realistic; good solution accuracy is dependent on mesh spacing and boundary conditions. The mathematical development of ARC2D begins with the strong conservation law form of the two-dimensional Navier-Stokes equations in Cartesian coordinates, which admits shock capturing. The Navier-Stokes equations can be transformed from Cartesian coordinates to generalized curvilinear coordinates in a manner that permits one computational code to serve a wide variety of physical geometries and grid systems. ARC2D includes an algebraic mixing length model to approximate the effect of turbulence. In cases of high Reynolds number viscous flows, thin layer approximation can be applied. ARC2D allows for a variety of solutions to stability boundaries, such as those encountered in flows with shocks. The user has considerable flexibility in assigning geometry and developing grid patterns, as well as in assigning boundary conditions. However, the ARC2D model is most appropriate for attached and mildly separated boundary layers; no attempt is made to model wake regions and widely separated flows. The techniques have been successfully used for a variety of inviscid and viscous flowfield calculations. The Cray version of ARC2D is written in FORTRAN 77 for use on Cray series computers and requires approximately 5Mb memory. The program is fully vectorized. The tape includes variations for the COS and UNICOS operating systems. Also included is a sample routine for CONVEX

Phenotyping of VIGS-mediated gene silencing in rice using a vector derived from a DNA virus.

Science.gov (United States)

Kant, Ravi; Dasgupta, Indranil

2017-07-01

Target genes in rice can be optimally silenced if inserted in antisense or hairpin orientation in the RTBV-derived VIGS vector and plants grown at 28 °C and 80% humidity after inoculation. Virus induced gene silencing (VIGS) is a method used to transiently silence genes in dicot as well as monocot plants. For the important monocot species rice, the Rice tungro bacilliform virus (RTBV)-derived VIGS system (RTBV-VIGS), which uses agroinoculation to initiate silencing, has not been standardized for optimal use. Here, using RTBV-VIGS, three sets of conditions were tested to achieve optimal silencing of the rice marker gene phytoene desaturase (pds). The effect of orientation of the insert in the RTBV-VIGS plasmid (sense, antisense and hairpin) on the silencing of the target gene was then evaluated using rice magnesium chelatase subunit H (chlH). Finally, the rice Xa21 gene, conferring resistance against bacterial leaf blight disease (BLB) was silenced using RTBV-VIGS system. In each case, real-time PCR-based assessment indicated approximately 40-80% fall in the accumulation levels of the transcripts of pds, chlH and Xa21. In the case of pds, the appearance of white streaks in the emerging leaves, and for chlH, chlorophyll levels and F v /F m ratio were assessed as phenotypes for silencing. For Xa21, the resistance levels to BLB were assessed by measuring the lesion length and the percent diseased areas of leaves, following challenge inoculation with Xanthomonas oryzae. In each case, the RTBV-MVIGS system gave rise to a discernible phenotype indicating the silencing of the respective target gene using condition III (temperature 28 °C, humidity 80% and 1 mM MES and 20 µM acetosyringone in secondary agrobacterium culture), which revealed the robustness of this gene silencing system for rice.

SU-E-I-10: Automatic Monitoring of Accumulated Dose Indices From DICOM RDSR to Improve Radiation Safety in X-Ray Angiography

International Nuclear Information System (INIS)

Omar, A; Bujila, R; Nowik, P; Karambatsakidou, A

2014-01-01

Purpose: To investigate the potential benefits of automatic monitoring of accumulated patient and staff dose indicators, i.e., CAK and KAP, from DICOM Radiation Dose Structured Reports (RDSR) in x-ray angiography (XA). Methods: Recently RDSR has enabled the convenient aggregation of dose indices and technique parameters for XA procedures. The information contained in RDSR objects for three XA systems, dedicated to different types of clinical procedures, has been collected and aggregated in a database for over one year using a system developed with open-source software at the Karolinska University Hospital. Patient weight was complemented to the RDSR data via an interface with the Hospital Information System (HIS). Results: The linearly approximated trend in KAP over a time period of a year for cerebrovascular, pelvic/peripheral vascular, and cardiovascular procedures showed a decrease of 12%, 20%, and 14%, respectively. The decrease was mainly due to hardware/software upgrades and new low-dose imaging protocols, and partially due to ongoing systematic radiation safety education of the clinical staff. The CAK was in excess of 3 Gy for 15 procedures, and exceeded 5 Gy for 3 procedures. The dose indices have also shown a significant dependence on patient weight for cardiovascular and pelvic/peripheral vascular procedures; a 10 kg shift in mean patient weight can result in a dose index increase of 25%. Conclusion: Automatic monitoring of accumulated dose indices can be utilized to notify the clinical staff and medical physicists when the dose index has exceeded a predetermined action level. This allows for convenient and systematic follow-up of patients in risk of developing deterministic skin injuries. Furthermore, trend analyses of dose indices over time is a valuable resource for the identification of potential positive or negative effects (dose increase/decrease) from changes in hardware, software, and clinical work habits

SU-E-I-10: Automatic Monitoring of Accumulated Dose Indices From DICOM RDSR to Improve Radiation Safety in X-Ray Angiography

Energy Technology Data Exchange (ETDEWEB)

Omar, A; Bujila, R; Nowik, P; Karambatsakidou, A [Karolinska University Hospital, Stockholm (Sweden)

2014-06-01

Purpose: To investigate the potential benefits of automatic monitoring of accumulated patient and staff dose indicators, i.e., CAK and KAP, from DICOM Radiation Dose Structured Reports (RDSR) in x-ray angiography (XA). Methods: Recently RDSR has enabled the convenient aggregation of dose indices and technique parameters for XA procedures. The information contained in RDSR objects for three XA systems, dedicated to different types of clinical procedures, has been collected and aggregated in a database for over one year using a system developed with open-source software at the Karolinska University Hospital. Patient weight was complemented to the RDSR data via an interface with the Hospital Information System (HIS). Results: The linearly approximated trend in KAP over a time period of a year for cerebrovascular, pelvic/peripheral vascular, and cardiovascular procedures showed a decrease of 12%, 20%, and 14%, respectively. The decrease was mainly due to hardware/software upgrades and new low-dose imaging protocols, and partially due to ongoing systematic radiation safety education of the clinical staff. The CAK was in excess of 3 Gy for 15 procedures, and exceeded 5 Gy for 3 procedures. The dose indices have also shown a significant dependence on patient weight for cardiovascular and pelvic/peripheral vascular procedures; a 10 kg shift in mean patient weight can result in a dose index increase of 25%. Conclusion: Automatic monitoring of accumulated dose indices can be utilized to notify the clinical staff and medical physicists when the dose index has exceeded a predetermined action level. This allows for convenient and systematic follow-up of patients in risk of developing deterministic skin injuries. Furthermore, trend analyses of dose indices over time is a valuable resource for the identification of potential positive or negative effects (dose increase/decrease) from changes in hardware, software, and clinical work habits.

Federal Health Care Center: VA and DOD Need to Address Ongoing Difficulties and Better Prepare for Future Integrations

Science.gov (United States)

2016-02-01

related documentation, performing data reliability checks (such as examining the data for missing values), and interviewing FHCC officials. After taking...and personnel Staffing, training, and the transfer of DOD civilian personnel to VA Xa Property Construction, transfer of property, and physical ...29For example, geriatric and mental health clinical areas were initially grouped with other

Human active X-specific DNA methylation events showing stability across time and tissues

Science.gov (United States)

Joo, Jihoon Eric; Novakovic, Boris; Cruickshank, Mark; Doyle, Lex W; Craig, Jeffrey M; Saffery, Richard

2014-01-01

The phenomenon of X chromosome inactivation in female mammals is well characterised and remains the archetypal example of dosage compensation via monoallelic expression. The temporal series of events that culminates in inactive X-specific gene silencing by DNA methylation has revealed a ‘patchwork' of gene inactivation along the chromosome, with approximately 15% of genes escaping. Such genes are therefore potentially subject to sex-specific imbalance between males and females. Aside from XIST, the non-coding RNA on the X chromosome destined to be inactivated, very little is known about the extent of loci that may be selectively silenced on the active X chromosome (Xa). Using longitudinal array-based DNA methylation profiling of two human tissues, we have identified specific and widespread active X-specific DNA methylation showing stability over time and across tissues of disparate origin. Our panel of X-chromosome loci subject to methylation on Xa reflects a potentially novel mechanism for controlling female-specific X inactivation and sex-specific dimorphisms in humans. Further work is needed to investigate these phenomena. PMID:24713664

Resolution of the crystal structure of the deficient perovskite LaNiO2.5 from neutron powder diffraction data

International Nuclear Information System (INIS)

Alonso, J.A.; Martinez-Lope, M.J.

1996-01-01

The oxygen-deficient perovskite LaNiO 2.5 has been prepared by controlled reduction of LaNiO 3 with Zr metal. The XRD pattern could be indexed in a monoclinic unit-cell with dimensions a 0 xa 0 xa 0 (a 0 : lattice parameter of the ideal cubic perovskite). The indexing of the neutron powder diffraction pattern needed a doubled cell to account for the superstructure reflections originated by the oxygen vacancy ordering and the tilting of the Ni coordination polyhedra. The structure was solved and refined from the neutron powder data. The oxygen vacancies are ordered in such a way that square planar NiO 4 and NiO 6 octahedra alternate in the ab plane along the [110] direction. Both kinds of Ni polyhedra are fairly distorted and tilted in order to optimize the La-O distances, giving rise to a highly strained structure of metastable character. In fact, the compound readily takes oxygen, above 175 C in air, to give the much more stable LaNiO 3 perovskite. (orig.)

New Insights into the Pros and Cons of the Clinical Use of Vitamin K Antagonists (VKAs Versus Direct Oral Anticoagulants (DOACs

Directory of Open Access Journals (Sweden)

Rick H. van Gorp

2015-11-01

Full Text Available Vitamin K-antagonists (VKA are the most widely used anticoagulant drugs to treat patients at risk of arterial and venous thrombosis for the past 50 years. Due to unfavorable pharmacokinetics VKA have a small therapeutic window, require frequent monitoring, and are susceptible to drug and nutritional interactions. Additionally, the effect of VKA is not limited to coagulation, but affects all vitamin K-dependent proteins. As a consequence, VKA have detrimental side effects by enhancing medial and intimal calcification. These limitations stimulated the development of alternative anticoagulant drugs, resulting in direct oral anticoagulant (DOAC drugs, which specifically target coagulation factor Xa and thrombin. DOACs also display non-hemostatic vascular effects via protease-activated receptors (PARs. As atherosclerosis is characterized by a hypercoagulable state indicating the involvement of activated coagulation factors in the genesis of atherosclerosis, anticoagulation could have beneficial effects on atherosclerosis. Additionally, accumulating evidence demonstrates vascular benefit from high vitamin K intake. This review gives an update on oral anticoagulant treatment on the vasculature with a special focus on calcification and vitamin K interaction.

Influences of the disease resistance conferred by the individual ...

African Journals Online (AJOL)

To research possible influences of the disease resistance conferred by different trans-resistance genes on the transgenic rice plants in their yields and grain quality, three transgenic rice lines, including two with the resistance genes Pi-d2 and Pi-d3, respectively, for rice blast, and one with the resistance gene Xa21 for rice ...

Neutral V production with 14.6 x A GeV/c silicon beams

International Nuclear Information System (INIS)

Eiseman, S.E.; Etkin, A.; Foley, K.J.; Hackenburg, R.W.; Longacre, R.S.; Love, W.A.; Morris, T.W.; Platner, E.D.; Saulys, A.C.; Lindenbaum, S.J.; Chan, C.S.; Kramer, M.A.; Zhao, K.; Hallman, T.J.; Madansky, L.; Bonner, B.E.; Buchanan, J.A.; Chiou, C.N.; Clement, J.M.; Corcoran, M.D.; Kruk, J.W.; Mutchler, G.S.; Nessi-Tedaldi, F.; Nessi, M.; Roberts, J.B.

1990-01-01

We present the results of a measurement of neutral V production with 14.6xA GeV/c Si beams on Au and Cu targets. The Λ and K s 0 yields were measured as a function of negative particle multiplicity. Effective temperatures were determined from an exponential fit to the transverse mass distributions. (orig.)

Hydrogenic donor in a quantum well with an electric field

International Nuclear Information System (INIS)

Jayakumar, K.; Balasubramanian, S.; Tomak, M.

1985-08-01

Variational calculations of the binding energy of a hydrogenic donor in a quantum well formed by GaAs and Gasub(1-x)A1sub(x)As with a constant electric field are performed for different electric fields and well widths. A critical electric field is defined and its variation with well width is presented. (author)

76 FR 17360 - Fisheries of the Exclusive Economic Zone Off Alaska; Octopus in the Bering Sea and Aleutian...

Science.gov (United States)

2011-03-29

.... 101126521-0640-02] RIN 0648-XA322 Fisheries of the Exclusive Economic Zone Off Alaska; Octopus in the Bering... allowable catch of octopus in the Bering Sea and Aleutian Islands (BSAI). This action is necessary to allow... subpart H of 50 CFR part 600 and 50 CFR part 679. The 2011 initial total allowable catch (ITAC) of octopus...

76 FR 64248 - Gulf of Mexico Reef Fish Fishery; Closure of the 2011 Gulf of Mexico Commercial Sector for...

Science.gov (United States)

2011-10-18

.... 040205043-4043-01] RIN 0648-XA766 Gulf of Mexico Reef Fish Fishery; Closure of the 2011 Gulf of Mexico... the commercial sector for greater amberjack in the exclusive economic zone (EEZ) of the Gulf of Mexico... Reef Fish Resources of the Gulf of Mexico (FMP). The FMP was prepared by the Gulf of Mexico Fishery...

