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Sample records for fibrinogen concentrate a potential

  1. Fibrinogen concentrate for bleeding - a systematic review

    DEFF Research Database (Denmark)

    Lunde, J; Stensballe, J; Wikkelsø, A

    2014-01-01

    Fibrinogen concentrate as part of treatment protocols increasingly draws attention. Fibrinogen substitution in cases of hypofibrinogenaemia has the potential to reduce bleeding, transfusion requirement and subsequently reduce morbidity and mortality. A systematic search for randomised controlled...... trials (RCTs) and non-randomised studies investigating fibrinogen concentrate in bleeding patients was conducted up to November 2013. We included 30 studies of 3480 identified (7 RCTs and 23 non-randomised). Seven RCTs included a total of 268 patients (165 adults and 103 paediatric), and all were...... determined to be of high risk of bias and none reported a significant effect on mortality. Two RCTs found a significant reduction in bleeding and five RCTs found a significant reduction in transfusion requirements. The 23 non-randomised studies included a total of 2825 patients, but only 11 of 23 studies...

  2. A viscometric method of measuring plasma fibrinogen concentrations.

    OpenAIRE

    Ernst, E.; Resch, K L; Saradeth, T.; A. Maier; Matrai, A

    1992-01-01

    A technique based on deducing the viscosity of serum from that of plasma was compared with the commonly used Clauss method. The two methods correlated closely (r = 0.914). The reproducibility of the viscometric method was slightly poorer than the Clauss technique at low fibrinogen concentrations, equal to that at medium fibrinogen concentrations, and marginally better at high concentrations. Fibrinogen can therefore be measured reasonably accurately with the viscometric method, and can be rec...

  3. Fibrinogen concentrate in bleeding patients

    DEFF Research Database (Denmark)

    Wikkelsø, Anne; Lunde, Jens; Johansen, Mathias

    2013-01-01

    Hypofibrinogenaemia is associated with increased morbidity and mortality, but the optimal treatment level, the use of preemptive treatment and the preferred source of fibrinogen remain disputed. Fibrinogen concentrate is increasingly used and recommended for bleeding with acquired haemostatic...

  4. Fibrinogen Concentrate Therapy in Complex Cardiac Surgery

    NARCIS (Netherlands)

    Bilecen, Suleyman; Peelen, Linda M.; Kalkman, Cor J.; Spanjersberg, Alexander J.; Moons, Karel G. M.; Nierich, Arno P.

    2013-01-01

    Objectives: Fibrinogen concentrate increasingly is used to treat coagulopathic bleeding in cardiac surgery although its effectiveness and safety have not been shown. The authors conducted a cohort study to quantify the effects of fibrinogen concentrate on postoperative blood loss and transfusion and

  5. Fibrinogen concentrates for bleeding trauma patients: what is the evidence?

    DEFF Research Database (Denmark)

    Meyer, Martin; Ostrowski, S R; Windeløv, N A

    2011-01-01

    A balanced transfusion of red blood cells, fresh frozen plasma and platelets are recommended for massively bleeding trauma patients. Fibrinogen concentrates could potentially lessen or replace the need for fresh frozen plasma and/or platelet transfusions.......A balanced transfusion of red blood cells, fresh frozen plasma and platelets are recommended for massively bleeding trauma patients. Fibrinogen concentrates could potentially lessen or replace the need for fresh frozen plasma and/or platelet transfusions....

  6. Effects of ophthalmic disease on concentrations of plasma fibrinogen and serum amyloid A in the horse.

    Science.gov (United States)

    Labelle, A L; Hamor, R E; Macneill, A L; Lascola, K M; Breaux, C B; Tolar, E L

    2011-07-01

    There is little scientific information available about the ability of ocular disease to cause a systemic inflammatory response. Horses are frequently affected with ocular disease and ensuring their systemic health prior to performing vision saving surgery under anaesthesia is essential for the successful treatment of ophthalmic disease. Ocular disease will cause elevations in the concentration of the acute phase proteins fibrinogen and serum amyloid A in peripheral blood. Whole blood and serum samples were obtained from 38 mature horses with ulcerative keratitis or uveitis and no evidence of systemic disease, 9 mature horses with no evidence of ocular or systemic disease (negative controls) and 10 mature horses with systemic inflammatory disease and no evidence of ocular disease (positive controls). Blood samples were assayed for concentrations of the acute phase proteins fibrinogen and serum amyloid A. Fibrinogen and serum amyloid A were significantly different in the positive control group compared to the negative control, corneal disease and uveitis groups (P<0.126). There was no significant difference between the negative control, corneal disease and uveitis groups (P<0.001). Ulcerative keratitis and anterior uveitis are not associated with elevated concentrations of the acute phase proteins fibrinogen and serum amyloid A in peripheral blood. When the clinician is presented with a patient with ocular disease and elevated plasma fibrinogen or serum amyloid A concentrations, a nonocular inflammatory focus should be suspected. © 2011 EVJ Ltd.

  7. Fibrinogen Concentrate in Dilutional Coagulopathy: a Dose Study in Pigs

    Science.gov (United States)

    2014-01-01

    safety issue leading to an increased risk of thrombosis has not yet been addressed. This study was conducted to investigate the effect of fibrinogen dose... thrombosis or throm- boembolic events. Neither did the histologic examination of all tissue slides provide any signs for arterial or venous thrombosis ...massive transfusions at an army combat support hospital. J Trauma 2008;64:S79-85. 21. Jax TW, Peters AJ, Plehn G, Schoebel FC. Hemostatic risk factors

  8. Perioperative dilutional coagulopathy treated with fresh frozen plasma and fibrinogen concentrate: a prospective randomized intervention trial.

    NARCIS (Netherlands)

    Lance, M.D.; Ninivaggi, M.; Schols, S.E.; Feijge, M.A.; Oehrl, S.K.; Kuiper, G.J.; Nikiforou, M.; Marcus, M.A.; Hamulyak, K.; Pampus, E.C.M. van; Cate, H. ten; Heemskerk, J.W.M.

    2012-01-01

    BACKGROUND AND OBJECTIVES: Treatment of dilutional coagulopathy by transfusing fresh frozen plasma (FFP) remains sub-optimal. We hypothesized that partial replacement of transfused FFP by fibrinogen concentrate results in improved coagulant activity and haemostasis. This was tested in a controlled c

  9. A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration.

    Science.gov (United States)

    de Vries, Paul S; Chasman, Daniel I; Sabater-Lleal, Maria; Chen, Ming-Huei; Huffman, Jennifer E; Steri, Maristella; Tang, Weihong; Teumer, Alexander; Marioni, Riccardo E; Grossmann, Vera; Hottenga, Jouke J; Trompet, Stella; Müller-Nurasyid, Martina; Zhao, Jing Hua; Brody, Jennifer A; Kleber, Marcus E; Guo, Xiuqing; Wang, Jie Jin; Auer, Paul L; Attia, John R; Yanek, Lisa R; Ahluwalia, Tarunveer S; Lahti, Jari; Venturini, Cristina; Tanaka, Toshiko; Bielak, Lawrence F; Joshi, Peter K; Rocanin-Arjo, Ares; Kolcic, Ivana; Navarro, Pau; Rose, Lynda M; Oldmeadow, Christopher; Riess, Helene; Mazur, Johanna; Basu, Saonli; Goel, Anuj; Yang, Qiong; Ghanbari, Mohsen; Willemsen, Gonneke; Rumley, Ann; Fiorillo, Edoardo; de Craen, Anton J M; Grotevendt, Anne; Scott, Robert; Taylor, Kent D; Delgado, Graciela E; Yao, Jie; Kifley, Annette; Kooperberg, Charles; Qayyum, Rehan; Lopez, Lorna M; Berentzen, Tina L; Räikkönen, Katri; Mangino, Massimo; Bandinelli, Stefania; Peyser, Patricia A; Wild, Sarah; Trégouët, David-Alexandre; Wright, Alan F; Marten, Jonathan; Zemunik, Tatijana; Morrison, Alanna C; Sennblad, Bengt; Tofler, Geoffrey; de Maat, Moniek P M; de Geus, Eco J C; Lowe, Gordon D; Zoledziewska, Magdalena; Sattar, Naveed; Binder, Harald; Völker, Uwe; Waldenberger, Melanie; Khaw, Kay-Tee; Mcknight, Barbara; Huang, Jie; Jenny, Nancy S; Holliday, Elizabeth G; Qi, Lihong; Mcevoy, Mark G; Becker, Diane M; Starr, John M; Sarin, Antti-Pekka; Hysi, Pirro G; Hernandez, Dena G; Jhun, Min A; Campbell, Harry; Hamsten, Anders; Rivadeneira, Fernando; Mcardle, Wendy L; Slagboom, P Eline; Zeller, Tanja; Koenig, Wolfgang; Psaty, Bruce M; Haritunians, Talin; Liu, Jingmin; Palotie, Aarno; Uitterlinden, André G; Stott, David J; Hofman, Albert; Franco, Oscar H; Polasek, Ozren; Rudan, Igor; Morange, Pierre-Emmanuel; Wilson, James F; Kardia, Sharon L R; Ferrucci, Luigi; Spector, Tim D; Eriksson, Johan G; Hansen, Torben; Deary, Ian J; Becker, Lewis C; Scott, Rodney J; Mitchell, Paul; März, Winfried; Wareham, Nick J; Peters, Annette; Greinacher, Andreas; Wild, Philipp S; Jukema, J Wouter; Boomsma, Dorret I; Hayward, Caroline; Cucca, Francesco; Tracy, Russell; Watkins, Hugh; Reiner, Alex P; Folsom, Aaron R; Ridker, Paul M; O'Donnell, Christopher J; Smith, Nicholas L; Strachan, David P; Dehghan, Abbas

    2016-01-15

    Genome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X-chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes indels. We conducted a genome-wide association analysis of 34 studies imputed to the 1000 Genomes Project reference panel and including ∼120 000 participants of European ancestry (95 806 participants with data on the X-chromosome). Approximately 10.7 million single-nucleotide polymorphisms and 1.2 million indels were examined. We identified 41 genome-wide significant fibrinogen loci; of which, 18 were newly identified. There were no genome-wide significant signals on the X-chromosome. The lead variants of five significant loci were indels. We further identified six additional independent signals, including three rare variants, at two previously characterized loci: FGB and IRF1. Together the 41 loci explain 3% of the variance in plasma fibrinogen concentration.

  10. Concentrations of serum amyloid A and plasma fibrinogen in horses undergoing emergency abdominal surgery.

    Science.gov (United States)

    Daniel, Alexander J; Leise, Britta S; Burgess, Brandy A; Morley, Paul S; Cloninger, Madison; Hassel, Diana M

    2016-05-01

    To compare the perioperative response of serum amyloid A (SAA) to fibrinogen in horses requiring exploratory celiotomy for colic and to determine if SAA could be used to predict complications and outcome. Prospective observational clinical study. University teaching hospital. Eighteen horses undergoing exploratory celiotomy for colic. Inclusion criteria for the study included survival and anesthetic recovery from exploratory celiotomy, no history of surgery within the past year. Blood was obtained via jugular venipuncture before surgery (time 0) and at 24, 48, 72, and 96 hours after recovery from anesthesia. Quantitative and semiquantitative fibrinogen, SAA, total nucleated cell counts, and total protein were evaluated at each time point. Multivariable linear regression was used to assess differences at each time point and after grouping horses according to duration of colic prior to surgery, strangulating surgical lesion or not, presence of systemic inflammatory response syndrome (SIRS) on admission, and postsurgical complications. Significant (P surgery compared to fibrinogen concentration, which only demonstrated a mild, clinically insignificant increase postsurgery. SAA concentrations were also significantly increased (P SIRS prior to surgery and postoperatively at 48 (P = 0.05) and 72 hours (P = 0.02) in horses that developed complications. Measurement of SAA is a more sensitive indicator of inflammation than fibrinogen in the perioperative period of horses requiring exploratory celiotomy for colic. Serial measurement of SAA at 48, 72, and 96 hours after surgery may be helpful to determine risk of complications and guide postoperative management. Measurement of SAA on admission also allows for quantification of SIRS when it is detected clinically. © Veterinary Emergency and Critical Care Society 2015.

  11. A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration

    DEFF Research Database (Denmark)

    de Vries, Paul S; Chasman, Daniel I; Sabater-Lleal, Maria

    2016-01-01

    Genome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes indels. W...

  12. A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration

    NARCIS (Netherlands)

    P.S. de Vries (Paul); D.I. Chasman (Daniel); M. Sabater-Lleal (Maria); M.-H. Chen (Ming-Huei); J.E. Huffman (Jennifer E.); M. Steri (Maristella); W. Tang (Weihong); A. Teumer (Alexander); R.E. Marioni (Riccardo); V. Grossmann (Vera); J.J. Hottenga (Jouke Jan); S. Trompet (Stella); M. Müller-Nurasyid (Martina); J.H. Zhao (Jing Hua); J. Brody (Jennifer); M.E. Kleber (Marcus); X. Guo (Xiuqing); J.J. Wang (Jie Jin); P. Auer (Paul); J. Attia (John); L.R. Yanek (Lisa); T.S. Ahluwalia (Tarunveer Singh); J. Lahti (Jari); C. Venturini (Cristina); T. Tanaka (Toshiko); L.F. Bielak (Lawrence F.); P.K. Joshi (Peter); A. Rocanin-Arjo (Ares); I. Kolcic (Ivana); P. Navarro (Pau); L.M. Rose (Lynda); C. Oldmeadow (Christopher); H. Riess (Helene); J. Mazur (Johanna); S. Basu (Saonli); A. Goel (Anuj); Q. Yang (Qiong); M. Ghanbari (Mohsen); Gonnekewillemsen; A. Rumley (Ann); E. Fiorillo (Edoardo); A.J. de Craen (Anton); A. Grotevendt (Anne); R.A. Scott (Robert); K.D. Taylor (Kent D.); G.E. Delgado (Graciela E.); J. Yao (Jie); A. Kifley (Annette); C. Kooperberg (Charles); Q. Qayyum (Rehan); L. Lopez (Lornam); T.L. Berentzen (Tina L.); K. Räikkönen (Katri); Massimomangino; S. Bandinelli (Stefania); P.A. Peyser (Patricia A.); S. Wild (Sarah); D.-A. Tregouet (David-Alexandre); A.F. Wright (Alan); J. Marten (Jonathan); T. Zemunik (Tatijana); A.C. Morrison (Alanna); B. Sennblad (Bengt); G.H. Tofler (Geoffrey); M.P.M. de Maat (Moniek); E.J.C. de Geus (Eco); G.D. Lowe (Gordon D.); M. Zoledziewska (Magdalena); N. Sattar (Naveed); H. Binder (Harald); U. Völker (Uwe); M. Waldenberger (Melanie); K.-T. Khaw (Kay-Tee); B. McKnight (Barbara); J. Huang (Jian); N.S. Jenny (Nancy); E.G. Holliday (Elizabeth); L. Qi (Lihong); M.G. Mcevoy (Mark G.); D.M. Becker (Diane); J.M. Starr (John); A.-P. Sarin; P.G. Hysi (Pirro); D.G. Hernandez (Dena); M.A. Jhun (Min A.); H. Campbell (Harry); A. Hamsten (Anders); F. Sarin (Fernando); W.L. McArdle (Wendy); P. Eline Slagboom; T. Zeller (Tanja); W. Koenig (Wolfgang); B. Psaty (Brucem); T. Haritunians (Talin); J. Liu (Jingmin); A. Palotie (Aarno); A.G. Uitterlinden (André); D.J. Stott (David J.); A. Hofman (Albert); O.H. Franco (Oscar); O. Polasek (Ozren); I. Rudan (Igor); P.-E. Morange (P.); J.F. Wilson (James F.); S.L. Kardia (Sharon L.r); L. Ferrucci (Luigi); T.D. Spector (Timothy); J.G. Eriksson (Johan G.); T. Hansen (Torben); I.J. Deary (Ian); L.C. Becker (Lewis); R.J. Scott (Rodney); P. Mitchell (Paul); W. März (Winfried); N.J. Wareham (Nick J.); A. Peters (Annette); A. Greinacher (Andreas); P.S. Wild (Philipp S.); J.W. Jukema (Jan Wouter); D.I. Boomsma (Dorret I.); C. Hayward (Caroline); F. Cucca (Francesco); R.P. Tracy (Russell); H. Watkins (Hugh); A.P. Reiner (Alex P.); A.R. Folsom (Aaron); P.M. Ridker (Paul); C.J. O'Donnell (Christopher J.); N.L. Smith (Nicholas L.); D.P. Strachan (David P.); A. Dehghan (Abbas)

    2016-01-01

    textabstractGenome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X-chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes

  13. Pre-emptive treatment with fibrinogen concentrate for postpartum haemorrhage

    DEFF Research Database (Denmark)

    Wikkelsø, A J; Edwards, H M; Afshari, A

    2015-01-01

    BACKGROUND: In early postpartum haemorrhage (PPH), a low concentration of fibrinogen is associated with excessive subsequent bleeding and blood transfusion. We hypothesized that pre-emptive treatment with fibrinogen concentrate reduces the need for red blood cell (RBC) transfusion in patients...... with PPH. METHODS: In this investigator-initiated, multicentre, double-blinded, parallel randomized controlled trial, we assigned subjects with severe PPH to a single dose of fibrinogen concentrate or placebo (saline). A dose of 2 g or equivalent was given to all subjects independent of body weight...... and the fibrinogen concentration at inclusion. The primary outcome was RBC transfusion up to 6 weeks postpartum. Secondary outcomes were total blood loss, total amount of blood transfused, occurrence of rebleeding, haemoglobin

  14. [Fibrin(ogen degradation product concentration (SFP) as a diagnostic parameter for the differentiation of artifical and essential blood in cerebrospinal fluid].

    Science.gov (United States)

    Hindersin, P; Heidrich, R

    1978-01-01

    The fibrin(ogen) degradation product concentration is another differential-diagnosis parameter for distinguishing between artificially blood-stained and essentially blood-stained CSF. Determination of the fibrin(ogen) degradation product concentration has been found to be a reliable method of recognizing natively and artificially blood-stained CSF as being different.

  15. The FIB-PPH trial: fibrinogen concentrate as initial treatment for postpartum haemorrhage: study protocol for a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Wikkelsoe Anne

    2012-07-01

    Full Text Available Abstract Background Postpartum haemorrhage (PPH remains a leading cause of maternal mortality worldwide. In Denmark 2% of parturients receive blood transfusion. During the course of bleeding fibrinogen (coagulation factor I may be depleted and fall to critically low levels, impairing haemostasis and thus worsening the ongoing bleeding. A plasma level of fibrinogen below 2 g/L in the early phase of postpartum haemorrhage is associated with subsequent development of severe haemorrhage. Use of fibrinogen concentrate allows high-dose substitution without the need for blood type crossmatch. So far no publications of randomised controlled trials involving acutely bleeding patients in the obstetrical setting have been published. This trial aims to investigate if early treatment with fibrinogen concentrate reduces the need for blood transfusion in women suffering severe PPH. Methods/Design In this randomised placebo-controlled double-blind multicentre trial, parturients with primary PPH are eligible following vaginal delivery in case of: manual removal of placenta (blood loss ≥ 500 ml or manual exploration of the uterus after the birth of placenta (blood loss ≥ 1000 ml. Caesarean sections are also eligible in case of perioperative blood loss ≥ 1000 ml. The exclusion criteria are known inherited haemostatic deficiencies, prepartum treatment with antithrombotics, pre-pregnancy weight Primary outcome is the need for blood transfusion. To investigate a 33% reduction in the need for blood transfusion, a total of 245 patients will be included. Four university-affiliated public tertiary care hospitals will include patients during a two-year period. Adverse events including thrombosis are assessed in accordance with International Conference on Harmonisation (ICH good clinical practice (GCP. Discussion A widespread belief in the benefits of early fibrinogen substitution in cases of PPH has led to increased off-label use. The FIB

  16. Effect of Fibrinogen Concentrate on Intraoperative Blood Loss Among Patients With Intraoperative Bleeding During High-Risk Cardiac Surgery: A Randomized Clinical Trial.

    Science.gov (United States)

    Bilecen, Süleyman; de Groot, Joris A H; Kalkman, Cor J; Spanjersberg, Alexander J; Brandon Bravo Bruinsma, George J; Moons, Karel G M; Nierich, Arno P

    2017-02-21

    Fibrinogen concentrate might partly restore coagulation defects and reduce intraoperative bleeding. To determine whether fibrinogen concentrate infusion dosed to achieve a plasma fibrinogen level of 2.5 g/L in high-risk cardiac surgery patients with intraoperative bleeding reduces intraoperative blood loss. A randomized, placebo-controlled, double-blind clinical trial conducted in Isala Zwolle, the Netherlands (February 2011-January 2015), involving patients undergoing elective, high-risk cardiac surgery (ie, combined coronary artery bypass graft [CABG] surgery and valve repair or replacement surgery, the replacement of multiple valves, aortic root reconstruction, or reconstruction of the ascending aorta or aortic arch) with intraoperative bleeding (blood volume between 60 and 250 mL suctioned from the thoracic cavity in a period of 5 minutes) were randomized to receive either fibrinogen concentrate or placebo. Intravenous, single-dose administration of fibrinogen concentrate (n = 60) or placebo (n = 60), targeted to achieve a postinfusion plasma fibrinogen level of 2.5 g/L. The primary outcome was blood loss in milliliters between intervention (ie, after removal of cardiopulmonary bypass) and closure of chest. Safety variables (within 30 days) included: in-hospital mortality, myocardial infarction, cerebrovascular accident or transient ischemic attack, renal insufficiency or failure, venous thromboembolism, pulmonary embolism, and operative complications. Among 120 patients (mean age; 71 [SD, 10] years, 37 women [31%]) included in the study, combined CABG and valve repair or replacement surgery comprised 72% of procedures and had a mean (SD) cardiopulmonary bypass time of 200 minutes (83) minutes. For the primary outcome, median blood loss in the fibrinogen group was 50 mL (interquartile range [IQR], 29-100 mL) compared with 70 mL (IQR, 33-145 mL) in the control group (P = .19), the absolute difference 20 mL (95% CI, -13 to 35 mL). There were 6 cases

  17. Relationship Between Blood Fibrinogen Concentration and Pathological Features of Cancer Patients: A 139-case Clinical Study

    Directory of Open Access Journals (Sweden)

    Da-Yong Lu

    2007-01-01

    Full Text Available Angiogenesis and coagulation are among the most consistent host responses to the presence of a malignant tissue. Pathological angiogenesis and coagulation are often occurred in patients with solid tumors, especially in the occurrence of neoplasm metastasis and as targets for anti-metastatic drugs such as antiangiogenesis agents, coagulation-mediated agents and anticancer drugs. Since fibrinogen (Fib is the most abundant and key haemostatic protein taking part in angiogenesis and coagulation, its biological and pathophysiological roles in cancer patients are intriguing. To continue foundational and translational research on Fib-related cancer pathogenesis, a phase II survey of 139 patients was carried out at the Central Hospital of Jing-An district and Shanghai University, Shanghai, China. The mean BFC of the cancer patients in this survey was overall about 35-50% greater than that in the normal population. This study showed that the mean BFC was higher in patients with long-distance metastases (N1M1 patients than in patients with no sign of long-distance metastases (N0M0 patients. Mean BFCs were 4.42 g/L (n= 21 in patients with lung cancer, 4.36 g/L, and in patients with hepatic cancer (n=5, and 4.63 g/L in patients with stomach cancer (n=8, all higher than the average value of the cancer patients overall (4.16 g/L. However, patients with bowel and colon cancers 3.79 g/L (n=16 showed lower than them. BFC levels increased with increasing cancer duration (latency > 1 year. There was a slight decrease in BFC after one or two treatment cycles, but a more marked decrease after surgery. We propose that the BFC level in cancer patients may be influenced by and related to many aspects of cancer progression such as metastatic conditions, tumor origins, patient’s pathological stage and disease latency. As an important first-hand pathologic-therapeutics relationship study, it provides evidence for the potentiality of a new approach of Fib-targeted as

  18. Analysis of the safety and pharmacodynamics of human fibrinogen concentrate in animals

    Energy Technology Data Exchange (ETDEWEB)

    Beyerle, Andrea, E-mail: andrea.beyerle@cslbehring.com [CSL Behring GmbH, Preclinical Research and Development, Marburg (Germany); Nolte, Marc W. [CSL Behring GmbH, Preclinical Research and Development, Marburg (Germany); Solomon, Cristina [CSL Behring GmbH, Medical Affairs, Marburg (Germany); Department of Anaesthesiology, Perioperative Medicine and General Intensive Care, Paracelsus Medical University, Salzburg (Austria); Herzog, Eva; Dickneite, Gerhard [CSL Behring GmbH, Preclinical Research and Development, Marburg (Germany)

    2014-10-01

    Fibrinogen, a soluble 340 kDa plasma glycoprotein, is critical in achieving and maintaining hemostasis. Reduced fibrinogen levels are associated with an increased risk of bleeding and recent research has investigated the efficacy of fibrinogen concentrate for controlling perioperative bleeding. European guidelines on the management of perioperative bleeding recommend the use of fibrinogen concentrate if significant bleeding is accompanied by plasma fibrinogen levels less than 1.5–2.0 g/l. Plasma-derived human fibrinogen concentrate has been available for therapeutic use since 1956. The overall aim of the comprehensive series of non-clinical investigations presented was to evaluate i) the pharmacodynamic and pharmacokinetic characteristics and ii) the safety and tolerability profile of human fibrinogen concentrate Haemocomplettan P® (RiaSTAP®). Pharmacodynamic characteristics were assessed in rabbits, pharmacokinetic parameters were determined in rabbits and rats and a safety pharmacology study was performed in beagle dogs. Additional toxicology tests included: single-dose toxicity tests in mice and rats; local tolerance tests in rabbits; and neoantigenicity tests in rabbits and guinea pigs following the introduction of pasteurization in the manufacturing process. Human fibrinogen concentrate was shown to be pharmacodynamically active in rabbits and dogs and well tolerated, with no adverse events and no influence on circulation, respiration or hematological parameters in rabbits, mice, rats and dogs. In these non-clinical investigations, human fibrinogen concentrate showed a good safety profile. This data adds to the safety information available to date, strengthening the current body of knowledge regarding this hemostatic agent. - Highlights: • A comprehensive series of pre-clinical investigations of human fibrinogen concentrate. • Human fibrinogen concentrate was shown to be pharmacodynamically active. • Human fibrinogen concentrate was well tolerated

  19. Epistatic and pleiotropic effects of polymorphisms in the fibrinogen and coagulation factor XIII genes on plasma fibrinogen concentration, fibrin gel structure and risk of myocardial infarction.

    Science.gov (United States)

    Mannila, Maria Nastase; Eriksson, Per; Ericsson, Carl-Göran; Hamsten, Anders; Silveira, Angela

    2006-03-01

    An intricate interplay between the genes encoding fibrinogen gamma (FGG), alpha (FGA) and beta (FGB), coagulation factor XIII (F13A1) and interleukin 6 (IL6) and environmental factors is likely to influence plasma fibrinogen concentration, fibrin clot structure and risk of myocardial infarction (MI). In the present study, the potential contribution of SNPs harboured in the fibrinogen, IL6 and F13A1 genes to these biochemical and clinical phenotypes was examined. A database and biobank based on 387 survivors of a first MI and population-based controls were used. Sixty controls were selected according to FGG 9340T > C [rs1049636] genotype for studies on fibrin clot structure using the liquid permeation method. The multifactor dimensionality reduction method was used for interaction analyses. We here report that the FGA 2224G > A [rs2070011] SNP (9.2%), plasma fibrinogen concentration (13.1%) and age (8.1%) appeared as independent determinants of fibrin gel porosity. The FGA 2224G > A SNP modulated the relation between plasma fibrinogen concentration and fibrin clot porosity. The FGG-FGA*4 haplotype, composed of the minor FGG 9340C and FGA 2224A alleles, had similar effects, supporting its reported protective role in relation to MI. Significant epistasis on plasma fibrinogen concentration was detected between the FGA 2224G > A and F13A1 Val34Leu [rs5985] SNPs (p FGG 9340T > C and FGB 1038G > A [rs1800791] SNPs appeared to interact on MI risk, explaining the association of FGG-FGB haplotypes with MI in the absence of effects of individual SNPs. Thus, epistatic and pleiotropic effects of polymorphisms contribute to the variation in plasma fibrinogen concentration, fibrin clot structure and risk of MI.