Direct Oral Anticoagulants in Emergency Trauma Admissions.

Science.gov (United States)

Maegele, Marc; Grottke, Oliver; Schöchl, Herbert; Sakowitz, Oliver A; Spannagl, Michael; Koscielny, Jürgen

2016-09-05

Direct (non-vitamin-K-dependent) oral anticoagulants (DOAC) are given as an alternative to vitamin K antagonists (VKA) to prevent stroke and embolic disease in patients with atrial fibrillation that is not due to pathology of the heart valves. Fatal hemorrhage is rarer when DOACs are given (nonvalvular atrial fibrillation: odds ratio [OR] 0.68; 95% confidence interval [95% CI: 0.48; 0.96], and venous thromboembolism: OR 0.54; [0.22; 1.32]). 48% of emergency trauma patients need an emergency operation or early surgery. Clotting disturbances elevate the mortality of such patients to 43%, compared to 17% in patients without a clotting disturbance. This underscores the impor tance of the proper, targeted treatment of trauma patients who are aking DOAC. This review is based on articles retrieved by a selective search in PubMed and on a summary of expert opinion and the recommendations of the relevant medical specialty societies. Peak DOAC levels are reached 2-4 hours after the drug is taken. In patients with normal renal and hepatic function, no drug accumulation, and no drug interactions, the plasma level of DOAC 24 hours after administration is generally too low to cause any clinically relevant risk of bleeding. The risk of drug accumulation is higher in patients with renal dysfunction (creatinine clearance [CrCl] of 30 mL/min or less). Dabigatran levels can be estimated from the thrombin time, ecarin clotting time, and diluted thrombin time, while levels of factor Xa inhibitors can be estimated by means of calibrated chromogenic anti-factor Xa activity tests. Routine clotting studies do not reliably reflect the anticoagulant activity of DOAC. Surgery should be postponed, if possible, until at least 24-48 hours after the last dose of DOAC. For patients with mild, non-life threatening hemorrhage, it suffices to discontinue DOAC; for patients with severe hemorrhage, there are special treatment algorithms that should be followed. DOACs in the setting of hemorrhage are a

Direct oral anticoagulants: An update.

Science.gov (United States)

Franco Moreno, Ana Isabel; Martín Díaz, Rosa María; García Navarro, María José

2017-12-30

Vitamin K antagonists were the only choice for chronic oral anticoagulation for more than half a century. Over the past few years, direct oral anticoagulants have emerged, including one direct thrombin inhibitor (dabigatran etexilate) and three factor Xa inhibitors (apixaban, edoxaban and rivaroxaban). In randomised controlled trials comparing direct oral anticoagulants with traditional vitamin K antagonists, the direct oral anticoagulants all showed a favourable benefit-risk balance in their safety and efficacy profile, in prevention of thromboembolic events in patients with atrial fibrillation and in the prevention and treatment of venous thromboembolism and acute coronary syndrome. In 2008, dabigatran was the first direct oral anticoagulant approved by the European Medicine Agency. Subsequently, rivaroxaban, apixaban and edoxaban were also authorised. This article reviews the evidence related to the use of these drugs. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Kaitsevägi hangib iseliikuvaid suurtükke / Andres Einmann

Index Scriptorium Estoniae

Einmann, Andres

2013-01-01

Kaitseministeerium kulutab tuleval aastal investeeringuteks 43,26 miljonit eurot. Kavas on hankida uut sõjatehnikat: suurtükke ja lahingumasinaid, teine Thales Raytheoni Ground Master 403 tüüpi radar, Sisu XA-188 soomukeid. Suurim projekt on viie kasarmu ehitamine: aasta lõpuks valmivad neli kasarmut Võrus, Jõhvis ja Ämaris ning peale selle renoveeritakse üks hoone Miinisadamas

Sphingosine-1-Phosphate and Its Receptors: A Mutual Link between Blood Coagulation and Inflammation

Directory of Open Access Journals (Sweden)

Shailaja Mahajan-Thakur

2015-01-01

Full Text Available Sphingosine-1-phosphate (S1P is a versatile lipid signaling molecule and key regulator in vascular inflammation. S1P is secreted by platelets, monocytes, and vascular endothelial and smooth muscle cells. It binds specifically to a family of G-protein-coupled receptors, S1P receptors 1 to 5, resulting in downstream signaling and numerous cellular effects. S1P modulates cell proliferation and migration, and mediates proinflammatory responses and apoptosis. In the vascular barrier, S1P regulates permeability and endothelial reactions and recruitment of monocytes and may modulate atherosclerosis. Only recently has S1P emerged as a critical mediator which directly links the coagulation factor system to vascular inflammation. The multifunctional proteases thrombin and FXa regulate local S1P availability and interact with S1P signaling at multiple levels in various vascular cell types. Differential expression patterns and intracellular signaling pathways of each receptor enable S1P to exert its widespread functions. Although a vast amount of information is available about the functions of S1P and its receptors in the regulation of physiological and pathophysiological conditions, S1P-mediated mechanisms in the vasculature remain to be elucidated. This review summarizes recent findings regarding the role of S1P and its receptors in vascular wall and blood cells, which link the coagulation system to inflammatory responses in the vasculature.

INTERNALISASI STANDAR HAM INTERNASIONAL DALAM PENGUJIAN UNDANG-UNDANG OLEH MAHKAMAH KONSTITUSI

Directory of Open Access Journals (Sweden)

Titon Slamet Kurnia

2016-06-01

Tulisan ini membahas isu proses internalisasi standar HAM internasional dalam forum domestik melalui mekanisme pengujian konstitusionalitas undang-undang oleh MKRI. Tulisan ini berargumen bahwa MKRI seyogianya mempertimbangkan standar HAM internasional dalam menguji konstitusionalitas undangundang berdasarkan Bab XA UUD NRI 1945. Argumen itu didasarkan pada preskripsi bahwa standar HAM internasional berlaku/mengikat kepada negara dan mensyaratkannya untuk menyesuaikan undangundang beserta tindakan pejabatnya dengan kaidah HAM internasional tersebut

Resonant Tunneling Quantum Well Integrated Optical Waveguide Modulator/ Switch

Science.gov (United States)

1994-07-01

perform this task. However, our search was not successful . Fortunately, we developed our own software as part of a Phase II SBIR program entitled...scattered waves can be represented as 5 Pinal 0794.3246 AF-QUANT Cont. No. F49620-94.C-0008 n=0T = tLt2.Le ikea (rrei2k2P, (I)i~k,Xa a, t1Lt2Le jklxa

Dosimetry characterization and clinical application of Exa skin: Bolus of high of high density for use with photons; Caracterizacion dosimetrica y aplicacion clinica de Exaskin: bolus de alta densidad para uso con fotones

Energy Technology Data Exchange (ETDEWEB)

Ortiz Seidel, M.; Velazquez Miranda, S.

2013-07-01

Bolus of high density eXaSkin of density 1.6 g/cm{sub 3} is calculated correctly in the planning systems, is easy to use and generates optimum coupling with the radiation area, at the same time which is easily reproducible in their placement, avoiding the use of electron beams. On the other hand its behavior varies very slightly with the presence of air gaps. (Author)

End modes in arrays of modulated Su–Schrieffer–Heeger chains

Indian Academy of Sciences (India)

2016-07-15

Jul 15, 2016 ... is not an edge mode. For no other combination of XA,. XB and φ investigated in this work, could one obtain such a spectrum. Wavefunction of all the edge modes is similar to that obtained in a chain with all NNN terms modulated. To study the effect of the presence of other chains and to find if such states are ...

The pepper Bs4C proteins are localized to the endoplasmic reticulum (ER) membrane and confer disease resistance to bacterial blight in transgenic rice.

Science.gov (United States)

Wang, Jun; Zeng, Xuan; Tian, Dongsheng; Yang, Xiaobei; Wang, Lanlan; Yin, Zhongchao

2018-03-30

Transcription activator-like effector (TALE)-dependent dominant disease resistance (R) genes in plants, also referred to as executor R genes, are induced on infection by phytopathogenic bacteria of the genus Xanthomonas harbouring the corresponding TALE genes. Unlike the traditional R proteins, the executor R proteins do not determine the resistance specificity and may function broadly in different plant species. The executor R gene Bs4C-R in the resistant genotype PI 235047 of the pepper species Capsicum pubescens (CpBs4C-R) confers disease resistance to Xanthomonas campestris pv. vesicatoria (Xcv) harbouring the TALE genes avrBsP/avrBs4. In this study, the synthetic genes of CpBs4C-R and two other Bs4C-like genes, the susceptible allele in the genotype PI585270 of C. pubescens (CpBs4C-S) and the CaBs4C-R homologue gene in the cultivar 'CM334' of Capsicum annum (CaBs4C), were characterized in tobacco (Nicotiana benthamiana) and rice (Oryza sativa). The Bs4C genes induced cell death in N. benthamiana. The functional Bs4C-eCFP fusion proteins were localized to the endoplasmic reticulum (ER) membrane in the leaf epidermal cells of N. benthamiana. The Xa10 promoter-Bs4C fusion genes in transgenic rice conferred strain-specific disease resistance to Xanthomonas oryzae pv. oryzae (Xoo), the causal agent of bacterial blight in rice, and were specifically induced by the Xa10-incompatible Xoo strain PXO99 A (pHM1avrXa10). The results indicate that the Bs4C proteins from pepper species function broadly in rice and the Bs4C protein-mediated cell death from the ER is conserved between dicotyledonous and monocotyledonous plants, which can be utilized to engineer novel and enhanced disease resistance in heterologous plants. © 2018 TEMASEK LIFE SCIENCES LABORATORY. MOLECULAR PLANT PATHOLOGY © 2018 JOHN WILEY & SONS LTD.

Activation of 125I-Factor IX and 125I-Factor X: Effect of tissue factor and Factor VII, Factor Xsub(a) and thrombin

International Nuclear Information System (INIS)

Oesterud, B.; Rapaport, S.I.

Activation of Factor IX and Factor X was studied by adding 125 I-Factor IX or 125 I-Factor X to reaction mixtures and quantitating cleavage products by reduced sodium dodecylsulfate gel electrophoresis. Thrombin failed to activate Factors IX or X; Factor Xsub(a) produced insignificant amounts of cleavage products of both factors. In contrast, the reaction product of tissue factor and Factor VII cleaved large amounts of both Factor IX and Factor X in purified systems and in plasma. In incubation mixtures of plasma containing added 125 I-Factor IX or 125 I-Factor X, tissue factor and Ca 2+ ions, the percentage of total radioactivity in the heavy chain peak of 125 I-IXsub(a) and the heavy chain of 125 I-Xsub(a) increased at a similar rate. When the tissue factor was diluted, similar curves were obtained for percent cleavage of 125 I-Factor IX and percent cleavage of 125 I-Factor X plotted against tissue factor concentration. These findings support the hypothesis that activation of Factor IX by the tissue factor-Factor VII reaction product represents a physiologically significant step in normal haemostasis. (author)

Review of fondaparinux sodium injection for the prevention of venous thromboembolism in patients undergoing surgery

Directory of Open Access Journals (Sweden)

David Bergqvist

2006-12-01

Full Text Available David BergqvistDepartment of Surgery, University Hospital, Uppsala, SwedenAbstract: The antithrombin binding sequence of heparin, a pentasaccharide, has been synthesized as fondaparinux, an indirect, selective, and reversible factor Xa inhibitor. It can be administered subcutaneously, is well absorbed, and has a half-life of c. 17 hours permitting once-daily injection. It has been evaluated in an extensive study program in major orthopedic surgery, including hip fracture, and in major abdominal surgery with a large proportion of surgery for cancer. The effect is at least as effective as for low-molecular-weight heparins and it has also been shown effective for extended prophylaxis in hip fracture patients. Several thousands of patients have been studied and the substance is safe, although a slightly higher frequency of bleedings is found than in patients on low-molecular-weight heparins. There is no specific antidote but if necessary, recombinant activated factor VII can be used. Other side-effects are rare. Fondaparinux is cost saving and sometimes cost neutral when compared with enoxaparin. Keywords: fondaparinux, venous thrombosis, venous thromboembolism, surgery, orthopedic surgery, major abdominal surgery, bleeding complications

Comparison of noise power spectrum methodologies in measurements by using various electronic portal imaging devices in radiation therapy

Energy Technology Data Exchange (ETDEWEB)

Son, Soon Yong [Dept. of Radiological Technology, Wonkwang Health Science University, Iksan (Korea, Republic of); Choi, Kwan Woo [Dept. of Radiology, Asan Medical Center, Seoul (Korea, Republic of); Jeong, Hoi Woun [Dept. of Radiological Technology, Baekseok Culture University College, Cheonan (Korea, Republic of); Kwon, Kyung Tae [Dep. of Radiological Technology, Dongnam Health University, Suwon (Korea, Republic of); Kim, Ki Won [Dept. of Radiology, Kyung Hee University Hospital at Gang-dong, Seoul (Korea, Republic of); Lee, Young Ah; Son, Jin Hyun; Min, Jung Whan [Shingu University College, Sungnam (Korea, Republic of)

2016-03-15

The noise power spectrum (NPS) is one of the most general methods for measuring the noise amplitude and the quality of an image acquired from a uniform radiation field. The purpose of this study was to compare different NPS methodologies by using megavoltage X-ray energies. The NPS evaluation methods in diagnostic radiation were applied to therapy using the International Electro-technical Commission standard (IEC 62220-1). Various radiation therapy (RT) devices such as TrueBeamTM(Varian), BEAMVIEWPLUS(Siemens), iViewGT(Elekta) and ClinacR iX (Varian) were used. In order to measure the region of interest (ROI) of the NPS, we used the following four factors: the overlapping impact, the non-overlapping impact, the flatness and penumbra. As for NPS results, iViewGT(Elekta) had the higher amplitude of noise, compared to BEAMVIEWPLUS (Siemens), TrueBeamTM(Varian) flattening filter, ClinacRiXaS1000(Varian) and TrueBeamTM(Varian) flattening filter free. The present study revealed that various factors could be employed to produce megavoltage imaging (MVI) of the NPS and as a baseline standard for NPS methodologies control in MVI.