  20. Acetylation and glycation of fibrinogen in vitro occur at specific lysine residues in a concentration dependent manner: A mass spectrometric and isotope labeling study

    Energy Technology Data Exchange (ETDEWEB)

    Svensson, Jan, E-mail: jan.svensson@ki.se [Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital (Solna), SE-171 76 Stockholm (Sweden); Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, SE-182 88 Stockholm (Sweden); Bergman, Ann-Charlotte [Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital (Solna), SE-171 76 Stockholm (Sweden); Adamson, Ulf [Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, SE-182 88 Stockholm (Sweden); Blombaeck, Margareta [Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital (Solna), SE-171 76 Stockholm (Sweden); Wallen, Hakan; Joerneskog, Gun [Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, SE-182 88 Stockholm (Sweden)

    2012-05-04

    Highlights: Black-Right-Pointing-Pointer Fibrinogen was incubated in vitro with glucose or aspirin. Black-Right-Pointing-Pointer Acetylations and glycations were found at twelve lysine sites by mass spectrometry. Black-Right-Pointing-Pointer The labeling by aspirin and glucose occurred dose-dependently. Black-Right-Pointing-Pointer No competition between glucose and aspirin for binding to fibrinogen was found. -- Abstract: Aspirin may exert part of its antithrombotic effects through platelet-independent mechanisms. Diabetes is a condition in which the beneficial effects of aspirin are less prominent or absent - a phenomenon called 'aspirin resistance'. We investigated whether acetylation and glycation occur at specific sites in fibrinogen and if competition between glucose and aspirin in binding to fibrinogen occurs. Our hypothesis was that such competition might be one explanation to 'aspirin resistance' in diabetes. After incubation of fibrinogen in vitro with aspirin (0.8 mM, 24 h) or glucose (100 mM, 5-10 days), we found 12 modified sites with mass spectrometric techniques. Acetylations in the {alpha}-chain: {alpha}K191, {alpha}K208, {alpha}K224, {alpha}K429, {alpha}K457, {alpha}K539, {alpha}K562, in the {beta}-chain: {beta}K233, and in the {gamma}-chain: {gamma}K170 and {gamma}K273. Glycations were found at {beta}K133 and {gamma}K75, alternatively {gamma}K85. Notably, the lysine 539 is a site involved in FXIII-mediated cross-linking of fibrin. With isotope labeling in vitro, using [{sup 14}C-acetyl]salicylic acid and [{sup 14}C]glucose, a labeling of 0.013-0.084 and 0.12-0.5 mol of acetylated and glycated adduct/mol fibrinogen, respectively, was found for clinically (12.9-100 {mu}M aspirin) and physiologically (2-8 mM glucose) relevant plasma concentrations. No competition between acetylation and glycation could be demonstrated. Thus, fibrinogen is acetylated at several lysine residues, some of which are involved in the cross-linking of

  1. Mechanisms of fibrinogen adsorption on latex particles determined by zeta potential and AFM measurements.

    Science.gov (United States)

    Adamczyk, Zbigniew; Bratek-Skicki, Anna; Dąbrowska, Paulina; Nattich-Rak, Małgorzata

    2012-01-10

    The adsorption of fibrinogen on polystyrene latex particles was studied using the concentration depletion method combined with the AFM detection of residual protein after adsorption. Measurements were carried out for a pH range of 3.5-11 and an ionic strength range of 10(-3)-0.15 M NaCl. First, the bulk physicochemical properties of fibrinogen and the latex particle suspension were characterized for this range of pH and ionic strength. The zeta potential and the number of uncompensated (electrokinetic) charges on the protein were determined from microelectrophoretic measurements. It was revealed that fibrinogen molecules exhibited amphoteric characteristics, being on average positively charged for pH adsorption of fibrinogen on latex for pH below 11. It was also proven that fibrinogen adsorption was irreversible, with the maximum surface concentration varying between 2.5 and 5 × 10(3) μm(-2) (weight concentration of a bare molecule was 1.4 to 2.8 mg m(-2)). These measurements revealed two main adsorption mechanisms of fibrinogen: (i) the unoriented (random) mechanism prevailing for lower ionic strength, where adsorbing molecules significantly penetrate the fuzzy polymeric layer on the latex core and (ii) the side-on adsorption mechanism prevailing for pH > 5.8 and a higher ionic strength of 0.15 M. It was also shown that in the latter case, variations in the zeta potential with the protein coverage could be adequately described in terms of the electrokinetic model, previously formulated for planar substrate adsorption. On the basis of these experimental data, an efficient procedure of preparing fibrinogen-covered latex particles of controlled monolayer structure and coverage was envisaged.

  2. Fibrinogen: a journey into biotechnology.

    Science.gov (United States)

    Bratek-Skicki, Anna; Żeliszewska, Paulina; Ruso, Juan M

    2016-10-26

    Fibrinogen has been known since the mid-nineteenth century. Although initially its interest had been within the field of physiology over time its study has spread to new disciplines such as biochemistry, colloids and interfaces or biotechnology. First, we will describe the bulk properties of the molecule as well as its supramolecular assembly with different ligands by using different techniques and theoretical models. In the next step we will analyze the interfacial properties, an important topic because fibrinogen is considered to be a major inhibitor of lung surfactants' function at the lining layer of alveoli. The final step will be devoted to its main application in biotechnology. Thus, the adsorption of fibrinogen at solid/electrolyte interfaces and at carrier particles will be discussed. The reversibility of adsorption, fibrinogen molecule orientation, and maximum coverage will be thoroughly discussed. The stability of fibrinogen monolayers formed at these surfaces with respect to pH and ionic strength cyclic changes will also be presented. Based on the physicochemical data, adsorption kinetics and colloid particle deposition measurements, probable adsorption mechanisms of fibrinogen on solid/electrolyte interfaces will be defined.

  3. Comparing efficacy and safety of fibrinogen concentrate to cryoprecipitate in bleeding patients

    DEFF Research Database (Denmark)

    Jensen, N H L; Stensballe, J; Afshari, A

    2016-01-01

    in total. No mortality was reported in the published papers. There were no differences in fibrinogen-level increase, bleeding, RBC transfusions or thromboembolic complications. The RCT showed a possible increased functional improvement of haemostasis after cryoprecipitate therapy compared to fibrinogen......BACKGROUND: Bleeding is associated with the depletion of fibrinogen, thus increasing the risk of coagulopathy, further bleeding and transfusion requirements. Both fibrinogen concentrate and cryoprecipitate replenish low plasma fibrinogen levels. This systematic review aims to identify and evaluate...... evidence of efficacy and safety of fibrinogen concentrate and cryoprecipitate in bleeding patients. METHOD: Cochrane Central Register of Controlled Trials (CENTRAL), Medline, EMBASE up to 2nd of March 2015 were among the electronic search strategies of randomized controlled trials and non...

  4. Rhodococcus equi pneumonia in foals: an assessment of the early diagnostic value of serum amyloid A and plasma fibrinogen concentrations in equine clinical practice.

    Science.gov (United States)

    Passamonti, F; Vardi, D M; Stefanetti, V; Marenzoni, M L; Prato, S; Cévese, P; Coletti, M; Pepe, M; Casagrande Proietti, P; Olea-Popelka, F

    2015-02-01

    Early diagnosis and prevention of Rhodococcus equi pneumonia in foals represent important goals for equine clinicians. Recent protocols for diagnosis and treatment of Rhodococcosis in foals typically rely on a multimodal approach based on sonographic evidence suggestive of pyogranulomas, sonographic abscess scores and laboratory findings including plasma fibrinogen concentrations, blood biochemistry testing and platelet and leukocyte counts. The aim of this study was to assess the utility of weekly testing of serum amyloid A (SAA) and plasma fibrinogen concentrations in foals to achieve early diagnosis of R. equi pneumonia prior to the onset of clinical signs. This testing was used to simulate a clinically practical screening procedure and compared with thoracic ultrasonography performed in parallel. The present study suggests that SAA does not represent a reliable early marker of Rhodococcosis when plasma concentrations are tested weekly. However, when clinical signs of R. equi pneumonia are present, SAA concentrations may allow clinicians to obtain 'real-time' indications concerning both the progress of infection and the effectiveness of therapy. This study raises the possibility that plasma fibrinogen monitoring starting at 1 week of age and repeated on a weekly basis, could serve as a screening test allowing clinicians to identify foals as suspected of R. equi infection. Future investigations regarding both physiological plasma fibrinogen concentrations in foals as well as fibrinogen kinetics in foals affected with R. equi pneumonia, including the establishment of appropriate reference intervals for the test method employed in this study, will be necessary in order to clarify this possibility. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Electrospun Fibrinogen-Polydioxanone Composite Matrix: Potential for In Situ Urologic Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Michael C. McManus, M.D.

    2008-06-01

    Full Text Available Our objective is to demonstrate an electrospun fibrinogen-PDO (polydioxanone composite scaffold will retain the superior cellular interaction of fibrinogen while producing a product with the functional strength needed for direct implantation. Fibrinogen-PDO composite scaffolds were electrospun with PDO ratios of 0% (pure fibrinogen, 10%, 20%, 30%, 40%, 50% and 100% (pure PDO and disinfected using standard methods. Scaffolds were seeded with human BSM (bladder smooth muscle cells and incubated with twice weekly media changes. Samples were removed at 7, 14 and 21 days for evaluation by collagen assay, scanning electron microscopy and histology. Cell seeding and culture demonstrated human BSM readily migrate throughout and remodel electrospun fibrinogen-PDO composite scaffolds with deposition of native collagen. Cell migration and collagen deposition increased with increasing fibrinogen concentration while scaffold integrity increased with increasing PDO concentration. Electrospun fibrinogen-PDO composite structures promote rapid cellular in-growth by human BSM while maintaining structural integrity. The fibrinogen to PDO ratio can be adjusted to achieve the desired properties required for a specific tissue engineering application. Our ultimate objective is to utilize this innovative biomaterial technology to produce an acellular, bioresorbable product that enables in situ tissue regeneration. While there is still much work to be done, these initial findings indicate fibrinogen-PDO composite scaffolds deserve further investigation.

  6. The role of fibrinogen: a new paradigm in the treatment of coagulopathic bleeding.

    Science.gov (United States)

    Sørensen, Benny; Tang, Mariann; Larsen, Ole H; Laursen, Peter N; Fenger-Eriksen, Christian; Rea, Catherine J

    2011-01-01

    Fibrinogen is involved in both primary and secondary hemostasis, playing an important role in platelet aggregation and the establishment of a fibrin network. Recent evidence suggests that very high levels of fibrinogen act as antithrombin and can reduce endogenous thrombin potential and compromise clot stability, particularly following a low tissue factor stimulus. Several laboratory methods for measuring plasma fibrinogen concentrations are available, but results vary depending on the type of method and the use of artificial colloid plasma expanders. Adopting only the Clauss method can provide erroneously high levels when used in patients who have received colloid plasma expanders. This may contribute to a hazardous delay or complete lack of treatment. Multiple in vitro experiments, animal studies, and proof-of-principle randomized, clinical studies have recently suggested that hemostatic intervention with a fibrinogen concentrate may be efficient and safe in controling perioperative bleeding. In particular, fibrinogen concentrate has a key role in improving clotting function and reducing blood loss in settings such as trauma and cardiothoracic surgery. However, prospective studies are needed to determine the clinical efficacy and safety of fibrinogen concentrate when used as a hemostatic intervention for patients with massive bleeding due to trauma or surgery.

  7. A comparison of the fibrinogen receptor distribution on adherent platelets using both soluble fibrinogen and fibrinogen immobilized on gold beads.

    Science.gov (United States)

    Estry, D W; Mattson, J C; Mahoney, G J; Oesterle, J R

    1991-04-01

    The distribution of fibrinogen receptors was determined on the surface of adherent platelets using both direct labeling with the ligand fibrinogen which was immobilized on gold particles (Fg-Au) and indirect immunogold (Ig-Au) labeling of bound soluble fibrinogen identified with a rabbit polyclonal anti-fibrinogen antibody. Two distinctly different patterns of labeling were obtained and appeared to depend on whether solid phase fibrinogen (Fg-Au) or soluble phase released fibrinogen were bound to the membrane receptor. The membrane-bound Fg-Au reorganized in patterns that closely mimicked the organization of the underlying cytoskeleton. In approximately 18% of the adherent platelets, Fg-Au was seen in channels or vesicle-like structures lying deep to the platelet surface suggesting internalization into the open canalicular system and/or endocytosis. The labeling pattern obtained when identifying the location of membrane-bound soluble released fibrinogen by Ig-Au was diffuse and lacked the organizational patterns characteristic of Fg-Au. Unlike the Fg-Au probe, early dendritic platelets were heavily labeled by the soluble phase fibrinogen using the Ig-Au technique. Although the label covered the entire exposed platelet membrane in fully spread platelets, labeling over the peripheral web was more dense than that over the intermediate or granulomere zone. The diffuse organization and heavier peripheral distributional pattern of the glycoprotein IIb-IIIa (GP IIb-IIIa) receptor in fixed, adherent platelets, was also seen with the GP IIb-IIIa receptor-specific antibody AP-2. The binding of both the Fg-Au and Ig-Au were inhibited using the tetrapeptide Arg-Gly-Asp-Ser (RGDS) (93% and 98% inhibition, respectively), AP-2 (98% and 97%, respectively) and platelets from patients with Glanzmann's thrombasthenia (GT) (99% and 98%, respectively). The data presented provides the first report that receptor reorganization, following binding of fibrinogen, appears to be related to

  8. The efficacy of fibrinogen concentrate compared with cryoprecipitate in major obstetric haemorrhage - an observational study.

    LENUS (Irish Health Repository)

    Ahmed, S

    2012-10-01

    Fibrinogen replacement is critical in major obstetric haemorrhage (MOH). Purified, pasteurised fibrinogen concentrate appears to have benefit over cryoprecipitate in ease of administration and safety but is unlicensed in pregnancy. In July 2009, the Irish Blood Transfusion Service replaced cryoprecipitate with fibrinogen.

  9. Management of congenital quantitative fibrinogen disorders: a Delphi consensus.

    Science.gov (United States)

    Casini, A; de Moerloose, P

    2016-11-01

    No evidence-based guidelines for the management of patients suffering from afibrinogenaemia and hypofibrinogenaemia are available. The aim of this study was to harmonize patient's care among invited haemophilia experts from Belgium, France and Switzerland. A Delphi-like methodology was used to reach a consensus on: prophylaxis, bleeding, surgery, pregnancy and thrombosis management. The main final statements are as follows: (i) a secondary fibrinogen prophylaxis should be started after a first life-threatening bleeding in patients with afibrinogenaemia; (ii) during prophylaxis the target trough fibrinogen level should be 0.5 g L(-1) ; (iii) if an adaptation of dosage is required, the frequency of infusions rather than the fibrinogen amount should be modified; (iv) afibrinogenaemic patients undergoing a surgery at high bleeding risk should receive fibrinogen concentrates regardless of the personal or family history of bleeding; (v) moderate hypofibrinogenaemic patients (i.e. ≥0.5 g L(-1) ) without previous bleeding (despite haemostatic challenges) undergoing a surgery at low bleeding risk may not receive fibrinogen concentrates as prophylaxis; (vi) monitoring the trough fibrinogen levels should be performed at least once a month throughout the pregnancy and a foetal growth and placenta development close monitoring by ultrasound is recommended; (vii) fibrinogen replacement should be started concomitantly to the introduction of anticoagulation in afibrinogenaemic patients suffering from a venous thromboembolic event; and (viii) low-molecular-weight heparin is the anticoagulant of choice in case of venous thromboembolism. The results of this initiative should help clinicians in the difficult management of patients with congenital fibrinogen disorders. © 2016 John Wiley & Sons Ltd.

  10. Fibrinogen and thrombin concentrations are critical for fibrin glue adherence in rat high-risk colon anastomoses

    Directory of Open Access Journals (Sweden)

    Eliseo Portilla-de Buen

    2014-04-01

    Full Text Available OBJECTIVE: Fibrin glues have not been consistently successful in preventing the dehiscence of high-risk colonic anastomoses. Fibrinogen and thrombin concentrations in glues determine their ability to function as sealants, healers, and/or adhesives. The objective of the current study was to compare the effects of different concentrations of fibrinogen and thrombin on bursting pressure, leaks, dehiscence, and morphology of high-risk ischemic colonic anastomoses using fibrin glue in rats. METHODS: Colonic anastomoses in adult female Sprague-Dawley rats (weight, 250-350 g treated with fibrin glue containing different concentrations of fibrinogen and thrombin were evaluated at post-operative day 5. The interventions were low-risk (normal or high-risk (ischemic end-to-end colonic anastomoses using polypropylene sutures and topical application of fibrinogen at high (120 mg/mL or low (40 mg/mL concentrations and thrombin at high (1000 IU/mL or low (500 IU/mL concentrations. RESULTS: Ischemia alone, anastomosis alone, or both together reduced the bursting pressure. Glues containing a low fibrinogen concentration improved this parameter in all cases. High thrombin in combination with low fibrinogen also improved adherence exclusively in low-risk anastomoses. No differences were detected with respect to macroscopic parameters, histopathology, or hydroxyproline content at 5 days post-anastomosis. CONCLUSIONS: Fibrin glue with a low fibrinogen content normalizes the bursting pressure of high-risk ischemic left-colon anastomoses in rats at day 5 after surgery.