Efficacy and safety of rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome: Rationale and design of the Trial on Rivaroxaban in AntiPhospholipid Syndrome (TRAPS) trial.

Science.gov (United States)

Pengo, V; Banzato, A; Bison, E; Zoppellaro, G; Padayattil Jose, S; Denas, G

2016-03-01

New oral anticoagulants may simplify long-term therapy in conditions requiring anticoagulation. Rivaroxaban is a direct factor Xa inhibitor that has been extensively studied and is now approved for the prevention and therapy of a number of thromboembolic conditions. This is a multicentre, randomized, open-label, study that will evaluate if Rivaroxaban 20 mg od (or 15 mg od in patients with moderate renal insufficiency) is non-inferior to warfarin (INR target 2.5), for the prevention of thromboembolic events, major bleeding and death in high risk (triple positive) patients with antiphospholipid syndrome. Secondary endpoints will assess the incidence of any individual component of the composite end point. An external adjudication committee will evaluate all suspected outcome events. This will be a unique trial, as it will enrol the biggest homogenous cohort of high risk APS individuals. The methods and the study design should be appropriate to achieve study results that are both scientifically valid and relevant to clinical practice. © The Author(s) 2015.

Old and new oral anticoagulants for secondary stroke prevention in atrial fibrillation

Directory of Open Access Journals (Sweden)

Tommaso Sacquegna

2015-12-01

Full Text Available Vitamin K antagonists, such as warfarin, used in oral anticoagulation therapy currently represent the standard drugs for the primary and secondary prevention of stroke in non-valvular atrial fibrillation (AF, with a relative risk reduction close to 70%. Newer oral anticoagulants, such as direct thrombin inhibitors (i.e., dabigatran and direct factor Xa inhibitors (i.e., apixaban and rivaroxaban have been recently compared with warfarin in large randomized trials for stroke prevention in AF. The new oral anticoagulants showed, compared with warfarin, no statistically significant difference in the rate of stroke or systemic embolism in secondary prevention (patients with previous transient ischemic attack or stroke subgroups. With regard to safety, the risk of intracranial bleeding was reduced with new anticoagulants compared with warfarin. Indirect treatment comparisons of clinical trials on secondary prevention cohorts showed no significant difference in efficacy among apixaban, rivaroxaban, and dabigatran; but dabigatran 110 mg was associated with less intracranial bleedings than rivaroxaban.

Acute kidney injury aggravated by treatment initiation with apixaban: Another twist of anticoagulant-related nephropathy

Directory of Open Access Journals (Sweden)

Sergey V. Brodsky

2017-12-01

Full Text Available Anticoagulant-related nephropathy (ARN was initially described in patients on warfarin (as warfarin-related nephropathy and recently in those using dabigatran. Herein, we report clinical history and kidney biopsy findings in a patient on apixaban (Eliquis. Initiation of treatment with apixaban resulted in aggravation of preexisting mild acute kidney injury (AKI. A few days after apixaban therapy, the patient became oligoanuric, and kidney biopsy showed severe acute tubular necrosis with numerous occlusive red blood cell casts. Only one out of 68 glomeruli with open capillary loops had small segmental cellular crescent. Therefore, there was major discrepancy between the degree of glomerular injury and the glomerular hematuria. Considering that the onset of this AKI was associated with apixaban treatment initiation, we propose that this patient had ARN associated with factor Xa inhibitor (apixaban, which has not previously been described. Monitoring of kidney function is recommended after initiation of anticoagulant therapy.

International Conference on Organometallic Chemistry (13th) Held in Torino, Europe on 4-9 September 1988. Abstracts

Science.gov (United States)

1988-09-09

190, 8057 ZUrich, Switzerland Joseph Edwin and William E.Geiger, Department of Chemistry, University of Vermont, Burlington, Vermont, 05405 Arnold L...On Synthesis Of Dialkyl d-Trimethylsilyloxyalkylphosphonates Zhao Yong-Zhen and Li Zhong- Rua Dpartment o chemistry, Hua Zhong Normal University, Wuhan...Jose Vicente. Jose-AntelC hAd. Na-Yeij~xa Qhicote. Ju~an-Francisco Gutliez-Jugo. Carmen Ramirez do Arel lano. Departamento do Oulmica InordanIca

Drug: D09737 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available D09737 Drug Epoetin kappa (INN); Epoetin kappa (genetical recombination) (Epoetin ...alfa biosimilar 1) (JAN); Epoetin alfa BS (TN) ... C809H1301N229O240S5 ... APPRLICDSR VLERYLLEAK EAENITTGCA EHCSLN...c category: 3999 ATC code: B03XA01 Chemical group: DG00177 ... See Epoetin alfa [DR:D03231] EPOR [HSA:2057] [KO:K05079] ... CAS: 879555-13-2 PubChem: 124490477 ...

Comparison of effective dose for imaging of mandible between multi-detector CT and cone-beam CT

International Nuclear Information System (INIS)

Jeong, Dae Kyo; Lee, Sang Chul; Huh, Kyung Hoe; Yi, Won Jin; Lee, Sam Sun; Choi, Soon Chul

2012-01-01

The aim of this study was to compare the effective dose for imaging of mandible between multi-detector computed tomography (MDCT) and cone-beam computed tomography (CBCT). An MDCT with low dose technique was also compared with them. Thermoluminescent dosimeter (TLD) chips were placed at 25 organ sites of an anthropomorphic phantom. The mandible of the phantom was exposed using 2 different types of MDCT units (Somatom Sensation 10 for standard-dose MDCT, Somatom Emotion 6 for low-dose MDCT) and 3 different CBCT units (AZ3000CT, Implagraphy, and Kavo 3D eXaM). The radiation absorbed dose was measured and the effective dose was calculated according to the ICRP 2007 report. The effective dose was the highest for Somatom Sensation 10 (425.84 μSv), followed by AZ3000CT (332.4 μSv), Somatom Emotion 6 (199.38 μSv), and 3D eXaM (111.6 μSv); it was the lowest for Implagraphy (83.09 μSv). The CBCT showed significant variation in dose level with different device. The effective doses of MDCTs were not significantly different from those of CBCTs for imaging of mandible. The effective dose of MDCT could be markedly decreased by using the low-dose technique.

Thermal-hydraulic analysis of research reactor core with different LEU fuel types using RELAP5

Energy Technology Data Exchange (ETDEWEB)

El-Sahlamy, Neama M. [Nuclear and Radiological Regulatory Authority, Cairo (Egypt)

2017-11-15

In the current work, comparisons between the core performances when using different LEU fuels are done. The fuels tested are UA1{sub X}-A1, U{sub 3}O{sub 8}-Al, and U{sub 3}Si{sub 2}-Al fuels with 19.7 % enrichment. Calculations are done using RELAP5 code to evaluate the thermal-hydraulic performance of the IAEA benchmark 10 MW reactor. First, a reassessment of the slow reactivity insertion transient with UA1{sub X}-A1 LEU fuel to compare the results with those reported in the IAEA TECDOC [1]. Then, comparisons between the thermal-hydraulic core performances when using the three LEU fuels are done. The assessment is performed at initial power of 1.0 W. The reactor power is calculated using the RELAP5 point kinetic model. The reactivity feedback, from changes in water density and fuel temperature, is considered for all cases. From the results it is noticed that U{sub 3}Si{sub 2}-Al fuel gives the best fuel performance since it has the minimum value of peak fuel temperature and the minimum peak clad surface temperature, as operating parameters. Also, it gives the maximum value of the Critical Heat Flux Ratio and the lowest tendency to flow instability occurrence.

Multiaxial ratcheting behavior of zirconium alloy tubes under combined cyclic axial load and internal pressure

Energy Technology Data Exchange (ETDEWEB)

Chen, G.; Zhang, X. [School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Xu, D.K. [Environmental Corrosion Center, Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016 (China); Li, D.H. [Hunan Taohuajiang Nuclear Power Co., Ltd, Yiyang, 413000 (China); Chen, X. [School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Zhang, Z., E-mail: zhe.zhang@tju.edu.cn [School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China)

2017-06-15

In this study, a series of uniaxial and multiaxial ratcheting tests were conducted at room temperature on zirconium alloy tubes. The experimental results showed that for uniaxial symmetrical cyclic test, the axial ratcheting strain ɛ{sub x} did not accumulate obviously in initial stage, but gradually increased up to 1% with increasing stress amplitude σ{sub xa}. For multiaxial ratcheting tests, the zirconium alloy tube was highly sensitive to both the axial stress amplitude σ{sub xa} and the internal pressure p{sub i}. The hoop ratcheting strain ɛ{sub θ} increased continuously with the increase of axial stress amplitude, whereas the evolution of axial ratcheting strain ɛ{sub x} was related to the axial stress amplitude. The internal pressure restricted the ratcheting accumulation in the axial direction, but promoted the hoop ratcheting strain on the contrary. The prior loading history greatly restrained the ratcheting behavior of subsequent cycling with a small internal pressure. - Highlights: •Uniaxial and multiaxial ratcheting behavior of the zirconium alloy tubes are investigated at room temperature. •The ratcheting depends greatly on the stress amplitude or internal pressure. •The interaction between the axial and hoop ratcheting mechanisms is greatly dependent on the internal pressure level. •The ratcheting is influenced significantly by the loading history of internal pressure.

A microbially derived tyrosine-sulfated peptide mimics a plant peptide hormone.

Science.gov (United States)

Pruitt, Rory N; Joe, Anna; Zhang, Weiguo; Feng, Wei; Stewart, Valley; Schwessinger, Benjamin; Dinneny, José R; Ronald, Pamela C

2017-07-01

The biotrophic pathogen Xanthomonas oryzae pv. oryzae (Xoo) produces a sulfated peptide named RaxX, which shares similarity to peptides in the PSY (plant peptide containing sulfated tyrosine) family. We hypothesize that RaxX mimics the growth-stimulating activity of PSY peptides. Root length was measured in Arabidopsis and rice treated with synthetic RaxX peptides. We also used comparative genomic analyses and reactive oxygen species burst assays to evaluate the activity of RaxX and PSY peptides. Here we found that a synthetic sulfated RaxX derivative comprising 13 residues (RaxX13-sY), highly conserved between RaxX and PSY, induces root growth in Arabidopsis and rice in a manner similar to that triggered by PSY. We identified residues that are required for activation of immunity mediated by the rice XA21 receptor but that are not essential for root growth induced by PSY. Finally, we showed that a Xanthomonas strain lacking raxX is impaired in virulence. These findings suggest that RaxX serves as a molecular mimic of PSY peptides to facilitate Xoo infection and that XA21 has evolved the ability to recognize and respond specifically to the microbial form of the peptide. © 2017 UT-Battelle LLC. New Phytologist © 2017 New Phytologist Trust.

Comparison of effective dose for imaging of mandible between multi-detector CT and cone-beam CT

Energy Technology Data Exchange (ETDEWEB)

Jeong, Dae Kyo; Lee, Sang Chul; Huh, Kyung Hoe; Yi, Won Jin; Lee, Sam Sun; Choi, Soon Chul [School of Dentistry, Seoul National University, Seoul (Korea, Republic of)

2012-06-15

The aim of this study was to compare the effective dose for imaging of mandible between multi-detector computed tomography (MDCT) and cone-beam computed tomography (CBCT). An MDCT with low dose technique was also compared with them. Thermoluminescent dosimeter (TLD) chips were placed at 25 organ sites of an anthropomorphic phantom. The mandible of the phantom was exposed using 2 different types of MDCT units (Somatom Sensation 10 for standard-dose MDCT, Somatom Emotion 6 for low-dose MDCT) and 3 different CBCT units (AZ3000CT, Implagraphy, and Kavo 3D eXaM). The radiation absorbed dose was measured and the effective dose was calculated according to the ICRP 2007 report. The effective dose was the highest for Somatom Sensation 10 (425.84 {mu}Sv), followed by AZ3000CT (332.4 {mu}Sv), Somatom Emotion 6 (199.38 {mu}Sv), and 3D eXaM (111.6 {mu}Sv); it was the lowest for Implagraphy (83.09 {mu}Sv). The CBCT showed significant variation in dose level with different device. The effective doses of MDCTs were not significantly different from those of CBCTs for imaging of mandible. The effective dose of MDCT could be markedly decreased by using the low-dose technique.

Multiaxial ratcheting behavior of zirconium alloy tubes under combined cyclic axial load and internal pressure

International Nuclear Information System (INIS)

Chen, G.; Zhang, X.; Xu, D.K.; Li, D.H.; Chen, X.; Zhang, Z.

2017-01-01

In this study, a series of uniaxial and multiaxial ratcheting tests were conducted at room temperature on zirconium alloy tubes. The experimental results showed that for uniaxial symmetrical cyclic test, the axial ratcheting strain ɛ x did not accumulate obviously in initial stage, but gradually increased up to 1% with increasing stress amplitude σ xa . For multiaxial ratcheting tests, the zirconium alloy tube was highly sensitive to both the axial stress amplitude σ xa and the internal pressure p i . The hoop ratcheting strain ɛ θ increased continuously with the increase of axial stress amplitude, whereas the evolution of axial ratcheting strain ɛ x was related to the axial stress amplitude. The internal pressure restricted the ratcheting accumulation in the axial direction, but promoted the hoop ratcheting strain on the contrary. The prior loading history greatly restrained the ratcheting behavior of subsequent cycling with a small internal pressure. - Highlights: •Uniaxial and multiaxial ratcheting behavior of the zirconium alloy tubes are investigated at room temperature. •The ratcheting depends greatly on the stress amplitude or internal pressure. •The interaction between the axial and hoop ratcheting mechanisms is greatly dependent on the internal pressure level. •The ratcheting is influenced significantly by the loading history of internal pressure.

Search for and study of the effective mass spectra of nucleon clusters produced in relativistic nucleon collisions

International Nuclear Information System (INIS)

Didenko, L.A.; Grishin, V.G.; Kuznetsov, A.A.

1991-01-01

The effective mass spectra of nucleon clusters, produced in p, d, He and C collisions with carbon nuclei at P=4.2xA GeV/c are studied. The results obtained show that clusters with proton multiplicity n p =2 and 3 can be interpreted as decay products of nucleon resonances with a width from a few MeV to a few tens MeV. 11 refs.; 6 figs.; 4 tabs

Single- and multiple-dose pharmacokinetics, pharmacodynamics, and safety of apixaban in healthy Chinese subjects [Corrigendum

Directory of Open Access Journals (Sweden)

Cui Y

2014-03-01

Full Text Available Cui Y, Song Y, Wang J, et al. Clinical Pharmacology: Advances and Applications. 2013;5(1:177–184.Note that on page 182, Figure 3 should be corrected as follows, with the line for mean anti-Xa activity extended through to 72 hours post dose on Day 9, and the Day 1 plasma apixaban concentration-time profile rendering error bars and symbols more visually apparent.Read the original article

Assessment of VME-PCI Interfaces with Linux Drivers

CERN Document Server

Schossmater, K; CERN. Geneva

2000-01-01

Abstract This report summarises the performance measurements and experiences recorded by testing three commercial VME-PCI interfaces with their Linux drivers. These interfaces are manufactured by Wiener, National Instruments and SBS Bit 3. The developed C programs are reading/writing a VME memory in different transfer modes via these interfaces. A dual processor HP Kayak XA-s workstation was used with the CERN certified Red Hat Linux 6.1 running on it.

Application of QA geoscience investigations

International Nuclear Information System (INIS)

Henderson, J.T.

1980-01-01

This paper discusses the evolution of a classical hardware QA program (as currently embodied in DOE/ALO Manual Chapter 08XA; NRC 10CFR Part 50, Appendix B; and other similar documents) into the present geoscience quality assurance programs that address eventual NRC licensing, if required. In the context of this paper, QA will be restricted to the tasks associated with nuclear repositories, i.e. site identification, selection, characterization, verification, and utilization

JPRS Report, Science & Technology, 16th International Congress of the International Society for Photogrammetry and Remote Sensing -- Volume 2

Science.gov (United States)

1989-01-27

Rego Barbosa, Osvaldo Caldas; MCT - MINISTERIO DA CIENCIA E TECNOLOGIA , INPE - INSTITUTO DE PESQUISAS ESPACIAIS, Rod. Presidente Dutra, km 40 12630...economic crisis tne country J.- xa^+ y recoanition from the governmental planners of the priorities ana importance of INPE’s role...87 8, 216 430 8, 646 The situation changed and in the last three years a clear -cove^is being observed. Not only Jh«* •=>«* fche u-er tenden y

Porphyrinic metal-organic framework/macroporous carbon composites for electrocatalytic applications

International Nuclear Information System (INIS)

Yin, Duanduan; Liu, Jian; Bo, Xiangjie; Li, Mian; Guo, Liping

2017-01-01

Graphical abstract: Zr-PorMOF/MPC composites were prepared, which used to detect H 2 O 2 and simultaneously detect UA, XA and HX Display Omitted -- Highlights: •Preparing Zr-PorMOF/MPC composites by a simple one-step solvothermal reaction. •Enhanced electrocatalytic activity at Zr-PorMOF/MPC than Zr-PorMOF and MPC. •A low detection limit, short response time and low applied potential towards H 2 O 2 reduction. •Simultaneous determination of UA, XA and HX. -- Abstract: In this work, a novel porphyrinic metal-organic framework-based composite has been successfully synthesized by a simple one-step solvothermal method through growing Zr-PorMOF on macroporous carbon (MPC). Porphyrin-base MOFs combining the structural adjustable of MOFs and the specific catalytic activity of biomimetic catalysts play an important role in electrocatalysis. A series of characterization show that the roles of MPC as follow: (1) MPC could avoid the agglomeration of Zr-PorMOF particles and increase the specific surface area; (2) MPC could improve the electrochemical stability of Zr-PorMOF particles; (3) MPC could reduce the electron transfer resistance. Therefore, MPC plays the role of the conductive bridges to provide facile charge transport. The obtained Zr-PorMOF/MPC composites exhibit much better electrocatalytic activity for the reduction of hydrogen peroxide (H 2 O 2 ) than the pristine Zr-PorMOF due to the synergy of Zr-PorMOF and MPC. This enzyme-free H 2 O 2 sensor shows two linear relationships in the ranges 0.5–137 μM (R 2 = 0.991, sensitivity = 66 μA mM −1 ) and 137–3587 μM (R 2 = 0.993, sensitivity = 16 μA mM −1 ), with a low over-potential at −0.2 V, a fast response time within 1 s and a low limit of detection (LOD) of 0.18 μM. Moreover, Zr-PorMOF/MPC composites were used to simultaneously detect uric acid (UA), xanthine (XA) and hypoxanthine (HX). These three substances are degradation products of purine metabolism. In addition, Zr-PorMOF/MPC composites

Regulation of Metastasis and DNA Damage Resistance Pathways by Transposable Elements

Science.gov (United States)

2014-10-01

significantly predictive of LMS expression in primary human tumors include: several TLRs, AIM2, IFI16, and RIG-I (Figure XA). 5 In order to test whether any of...108-121, October 2014. Highlighted in Cell 2014, Arnoult N and Karlseder J. ALT Telomeres Borrow from Meiosis to Get Moving. 8. Sawyer SL, Tian L...Approved for Public Release; Distribution Unlimited The views, opinions and/or findings contained in this report are those of the author(s) and

Xanthogranulomatous Appendicitis in a Child: Report of a Case and Review of the Literature

OpenAIRE

Al-Rawabdeh, Sura M.; Prasad, Vinay; King, Denis R.; Kahwash, Samir B.

2013-01-01

Xanthogranulomatous inflammation is a well-described inflammatory process, which may involve any organ but is most frequently encountered in the gall bladder and the kidney. There are rare reports of xanthogranulomatous appendicitis (XA) in the adult population, but only one brief mention of such a diagnosis in a child. In this report, we describe the case of an 11-year-old boy who presented with clinical signs and symptoms of acute appendicitis necessitating appendectomy. Upon microscopic ex...

Factors and factorizations of graphs proof techniques in factor theory

CERN Document Server

Akiyama, Jin

2011-01-01

This book chronicles the development of graph factors and factorizations. It pursues a comprehensive approach, addressing most of the important results from hundreds of findings over the last century. One of the main themes is the observation that many theorems can be proved using only a few standard proof techniques. This stands in marked contrast to the seemingly countless, complex proof techniques offered by the extant body of papers and books. In addition to covering the history and development of this area, the book offers conjectures and discusses open problems. It also includes numerous explanatory figures that enable readers to progressively and intuitively understand the most important notions and proofs in the area of factors and factorization.

Characterization of currently marketed heparin products: key tests for quality assurance.

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Keire, David A; Ye, Hongping; Trehy, Michael L; Ye, Wei; Kolinski, Richard E; Westenberger, Benjamin J; Buhse, Lucinda F; Nasr, Moheb; Al-Hakim, Ali

2011-01-01

During the 2007-2008 heparin crisis, it was found that the United States Pharmacopeia (USP) testing monograph for unfractionated heparin sodium (UFH) did not detect the presence of the contaminant, oversulfated chondroitin sulfate (OSCS) in heparin. In response to this concern, new tests and specifications were developed by the Food and Drug Administration (FDA) and USP and put in place to not only detect the contaminant OSCS but also to improve assurance of quality and purity of the drug product. Additional tests were also developed to monitor the heparin supply chain for other possible economically motivated additives or impurities. In 2009, a new USP monograph was put in place that includes 500 MHz (1)H NMR, SAX-HPLC, %galactosamine in total hexosamine, and anticoagulation time assays with purified factor IIa or factor Xa. These tests represent orthogonal approaches for UFH identification, measurement of bioactivity, and for detection of process impurities or contaminants in UFH. The FDA has applied these analytical approaches to the study of UFH active pharmaceutical ingredients in the marketplace. Here, we describe results from a comprehensive survey of UFH collected from seven different sources after the 2009 monograph revision and compare these data with results obtained on other heparin samples collected during the 2007-2008 crisis.

Graphene prepared by one-pot solvent exfoliation as a highly sensitive platform for electrochemical sensing

Energy Technology Data Exchange (ETDEWEB)

Wu, Can; Cheng, Qin [Key Laboratory for Large-Format Battery Materials and System, Ministry of Education, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan 430074 (China); Wu, Kangbing, E-mail: kbwu@hust.edu.cn [Key Laboratory for Large-Format Battery Materials and System, Ministry of Education, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan 430074 (China); Wu, Gang [Materials Physics and Applications Division, Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Li, Qing, E-mail: qing_li_2@brown.edu [Materials Physics and Applications Division, Los Alamos National Laboratory, Los Alamos, NM 87545 (United States)

2014-05-01

Highlights: • Graphene was prepared by one-step solvent exfoliation as superior electrode material. • Compared with RGO, prepared graphene exhibited stronger signal enhancement. • A widespread and highly-sensitive electrochemical sensing platform was constructed. - Abstract: Graphene was easily obtained via one-step ultrasonic exfoliation of graphite powder in N-methyl-2-pyrrolidone. Scanning electron microscopy, transmission electron microscopy, Raman and particle size measurements indicated that the exfoliation efficiency and the amount of produced graphene increased with ultrasonic time. The electrochemical properties and analytical applications of the resulting graphene were systematically studied. Compared with the predominantly-used reduced graphene oxides, the obtained graphene by one-step solvent exfoliation greatly enhanced the oxidation signals of various analytes, such as ascorbic acid (AA), dopamine (DA), uric acid (UA), xanthine (XA), hypoxanthine (HXA), bisphenol A (BPA), ponceau 4R, and sunset yellow. The detection limits of AA, DA, UA, XA, HXA, BPA, ponceau 4R, and sunset yellow were evaluated to be 0.8 μM, 7.5 nM, 2.5 nM, 4 nM, 10 nM, 20 nM, 2 nM, and 1 nM, which are much lower than the reported values. Thus, the prepared graphene via solvent exfoliation strategy displays strong signal amplification ability and holds great promise in constructing a universal and sensitive electrochemical sensing platform.

A need for evidence-based clinical practice guidelines for the use of heparins in the elderly

Directory of Open Access Journals (Sweden)

Isabelle Gouin-Thibault

2010-04-01

Full Text Available Isabelle Gouin-Thibault1,2, Virginie Siguret1,2, Eric Pautas2,31Assistance Publique Hôpitaux de Paris, Laboratoire d’Hématologie, Hôpital Charles Foix, Paris, France; 2Université Paris Descartes, INSERM U, Paris, France; 3Assistance Publique Hôpitaux de Paris, Unité de Gériatrie Aiguë, Hôpital Charles Foix, Paris, FranceAbstract: Low-molecular-weight heparins (LMWHs have been widely studied in pivotal clinical trials or in several meta-analyses. However, the safety and optimal use of LMWHs in high-risk patients such as the very elderly remains uncertain since these patients are usually excluded from clinical trials. In terms of LMWHs in the elderly, the main concerns are renal failure and the risk of accumulation. A clinical approach consisting of a LMWH dose reduction in the elderly should be considered with great caution in terms of efficacy, since it has been tested neither in the treatment of VTE nor in VTE prophylaxis. If monitoring is considered in patients receiving therapeutic dose LMWHs, appropriate target ranges for peak anti-Xa activity levels should be used and so far, no anti-Xa activity-based guidelines have been issued. Moreover, no data support any laboratory monitoring in elderly patients treated with prophylactic dose LMWHs.Keywords: elderly patients, low-molecular-weight heparin, renal insufficiency, evidence-based medicine

A linear functional differential equation with distributions in the input

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Vadim Z. Tsalyuk

2003-10-01

Full Text Available This paper studies the functional differential equation $$ dot x(t = int_a^t {d_s R(t,s, x(s} + F'(t, quad t in [a,b], $$ where $F'$ is a generalized derivative, and $R(t,cdot$ and $F$ are functions of bounded variation. A solution is defined by the difference $x - F$ being absolutely continuous and satisfying the inclusion $$ frac{d}{dt} (x(t - F(t in int_a^t {d_s R(t,s,x(s}. $$ Here, the integral in the right is the multivalued Stieltjes integral presented in cite{VTs1} (in this article we review and extend the results in cite{VTs1}. We show that the solution set for the initial-value problem is nonempty, compact, and convex. A solution $x$ is said to have memory if there exists the function $x$ such that $x(a = x(a$, $x(b = x(b$, $ x(t in [x(t-0,x(t+0]$ for $t in (a,b$, and $frac{d}{dt} (x(t - F(t = int_a^t {d_s R(t,s,{x}(s}$, where Lebesgue-Stieltjes integral is used. We show that such solutions form a nonempty, compact, and convex set. It is shown that solutions with memory obey the Cauchy-type formula $$ x(t in C(t,ax(a + int_a^t C(t,s, dF(s. $$