  11. Fibrinogen concentration and its role in CVD risk in black South Africans - effect of urbanisation

    NARCIS (Netherlands)

    Pieters, Marlien; De Maat, Moniek P. M.; Jerling, Johann C.; Hoekstra, Tiny; Kruger, Annamarie

    2011-01-01

    The aim of this study was to investigate correlates of fibrinogen concentration in black South Africans, as well as its association with cardiovascular disease (CVD) risk and whether urbanisation influences this association. A total of 1,006 rural and 1,004 urban black South Africans from the PURE s

  12. Fibrinogen as a key regulator of inflammation in disease.

    Science.gov (United States)

    Davalos, Dimitrios; Akassoglou, Katerina

    2012-01-01

    The interaction of coagulation factors with the perivascular environment affects the development of disease in ways that extend beyond their traditional roles in the acute hemostatic cascade. Key molecular players of the coagulation cascade like tissue factor, thrombin, and fibrinogen are epidemiologically and mechanistically linked with diseases with an inflammatory component. Moreover, the identification of novel molecular mechanisms linking coagulation and inflammation has highlighted factors of the coagulation cascade as new targets for therapeutic intervention in a wide range of inflammatory human diseases. In particular, a proinflammatory role for fibrinogen has been reported in vascular wall disease, stroke, spinal cord injury, brain trauma, multiple sclerosis, Alzheimer's disease, rheumatoid arthritis, bacterial infection, colitis, lung and kidney fibrosis, Duchenne muscular dystrophy, and several types of cancer. Genetic and pharmacologic studies have unraveled pivotal roles for fibrinogen in determining the extent of local or systemic inflammation. As cellular and molecular mechanisms for fibrinogen functions in tissues are identified, the role of fibrinogen is evolving from a marker of vascular rapture to a multi-faceted signaling molecule with a wide spectrum of functions that can tip the balance between hemostasis and thrombosis, coagulation and fibrosis, protection from infection and extensive inflammation, and eventually life and death. This review will discuss some of the main molecular links between coagulation and inflammation and will focus on the role of fibrinogen in inflammatory disease highlighting its unique structural properties, cellular targets, and signal transduction pathways that make it a potent proinflammatory mediator and a potential therapeutic target.

  13. Relationship between physical activity and plasma fibrinogen concentrations in adults without chronic diseases.

    Directory of Open Access Journals (Sweden)

    Manuel A Gomez-Marcos

    Full Text Available OBJECTIVE: To analyze the relationship between regular physical activity, as assessed by accelerometer and 7-day physical activity recall (PAR, and plasma fibrinogen concentrations. METHODS: A cross-sectional study in a previously established cohort of healthy subjects was performed. This study analyzed 1284 subjects who were included in the EVIDENT study (mean age 55.0±13.6 years; 60.90% women. Fibrinogen concentrations were measured in blood plasma. Physical activity was assessed with a 7-day PAR (metabolic equivalents (METs/hour/week and GT3X ActiGraph accelerometer (counts/minute for 7 days. RESULTS: Physical exercise, which was evaluated with both an accelerometer (Median: 237.28 counts/minute and 7-day PAR (Median: 8 METs/hour/week. Physical activity was negatively correlated with plasma fibrinogen concentrations, which was evaluated by counts/min (r = -0.100; p<0.001 and METs/hour/week (r = -0.162; p<0.001. In a multiple linear regression analysis, fibrinogen concentrations of the subjects who performed more physical activity (third tertile of count/minute and METs/hour/week respect to subjects who performed less (first tertile, maintained statistical significance after adjustments for age and others confounders (β = -0.03; p = 0.046 and β = -0.06; p<0.001, respectively. CONCLUSIONS: Physical activity, as assessed by accelerometer and 7-day PAR, was negatively associated with plasma fibrinogen concentrations. This relation is maintained in subjects who performed more exercise even after adjusting for age and other confounders.

  14. Fibrinogen as a therapeutic target for bleeding: a review of critical levels and replacement therapy.

    Science.gov (United States)

    Levy, Jerrold H; Welsby, Ian; Goodnough, Lawrence T

    2014-05-01

    Fibrinogen plays a critical role in achieving and maintaining hemostasis and is fundamental to effective clot formation. There is increasing awareness of the important role of fibrinogen as a key target for the treatment and prevention of acquired bleeding. Fibrinogen is the first coagulation factor to fall to critically low levels (fibrinogen levels range from 2.0 to 4.5 g/L), and current guidelines recommend maintaining the plasma fibrinogen level above 1.5 g/L. Fibrinogen supplementation can be achieved using plasma or cryoprecipitate; however, there are a number of safety concerns associated with these allogeneic blood products and there is a lack of high-quality evidence to support their use. Additionally, there is sometimes a long delay associated with the preparation of frozen products for infusion. Fibrinogen concentrate provides a promising alternative to allogeneic blood products and has a number of advantages: it allows a standardized dose of fibrinogen to be rapidly administered in a small volume, has a very good safety profile, and is virally inactivated as standard. Administration of fibrinogen concentrate, often guided by point-of-care viscoelastic testing to allow individualized dosing, has been successfully used as hemostatic therapy in a range of clinical settings, including cardiovascular surgery, postpartum hemorrhage, and trauma. Results show that fibrinogen concentrate is associated with a reduction or even total avoidance of allogeneic blood product transfusion. Fibrinogen concentrate represents an important option for the treatment of coagulopathic bleeding; further studies are needed to determine precise dosing strategies and thresholds for fibrinogen supplementation.

  15. The effect of Ramadan fasting and physical activity on homocysteine and fibrinogen concentrations in overweight women

    Directory of Open Access Journals (Sweden)

    Seyyed Reza Attarzadeh Hosseini

    2014-12-01

    Full Text Available Introduction: Increased levels of certain markers like fibrinogen and Homocysteine are independently associated with an increased risk of cardiovascular diseases. Considering the numerous favorable effects of healthful nutrition and physical activity on reducing the risk of atherosclerosis, in this study we intend to take into account fasting and physical activity during the month of Ramadan and their impacts on Homocysteine and fibrinogen concentrations in overweight women. Materials and Methods: In this experiment, 22 overweight and obese women with a body mass index (BMI of greater than 25 kg/m2 aging from 20 to 45 years were enrolled into two groups by means of targeted-sampling method. One group involved fasting accompanied with regular physical activity (12 subjects and the other group involved only fasting (10 subjects. The protocol for the physical activity group consisted of three 60-minute sessions of aerobic exercise per week with a 50%- 65% heart rate reserved. Towards the end of Ramadan, the anthropometric and blood levels of Homocysteine and fibrinogen were closely measured. Data were analyzed using repeated measures and the significance level of P≤0 /05 was considered. Findings: A month of fasting along with regular physical activity did not prove to have any noticeable effects on the level of fibrinogen while a significant increase in the Homocysteine levels was discovered (P

  16. Fibrinogen and atherosclerosis: A study in transgenic mice

    NARCIS (Netherlands)

    Koopman, J.; Maas, A.; Rezaee, F.; Havekes, L.; Verheijen, J.; Gijbels, M.; Haverkate, F.

    1997-01-01

    Atherosclerosis is a multifactorial disease that is influenced by both genetic and environmental factors. Recent epidemiological studies have shown that the combination of elevated VLDL/LDL concentrations and elevated fibrinogen levels results in a strong increase of the risk for cardiovascular dise

  17. Fibrinogen and atherosclerosis: A study in transgenic mice

    NARCIS (Netherlands)

    Koopman, J.; Havekes, L.; Verheijen, J.; Gijbels, M.; Haverkate, F.

    1996-01-01

    Atherosclerosis is a multifactorial disease that is influenced by both genetic and environmental factors. Recent epidemiological studies have shown that the combination of elevated VLDL/LDL concentrations and elevated fibrinogen levels results in a strong increase of the risk for cardiovascular dise

  18. Concentration-dependent effect of fibrinogen on IgG-specific antigen binding and phagocytosis.

    Science.gov (United States)

    Boehm, Tobias Konrad; Sojar, Hakimuddin; Denardin, Ernesto

    2010-01-01

    In this paper, we aim to characterize fibrinogen-IgG interactions, and explore how fibrinogen alters IgG-mediated phagocytosis. Using enzyme-linked binding assays, we found that fibrinogen binding to IgG is optimized for surfaces coated with high levels of IgG. Using a similar method, we have shown that for an antigen unable to specifically bind fibrinogen, fibrinogen enhances binding of antibodies towards that antigen. For binding of IgG antibodies to cells expressing Fc receptors, we found a bimodal binding response, where low levels of fibrinogen enhance binding of antibody to Fc receptors and high levels reduce it. This corresponds to a bimodal effect on phagocytosis of IgG-coated particles, which is inhibited in the presence of excess IgG during coating of the particles with antibodies and fibrinogen. We conclude that fibrinogen can modulate phagocytosis of IgG-coated particles in vitro by changing IgG binding behavior, and that high fibrinogen levels could negatively affect phagocytosis.

  19. High plasma fibrinogen concentration and platelet count unfavorably impact survival in non-small cell lung cancer patients with brain metastases.

    Science.gov (United States)

    Zhu, Jian-Fei; Cai, Ling; Zhang, Xue-Wen; Wen, Yin-Sheng; Su, Xiao-Dong; Rong, Tie-Hua; Zhang, Lan-Jun

    2014-02-01

    High expression of fibrinogen and platelets are often observed in non-small cell lung cancer (NSCLC) patients with local regional or distant metastasis. However, the role of these factors remains unclear. The aims of this study were to evaluate the prognostic significance of plasma fibrinogen concentration and platelet count, as well as to determine the overall survival of NSCLC patients with brain metastases. A total of 275 NSCLC patients with brain metastasis were enrolled into this study. Univariate analysis showed that high plasma fibrinogen concentration was associated with age≥65 years (P = 0.011), smoking status (P = 0.009), intracranial symptoms (P = 0.022), clinical T category (P = 0.010), clinical N category (P = 0.003), increased partial thromboplastin time (P low plasma fibrinogen concentration demonstrated longer overall survival compared with those with high plasma fibrinogen concentration (median, 17.3 months versus 11.1 months; P≤0.001). A similar result was observed for platelet counts (median, 16.3 months versus 11.4 months; P = 0.004). Multivariate analysis showed that both plasma fibrinogen concentration and platelet count were independent prognostic factors for NSCLC with brain metastases (R2 = 1.698, P high plasma fibrinogen concentration and platelet count indicate poor prognosis for NSCLC patients with brain metastases. Thus, these two biomarkers might be independent prognostic predictors for this subgroup of NSCLC patients.

  20. A genetic instrument for Mendelian randomization of fibrinogen.

    Science.gov (United States)

    Ken-Dror, Gie; Humphries, Steve E; Kumari, Meena; Kivimaki, Mika; Drenos, Fotios

    2012-04-01

    Mendelian randomization studies on fibrinogen commonly use a single genetic variant as an instrument, but this may explain only a small proportion of the total phenotypic variance. We examined the contribution of multiple common single nucleotide polymorphisms (SNPs) and haplotypes in the entire fibrinogen gene cluster to plasma fibrinogen levels in two prospective cohorts, for use as instruments in future Mendelian randomization studies. Genotypes for 20 SNPs were determined in 2,778 middle-age (49-64 years) men from the Second-Northwick-Park-Heart Study (NPHS-II). These were replicated in 3,705 men from the Whitehall-II study (WH-II). Plasma fibrinogen levels were determined six times in NPHS-II and three times in WH-II. The minor alleles of four SNPs from the FGB gene, two from the FGA gene, and one from the FGG gene were associated with higher plasma fibrinogen levels. SNP rs1800790 (-455G>A) commonly used in Mendelian randomization studies was associated with R2=1.22% of the covariate adjusted residual variance in fibrinogen level. A variable selection procedure identified one additional SNP: rs2070011 (FGA) altogether explaining R2=1.45% of the residual variance in fibrinogen level. Using these SNPs no evidence for causality between the fibrinogen levels and coronary heart diseases was found in instrumental variables analysis. In the replication cohort, WH-II, the effects of the two SNPs on fibrinogen levels were consistent with the NPHS-II results. There is statistical evidence for several functional sites in the fibrinogen gene cluster that determine an individual's plasma fibrinogen levels. Thus, a combination of several SNPs will provide a stronger instrument for fibrinogen Mendelian randomization studies.

  1. A randomized, double blind trial of prophylactic fibrinogen to reduce bleeding in cardiac surgery.

    Science.gov (United States)

    Sadeghi, Mostafa; Atefyekta, Reza; Azimaraghi, Omid; Marashi, Seyed Mojtaba; Aghajani, Yasaman; Ghadimi, Fatemeh; Spahn, Donat R; Movafegh, Ali

    2014-01-01

    Postoperative bleeding has a great clinical importance and can contribute to increased mortality and morbidity in patients undergoing coronary artery bypass graft surgery. In this prospective, randomized, double-blind study, we evaluated the effect of prophylactic administration of fibrinogen concentrate on post-coronary artery bypass graft surgery bleeding. A total of 60 patients undergoing coronary artery bypass surgery were randomly divided into two groups. Patients in the fibrinogen group received 1g of fibrinogen concentrate 30 min prior to the operation, while patients in the control group received placebo. Post-operative bleeding volumes, prothrombin time, partial thromboplastin time, INR, hemoglobin and transfused blood products in both groups were recorded. A strict red blood cell transfusion protocol was used in all patients. There were no significant differences between intra-operative packed red blood cells infusion in the studied groups (1.0±1.4 in fibrinogen group, and 1.3±1.1 in control group). Less postoperative bleeding was observed in the fibrinogen group (477±143 versus 703±179, p=0.0001). Fifteen patients in the fibrinogen group and 21 in the control group required post-op packed red blood cells infusion (p=0.094). No thrombotic event was observed through 72 h after surgery. Prophylactic fibrinogen reduces post-operative bleeding in patients undergoing coronary artery bypass graft. Copyright © 2013 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

  2. Antimicrobial activity of fibrinogen and fibrinogen-derived peptides--a novel link between coagulation and innate immunity.

    Science.gov (United States)

    Påhlman, L I; Mörgelin, M; Kasetty, G; Olin, A I; Schmidtchen, A; Herwald, H

    2013-05-01

    Fibrinogen is a key player in the blood coagulation system, and is upon activation with thrombin converted into fibrin that subsequently forms a fibrin clot. In the present study, we investigated the role of fibrinogen in the early innate immune response. Here we show that the viability of fibrinogen-binding bacteria is affected in human plasma activated with thrombin. Moreover, we found that the peptide fragment GHR28 released from the β-chain of fibrinogen has antimicrobial activity against bacteria that bind fibrinogen to their surface, whereas non-binding strains are unaffected. Notably, bacterial killing was detected in Group A Streptococcus bacteria entrapped in a fibrin clot, suggesting that fibrinogen and coagulation is involved in the early innate immune system to quickly wall off and neutralise invading pathogens.