Factor XII (Hageman factor) deficiency

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... this page: //medlineplus.gov/ency/article/000545.htm Factor XII (Hageman factor) deficiency To use the sharing features on this ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

Functional and structural characterization of recombinant dermcidin-1L, a human antimicrobial peptide

International Nuclear Information System (INIS)

Lai Yuping; Peng Yifei; Zuo Yi; Li Jun; Huang Jing; Wang Linfa; Wu Zirong

2005-01-01

Antimicrobial peptides from human skin are an important component of the innate immune response and play a key role as a first line of defense against infections. One such peptide is the recently discovered dermcidin-1L. To better understand its mechanism and to further investigate its antimicrobial spectrum, recombinant dermcidin-1L was expressed in Escherichia coli as a fusion protein and purified by affinity chromatography. The fusion protein was cleaved by factor Xa protease to produce recombinant dermcidin-1L. Antimicrobial and hemolytic assays demonstrated that dermcidin-1L displayed microbicidal activity against several opportunistic nosocomial pathogens, but no hemolytic activity against human erythrocytes even at concentrations up to 100 μM. Structural studies performed by circular dichroism spectroscopy indicated that the secondary structure of dermcidin-1L was very flexible, and both α-helix and β-sheet structures might be required for the antimicrobial activity. Our results confirmed previous findings indicating that dermcidin-1L could have promising therapeutic potentials and shed new light on the structure-function relationship of dermcidin-1L

A general analytical expression for the three-dimensional Franck-Condon integral and simulation of the photodetachment spectrum of the PO2- anion

Science.gov (United States)

Liang, Jun; Cui, Fang; Wang, Ru; Huang, Wei; Cui, Zhifeng

2013-04-01

Calculations of Franck-Condon factors are crucial for interpreting vibronic spectra of molecules and studying nonradiative processes. We have derived straightforwardly a more general analytical expression for the calculation of the three-dimensional Franck-Condon overlap integrals on the basis of harmonic oscillator approximation under the influence of mode mixing effects. This new analytical expression was applied to study the photoelectron spectra of PO2-. The theoretical spectrum obtained by employing CCSD(T) values is in excellent agreement with the observed one. An 'irregular spacing' observed in the experimental photoelectron spectrum of PO2- is interpreted as contributing from a hot-band sequence of the bending vibration ω2 and combination bands of the stretching vibration ω1 and the bending vibration ω2. In addition, the equilibrium geometry parameters, r(O-P) = 1.495 ± 0.005 Å and ∠(O-P-O) = 119.5 ± 0.5°, of theXA1 state of PO2-, are derived by employing an iterative Franck-Condon analysis procedure in the spectral simulation.

Click-coated, heparinized, decellularized vascular grafts.

Science.gov (United States)

Dimitrievska, Sashka; Cai, Chao; Weyers, Amanda; Balestrini, Jenna L; Lin, Tylee; Sundaram, Sumati; Hatachi, Go; Spiegel, David A; Kyriakides, Themis R; Miao, Jianjun; Li, Guoyun; Niklason, Laura E; Linhardt, Robert J

2015-02-01

A novel method enabling the engineering of a dense and appropriately oriented heparin-containing layer on decellularized aortas has been developed. Amino groups of decellularized aortas were first modified to azido groups using 3-azidobenzoic acid. Azide-clickable dendrons were attached onto the azido groups through "alkyne-azide" click chemistry, affording a tenfold amplification of adhesions sites. Dendron end groups were finally decorated with end-on modified heparin chains. Heparin chains were oriented like heparan sulfate groups on native endothelial cells surface. X-ray photoelectron spectroscopy, nuclear magnetic resonance imaging, mass spectrometry and Fourier transform infrared FTIR spectroscopy were used to characterize the synthesis steps, building the final heparin layered coatings. The continuity of the heparin coating was verified using fluorescent microscopy and histological analysis. The efficacy of heparin linkage was demonstrated with factor Xa anti-thrombogenic assay and platelet adhesion studies. The results suggest that oriented heparin immobilization to decellularized aortas may improve the in vivo blood compatibility of decellularized aortas and vessels. Copyright © 2014 Acta Materialia Inc. All rights reserved.

Intracranial subdural hematomas with elevated rivaroxaban concentration and subsequently detected spinal subdural hematoma: A case report.

Science.gov (United States)

Yamaguchi, Yoshitaka; Koga, Masatoshi; Matsuki, Takayuki; Hino, Tenyu; Yokota, Chiaki; Toyoda, Kazunori

2016-07-01

A 79-year-old lean man with a height of 157cm and weight of 42kg (body mass index, 17.2kg/m(2)) receiving rivaroxaban developed an intracranial subdural hematoma and was treated conservatively. Because he had a reduced creatinine clearance of 44mL/min, his dosage of rivaroxaban was reduced from 15 to 10mg daily according to official Japanese prescribing information. However, he developed bilateral intracranial subdural hematomas 2weeks later. Plasma rivaroxaban concentration on anti-factor Xa chromogenic assay was elevated at 301ng/mL, suggesting excessive accumulation. He underwent burr hole drainage and resumed anticoagulation with warfarin. Subsequently, he developed a lumbosacral hematoma. He was treated conservatively and discharged without neurological sequelae. The main cause of the increased concentration of rivaroxaban was believed to be his older age and low body weight. The etiology of the spinal hematoma was suspected to be the migration of intracranial hematoma to the spinal subdural space. Copyright © 2016 Elsevier Ltd. All rights reserved.

Non-valvular atrial fibrillation: impact of apixaban on patient outcomes

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Ioannou A

2017-11-01

Full Text Available Adam Ioannou,1 Irene Tsappa,2 Sofia Metaxa,3 Constantinos G Missouris2,3 1Cardiology Department, Royal Free NHS Foundation Trust, London, UK; 2Cardiology Department, Medical School, University of Cyprus, Nicosia, Cyprus; 3Cardiology Department, Frimley Health NHS Foundation Trust, London, UK Abstract: Atrial fibrillation is the most common arrhythmia worldwide, and carries a significantly increased risk of thromboembolic stroke. Initially, vitamin K antagonists were used as stroke prophylaxis; but more recently, a group of drugs known as novel oral anticoagulants have been developed. Apixaban belongs to this group of drugs, and is a factor Xa inhibitor that has emerged as a popular pharmacological agent worldwide. In this review, we will provide an overview of the pivotal trials in the development of apixaban, while also critically evaluating the new emerging real-world data, and discussing the effectiveness, safety, economic viability and future prospects of apixaban and how it impacts on patient outcomes in those with non-valvular atrial fibrillation. Keywords: apixaban, atrial fibrillation, warfarin, stroke, bleeding

Representation of molecular structure using quantum topology with inductive logic programming in structure-activity relationships.

Science.gov (United States)

Buttingsrud, Bård; Ryeng, Einar; King, Ross D; Alsberg, Bjørn K

2006-06-01

The requirement of aligning each individual molecule in a data set severely limits the type of molecules which can be analysed with traditional structure activity relationship (SAR) methods. A method which solves this problem by using relations between objects is inductive logic programming (ILP). Another advantage of this methodology is its ability to include background knowledge as 1st-order logic. However, previous molecular ILP representations have not been effective in describing the electronic structure of molecules. We present a more unified and comprehensive representation based on Richard Bader's quantum topological atoms in molecules (AIM) theory where critical points in the electron density are connected through a network. AIM theory provides a wealth of chemical information about individual atoms and their bond connections enabling a more flexible and chemically relevant representation. To obtain even more relevant rules with higher coverage, we apply manual postprocessing and interpretation of ILP rules. We have tested the usefulness of the new representation in SAR modelling on classifying compounds of low/high mutagenicity and on a set of factor Xa inhibitors of high and low affinity.

Eisenia fetida Protease-III-1 Functions in Both Fibrinolysis and Fibrogenesis

Directory of Open Access Journals (Sweden)

Jing Zhao

2007-01-01

Full Text Available The fibrinolytic function of earthworm protease-III-1 (EfP-III-1 has been studied in recent years. Here, we found that EfP-III-1 acted not only in fibrinogenolysis, but also in fibrogenesis. We have used EfP-III-1 to hydrolyze fibrinogen, and to activate plasminogen and prothrombin. Based on the N-terminal sequences of the hydrolytic fragments, EfP-III-1 was showed to specifically recognize the carboxylic sites of arginine and lysine. Analyses by fibrinogenolysis mapping and amino acid sequencing revealed that the isozyme could cleave the alpha, beta, and gamma chains of fibrinogen, showing a high α-fibrinogenase, moderate β-fibrinogenase, and low γ-fibrinogenase activities. Interestingly, EfP-III-1 activated plasminogen and released active plasmin, suggesting a tPA-like function. Furthermore, EfP-III-1 showed a factor Xa-like function on prothrombin, producing alpha-thrombin. The function in both activating prothrombin and catalyzing fibrinogenolysis suggests that EfP-III-1 may play a role in the balance between procoagulation and anticoagulation.

Outcomes With Edoxaban Versus Warfarin in Patients With Previous Cerebrovascular Events

DEFF Research Database (Denmark)

Rost, Natalia S; Giugliano, Robert P; Ruff, Christian T

2016-01-01

BACKGROUND AND PURPOSE: Patients with atrial fibrillation and previous ischemic stroke (IS)/transient ischemic attack (TIA) are at high risk of recurrent cerebrovascular events despite anticoagulation. In this prespecified subgroup analysis, we compared warfarin with edoxaban in patients with ver......BACKGROUND AND PURPOSE: Patients with atrial fibrillation and previous ischemic stroke (IS)/transient ischemic attack (TIA) are at high risk of recurrent cerebrovascular events despite anticoagulation. In this prespecified subgroup analysis, we compared warfarin with edoxaban in patients...... with versus without previous IS/TIA. METHODS: ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) was a double-blind trial of 21 105 patients with atrial fibrillation randomized to warfarin (international normalized ratio......). Because only HDER is approved, we focused on the comparison of HDER versus warfarin. RESULTS: Of 5973 (28.3%) patients with previous IS/TIA, 67% had CHADS2 (congestive heart failure, hypertension, age, diabetes, prior stroke/transient ischemic attack) >3 and 36% were ≥75 years. Compared with 15 132...

Effects of Oscillation Frequency and Amplitude on Separation in an Unsteady Turbulent Flow.

Science.gov (United States)

1980-09-01

be performed with much of the aircraft immersed in turbulent flow. When in operation near the ground or landing platform , unsteady, turbulent flow...34 - .-,...i ,aXa. 8O- IDa I"l N 0 N( ’A0 󈧨 a r. 0 a 0.a " - M - if l’ . t 1 - o t I.- I.- 𔃻 I I I Ni ilNl 1i * 11 it O ag 0) - -i "NUm M CA myp WiX ~ U’iCL

"XANSONS for COD": a new small BOINC project in crystallography

Science.gov (United States)

Neverov, Vladislav S.; Khrapov, Nikolay P.

2018-04-01

"XANSONS for COD" (http://xansons4cod.com) is a new BOINC project aimed at creating the open-access database of simulated x-ray and neutron powder diffraction patterns for nanocrystalline phase of materials from the collection of the Crystallography Open Database (COD). The project uses original open-source software XaNSoNS to simulate diffraction patterns on CPU and GPU. This paper describes the scientific problem this project solves, the project's internal structure, its operation principles and organization of the final database.

Linearizability conditions for Lotka-Volterra planar complex cubic systems

International Nuclear Information System (INIS)

Gine, Jaume; Romanovski, Valery G

2009-01-01

In this paper, we investigate the linearizability problem for the two-dimensional planar complex system x-dot=x(1-a 10 x-a 01 y-a 20 x 2 -a 11 xy-a 02 y 2 ), y-dot=(1-b 10 x-b 01 y-b 20 x 2 -b 11 xy-b 02 y 2 ). The necessary and sufficient conditions for the linearizability of this system are found. From them the conditions for isochronicity of the corresponding real system can be derived

Materials Research at Stanford University, 1 July 1980-30 June 1981.

Science.gov (United States)

1981-07-01

extract such information from the tunneling that is subject to corrections required to account for both an apparent region of depressed superconductivity...temperature for the f irst time, Pre 1 im i na ry measurenh.nts show that tile detector is capable of a noise temperature for pul se detect.ion of 3 inK ...phases and couples it into a SQUID via a superconducting transformer. Because XA> XB, changes in the distribution of A & B phases cause changes in

Fourteen-Day Subacute Intravenous Toxicity Study of Hypertonic Saline/ Dextran 70 (Trade name) and its Constituents in New Zealand White Rabbits

Science.gov (United States)

1989-11-01

of Hypertonic Saline/Dextran 70C and its Constituents in New Zealand White Rabbits," Toxicology Series 248, was audited on 20 October 1989. CAROLYNM...at tA "e a .6 L C C o L a L Lm .. .. a. a4 1 . . ao 3.&ow2 aCCa .0 00 c -C a- 4;. *; a 0O .. t x.T 2Cu u . u uu0 0 Uc L 01 2.:4A.1 4xa&C -I - -N .CA -e

Reversal Strategies for NOACs: State of Development, Possible Clinical Applications and Future Perspectives.

Science.gov (United States)

Husted, Steen; Verheugt, Freek W A; Comuth, Willemijn J

2016-01-01

The non-vitamin K antagonist oral anticoagulants (NOACs) are used for thromboembolic prophylaxis of patients with atrial fibrillation and in the treatment as well as secondary prophylaxis of patients with venous thromboembolism. Even though NOACs have a better safety profile than vitamin K antagonists (VKAs), there will still be bleeding complications on NOAC treatment. In some cases, stopping the NOAC and non-drug-related management such as manual compression and interventional endoscopy will be sufficient to stop the bleeding. In more serious bleeding events and before acute surgery, coagulation factor concentrates or NOAC-specific antidotes could be used. Coagulation factor concentrates can be used in patients with haemophilia and to reverse the effect of VKAs but, in NOAC-treated patients, results are inconsistent and these agents could potentially have pro-thrombotic effects. Specific antidotes for NOACs are expected to be on the market soon. Phase III clinical trials with a humanized antibody fragment directed against dabigatran (idarucizumab) and recombinant, modified factor Xa (andexanet alfa) are ongoing. A molecule (aripazine) with broad activity against various anticoagulants including NOACs is currently undergoing phase II trials. For use of these specific antidotes, it is desirable that measurements for coagulation activity with a short response delay are widely available for the different NOACs and further research in this field is needed. Furthermore, guidelines for antidote use, including general measures for the treatment of NOAC-related bleeding, should be available.

Optimal duration of anticoagulation in patients with venous thromboembolism.

Science.gov (United States)

Prandoni, Paolo; Piovella, Chiara; Spiezia, Luca; Dalla Valle, Fabio; Pesavento, Raffaele

2011-07-01

The risk of recurrent venous thromboembolism (VTE) approaches 40 per cent of all patients after 10 yr of follow up. This risk is higher in patients with permanent risk factors of thrombosis such as active cancer, prolonged immobilization from medical diseases, and antiphospholipid syndrome; in carriers of several thrombophilic abnormalities, including deficiencies of natural anticoagulants; and in patients with unprovoked presentation. Patients with permanent risk factors of thrombosis should receive indefinite anticoagulation, consisting of subtherapeutic doses of low molecular weight heparin in cancer patients, and oral anticoagulants in all other conditions. Patients whose VTE is triggered by major surgery or trauma should be offered three months of anticoagulation. Patients with unprovoked VTE, including carriers of thrombophilia, and those whose thrombotic event is associated with minor risk factors (such as hormonal treatment, minor injuries, long travel) should receive at least three months of anticoagulation. The decision as to go on or discontinue anticoagulation after this period should be individually tailored and balanced against the haemorrhagic risk. Post-baseline variables, such as the D-dimer determination and the ultrasound assessment of residual thrombosis can help identify those patients in whom anticoagulation can be safely discontinued. As a few emerging anti-Xa and anti-IIa compounds seem to induce fewer haemorrhagic complications than conventional anticoagulation, while preserving at least the same effectiveness, these have the potential to open new scenarios for decisions regarding the duration of anticoagulation in patients with VTE.

Factors affecting construction performance: exploratory factor analysis

Science.gov (United States)

Soewin, E.; Chinda, T.

2018-04-01

The present work attempts to develop a multidimensional performance evaluation framework for a construction company by considering all relevant measures of performance. Based on the previous studies, this study hypothesizes nine key factors, with a total of 57 associated items. The hypothesized factors, with their associated items, are then used to develop questionnaire survey to gather data. The exploratory factor analysis (EFA) was applied to the collected data which gave rise 10 factors with 57 items affecting construction performance. The findings further reveal that the items constituting ten key performance factors (KPIs) namely; 1) Time, 2) Cost, 3) Quality, 4) Safety & Health, 5) Internal Stakeholder, 6) External Stakeholder, 7) Client Satisfaction, 8) Financial Performance, 9) Environment, and 10) Information, Technology & Innovation. The analysis helps to develop multi-dimensional performance evaluation framework for an effective measurement of the construction performance. The 10 key performance factors can be broadly categorized into economic aspect, social aspect, environmental aspect, and technology aspects. It is important to understand a multi-dimension performance evaluation framework by including all key factors affecting the construction performance of a company, so that the management level can effectively plan to implement an effective performance development plan to match with the mission and vision of the company.

A randomized direct comparison of the pharmacokinetics and pharmacodynamics of apixaban and rivaroxaban

Directory of Open Access Journals (Sweden)

Frost C

2014-11-01

Full Text Available Charles Frost,1 Yan Song,1 Yu Chen Barrett,1 Jessie Wang,2 Janice Pursley,3 Rebecca A Boyd,4 Frank LaCreta1 1Exploratory Clinical and Translational Research, 2Exploratory Development Global Biometric Sciences, 3Analytical and Bioanalytical Development, Bristol-Myers Squibb Company, Princeton, NJ, USA; 4Global Innovative Pharma Business Clinical Pharmacology, Pfizer Inc., Groton, CT, USA Background: Currently, there are no direct comparisons of apixaban and rivaroxaban, two new oral direct factor Xa inhibitors approved for management of thromboembolic disorders. Objective: Compare the pharmacokinetics and anti-factor Xa activity (AXA of apixaban and rivaroxaban. Methods: In this randomized, open-label, two-period, two-treatment crossover study, healthy subjects (N=14 received apixaban 2.5 mg twice daily (BID and rivaroxaban 10 mg once daily (QD for 4 days with a ≥4.5-day washout. Plasma samples were obtained for pharmacokinetic and AXA assessments; parameters were calculated using noncompartmental methods. Results: Median time-to-maximum concentration was 2 hours for both compounds, and the mean half-life was 8.7 and 7.9 hours for apixaban and rivaroxaban, respectively. Daily exposure, the area under the curve (AUC(0–24, appeared similar for rivaroxaban (1,094 ng · h/mL and apixaban (935 ng · h/mL, whereas mean peak-to-trough plasma concentration ratio was 3.6-fold greater for rivaroxaban (16.9 than apixaban (4.7. Coefficient of variation for exposure parameters (AUC0–24, Cmax, Cmin was 20%–24% for apixaban versus 29%–46% for rivaroxaban. Peak AXA, AXA AUC(0–24, and AXA fluctuation were ~2.5-, 1.3-, and 3.5-fold higher for rivaroxaban than apixaban, respectively. Trough concentrations and AXA were lower for rivaroxaban (10 ng/mL and 0.17 IU/mL vs 17 ng/mL and 0.24 IU/mL for apixaban, respectively. Rivaroxaban exhibited a steeper concentration–AXA response (slope: 0.0172 IU/ng vs 0.0134 IU/ng for apixaban, P<0.0001. Conclusion

Installation Restoration Program. Phase 2. Confirmation/Quantification. Stage 1. Problem Confirmation Study: Otis Air National Guard Base, Massachusetts, Air National Guard Support Center, Andrews Air Force Base, Maryland.

Science.gov (United States)

1985-09-04

six surface water sampling locations are recommended. If there are any existing private wells off-Base in the vicinity of the Cranberry Bog south of the... Cranberry Bog *Scale: 1" 800’ 0800 0 400 800 FIGURE 1-9 SITE MAP FOR PETROL FUEL STORAGE AREA 102 A _XA LA.*. the middle 1950’s, the 14,000 and 22,500 balrel...flat, plain sloping gently to the south. Elevations generally range from 100 to 140 feet above mean sea level (MSL). Numerous depressions , frequently

Proceedings of the Conference on the Design of Experiments in Army Research Development and Testing (31st) Held at the Madison, Wisconsin on 23-25 October 1986

Science.gov (United States)

1986-06-01

indicates a ne ed for corrective action. If the scheme is applied to each of three employe es, the total sample is n = 6,000, about 12 percent of workload...x8 implies B. It should be noted that the calculations of xA and x8 yield wor st case va 1 ues if the null hypotheses are inequa 1 iti es. Each...parameter n is assumed to be independent of ~· Glaser (1984) employes a more general formulation with the Weibull distribution assuming that the

Proceedings of the Army Numerical Analysis Conference (11th) Held at Frankford Arsenal, Philadelphia, Pa., on 13-14 February 1974

Science.gov (United States)

1974-12-01

World Conference on Earthquake Engineering, Santiago, Chile , January 13 - 18, 1969. 2. English, G. W., and Adams, P. F., "Experiments on Laterally... Chile , January 13 - 18, 1969. 4. Wakabayashi, M., "Frames Under Strong Impulsive, Wind or Seismic Loading", Proceedings of the International...while 501 / f(Vzb) = A.. ,. » _i/.. \\i i .. rv»i* e’(x ) + u.[g’(x ) - g’ixj] + vb[h’(xa) - h’(xb)] + V’^ + vIh ’(xb) (uaWV V Lhl

Statistical coronary motion models for 2D + t/3D registration of X-ray coronary angiography and CTA

DEFF Research Database (Denmark)

Baka, N.; Metz, C. T.; Schultz, C.

2013-01-01

Accurate alignment of intra-operative X-ray coronary angiography (XA) and pre-operative cardiac CT angiography (CTA) may improve procedural success rates of minimally invasive coronary interventions for patients with chronic total occlusions. It was previously shown that incorporating patient...... specific coronary motion extracted from 4D CTA increases the robustness of the alignment. However, pre-operative CTA is often acquired with gating at end-diastole, in which case patient specific motion is not available. For such cases, we investigate the possibility of using population based coronary...

Impacts and adaptation of the cropping systems to climate change in the Northeast Farming Region of China

DEFF Research Database (Denmark)

Yin, Xiaogang; Olesen, Jørgen Eivind; Wang, M.

2016-01-01

The Northeast Farming Region of China (NFR) is a very important crop growing area, comprising seven sub-regions: Xing’anling (XA), Sanjiang (SJ), Northwest Songliao (NSL), Central Songliao (CSL), Southwest Songliao (SSL), Changbaishan (CB) and Liaodong (LD), which has been severely affected...... to become more severe for crop production under climate change. Adaptation measures that have already been implemented in recent decades to cope with current climatic limitations include changes in timing of cultivation, variety choice, soil tillage practices, crop protection, irrigation and use of plastic...

Phased-Array Monolithic PEM for FT Spectrometry With Applications in Explosive Detection and CB Defense

Science.gov (United States)

2008-12-01

developed in house; this interface allows the problem set up in COM- SOL to be transferred, via COMSOL Script (COMSOL AB, 2006), Java /JNI and C...wave that propagates along the x axis and gene- rates a local oscillation of amplitude )(0 xA , phase )(0 x , and angular frequency . If the...κ , where  /2k is the (real) wavenumber. Fig. 3b shows a set of N point sources at N  ...21 and oscillating with the same angular

Factorization and non-factorization in diffractive hard scattering

International Nuclear Information System (INIS)

Berera, Arjun

1997-01-01

Factorization, in the sense defined for inclusive hard scattering, is discussed for diffractive hard scattering. A factorization theorem similar to its inclusive counterpart is presented for diffractive DIS. For hadron-hadron diffractive hard scattering, in contrast to its inclusive counterpart, the expected breakdown of factorization is discussed. Cross section estimates are given from a simple field theory model for non-factorizing double-pomeron-exchange (DPE) dijet production with and without account for Sudakov suppression

Crystal Structure of Human Factor VIII: Implications for the Formation of the Factor IXa-Factor VIIIa Complex

Energy Technology Data Exchange (ETDEWEB)

Ngo, J.C.; Huang, M.; Roth, D.A.; Furie, B.C.; Furie, B. (Wyeth); (MBL)

2008-06-03

Factor VIII is a procofactor that plays a critical role in blood coagulation, and is missing or defective in hemophilia A. We determined the X-ray crystal structure of B domain-deleted human factor VIII. This protein is composed of five globular domains and contains one Ca{sup 2+} and two Cu{sup 2+} ions. The three homologous A domains form a triangular heterotrimer where the A1 and A3 domains serve as the base and interact with the C2 and C1 domains, respectively. The structurally homologous C1 and C2 domains reveal membrane binding features. Based on biochemical studies, a model of the factor IXa-factor VIIIa complex was constructed by in silico docking. Factor IXa wraps across the side of factor VIII, and an extended interface spans the factor VIII heavy and light chains. This model provides insight into the activation of factor VIII and the interaction of factor VIIIa with factor IXa on the membrane surface.

Crystal Structure of Human Factor VIII: Implications for the Formation of the Factor IXa-Factor VIIIa Complex

Energy Technology Data Exchange (ETDEWEB)

Chi Ki Ngo,J.; Huang, M.; Roth, D.; Furie, B.; Furie, B.

2008-01-01

Factor VIII is a procofactor that plays a critical role in blood coagulation, and is missing or defective in hemophilia A. We determined the X-ray crystal structure of B domain-deleted human factor VIII. This protein is composed of five globular domains and contains one Ca(2+) and two Cu(2+) ions. The three homologous A domains form a triangular heterotrimer where the A1 and A3 domains serve as the base and interact with the C2 and C1 domains, respectively. The structurally homologous C1 and C2 domains reveal membrane binding features. Based on biochemical studies, a model of the factor IXa-factor VIIIa complex was constructed by in silico docking. Factor IXa wraps across the side of factor VIII, and an extended interface spans the factor VIII heavy and light chains. This model provides insight into the activation of factor VIII and the interaction of factor VIIIa with factor IXa on the membrane surface.