  3. Monitoring the effects of fibrinogen concentration on blood coagulation using quartz crystal microbalance (QCM) and its comparison with thromboelastography

    Science.gov (United States)

    Lakshmanan, Ramji S.; Efremov, Vitaly; Cullen, Sinéad; Byrne, Barry; Killard, Anthony J.

    2013-05-01

    Fibrinogen has been identified as a major risk factor in cardiovascular disorders. Fibrinogen (340 kDa) is a soluble dimeric glycoprotein found in plasma and is a major component of the coagulation cascade. It has been identified as a major risk factor in cardiovascular disorders. The time taken for its conversion to fibrin is usually used as an "endpoint" in most clot-based assays, without any information on dynamic changes in physical properties or kinetics of a forming clot. A global coagulation profile as measured by Thromboelastography® (TEG®) provides information on both the time and kinetics of changes in physical property of the forming clot. In this work, Quartz crystal microbalance (QCM), which is a piezoelectric resonator has been used to study coagulation of plasma and compared with TEG. The changes in resonant frequency (Δf) and half width at half maximum (HWHM or ΔΓ) were used to evaluate effect of fibrinogen concentration. It has been shown that TEG is less sensitive to low concentrations of fibrinogen and dilution while QCM is able to monitor clot formation in both the circumstances.

  4. A novel fibrin gel derived from hyaluronic acid-grafted fibrinogen

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Chiung L; Chen, Hui W; Wang, Tzu C; Wang, Yng J, E-mail: wang@ym.edu.tw [Institute of Biomedical Engineering, National Yang Ming University, No. 155, Sec. 2, Li-Nung St., Shih-Pai, Taipei, Taiwan 112 (China)

    2011-04-15

    Fibrinogen is a major plasma protein that forms a three-dimensional fibrin gel upon being activated by thrombin. In this study, we report the synthesis and potential applications of hybrid molecules composed of fibrinogen coupled to the reducing ends of short-chain hyaluronic acids (sHAs) by reductive amination. The grafting of sHAs to fibrinogen was verified by analyzing particle size, zeta potential and gel-electrophoretic mobility of the hybrid molecules. The sHA-fibrinogen hybrid molecules with graft ratios (sHA/fibrinogen) of up to 6.5 retained the ability to form gels in response to thrombin activation. The sHA-fibrin gels were transparent in appearance and exhibited high water content, which were characteristics distinct from those of gels formed by mixtures of sHAs and fibrinogen. The potential applications of the sHA-fibrin gels were evaluated. The sHA-fibrinogen gel with a graft ratio of 3.6 (S3.6F) was examined for its ability to encapsulate and support the differentiation of ATDC5 chondrocyte-like cells. Compared with the fibrinogen-formed gel, cells cultured in the S3.6F gel exhibited increased lacunae formation; moreover, the abundance of cartilaginous extracellular matrix molecules and the expression of chondrocyte marker genes, such as aggrecan, collagen II and Sox9, were also significantly increased. Our data suggest that the three-dimensional gel formed by the sHA-fibrinogen hybrid is a better support than the fibrin gel for chondrogenesis induction.

  5. Human fibrinogen monolayers on latex particles: role of ionic strength.

    Science.gov (United States)

    Bratek-Skicki, Anna; Żeliszewska, Paulina; Adamczyk, Zbigniew; Cieśla, Michał

    2013-03-19

    The adsorption of human serum fibrinogen on polystyrene latex particles was studied using the microelectrophoretic and concentration depletion methods. Measurements were carried out for pH 3.5 and an ionic strength range of 10(-3) to 0.15 M NaCl. The electrophoretic mobility of latex was determined as a function of the amount of adsorbed fibrinogen (surface concentration). A monotonic increase in the electrophoretic mobility (zeta potential) of the latex was observed, indicating a significant adsorption of fibrinogen on latex for all ionic strengths. No changes in the latex mobility were observed for prolonged time periods, suggesting the irreversibility of fibrinogen adsorption. The maximum coverage of fibrinogen on latex particles was precisely determined using the depletion method. The residual protein concentration after making contact with latex particles was determined by electrokinetic measurements and AFM imaging where the surface coverage of fibrinogen on mica was quantitatively determined. The maximum fibrinogen coverage increased monotonically with ionic strength from 1.8 mg m(-2) for 10(-3) M NaCl to 3.6 mg m(-2) for 0.15 M NaCl. The increase in the maximum coverage was interpreted in terms of the reduced electrostatic repulsion among adsorbed fibrinogen molecules. The experimental data agree with theoretical simulations made by assuming a 3D unoriented adsorption of fibrinogen. The stability of fibrinogen monolayers on latex was also determined in ionic strength cycling experiments. It was revealed that cyclic variations in NaCl concentration between 10(-3) and 0.15 M induced no changes in the latex electrophoretic mobility, suggesting that there were no irreversible molecule orientation changes in the monolayers. On the basis of these experimental data, a robust procedure of preparing fibrinogen monolayers on latex particles of well-controlled coverage was proposed.

  6. Discrimination between Fibrin and Fibrinogen by a Monoclonal Antibody against a Synthetic Peptide

    Science.gov (United States)

    Scheefers-Borchel, Ursula; Muller-Berghaus, Gert; Fuhge, Peter; Eberle, Reinhard; Heimburger, Nobert

    1985-10-01

    Circulating soluble fibrin, observed in the blood of patients with ongoing intravascular coagulation, is generated from the plasma protein fibrinogen by the limited proteolytic action of thrombin. We report the production of a monoclonal antibody that discriminates between fibrin and fibrinogen in blood. The synthetic hexapeptide Gly-Pro-Arg-Val-Val-Glu, representing the amino terminus of the α chain of human fibrin, was used as immunogen. This hexapeptide is located within the Aα chain of fibrinogen but becomes the amino terminus of the fibrin α chain, after fibrinopeptide A is removed by the action of thrombin, and thus becomes accessible for antibody binding. The monoclonal antibody we have prepared can discriminate between fibrin and fibrinogen and thus can be used in assay systems to quantitate soluble fibrin or, potentially, to image fibrin-rich thrombi.

  7. Modulation of Dental Pulp Stem Cell Odontogenesis in a Tunable PEG-Fibrinogen Hydrogel System

    OpenAIRE

    Qiqi Lu; Mirali Pandya; Abdul Jalil Rufaihah; Vinicius Rosa; Huei Jinn Tong; Dror Seliktar; Wei Seong Toh

    2015-01-01

    Injectable hydrogels have the great potential for clinical translation of dental pulp regeneration. A recently developed PEG-fibrinogen (PF) hydrogel, which comprises a bioactive fibrinogen backbone conjugated to polyethylene glycol (PEG) side chains, can be cross-linked after injection by photopolymerization. The objective of this study was to investigate the use of this hydrogel, which allows tuning of its mechanical properties, as a scaffold for dental pulp tissue engineering. The cross-li...

  8. β-FIBRINOGEN PROMOTER-455 G/A (HaeⅢ) POLYMORPHISM PREDICTION OF PLASMA FIBRINOGEN BUT NOT OF ISCHEMIC CEREBROVASCULAR DISEASE

    Institute of Scientific and Technical Information of China (English)

    毕胜; 王德生; 李国忠; 温世荣; 潘尚哈

    2004-01-01

    Objective The-455 G/A (HaeⅢ) polymorphism of β-fibrinogen gene influences levels of plasma fibrinogen. We further investigated whether it influences the risk of ischemic cerebrovascular disease. Methods We accumulated 134 acute ischemic cerebrovascular disease (ICVD) cases and compared their -455 G/A status with a control group (n = 166). The β-fibrinogen gene -455 G/A polymorphism was analyzed for all subjects by PCR-RFLP with the restrictive enzyme HaeⅢ. Results Plasma fibrinogen was higher in AA homozygous participants (341 mg/dL) than in participants carrying the G allele: GA (290 mg/dL), GG (298 mg/dL) in the control group. Plasma fibrinogen was also higher in AA homozygous patients (353 mg/dL) than in cases carrying the G allele: GA (287mg/dL), GG (302 mg/dL) in the ICVD group. However, there was no significant association between β-fibrinogen gene -455 G/A polymorphism and ICVD group. Conclusions Although a small effect cannot be excluded, β-fibrinogen gene -455 G/A polymorphism is an independent predictor of plasma fibrinogen, but not of ischemic cerebrovascular disease.

  9. The -148 C/T fibrinogen gene polymorphism and fibrinogen levels in ischaemic stroke: a case-control study

    NARCIS (Netherlands)

    M.P.J. van Goor (Marie-Louise); E.B. Gómez García (Encarna); F.W.G. Leebeek (Frank); G.J. Brouwers (Geert Jan); P.J. Koudstaal (Peter Jan); D.W.J. Dippel (Diederik)

    2005-01-01

    textabstractBACKGROUND: To determine whether -148 C/T fibrinogen gene promoter polymorphism increases stroke risk by modifying the fibrinogen level. DESIGN: A case-control study of patients with first ever ischaemic stroke, confirmed by computed tomography. METHODS: Venous blood samples were

  10. Fibrinogen depletion in trauma: early, easy to estimate and central to trauma-induced coagulopathy.

    Science.gov (United States)

    Davenport, Ross; Brohi, Karim

    2013-09-24

    Fibrinogen is fundamental to hemostasis and falls rapidly in trauma hemorrhage, although levels are not routinely measured in the acute bleeding episode. Prompt identification of critically low levels of fibrinogen and early supplementation has the potential to correct trauma-induced coagulation and improve outcomes. Early estimation of hypofibrinogenemia is possible using surrogate markers of shock and hemorrhage; for example, hemoglobin and base excess. Rapid replacement with fibrinogen concentrate or cryoprecipitate should be considered a clinical priority in major trauma hemorrhage.

  11. Fibrinogen matrix deposited on the surface of biomaterials acts as a natural anti-adhesive coating.

    Science.gov (United States)

    Safiullin, Roman; Christenson, Wayne; Owaynat, Hadil; Yermolenko, Ivan S; Kadirov, Marsil K; Ros, Robert; Ugarova, Tatiana P

    2015-10-01

    Adsorption of fibrinogen on the luminal surface of biomaterials is a critical early event during the interaction of blood with implanted vascular graft prostheses which determines their thrombogenicity. We have recently identified a nanoscale process by which fibrinogen modifies the adhesive properties of various surfaces for platelets and leukocytes. In particular, adsorption of fibrinogen at low density promotes cell adhesion while its adsorption at high density results in the formation of an extensible multilayer matrix, which dramatically reduces cell adhesion. It remains unknown whether deposition of fibrinogen on the surface of vascular graft materials produces this anti-adhesive effect. Using atomic force spectroscopy, single cell force spectroscopy, and standard adhesion assays with platelets and leukocytes, we have characterized the adhesive and physical properties of the contemporary biomaterials, before and after coating with fibrinogen. We found that uncoated PET, PTFE and ePTFE exhibited high adhesion forces developed between the AFM tip or cells and the surfaces. Adsorption of fibrinogen at the increasing concentrations progressively reduced adhesion forces, and at ≥2 μg/ml all surfaces were virtually nonadhesive. Standard adhesion assays performed with platelets and leukocytes confirmed this dependence. These results provide a better understanding of the molecular events underlying thrombogenicity of vascular grafts.

  12. High plasma fibrinogen concentration and platelet count unfavorably impact survival in non-small cell lung cancer patients with brain metastases

    Institute of Scientific and Technical Information of China (English)

    Jian-Fei Zhu; Ling Cai; Xue-Wen Zhang; Yin-Sheng Wen; Xiao-Dong Su; Tie-Hua Rong; Lan-Jun Zhang

    2014-01-01

    High expression of fibrinogen and platelets are often observed in non-smal celllung cancer (NSCLC) patients with local regional or distant metastasis. However, the role of these factors remains unclear. The aims of this study were to evaluate the prognostic significance of plasma fibrinogen concentration and platelet count, as wel as to determine the overal survival of NSCLC patients with brain metastases. A total of 275 NSCLC patients with brain metastasis were enrolled into this study. Univariate analysis showed that high plasma fibrinogen concentration was associated with age≥65 years (P = 0.011), smoking status (P = 0.009), intracranial symptoms (P = 0.022), clinical T category (P = 0.010), clinical N category (P = 0.003), increased partial thromboplastin time (P < 0.001), and platelet count (P < 0.001). Patients with low plasma fibrinogen concentration demonstrated longer overall survival compared with those with high plasma fibrinogen concentration (median, 17.3 months versus 11.1 months;P≤0.001). A similar result was observed for platelet counts (median, 16.3 months versus 11.4 months;P = 0.004). Multivariate analysis showed that both plasma fibrinogen concentration and platelet count were independent prognostic factors for NSCLC with brain metastases (R2 = 1.698,P < 0.001 andR2 = 1.699,P < 0.001, respectively). Our results suggest that high plasma fibrinogen concentration and platelet count indicate poor prognosis for NSCLC patients with brain metastases. Thus, these two biomarkers might be independent prognostic predictors for this subgroup of NSCLC patients.

  13. Effect of storage conditions on prothrombin time, activated partial thromboplastin time and fibrinogen concentration on canine plasma samples

    Science.gov (United States)

    Casella, Stefania; Giannetto, Claudia; Giudice, Elisabetta

    2010-01-01

    The present study was to assess the effect of storage conditions on prothrombin time (PT), activated partial thromboplastin time (aPTT) and fibrinogen concentration in blood samples of healthy dogs. Thirty-five dogs of various breeds were included in the study. Citrated blood samples were obtained and plasma was divided into four aliquots to assess selected clotting parameters by means of a coagulometer. The first aliquot was analysed within 1 h after collection, while the remaining 3 were stored at 8℃ for 4, 8 and 24 h, respectively. One-way repeated measures analysis of variance documented a significant decreasing effect on PT at 24 h compared to 8 h and on fibrinogen concentration after 8 and 24 h compared to sampling time and at 4 and 24 h compared to 8 h post sampling. In conclusion, the results of this study indicate that only fibrinogen appears prone to significant decrease. In fact, aPTT is not substantially affected by refrigeration for at least 24 h post sampling and PT showed a statistical difference that does not necessary indicate biological significance as the results obtained were within reference intervals for the dog. PMID:20458152

  14. Importance of fibrinogen in dilutional coagulopathy after neurosurgical procedures: A descriptive study

    Directory of Open Access Journals (Sweden)

    Shalini Nair

    2016-01-01

    Full Text Available Background and Aims : The routine management of coagulopathy during surgery involves assessing haemoglobin, prothrombin time (PT, activated partial thromboplastin time (aPTT and platelets. Correction of these parameters involves administration of blood, fresh frozen plasma and platelet concentrates. The study was aimed at identifying the most common coagulation abnormality during neurosurgical procedures and the treatment of dilutional coagulopathy with blood components. Methods : During 2 years period, all adult patients undergoing neurosurgical procedures who were transfused two or more units of red cells were prospectively evaluated for the presence of a coagulopathy. PT, aPTT, platelet count and fibrinogen levels were estimated before starting a component therapy. Results : After assessing PT, aPTT, platelet count and fibrinogen levels following two or more blood transfusions, thirty patients were found to have at least one abnormal parameter that required administration of a blood product. The most common abnormality was a low fibrinogen level, seen in 26 patients; this was the only abnormality in three patients. No patient was found to have an abnormal PT or aPTT without either the fibrinogen concentration or platelet count or both being low. Conclusion : Low fibrinogen concentration was the most common coagulation abnormality found after blood transfusions for neurosurgical procedures.

  15. Gelation of fibrinogen in plasma. A kinetic study by turbidity measurement.

    Science.gov (United States)

    Regañon, E; Vila, V; Aznar, J

    1984-01-01

    Studies of the turbidity profiles of diluted (1/55, v/v) normal plasma, thrombin activity free serum plus commercial fibrinogen, and 0.15 M NaCl, pH 7.4, plus commercial fibrinogen, activated by thrombin or reptilase and measured at 350 nm, have shown that the latency time (LT) hardly varies for the fibrinogen concentration within limits of 0.03-0.15 mg/ml; however, it does vary for the thrombin concentration. The rate of gelation (RG) varies linearly with the fibrinogen (FG) concentration, conforming to the equation RG = 0.027 (FG)1.8; it hardly varies for thrombin concentrations greater than 0.50 NIH U/ml. On the other hand, RG values obtained for 0.46 NIH U/ml of thrombin or 0.92 BU/ml of reptilase show no significant differences. The variation in LT for the thrombin or reptilase concentration allows the rate of activation to be estimated, giving values of 5.9 X 10(-12) and 3.2 X 10(-12) mol/U/s, respectively, for a fibrinogen concentration in plasma of 1.1 X 10(-10) mol/ml. The mean value estimated for the ratio LT/FG in normal plasma is 35.76 +/- 18.3 and 85.62 +/- 18.3 s mg-1 ml for activation by thrombin and reptilase, respectively. We have studied in normal plasma the parameters that define the gelation of fibrin as measured by turbidity curves and their variation according to the fibrinogen concentration. This permits us to establish the kinetics of fibrin gel formation and normal range values.

  16. A study of the conditions and accuracy of the thrombin time assay of plasma fibrinogen

    DEFF Research Database (Denmark)

    Jespersen, J; Sidelmann, Johannes Jakobsen

    1982-01-01

    The conditions, accuracy, precision and possible error of the thrombin time assay of plasma fibrinogen are determined. Comparison with an estimation of clottable protein by absorbance at 280 nm gave a correlation coefficient of 0.96 and the regression line y = 1.00 x + 0.56 (n = 34). Comparison...... with a radial immunodiffusion method yielded the correlation coefficient 0.97 and the regression line y = 1.18 x = 2.47 (n = 26). The presence of heparin in clinically applied concentrations produced a slight shortening of the clotting times. The resulting error in the estimated concentrations of fibrinogen...

  17. Fibrinogen Test

    Science.gov (United States)

    ... be limited. Home Visit Global Sites Search Help? Fibrinogen Share this page: Was this page helpful? Also known as: Factor I; Fibrinogen Activity; Functional Fibrinogen; Fibrinogen Antigen; Plasma Fibrinogen; Hypofibrinogenemia ...

  18. Fibrinogen: A Marker in Predicting Diabetic Foot Ulcer Severity

    Directory of Open Access Journals (Sweden)

    X. H. Li

    2016-01-01

    Full Text Available Aims. To examine whether fibrinogen levels are a valuable biomarker for assessing disease severity and monitoring disease progression in patients with diabetic foot ulcer (DFU. Methods. A retrospective study was designed to examine the utility of fibrinogen in estimating disease severity in patients with DFU admitted to our hospital between January 2015 and January 2016. In total, 152 patients with DFU were enrolled in the study group, and 52 age and gender matched people with diabetes but no DFU were included as the control group. DFU severity was assessed using Wagner criteria. Results. Patients with DFU were divided into 2 subgroups based on the Wagner criteria. Mean fibrinogen values were significantly higher in patients with DFU grade ≧ 3 compared to those with DFU grades 1-2 (5.23 ± 1.37 g/L versus 3.61 ± 1.04 g/L. Using ROC statistic, a cut-off value of 5.13 g/L indicated the possible amputation with a sensitivity of 81.8% and a specificity of 78.9% (positive predictive value [PPV] 78.6%, negative predictive value [89.0%]. Fibrinogen values were found to be correlated with CRP levels, neutrophil, and WBC count. Conclusions. Fibrinogen levels might be a valuable tool for assessing the disease severity and monitoring the disease progression in patients with DFU.

  19. FbsA-Driven Fibrinogen Polymerization: A Bacterial ``Deceiving Strategy''

    Science.gov (United States)

    Pierno, Matteo; Maravigna, Laura; Piazza, Roberto; Visai, Livia; Speziale, Pietro

    2006-01-01

    We show that FbsA, a cell wall protein of the bacterium Streptococcus agalactiae, promotes large-scale aggregation of human plasma fibrinogen, leading to the formation of a semiflexible polymerlike network. This extensive aggregation process takes place not only in solution, but also on FbsA-functionalized colloidal particles, and leads to the formation of a thick layer on the bacterial cell wall itself, which becomes an efficient mask against phagocytosis.

  20. Influence of a constant magnetic field on the fibrinogen-fibrin system. [in blood coagulation process

    Science.gov (United States)

    Matskevichene, V. B.; Platonova, A. T.

    1974-01-01

    The effect of a constant magnetic field with a strength of 2500 oersteds on the fibrinogen-fibrin system was studied in the organism of healthy rabbits with exposure times of 1 and 5 hours. The results obtained indicate disruptions in the stage of conversion of fibrinogen to fibrin and an increase in the amount of fibrinogen.

  1. A novel role for the fibrinogen Asn-Gly-Arg (NGR) motif in platelet function.

    Science.gov (United States)

    Moriarty, Róisín; McManus, Ciara A; Lambert, Matthew; Tilley, Thea; Devocelle, Marc; Brennan, Marian; Kerrigan, Steven W; Cox, Dermot

    2015-02-01

    The integrin αIIbβ3 on resting platelets can bind to immobilised fibrinogen resulting in platelet spreading and activation but requires activation to bind to soluble fibrinogen. αIIbβ3 is known to interact with the general integrin-recognition motif RGD (arginine-glycine-aspartate) as well as the fibrinogen-specific γ-chain dodecapeptide; however, it is not known how fibrinogen binding triggers platelet activation. NGR (asparagine-glycine-arginine) is another integrin-recognition sequence present in fibrinogen and this study aims to determine if it plays a role in the interaction between fibrinogen and αIIbβ3. NGR-containing peptides inhibited resting platelet adhesion to fibrinogen with an IC50 of 175 µM but failed to inhibit the adhesion of activated platelets to fibrinogen (IC50> 500 µM). Resting platelet adhesion to mutant fibrinogens lacking the NGR sequences was reduced compared to normal fibrinogen under both static and shear conditions (200 s⁻¹). However, pre-activated platelets were able to fully spread on all types of fibrinogen. Thus, the NGR motif in fibrinogen is the site that is primarily responsible for the interaction with resting αIIbβ3 and is responsible for triggering platelet activation.

  2. The role of fibrinogen and haemostatic assessment in postpartum haemorrhage: preparations for a randomised controlled trial.

    Science.gov (United States)

    Wikkelsø, Anne Juul

    2015-04-01

    Pregnancy is a state of hypercoagulobility that might be an evolutionary way of protecting parturients from exsanguination following child birth. Observational studies suggest an association between a low level of fibrinogen (coagulation factor I) at the start of postpartum haemorrhage (PPH) and subsequent severity of bleeding. Fibrinogen concentrate may be prescribed to correct acquired hypofibrinogenaemia, but evidence is lacking regarding the treatment efficacy. This thesis assesses the current evidence for the use of fibrinogen concentrate and haemostatic assessment in bleeding patients with special attention to the obstetrical population. It includes five papers: In Paper I the benefits or harms of fibrinogen concentrate in bleeding patients in general was evaluated using a systematic Cochrane review methodology with metaanalysis of all published randomized controlled trials (RCTs). Six trials with high risk of bias were included (248 patients). Fibrinogen appeared to reduce the need of allogenic transfusions by 53%. However, the included trials were conducted only in an elective surgical setting with a population of mainly cardiac surgical patients. Paper II was also a systematic review based on Cochrane methodology evaluating the use of viscoelastic haemostatic assays to guide haemostatic transfusion in bleeding patients. Nine RCTs (776 patients) with high risk of bias were included primarily in elective cardiac surgical patients and none were specific for the obstetric subpopulation. Viscoelastic haemostatic assay guided transfusion algorithm reduced blood loss and the proportion of patients exposed to fresh frozen plasma (FFP) or platelets. In both studies, we were unable to make firm conclusion on our primary outcome, "all cause mortality" due to lack of adequate data. Paper III was based on two national Danish registries evaluating the predictability of postpartum blood transfusion. Prediction was found difficult. However, retained placental parts seemed

  3. Fibrinogen stability under surfactant interaction.

    Science.gov (United States)

    Hassan, Natalia; Barbosa, Leandro R S; Itri, Rosangela; Ruso, Juan M

    2011-10-01

    Differential scanning calorimetry (DSC), circular dichroism (CD), difference spectroscopy (UV-vis), Raman spectroscopy, and small-angle X-ray scattering (SAXS) measurements have been performed in the present work to provide a quantitatively comprehensive physicochemical description of the complexation between bovine fibrinogen and the sodium perfluorooctanoate, sodium octanoate, and sodium dodecanoate in glycine buffer (pH 8.5). It has been found that sodium octanoate and dodecanoate act as fibrinogen destabilizer. Meanwhile, sodium perfluorooctanoate acts as a structure stabilizer at low molar concentration and as a destabilizer at high molar concentration. Fibrinogen's secondary structure is affected by all three studied surfactants (decrease in α-helix and an increase in β-sheet content) to a different extent. DSC and UV-vis revealed the existence of intermediate states in the thermal unfolding process of fibrinogen. In addition, SAXS data analysis showed that pure fibrinogen adopts a paired-dimer structure in solution. Such a structure is unaltered by sodium octanoate and perfluoroctanoate. However, interaction of sodium dodecanoate with the fibrinogen affects the protein conformation leading to a complex formation. Taken together, all results evidence that both surfactant hydrophobicity and tail length mediate the fibrinogen stability upon interaction. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Fibrinogen beta variants confer protection against coronary artery disease in a Greek case-control study

    Directory of Open Access Journals (Sweden)

    Zakopoulos Nikolaos

    2010-02-01

    Full Text Available Abstract Background Although plasma fibrinogen levels are related to cardiovascular risk, data regarding the role of fibrinogen genetic variation in myocardial infarction (MI or coronary artery disease (CAD etiology remain inconsistent. The purpose of the present study was to investigate the effect of fibrinogen A (FGA, fibrinogen B (FGB and fibrinogen G (FGG gene SNPs and haplotypes on susceptibility to CAD in a homogeneous Greek population. Methods We genotyped for rs2070022, rs2070016, rs2070006 in FGA gene, the rs7673587, rs1800789, rs1800790, rs1800788, rs1800787, rs4681 and rs4220 in FGB gene and for the rs1118823, rs1800792 and rs2066865 SNPs in FGG gene applying an arrayed primer extension-based genotyping method (APEX-2 in a sample of CAD patients (n = 305 and controls (n = 305. Logistic regression analysis was used to calculate odds ratios (ORs and 95% confidence intervals (CIs, before and after adjustment for potential confounders. Results None of the FGA and FGG SNPs and FGA, FGB, FGG and FGA-FGG haplotypes was associated with disease occurrence after adjustment. Nevertheless, rs1800787 and rs1800789 SNPs in FGB gene seem to decrease the risk of CAD, even after adjustment for potential confounders (OR = 0.42, 95%CI: 0.19-0.90, p = 0.026 and OR = 0.44, 95%CI:0.21-0.94, p = 0.039, respectively. Conclusions FGA and FGG SNPs as well as FGA, FGB, FGG and FGA-FGG haplotypes do not seem to be important contributors to CAD occurrence in our sample. On the contrary, FGB rs1800787 and rs1800789 SNPs seem to confer protection to disease onset lowering the risk by about 50% in homozygotes for the minor alleles.

  5. Human fibrinogen adsorption on positively charged latex particles.

    Science.gov (United States)

    Zeliszewska, Paulina; Bratek-Skicki, Anna; Adamczyk, Zbigniew; Cieśla, Michał

    2014-09-23

    Fibrinogen (Fb) adsorption on positively charged latex particles (average diameter of 800 nm) was studied using the microelectrophoretic and the concentration depletion methods based on AFM imaging. Monolayers on latex were adsorbed from diluted bulk solutions at pH 7.4 and an ionic strength in the range of 10(-3) to 0.15 M where fibrinogen molecules exhibited an average negative charge. The electrophoretic mobility of the latex after controlled fibrinogen adsorption was systematically measured. A monotonic decrease in the electrophoretic mobility of fibrinogen-covered latex was observed for all ionic strengths. The results of these experiments were interpreted according to the three-dimensional electrokinetic model. It was also determined using the concentration depletion method that fibrinogen adsorption was irreversible and the maximum coverage was equal to 0.6 mg m(-2) for ionic strength 10(-3) M and 1.3 mg m(-2) for ionic strength 0.15 M. The increase of the maximum coverage was confirmed by theoretical modeling based on the random sequential adsorption approach. Paradoxically, the maximum coverage of fibrinogen on positively charged latex particles was more than two times lower than the maximum coverage obtained for negative latex particles (3.2 mg m(-2)) at pH 7.4 and ionic strength of 0.15 M. This was interpreted as a result of the side-on adsorption of fibrinogen molecules with their negatively charged core attached to the positively charged latex surface. The stability and acid base properties of fibrinogen monolayers on latex were also determined in pH cycling experiments where it was observed that there were no irreversible conformational changes in the fibrinogen monolayers. Additionally, the zeta potential of monolayers was more positive than the zeta potential of fibrinogen in the bulk, which proves a heterogeneous charge distribution. These experimental data reveal a new, side-on adsorption mechanism of fibrinogen on positively charged surfaces and

  6. Surface modification of CoCr alloy using varying concentrations of phosphoric and phosphonoacetic acids: albumin and fibrinogen adsorption, platelet adhesion, activation, and aggregation studies.