Reusable Launch Vehicle Technology Program

Science.gov (United States)

Freeman, Delma C., Jr.; Talay, Theodore A.; Austin, R. Eugene

1997-01-01

Industry/NASA reusable launch vehicle (RLV) technology program efforts are underway to design, test, and develop technologies and concepts for viable commercial launch systems that also satisfy national needs at acceptable recurring costs. Significant progress has been made in understanding the technical challenges of fully reusable launch systems and the accompanying management and operational approaches for achieving a low cost program. This paper reviews the current status of the RLV technology program including the DC-XA, X-33 and X-34 flight systems and associated technology programs. It addresses the specific technologies being tested that address the technical and operability challenges of reusable launch systems including reusable cryogenic propellant tanks, composite structures, thermal protection systems, improved propulsion and subsystem operability enhancements. The recently concluded DC-XA test program demonstrated some of these technologies in ground and flight test. Contracts were awarded recently for both the X-33 and X-34 flight demonstrator systems. The Orbital Sciences Corporation X-34 flight test vehicle will demonstrate an air-launched reusable vehicle capable of flight to speeds of Mach 8. The Lockheed-Martin X-33 flight test vehicle will expand the test envelope for critical technologies to flight speeds of Mach 15. A propulsion program to test the X-33 linear aerospike rocket engine using a NASA SR-71 high speed aircraft as a test bed is also discussed. The paper also describes the management and operational approaches that address the challenge of new cost effective, reusable launch vehicle systems.

Mechanisms and attenuation of hemostatic activation during extracorporeal circulation.

Science.gov (United States)

Despotis, G J; Avidan, M S; Hogue, C W

2001-11-01

Patients undergoing cardiac surgery with cardiopulmonary bypass are at risk for excessive microvascular bleeding, which often leads to transfusion of allogeneic blood and blood components as well as reexploration in a smaller subset of patients. Excessive bleeding after cardiac surgery is generally related to a combination of several alterations in the hemostatic system pertaining to hemodilution, excessive activation of the hemostatic system, and potentially the use of newer, longer-acting antiplatelet or antithrombotic agents. Although several nonpharmacologic strategies have been proposed, this review summarizes the role of pharmacologic interventions as means to attenuate the alterations in the hemostatic system during CPB in an attempt to reduce excessive bleeding, transfusion, and reexploration. Specifically, agents that inhibit platelets, fibrinolysis, factor Xa and thrombin, as well as broad-spectrum agents, have been investigated with respect to their role in reducing consumption of clotting factors and better preservation of platelet function. Prophylactic administration of agents with antifibrinolytic, anticoagulant, and possibly antiinflammatory properties can decrease blood loss and transfusion. Although aprotinin seems to be the most effective blood conservation agent (which is most likely related to its broad-spectrum nature), agents with isolated antifibrinolytic properties may be as effective in low-risk patients. The ability to reduce blood product transfusions and to decrease operative times and reexploration rates favorably affects patient outcomes, availability of blood products, and overall health care costs.

Complement Activation in Arterial and Venous Thrombosis is Mediated by Plasmin

Directory of Open Access Journals (Sweden)

Jonathan H. Foley

2016-03-01

Full Text Available Thrombus formation leading to vaso-occlusive events is a major cause of death, and involves complex interactions between coagulation, fibrinolytic and innate immune systems. Leukocyte recruitment is a key step, mediated partly by chemotactic complement activation factors C3a and C5a. However, mechanisms mediating C3a/C5a generation during thrombosis have not been studied. In a murine venous thrombosis model, levels of thrombin–antithrombin complexes poorly correlated with C3a and C5a, excluding a central role for thrombin in C3a/C5a production. However, clot weight strongly correlated with C5a, suggesting processes triggered during thrombosis promote C5a generation. Since thrombosis elicits fibrinolysis, we hypothesized that plasmin activates C5 during thrombosis. In vitro, the catalytic efficiency of plasmin-mediated C5a generation greatly exceeded that of thrombin or factor Xa, but was similar to the recognized complement C5 convertases. Plasmin-activated C5 yielded a functional membrane attack complex (MAC. In an arterial thrombosis model, plasminogen activator administration increased C5a levels. Overall, these findings suggest plasmin bridges thrombosis and the immune response by liberating C5a and inducing MAC assembly. These new insights may lead to the development of strategies to limit thrombus formation and/or enhance resolution.

The optimal duration of anticoagulant therapy after unprovoked venous thromboembolism - still a challenging issue.

Science.gov (United States)

Elmi, Giovanna; Di Pasquale, Giuseppe; Pesavento, Raffaele

2017-03-01

As about 50 % of patients with unprovoked venous thromboembolism (VTE) will develop new episodes after discontinuing therapy, indefinite treatment is suggested in patients with low or moderate bleeding risk. Baseline and post-baseline factors can help clinicians to identify patients at high risk of recurrence, who require extended treatment. Residual vein obstruction and D-dimer assay have been shown to be suitable methods for assessing the risk of VTE recurrences after a first unprovoked VTE. In treatment for VTE the use of direct oral anticoagulants (DOAC) is growing instead of the standard adjusted dose of vitamin K antagonists. The DOAC safety profile has recently been strengthened with systematic reviews and meta-analyses. Idarucizumab is only approved for the reversal of dabigatran etexilate; intravenous antidotes for factor Xa inhibitors are under development. Their advent is of great interest. In the extended treatment of VTE sulodexide has been demonstrated to significantly decrease the risk of recurrences with an excellent safety profile. Aspirin is substantially less effective than oral anticoagulants in preventing recurrences but could play a role among patients who decided to stop anticoagulants. In conclusion, for the secondary prevention of VTE several options are available, without a recognised best choice regarding the treatment duration and the choice of drugs. An individual strategy taking into account risk of recurrence, bleeding risk, therapeutic options, and patient preferences is appropriate.

Activation of factor VII bound to tissue factor: a key early step in the tissue factor pathway of blood coagulation.

OpenAIRE

Rao, L V; Rapaport, S I

1988-01-01

Whether the factor VII/tissue factor complex that forms in tissue factor-dependent blood coagulation must be activated to factor VIIa/tissue factor before it can activate its substrates, factor X and factor IX, has been a difficult question to answer because the substrates, once activated, back-activate factor VII. Our earlier studies suggested that human factor VII/tissue factor cannot activate factor IX. Studies have now been extended to the activation of factor X. Reaction mixtures were ma...

Risk Factors

Science.gov (United States)

... cells do not invade nearby tissues or spread. Risk Factors Key Points Factors That are Known to ... chemicals . Factors That are Known to Increase the Risk of Cancer Cigarette Smoking and Tobacco Use Tobacco ...

Determining the Number of Factors in P-Technique Factor Analysis

Science.gov (United States)

Lo, Lawrence L.; Molenaar, Peter C. M.; Rovine, Michael

2017-01-01

Determining the number of factors is a critical first step in exploratory factor analysis. Although various criteria and methods for determining the number of factors have been evaluated in the usual between-subjects R-technique factor analysis, there is still question of how these methods perform in within-subjects P-technique factor analysis. A…

Aplicación de los microcontroladores a la docencia de sistemas digitales: “Termómetro digital a tiempo real y conexión serie a PC”

OpenAIRE

Ramírez Mendoza, Agurtzane

2006-01-01

El objetivo de este Trabajo de Fin de Carrera es servir de referencia para una práctica de la asignatura de Sistemas Electrónicos Digitales. Se diseñará el hardware y el software necesario para que, paso a paso, los alumnos de esta asignatura entren en contacto con el mundo de los microcontrolador, y más concretamente con el PIC16F87XA. Mediante pasos sencillos el alumno tomará contacto con los periféricos más importantes de este microcontrolador, formándose una base consist...

AFRRI (Armed Forces Radiobiology Research Institute) Reports, April-June 1989.

Science.gov (United States)

1989-07-01

pared w ith ) -rav photons, and 1. 34 compared "with bremisstrahlu ng X ra\\ys. Bremsstrahlung radiation was also signiticantl\\ more effective than...nes) ( . IS. /9). 1 kxporiielhxlation ol’[DN ’\\ has also been correlated xA iti celular dittlcrentiatiori (13. 14). (C- 13011\\N I F- I I5 cells, a...ith l)LA- aler I ss cek ss th iether I S II W, 1t). 6))- 10’. 12)) nonidentical man . pared to tile flask boosted w\\ith lo)’. or 241) ,It)’ mnonuucar

Analise funcional das traduccións en linguas en proceso de normalización: o caso da traducción do comic en galego

OpenAIRE

Sinner, Carsten

2002-01-01

In the case of the Galician language, the translation of comics is quite important, because it contributes to the normalization of use of the Galician language and allows young readers to become familiar with the norm. The article focusses on an analysis of the Galician translation with the French original and a Spanish version of the text.

[gl] A traducción de comics, no caso do galego xoga un papel moi importante xa que o seu obxectivo é sobre todo normalizar o uso da lin...

High-resolution mid-IR spectrometer based on frequency upconversion

DEFF Research Database (Denmark)

Hu, Qi; Dam, Jeppe Seidelin; Pedersen, Christian

2012-01-01

We demonstrate a novel approach for high-resolution spectroscopy based on frequency upconversion and postfiltering by means of a scanning Fabryx2013;Perot interferometer. The system is based on sum-frequency mixing, shifting the spectral content from the mid-infrared to the near-visible region al......-frequency 1064xA0;nm laser. We investigate water vapor emission lines from a butane burner and compare the measured results to model data. The presented method we suggest to be used for real-time monitoring of specific gas lines and reference signals....

Heparanase enhances the generation of activated factor X in the presence of tissue factor and activated factor VII.

Science.gov (United States)

Nadir, Yona; Brenner, Benjamin; Fux, Liat; Shafat, Itay; Attias, Judith; Vlodavsky, Israel

2010-11-01

Heparanase is an endo-β-D-glucuronidase dominantly involved in tumor metastasis and angiogenesis. Recently, we demonstrated that heparanase is involved in the regulation of the hemostatic system. Our hypothesis was that heparanase is directly involved in activation of the coagulation cascade. Activated factor X and thrombin were studied using chromogenic assays, immunoblotting and thromboelastography. Heparanase levels were measured by enzyme-linked immunosorbent assay. A potential direct interaction between tissue factor and heparanase was studied by co-immunoprecipitation and far-western assays. Interestingly, addition of heparanase to tissue factor and activated factor VII resulted in a 3- to 4-fold increase in activation of the coagulation cascade as shown by increased activated factor X and thrombin production. Culture medium of human embryonic kidney 293 cells over-expressing heparanase and its derivatives increased activated factor X levels in a non-enzymatic manner. When heparanase was added to pooled normal plasma, a 7- to 8-fold increase in activated factor X level was observed. Subsequently, we searched for clinical data supporting this newly identified role of heparanase. Plasma samples from 35 patients with acute leukemia at presentation and 20 healthy donors were studied for heparanase and activated factor X levels. A strong positive correlation was found between plasma heparanase and activated factor X levels (r=0.735, P=0.001). Unfractionated heparin and an inhibitor of activated factor X abolished the effect of heparanase, while tissue factor pathway inhibitor and tissue factor pathway inhibitor-2 only attenuated the procoagulant effect. Using co-immunoprecipitation and far-western analyses it was shown that heparanase interacts directly with tissue factor. Overall, our results support the notion that heparanase is a potential modulator of blood hemostasis, and suggest a novel mechanism by which heparanase increases the generation of activated

Transforming growth factor alpha, Shope fibroma growth factor, and vaccinia growth factor can replace myxoma growth factor in the induction of myxomatosis in rabbits.

Science.gov (United States)

Opgenorth, A; Nation, N; Graham, K; McFadden, G

1993-02-01

The epidermal growth factor (EGF) homologues encoded by vaccinia virus, myxoma virus, and malignant rabbit fibroma virus have been shown to contribute to the pathogenicity of virus infection upon inoculation of susceptible hosts. However, since the primary structures of these growth factors and the disease profiles induced by different poxvirus genera vary substantially, the degree to which the various EGF homologues perform similar roles in viral pathogenesis remains unclear. In order to determine whether different EGF-like growth factors can perform qualitatively similar functions in the induction of myxomatosis in rabbits, we created recombinant myxoma virus variants in which the native growth factor, myxoma growth factor (MGF), was disrupted and replaced with either vaccinia virus growth factor, Shope fibroma growth factor, or rat transforming growth factor alpha. Unlike the control virus containing an inactivated MGF gene, which caused marked attenuation of the disease syndrome and substantially less proliferation of the epithelial cell layers in the conjunctiva and respiratory tract, the recombinant myxoma virus strains expressing heterologous growth factors produced infections which were both clinically and histopathologically indistinguishable from wild-type myxomatosis. We conclude that these poxviral and cellular EGF-like growth factors, which are diverse with respect to primary structure and origin, have similar biological functions in the context of myxoma virus pathogenesis and are mitogenic for the same target cells.

Factor concentrates for the treatment of factor XIII deficiency.

Science.gov (United States)

Gootenberg, J E

1998-11-01

Factor XIII deficiency is a severe autosomal recessive bleeding disorder associated with a characteristic pattern of neonatal hemorrhage and a lifelong bleeding diathesis. Even relatively minor trauma can be followed by prolonged and recurrent bleeding. Intracranial hemorrhage is a frequent complication. With the development of safe and effective factor XIII concentrates, reliable prophylactic treatment is possible. Two plasma-derived, virus-inactivated factor XIII concentrates are currently in production. The first, Fibrogammin P, (Centeon LLC, King of Prussia, PA, USA; and Centeon Pharma GmbH, Marburg, Germany) is marketed in Europe, South America, South Africa, and Japan. It is distributed in the United States under a Food and Drug Administration Investigational New Drug Application. A second factor XIII concentrate (Bio Products Laboratory, Elstree, UK) is available for use only on a "named patient" compassionate basis in the United Kingdom. Patients with factor XIII deficiency who receive appropriately timed periodic infusions of such factor XIII concentrates are able to live normal lives, free from catastrophic bleeding episodes.