    Science.gov (United States)

    Thiruppathi, Eagappanath; Larson, Mark K; Mani, Gopinath

    2015-01-01

    CoCr alloy is commonly used in various cardiovascular medical devices for its excellent physical and mechanical properties. However, the formation of blood clots on the alloy surfaces is a serious concern. This research is focused on the surface modification of CoCr alloy using varying concentrations (1, 25, 50, 75, and 100 mM) of phosphoric acid (PA) and phosphonoacetic acid (PAA) to generate various surfaces with different wettability, chemistry, and roughness. Then, the adsorption of blood plasma proteins such as albumin and fibrinogen and the adhesion, activation, and aggregation of platelets with the various surfaces generated were investigated. Contact angle analysis showed PA and PAA coatings on CoCr provided a gradient of hydrophilic surfaces. FTIR showed PA and PAA were covalently bound to CoCr surface and formed different bonding configurations depending on the concentrations of coating solutions used. AFM showed the formation of homogeneous PA and PAA coatings on CoCr. The single and dual protein adsorption studies showed that the amount of albumin and fibrinogen adsorbed on the alloy surfaces strongly depend on the type of PA and PAA coatings prepared by different concentrations of coating solutions. All PA coated CoCr showed reduced platelet adhesion and activation when compared to control CoCr. Also, 75 and 100 mM PA-CoCr showed reduced platelet aggregation. For PAA coated CoCr, no significant difference in platelet adhesion and activation was observed between PAA coated CoCr and control CoCr. Thus, this study demonstrated that CoCr can be surface modified using PA for potentially reducing the formation of blood clots and improving the blood compatibility of the alloy.

  7. HIGH D-DIMER LEVELS PREDICT A POOR OUTCOME IN PATIENTS WITH SEVERE TRAUMA, EVEN WITH HIGH FIBRINOGEN LEVELS ON ARRIVAL: A MULTICENTER RETROSPECTIVE STUDY.

    Science.gov (United States)

    Hayakawa, Mineji; Maekawa, Kunihiko; Kushimoto, Shigeki; Kato, Hiroshi; Sasaki, Junichi; Ogura, Hiroshi; Matauoka, Tetsuya; Uejima, Toshifumi; Morimura, Naoto; Ishikura, Hiroyasu; Hagiwara, Akiyoshi; Takeda, Munekazu; Kaneko, Naoyuki; Saitoh, Daizoh; Kudo, Daisuke; Kanemura, Takashi; Shibusawa, Takayuki; Furugori, Shintaro; Nakamura, Yoshihiko; Shiraishi, Atsushi; Murata, Kiyoshi; Mayama, Gou; Yaguchi, Arino; Kim, Shiei; Takasu, Osamu; Nishiyama, Kazutaka

    2016-03-01

    Elevated D-dimer level in trauma patients is associated with tissue damage severity and is an indicator of hyperfibrinolysis during the early phase of trauma. To investigate the interacting effects of fibrinogen and D-dimer levels on arrival at the emergency department for massive transfusion and mortality in severe trauma patients in a multicenter retrospective study. This study included 519 adult trauma patients with an injury severity score ≥16. Patients with ≥10 units of red cell concentrate transfusion and/or death during the first 24 h were classified as having a poor outcome. Receiver operating characteristic curve analysis for predicting poor outcome showed the optimal cut-off fibrinogen and D-dimer values to be 190 mg/dL and 38 mg/L, respectively. On the basis of these values, patients were divided into four groups: low D-dimer (high fibrinogen (>190 mg/dL), low D-dimer (low fibrinogen (≤190 mg/dL), high D-dimer (≥38 mg/L)/high fibrinogen (>190 mg/dL), and high D-dimer (≥38 mg/L)/low fibrinogen (≤190 mg/dL). The survival rate was lower in the high D-dimer/low fibrinogen group than in the other groups. Moreover, the survival rate was lower in the high D-dimer/high fibrinogen group than in the low D-dimer/high fibrinogen and low D-dimer/low fibrinogen groups. High D-dimer level on arrival is a strong predictor of early death or requirement for massive transfusion in severe trauma patients, even with high fibrinogen levels.

  8. Evolution and potential function of fibrinogen-like domains across twelve Drosophila species

    Directory of Open Access Journals (Sweden)

    Middha Sumit

    2008-05-01

    Full Text Available Abstract Background The fibrinogen-like (FBG domain consists of approximately 200 amino acid residues, which has high sequence similarity to the C-terminal halves of fibrinogen β and γ chains. Fibrinogen-related proteins (FREPs containing one or more FBG domains are found universally in vertebrates and invertebrates. In invertebrates, FREPs are involved in immune responses and other aspects of physiology. To understand the complexity of this gene family in Drosophila, we analyzed FREPs in twelve Drosophila species. Results Using the genome data from 12 Drosophila species, we identified FBG domains in each species. The results show that the gene numbers in each species vary from 14 genes up to 43 genes. Using sequence profile analysis, we found that FBG domains have high sequence similarity and are highly conserved throughout. By comparison of structure and sequence conservation, some of the FBG domains in Drosophila melanogaster are predicted to function in recognition of carbohydrates and their derivatives on the surface of microorganisms in innate immunity. Conclusion Sequence and structural analyses show that FREP family across 12 Drosophila species contains conserved FBG domains. Expansion of the FREP families in Drosophila is mainly accounted by a major expansion of FBG domains.

  9. Tracer diffusion inside fibrinogen layers

    Science.gov (United States)

    Cieśla, Michał; Gudowska-Nowak, Ewa; Sagués, Francesc; Sokolov, Igor M.

    2014-01-01

    We investigate the obstructed motion of tracer (test) particles in crowded environments by carrying simulations of two-dimensional Gaussian random walk in model fibrinogen monolayers of different orientational ordering. The fibrinogen molecules are significantly anisotropic and therefore they can form structures where orientational ordering, similar to the one observed in nematic liquid crystals, appears. The work focuses on the dependence between level of the orientational order (degree of environmental crowding) of fibrinogen molecules inside a layer and non-Fickian character of the diffusion process of spherical tracer particles moving within the domain. It is shown that in general particles motion is subdiffusive and strongly anisotropic, and its characteristic features significantly change with the orientational order parameter, concentration of fibrinogens, and radius of a diffusing probe.

  10. Tracer diffusion inside fibrinogen layers

    CERN Document Server

    Cieśla, Michał; Sagués, Francesc; Sokolov, Igor M

    2013-01-01

    We investigate the motion of tracer (test) particles in crowded environments by carrying simulations of two-dimensional Gaussian random walk in model fibrinogen monolayers of different orientational ordering. The fibrinogen molecules are significantly anisotropic and therefore they can form structures where orientational ordering, similar to the one observed in nematic liquid crystals, appears. The work focuses on the dependence between level of the orientational order (degree of environmental crowding) of fibrinogen molecules inside a layer and non-Fickian character of the diffusion process of spherical tracer particles moving within the domain. It is shown that in general particles motion is subdiffusive and strongly anisotropic, and its characteristic features significantly change with the orientational order parameter, concentration of fibrinogens and radius of a diffusing probe.

  11. Fibrinogen drives dystrophic muscle fibrosis via a TGFbeta/alternative macrophage activation pathway.

    Science.gov (United States)

    Vidal, Berta; Serrano, Antonio L; Tjwa, Marc; Suelves, Mònica; Ardite, Esther; De Mori, Roberta; Baeza-Raja, Bernat; Martínez de Lagrán, María; Lafuste, Peggy; Ruiz-Bonilla, Vanessa; Jardí, Mercè; Gherardi, Romain; Christov, Christo; Dierssen, Mara; Carmeliet, Peter; Degen, Jay L; Dewerchin, Mieke; Muñoz-Cánoves, Pura

    2008-07-01

    In the fatal degenerative Duchenne muscular dystrophy (DMD), skeletal muscle is progressively replaced by fibrotic tissue. Here, we show that fibrinogen accumulates in dystrophic muscles of DMD patients and mdx mice. Genetic loss or pharmacological depletion of fibrinogen in these mice reduced fibrosis and dystrophy progression. Our results demonstrate that fibrinogen-Mac-1 receptor binding, through induction of IL-1beta, drives the synthesis of transforming growth factor-beta (TGFbeta) by mdx macrophages, which in turn induces collagen production in mdx fibroblasts. Fibrinogen-produced TGFbeta further amplifies collagen accumulation through activation of profibrotic alternatively activated macrophages. Fibrinogen, by engaging its alphavbeta3 receptor on fibroblasts, also directly promotes collagen synthesis. These data unveil a profibrotic role of fibrinogen deposition in muscle dystrophy.

  12. Clotting of mammalian fibrinogens by papain: a re-examination.

    Science.gov (United States)

    Doolittle, Russell F

    2014-10-28

    Papain has long been known to cause the gelation of mammalian fibrinogens. It has also been reported that papain-fibrin is insoluble in dispersing solvents like strong urea or sodium bromide solutions, similar to what is observed with thrombin-generated clots in the presence of factor XIIIa and calcium. In those old studies, both the gelation and subsequent clot stabilization were attributed to papain, although the possibility that the second step might be due to contaminating factor XIII in fibrinogen preparations was considered. I have revisited this problem in light of knowledge acquired over the past half-century about thiol proteases like papain, which mostly cleave peptide bonds, and transglutaminases like factor XIIIa that catalyze the formation of ε-lysyl-γ-glutamyl cross-links. Recombinant fibrinogen, inherently free of factor XIII and other plasma proteins, formed a stable gel when treated with papain alone. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that the intermolecular cross-linking in papain-fibrin leads to γ-chain dimers, trimers, and tetramers, just as is the case with thrombin-factor XIIIa-stabilized fibrin. Mass spectrometry of bands excised from gels showed that the cross-linked material is quite different from what occurs with factor XIIIa, however. With papain, the cross-linking occurs between γ chains in neighboring protofibrils becoming covalently linked in a "head-to-tail" fashion by a transpeptidation reaction involving the α-amino group of γ-Tyr1 and a papain cleavage site at γ-Gly403 near the carboxy terminus, rather than by the (reciprocal) "tail-to-tail" manner that occurs with factor XIIIa and that depends on cross-links between γ-Lys406 and γ-Gln398.

  13. Clinical and Prognostic Effect of Plasma Fibrinogen in Renal Cell Carcinoma: A Meta-Analysis

    Science.gov (United States)

    Hong, Mei; Jing, Suoshi; Liu, Xingchen; Wang, Hanzhang; Wang, Xinping; Kaushik, Dharam; Rodriguez, Ronald

    2017-01-01

    Background. Although numerous studies have shown that plasma fibrinogen is linked to renal cell carcinoma (RCC) risk, the consistency and magnitude of the effect of plasma fibrinogen are unclear. The aim of the study was to explore the association between plasma fibrinogen and RCC prognosis. Methods. An electronic search of Embase, PubMed/MEDLINE, and the Cochrane databases was performed to identify relevant studies published prior to June 1, 2016. Results. A total of 3744 patients with RCC from 7 published studies were included in the meta-analysis. The prognostic and clinical relevance of plasma fibrinogen are evaluated in RCC patients. Statistical significance of the combined hazard ratio (HR) was detected for overall survival, cancer-specific survival, and disease-free survival. Our pooled results showed that elevated plasma fibrinogen was significantly associated with clinical stage and Fuhrman grading. The level of plasma fibrinogen was not found to be associated with tumor type and gender. Conclusions. Elevated plasma fibrinogen is a strong indicator of poorer prognosis of patients with RCC, whereas the plasma fibrinogen is not significantly associated with tumor type. Therefore, plasma fibrinogen could be used in patients with RCC for risk stratification and decision providing a proper therapeutic strategy.

  14. Clinical and Prognostic Effect of Plasma Fibrinogen in Renal Cell Carcinoma: A Meta-Analysis.

    Science.gov (United States)

    Tian, Yuejun; Hong, Mei; Jing, Suoshi; Liu, Xingchen; Wang, Hanzhang; Wang, Xinping; Kaushik, Dharam; Rodriguez, Ronald; Wang, Zhiping

    2017-01-01

    Background. Although numerous studies have shown that plasma fibrinogen is linked to renal cell carcinoma (RCC) risk, the consistency and magnitude of the effect of plasma fibrinogen are unclear. The aim of the study was to explore the association between plasma fibrinogen and RCC prognosis. Methods. An electronic search of Embase, PubMed/MEDLINE, and the Cochrane databases was performed to identify relevant studies published prior to June 1, 2016. Results. A total of 3744 patients with RCC from 7 published studies were included in the meta-analysis. The prognostic and clinical relevance of plasma fibrinogen are evaluated in RCC patients. Statistical significance of the combined hazard ratio (HR) was detected for overall survival, cancer-specific survival, and disease-free survival. Our pooled results showed that elevated plasma fibrinogen was significantly associated with clinical stage and Fuhrman grading. The level of plasma fibrinogen was not found to be associated with tumor type and gender. Conclusions. Elevated plasma fibrinogen is a strong indicator of poorer prognosis of patients with RCC, whereas the plasma fibrinogen is not significantly associated with tumor type. Therefore, plasma fibrinogen could be used in patients with RCC for risk stratification and decision providing a proper therapeutic strategy.

  15. Interaction of human fibrinogen receptor (GPⅡb-Ⅲa) with decorsin

    Institute of Scientific and Technical Information of China (English)

    Jie YANG; Chen-yang ZHAN; Xian-chi DONG; Kun YANG; Fu-xiang WANG

    2004-01-01

    AIM: To build up the structure of human fibrinogen receptor GPⅡb-Ⅲa, subsequently combined with its antagonist decorsin, and to investigate the interaction between decorsin and its receptor GPⅡb-Ⅲa at the molecular level.METHODS: A three-dimensional (3D) molecular model of human fibrinogen receptor GPⅡb-Ⅲa was generated by InsightⅡ, a distance geometry-based homologous modeling package. The structure of human fibrinogen receptor GPⅡb-Ⅲa was built by the InsightⅡ/Homology module using the corresponding of integrin alphaVbeta3 (PDB filecode 1JV2) as the template. Then the primary structures were optimized by energy minimization. Subsequently the structural model was docked with its antagonist decorsin (PDB filecode ldec). RESULTS: A good substratereceptor interaction model was achieved. The interaction sites with decorsin converge at domain 8 (βA domain of β3 subunit) of GPⅡb-Ⅲa. The direct interatomic contacts were made between 16 GPⅡb/Ⅲa residues and 10 decorsin amino-acid residues. These included van der Waals contacts, electrostatic interaction, hydrogen bond,and salt bridge. Residues in contact were concentrated in four dispersed regions of human GPⅡb-Ⅲa: the RGD reaction motif (118-132 of GPⅢa), the span from 210 to 213 of GPⅢa, Thr182 residue and Asp251 residue of GPⅢa; and they were distributed over five segments of decorsin: Aspl0 residue, Asnl8 and Lysl9 residues, Arg28 residue, RGD motif, and Asp35-Pro36-Tyr37 segment. CONCLUSION: This complex model plays an important role in development and research of some new drugs, especially a new guided fusion-type fibrinogen receptor antagonist.

  16. A study on human serum albumin influence on glycation of fibrinogen

    Energy Technology Data Exchange (ETDEWEB)

    Kielmas, Martyna; Szewczuk, Zbigniew; Stefanowicz, Piotr, E-mail: Piotr.stefanowicz@chem.uni.wroc.pl

    2013-09-13

    Highlights: •The glycation of fibrinogen was investigated by isotopic labeling method. •The potential glycation sites in fibrinogen were identified. •Human serum albumin (HSA) inhibits the glycation of fibrinogen. •The effect of HSA on fibrinogen glycation is sequence-dependent. -- Abstract: Although in vivo glycation proceeds in complex mixture of proteins, previous studies did not take in consideration the influence of protein–protein interaction on Maillard reaction. The aim of our study was to test the influence of human serum albumin (HSA) on glycation of fibrinogen. The isotopic labeling using [{sup 13}C{sub 6}] glucose combined with LC-MS were applied as tool for identification possible glycation sites in fibrinogen and for evaluation the effect of HSA on the glycation level of selected amino acids in fibrinogen. The obtained data indicate that the addition of HSA protects the fibrinogen from glycation. The level of glycation in presence of HSA is reduced by 30–60% and depends on the location of glycated residue in sequence of protein.