Epidermal growth factor and insulin-like growth factor I upregulate the expression of the epidermal growth factor system in rat liver

DEFF Research Database (Denmark)

Bor, M V; Sørensen, B S; Vinter-Jensen, L

2000-01-01

BACKGROUND/AIM: Both epidermal growth factor and insulin-like growth factor I play a role in connection with the liver. In the present study, the possible interaction of these two growth factor systems was studied by investigating the effect of epidermal growth factor or insulin-like growth factor...... I treatment on the expression of the epidermal growth factor receptor, and its activating ligands, transforming growth factor-alpha and epidermal growth factor. METHODS: Fifty-five male rats received no treatment, human recombinant epidermal growth factor or human recombinant insulin-like growth.......8+/-1.6 fmol/mg protein epidermal growth factor and 144+/-22 fmol/mg protein transforming growth factor-alpha. Both epidermal growth factor and insulin-like growth factor I treatment increased the expression of mRNA for transforming growth factor-alpha and epidermal growth factor receptor, as well...

Inhibition of platelet aggregation and thrombosis by indole alkaloids isolated from the edible insect Protaetia brevitarsis seulensis (Kolbe).

Science.gov (United States)

Lee, JungIn; Lee, Wonhwa; Kim, Mi-Ae; Hwang, Jae Sam; Na, MinKyun; Bae, Jong-Sup

2017-06-01

Protaetia brevitarsis seulensis (Kolbe) has been temporarily registered as a food material by the Ministry of Food and Drug Safety of Korea (MFDS). The current study aimed to discover small antithrombotic molecules from this edible insect. Five indole alkaloids, 5-hydroxyindolin-2-one (1), (1R,3S)-1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (2), (1S,3S)-1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (3), (3S)-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (4) and L-tryptophan (5), were isolated from the insect. Among them, compounds 1 and 2 prolonged aPTT and PT and impaired thrombin and FXa generation on HUVEC surface. Moreover, these compounds inhibited platelet aggregation. Antithrombotic effects of compounds 1 and 2 were further confirmed in pre-clinical models of pulmonary embolism and arterial thrombosis. Collectively, these results demonstrated that compounds 1 and 2 could be effective antithrombotic agents and serve as new scaffolds for the development of antithrombotic drug. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Cloning and expression of a novel antifreeze protein AFP72 from the beetle Tenebrio molitor.

Science.gov (United States)

Yan, Qing-Hua; Yang, Li; Wang, Qing; Zhang, Hui-Rong; Shao, Qiang

2012-01-01

A novel antifreeze protein AFP72 cDNA (GenBbank accession No. AY929389) was obtained by RT-PCR from Tenebrio molitor. The 216 bp fragment encodes a protein of 72 amino acid residues. Sequence analysis revealed that the cDNA displays a high degree of homology with T. molitor antifreeze proteins, ranging up to 90.78%. Recombinant plasmids pMAL-p2X-afp72 and pMAL-c2X-afp72 were transferred into E. coil TBI to induce a MBP fusion protein by IPTG. The target fusion protein was released from the periplasm and cytoplasm by the cold osmotic shock procedure and sonication respectively. The content of the fusion protein came up to 38.9 and 41.5% of the total dissolved protein, respectively. The fusion protein was purified through an amylose affinity column, and incised by factor Xa. Molecular sieve chromatography was used to achieve a high state of purity of the target protein. The purified target protein displayed a single band in SDS-PAGE. The fusion protein was shown to increase resistance to low temperatures in bacteria. This finding could help in further investigations of the properties and function of antifreeze proteins.

Preparation, Crystallization and X-ray Diffraction Analysis to 1.5 A Resolution of Rat Cysteine Dioxygenase, a Mononuclear Iron Enzyme Responsible for Cysteine Thiol Oxidation

Energy Technology Data Exchange (ETDEWEB)

Simmons,C.; Hao, Q.; Stipanuk, M.

2005-01-01

Cysteine dioxygenase (CDO; EC 1.13.11.20) is an {approx}23 kDa non-heme iron metalloenzyme that is responsible for the oxidation of cysteine by O2, yielding cysteinesulfinate. CDO catalyzes the first step in the conversion of cysteine to taurine, as well as the first step in the catabolism of cysteine to pyruvate plus sulfate. Recombinant rat CDO was heterologously expressed, purified and crystallized. The protein was expressed as a fusion protein bearing a polyhistidine tag to facilitate purification, a thioredoxin tag to improve solubility and a factor Xa cleavage site to permit removal of the entire N-terminus, leaving only the 200 amino acids inherent to the native protein. A multi-step purification scheme was used to achieve >95% purity of CDO. The optimal CDO crystals diffracted to 1.5 Angstroms resolution and belonged to space group P4{sub 3}2{sub 1}2 or P4{sub 1}2{sub 1}2, with unit-cell parameters a = b = 57.55, c = 123.06 Angstrom, {alpha} = {beta} = {gamma} = 90. CDO shows little homology to any other proteins; therefore, the structure of the enzyme will be determined by ab initio phasing using a selenomethionyl derivative.

New strategies for the treatment of acute venous thromboembolism.

Science.gov (United States)

Prandoni, Paolo; Lensing, Anthonie W A; Pesavento, Raffaele

2006-11-01

In recent years, new opportunities have emerged that have the potential to change rapidly the therapeutic scenario of patients with acute venous thromboembolism (VTE). Selected patients with deep vein thrombosis (DVT) can be treated effectively and safely at home with fixed doses of low molecular weight heparins. The prompt administration of compression elastic stockings in addition to anticoagulant drugs in patients with acute DVT has the potential to halve the rate of late postthrombotic sequelae. The long-term use of low molecular weight heparins is likely to be more effective than oral anticoagulants for the secondary prevention of VTE in patients with advanced malignancy. Patients with pulmonary embolism and right ventricular dysfunction might benefit from the early administration of thrombolytic drugs in combination with heparin to a greater extent than from heparin alone. Despite an impressive amount of clinical information on the proper duration of oral anticoagulants in patients with unprovoked VTE, the optimal long-term treatment of these patients remains undefined. Finally, new categories of drugs are emerging that have the potential to replace conventional anticoagulants in the near future. They include compounds that inhibit factor Xa or thrombin.

[Use of rivaroxaban in real-life treatment of venous thromboembolism: results of the TEV Survey, an Italian epidemiological study].

Science.gov (United States)

Pesavento, Raffaele; Iori, Ido

2017-03-01

Rivaroxaban is a direct and selective inhibitor of factor Xa. The randomized clinical trials EINSTEIN evaluated the efficacy and safety of rivaroxaban for the treatment of venous thromboembolism (VTE) proving that the drug was non-inferior to standard treatment. The aim of this survey was to describe how rivaroxaban was used in a group of "real-life" patients with VTE. Between June and October 2014, physicians collected aggregate data, through an online questionnaire, on consecutive patients affected by VTE and treated with rivaroxaban in the previous 6 months. Descriptive statistics were performed on the collected data. A total of 345 questionnaires were filled out. The mean age of patients was 62 years, with a low prevalence of concomitant diseases and/or pharmacological treatments. Deep vein thrombosis was diagnosed in 90% of patients and pulmonary embolism in 47%; only 48% was hospitalized. Rivaroxaban was prescribed at the recommended doses and/or regimen in no more than 60% of cases. In 96% of patients, the initial therapeutic plan did not require changes. Adherence to the therapeutic plan and overall patient satisfaction with therapy were high. Rivaroxaban was found easy to use and was highly appreciated by patients.

Does prior administration of enoxaparin influence the effects of levobupivacaine on blood clotting? Assessment using the Thrombelastograph.

LENUS (Irish Health Repository)

Leonard, S A

2012-02-03

The low molecular weight heparin, enoxaparin (by inhibition of factors Xa and IIa) and amide local anaesthetics (by altering platelet function) exert anti-clotting effects. Although these agents are often used in combination during the perioperative period, their potential interactive effect on clotting has not been defined. Blood from 10 ASA I-II patients who received enoxaparin 0.5 mg kg(-1) s.c. was studied using a Thrombelastograph (TEG) either alone or in combination with levobupivacaine (2.5 mg ml(-1) or 2.5 microg ml(-1)) or saline (50% dilution). In blood from patients who had received enoxaparin 0.5 mg kg(-1) s.c. 12 h previously, levobupivacaine 2.5 mg ml(-1) (but not 2.5 microg ml(-1)) produced significant changes in TEG clotting parameters (mean (SD) 15.7 (4.8) mm, 29.6 (25.6) mm, 34.4 (14.6) mm, 34.3 (12.2) degrees compared with control values of 6.1 (1.3) mm, 2.5 (0.5) mm, 63.5 (6.4) mm and 74.1 (2.9) degrees for r, K, MA, and alpha angle respectively).

Hemophilia B with mutations at glycine-48 of factor IX exhibited delayed activation by the factor VIIa-tissue factor complex.

Science.gov (United States)

Wu, P C; Hamaguchi, N; Yu, Y S; Shen, M C; Lin, S W

2000-10-01

Gly-48 is in the conserved DGDQC sequence (residues 47-51 of human factor IX) of the first EGF (EGF-1)-like domain of factor IX. The importance of the Gly-48 is manifested by two hemophilia B patients; factor IXTainan and factor IXMalmo27, with Gly-48 replaced by arginine (designated IXG48R) and valine (IXG48V), respectively. Both patients were CRM+ exhibiting mild hemophilic episodes with 25% (former) and 19% (latter) normal clotting activities. We characterize both factor IX variants to show the roles of Gly-48 and the conservation of the DGDQC sequence in factor IX. Purified plasma and recombinant factor IX variants exhibited approximately 26%-27% normal factor IX's clotting activities with G48R or G48V mutation. Both variants depicted normal quenching of the intrinsic fluorescence by increasing concentrations of calcium ions and Tb3+, indicating that arginine and valine substitution for Gly-48 did not perturb the calcium site in the EGF-1 domain. Activation of both mutants by factor XIa appeared normal. The reduced clotting activity of factors IXG48R and IXG48V was attributed to the failure of both mutants to cleavage factor X: in the presence of only phospholipids and calcium ions, both mutants showed a 4 to approximately 7-fold elevation in Km, and by adding factor VIIIa to the system, although factor VIIIa potentiated the activation of factor X by the mutants factor IXaG48R and factor IXaG48V, a 2 to approximately 3-fold decrease in the catalytic function was observed with the mutant factor IXa's, despite that they bound factor VIIIa on the phospholipid vesicles with only slightly reduced affinity when compared to wild-type factor IXa. The apparent Kd for factor VIIIa binding was 0.83 nM for normal factor IXa, 1.74 nM for IXaG48R and 1.4 nM for IXaG48V. Strikingly, when interaction with the factor VIIa-TF complex was examined, both mutations were barely activated by the VIIa-TF complex and they also showed abnormal interaction with VIIa-TF in bovine

The importance of residues 195-206 of human blood clotting factor VII in the interaction of factor VII with tissue factor

International Nuclear Information System (INIS)

Wildgoose, P.; Kisiel, W.; Kazim, A.L.

1990-01-01

Previous studies indicated that human and bovine factor VII exhibit 71% amino acid sequence identity. In the present study, competition binding experiments revealed that the interaction of human factor VII with cell-surface human tissue factor was not inhibited by 100-fold molar excess of bovine factor VII. This finding indicated that bovine and human factor VII are not structurally homologous in the region(s) where human factor VII interacts with human tissue factor. On this premise, the authors synthesized three peptides corresponding to regions of human factor VII that exhibited marked structural dissimilarity to bovine factor VII; these regions of dissimilarity included residues 195-206, 263-274, and 314-326. Peptide 195-206 inhibited the interaction of factor VII with cell-surface tissue factor and the activation of factor X by a complex of factor VIIa and tissue factor half-maximally at concentrations of 1-2 mM. A structurally rearranged form of peptide 195-206 containing an aspartimide residue inhibited these reactions half-maximally at concentrations of 250-300 μM. In contrast, neither peptide 263-274 nor peptide 314-326, at 2 mM concentration, significantly affected either factor VIIa interaction with tissue factor or factor VIIa-mediated activation of factor X. The data provide presumptive evidence that residues 195-206 of human factor VII are involved in the interaction of human factor VII with the extracellular domain of human tissue factor apoprotein

[Coagulation factor VII levels in uremic patients and theirs influence factors].

Science.gov (United States)

Fang, Jun; Xia, Ling-Hui; Wei, Wen-Ning; Song, Shan-Jun

2004-12-01

This study was aimed to investigate coagulation factor VII level in uremic patients with chronic renal failure and to explore theirs influence factors. The plasma levels of coagulation factor VII were detected in 30 uremic patients with chronic renal failure before and after hemodialysis for 1 month, the factor VII activity (FVII:C) was determined by one-stage coagulation method, while activated factor VII (FVIIa) was measured by one-stage coagulation method using recombinant soluble tissue factor, and factor VII antigen was detected by ELISA. The results showed that: (1) The FVIIa, FVII:C and FVIIAg levels in chronic uremic patients before hemodialysis were 4.00 +/- 0.86 microg/L, (148.5 +/- 40.4)% and (99.8 +/- 21.1)% respectively, which were significantly increased, as compared with healthy controls [2.77 +/- 1.02 microg/L, (113.1 +/- 33.0)% and (73.7 +/- 18.3)% respectively, P factor VII was positively correlated with levels of blood uria nitrogen and serum creatinine before hemodialysis but not after hemodialysis. It is concluded that the enhanced levels of coagulation factor VII in chronic uremic patients suggested abnormal activated state, herperactivity and elevated production of factor VII which correlated with renal functional injury. The abnormality of factor VII in uremia may be aggravated by hemodialysis. Coagulation factor (FVII) may be a risk factor for cardiovascular events in uremic patients who especially had been accepted long-term hemodialysis.