  17. Electrospun nanofibre fibrinogen for urinary tract tissue reconstruction

    Energy Technology Data Exchange (ETDEWEB)

    McManus, Michael [Department of Surgery, Division of Urology, Virginia Commonwealth University, Richmond, VA 23298-0230 (United States); Boland, Eugene [Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23298-0694 (United States); Sell, Scott [Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23298-0694 (United States); Bowen, Whitney [Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23298-0694 (United States); Koo, Harry [Department of Surgery, Division of Urology, Virginia Commonwealth University, Richmond, VA 23298-0230 (United States); Simpson, David [Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA 23298-0709 (United States); Bowlin, Gary [Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23298-0694 (United States)

    2007-12-15

    The purpose of this study was to demonstrate that human bladder smooth muscle cells (HBSM) remodel electrospun fibrinogen mats. Fibrinogen scaffolds were electrospun and disinfected using standard methods. Scaffolds were seeded with 5 x 10{sup 4} HBSM per scaffold. Cultures were supplemented with aprotinin concentrations of 0 KIU ml{sup -1} (no aprotinin), 100 KIU ml{sup -1} or 1000 KIU ml{sup -1} and incubated with twice weekly media changes. Samples were removed for evaluation at 1, 3, 7 and 14 days. Cultured scaffolds were evaluated with a WST-1 cell proliferation assay, scanning electron microscopy and histology. Cell culture demonstrated that HBSM readily migrated into and initiated remodelling of the electrospun fibrinogen scaffolds by deposition of collagen. Proliferation was suppressed during this initial phase with respect to a 2D control due to cell migration. Histology confirmed that proliferation increased during the later stages of remodelling. Remodelling was slower at higher aprotinin concentrations. These results demonstrate that HBSM rapidly remodel an electrospun fibrinogen scaffold and deposit native collagen. The process can be modulated using aprotinin, a protease inhibitor. These initial findings indicate that there is tremendous potential for electrospun fibrinogen as a urologic tissue engineering scaffold with the ultimate goal of producing an implantable acellular product that would promote cellular in-growth and in situ tissue regeneration.

  18. ESTABLISHMENT OF A FIBRINOGEN REFERENCE INTERVAL IN ORNATE BOX TURTLES (TERRAPENE ORNATA ORNATA).

    Science.gov (United States)

    Parkinson, Lily; Olea-Popelka, Francisco; Klaphake, Eric; Dadone, Liza; Johnston, Matthew

    2016-09-01

    This study sought to establish a reference interval for fibrinogen in healthy ornate box turtles ( Terrapene ornata ornata). A total of 48 turtles were enrolled, with 42 turtles deemed to be noninflammatory and thus fitting the inclusion criteria and utilized to estimate a fibrinogen reference interval. Turtles were excluded based upon physical examination and blood work abnormalities. A Shapiro-Wilk normality test indicated that the noninflammatory turtle fibrinogen values were normally distributed (Gaussian distribution) with an average of 108 mg/dl and a 95% confidence interval of the mean of 97.9-117 mg/dl. Those turtles excluded from the reference interval because of abnormalities affecting their health had significantly different fibrinogen values (P = 0.313). A reference interval for healthy ornate box turtles was calculated. Further investigation into the utility of fibrinogen measurement for clinical usage in ornate box turtles is warranted.

  19. A method to measure thrombin activity in a mixture of fibrinogen and thrombin powders.

    Science.gov (United States)

    DeAnglis, Ashley P; Nur, Israel; Gorman, Anne J; Meidler, Roberto

    2017-03-01

    Thrombin and fibrinogen powders are the active components of advanced surgical hemostasis products including the EVARREST Fibrin Sealant Patch. Measuring the enzymatic activity of thrombin in the presence of fibrinogen is challenging, as hydration of the powders in a neutral aqueous environment will cause the enzyme to rapidly react with the fibrinogen to form a fibrin clot, which in turn binds and entraps the enzyme thus preventing subsequent measurement of thrombin activity. A novel approach has been developed to overcome this challenge. After isolation of the mixture of powders, an alkaline carbonate solution is used to solubilize the proteins, while reversibly inhibiting the activity of thrombin and preventing clot formation. Once the powders have been fully solubilized, thrombin activity can be restored by neutralization in a buffered fibrinogen solution resulting in fibrin clot formulation. The rate of clot formation can be quantified in a coagulometer to determine the thrombin activity of the original powder. Samples coated with powders containing fibrinogen and varying amounts of thrombin were tested using the method described herein. The results demonstrated that the method could consistently measure the activity of (alpha) thrombin in the presence of fibrinogen over a broad range of thrombin activity levels. The test was successfully validated according to International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use Guidelines and thus is suitable for use as part of a commercial manufacturing process. A method has been developed that enables thrombin activity to be measured in a mixture of fibrinogen and thrombin powders.

  20. A method to measure thrombin activity in a mixture of fibrinogen and thrombin powders

    Science.gov (United States)

    DeAnglis, Ashley P.; Nur, Israel; Gorman, Anne J.; Meidler, Roberto

    2017-01-01

    Thrombin and fibrinogen powders are the active components of advanced surgical hemostasis products including the EVARREST Fibrin Sealant Patch. Measuring the enzymatic activity of thrombin in the presence of fibrinogen is challenging, as hydration of the powders in a neutral aqueous environment will cause the enzyme to rapidly react with the fibrinogen to form a fibrin clot, which in turn binds and entraps the enzyme thus preventing subsequent measurement of thrombin activity. A novel approach has been developed to overcome this challenge. After isolation of the mixture of powders, an alkaline carbonate solution is used to solubilize the proteins, while reversibly inhibiting the activity of thrombin and preventing clot formation. Once the powders have been fully solubilized, thrombin activity can be restored by neutralization in a buffered fibrinogen solution resulting in fibrin clot formulation. The rate of clot formation can be quantified in a coagulometer to determine the thrombin activity of the original powder. Samples coated with powders containing fibrinogen and varying amounts of thrombin were tested using the method described herein. The results demonstrated that the method could consistently measure the activity of (alpha) thrombin in the presence of fibrinogen over a broad range of thrombin activity levels. The test was successfully validated according to International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use Guidelines and thus is suitable for use as part of a commercial manufacturing process. A method has been developed that enables thrombin activity to be measured in a mixture of fibrinogen and thrombin powders. PMID:26991860

  1. A novel fibrinogen B beta chain frameshift mutation causes congenital afibrinogenaemia.

    Science.gov (United States)

    Zhang, Jian; Zhao, Xiaojuan; Wang, Zhaoyue; Yu, Ziqiang; Cao, Lijuan; Zhang, Wei; Bai, Xia; Ruan, Changgeng

    2013-07-01

    Congenital afibrinogenaemia is a rare autosomal recessive disorder caused by various mutations within the fibrinogen genes FGA, FGB and FGG. Ins/del mutations in FGB are extremely rare. We report a patient with afibrinogenaemia who suffered from umbilical cord bleeding and repeated bleeding episodes. His plasma fibrinogen levels could not be detected using the Clauss method and immunological methods. Molecular analyses revealed homozygosity in a novel four bases insertion in codon 40 of FGB exon 2 (g. 2833_2834 ins GTTT), which resulted in a truncated 50-residue polypeptide that contained 11 exceptional abnormal residues. In the transient expression experiments, mutant fibrinogen could be detected at higher level than wild-type fibrinogen in COS-7 cell lysates but not in culture media. These results suggest that the homozygous mutation in FGB could be responsible for congenital afibrinogenaemia in this patient. This frameshift mutation could impair fibrinogen assembly and secretion without influencing the protein synthesis.

  2. A novel fibrinogen mutation (γ Thr277Arg) causes hereditary hypofibrinogenemia in a Chinese family.

    Science.gov (United States)

    Zhu, Liqing; Wang, Mingshan; Xie, Haixiao; Jin, Yanhui; Yang, Lihong; Xu, Pengfei

    2013-09-01

    Congenital hypofibrinogenemia is a rare disorder caused by heterozygous mutations in one of the three fibrinogen genes--fibrinogen α-chain (FGA), fibrinogen β-chain (FGB) and fibrinogen γ-chain (FGG)--which code for the Aα, Bβ and γ chains, respectively. In this study, we identified a genetic defect in the FGG underlying the hypofibrinogenemia. The proposita had a prolonged blood clotting time (thrombin time 24.5 s, prothrombin time 16.8 s) and a low level of plasma fibrinogen (0.71 g/l by Clauss method and 0.79 g/l by immunoturbidimetry). DNA screening of the whole fibrinogen gene revealed a heterozygous GC mutation at nucleotide 7482 in her FGG gene. Her father and her half-brother are also heterozygous for this mutation. This mutation contributes to Thr277 → Arg in the γ chain of fibrinogen. To the best of our knowledge, this is the first report of such a mutation that is associated with hypofibrinogenemia.

  3. Combination of Fibrinogen and High-sensitivity C-reactive Protein Measurements is Potential in Identification of Acute Coronary Syndrome

    Directory of Open Access Journals (Sweden)

    Djanggan Sargowo

    2015-04-01

    Full Text Available BACKGROUND: Acute myocardial infarction (AMI is one of cardiovascular diseases with high morbidity and mortality rates. Novel biomarkers that can detect accurately acute coronary syndrome (ACS at early stage, are necessary to improve current strategies and/or to identify subjects who are at risk. Fibrinogen and high-sensitivity C-reactive protein (hs-CRP roles in inflammation process could be potential for ACS early detection. This study was conducted to evaluate measurements of fibrinogen and hs-CRP on ACS. METHODS: An analytic observational study with cross sectional approach was conducted on patients with Troponin I positive. After signing informed consent, anamnesis and complete blood count were conducted. Besides that, liver function, renal function, and blood glucose tests were conducted as well. Samples of selected subjects were quantified with enzyme-linked immunosorbent assay (ELISA for Troponin I, fibrinogen and hs-CRP. Then statistical analyses were performed. RESULTS: There were 76 subjects in each ACS and non-ACS groups. ACS group showed significant higher levels of both fibrinogen and hs-CRP compared to Non-ACS group (p=0.000. Among evaluated risk factors, diabetes mellitus (DM (p=0.003 and hypertension (p=0.000 were significantly higher in ACS group than in non-ACS group. Among evaluated clinical factors, blood glucose (p=0.001 and age (p=0.000 were significantly higher in ACS group than in non-ACS group. Combination of fibrinogen and hs-CRP measurements showed the highest sensitivity (75.00%, specificity (80.26%, accuracy (77.63%, positive predictive value (79.19% and negative predictive value (76.25%. CONCLUSIONS: Since fibrinogen and hs-CRP were increased in ACS group and combination of fibrinogen and hs-CRP measurements showed the highest sensitivity, specificity, accuracy, positive predictive value and negative predictive value, we suggest that combination of fibrinogen and hs-CRP measurements could give added value to

  4. High-performance scaffolds on titanium surfaces: Osteoblast differentiation and mineralization promoted by a globular fibrinogen layer through cell-autonomous BMP signaling

    Energy Technology Data Exchange (ETDEWEB)

    Horasawa, Noriko, E-mail: horasawa@po.mdu.ac.jp [Department of Dental Materials, Matsumoto Dental University, 1780 Hiro-oka Gobara, Shiojiri, Nagano 399-0781 (Japan); Yamashita, Teruhito [Institute for Oral Science, Matsumoto Dental University, 1780 Hiro-oka Gobara, Shiojiri, Nagano 399-0781 (Japan); Uehara, Shunsuke; Udagawa, Nobuyuki [Department of Biochemistry, Matsumoto Dental University, 1780 Hiro-oka Gobara, Shiojiri, Nagano 399-0781 (Japan)

    2015-01-01

    Titanium has been widely used as a dental implant material. However, it takes several months for the implant body to bind with the jawbone. To develop new bioactive modification on titanium surfaces to achieve full osseointegration expeditiously, we used fibrinogen and fibronectin as bioactive scaffolds on the titanium plate, which are common extracellular matrix (ECM) proteins. We analyzed the features of the surface of ECM-modified titanium plates by atomic force microscopy and Fourier transform infrared spectrophotometry. We also evaluated the effect of ECM modification on promoting the differentiation and mineralization of osteoblasts on these surfaces. Fibrinogen had excellent adsorption on titanium surfaces even at low concentrations, due to the binding ability of fibrinogen via its RGD motif. The surface was composed of a fibrinogen monolayer, in which the ratio of β-sheets was decreased. Osteoblast proliferation on ECM-modified titanium surface was significantly promoted compared with titanium alone. Calcification on the modified surface was also accelerated. These ECM-promoting effects correlated with increased expression of bone morphogenetic proteins (BMPs) by the osteoblasts themselves and were inhibited by Noggin, a BMP inhibitor. These results suggest that the fibrinogen monolayer-modified titanium surface is recognized as bioactive scaffolds and promotes bone formation, resulting in the acceleration of osseointegration. - Highlights: • Fibrinogen had an excellent adsorption on titanium at low concentrations. • Fibrinogen on titanium formed composite layer with a decrease in β-sheet structure. • Osteoblast proliferation and calcification on the ECM-modified titanium plates were significant. • These effects of fibrinogen were increased of BMPs by osteoblasts themselves. • The scaffolds of fibrinogen on titanium might accelerate osseointegration.

  5. Mechanisms of fibrinogen adsorption at solid substrates.

    Science.gov (United States)

    Adamczyk, Zbigniew; Bratek-Skicki, Anna; Żeliszewska, Paulina; Wasilewska, Monika

    2014-01-01

    The aim of this work was to critically review recent results pertinent to fibrinogen adsorption at solid/electrolyte interfaces with the emphasis focused on a quantitative analysis of these processes in terms of the electrostatic interactions. Accordingly, in the first part, the primary chemical structure of fibrinogen is analyzed. Physicochemical data pertinent to the bulk properties derived from hydrodynamic, dynamic light scattering and micro-electrophoretic measurements aided by theoretical modeling are discussed. Possible conformations and the effective charge distribution over the fibrinogen molecule for various pH an ionic strength are defined, especially the semi-collapsed conformation prevailing at physiological conditions. Adsorption kinetics of fibrinogen at hydrophilic and hydrophobic (polymer modified) substrates determined by various techniques is described. Adsorption at polymeric carrier particles, pertinent to immunological assays, studied in terms of electrokinetic and concentration depletion methods, are also considered. The reversibility of adsorption, fibrinogen molecule orientations and maximum coverages are thoroughly discussed. The stability of fibrinogen monolayers formed at these carrier particles in respect to pH and ionic strength cyclic changes is also discussed. In the final section interactions and deposition of model colloid particles on fibrinogen monolayers are analyzed which allows one to derive valuable information about molecule orientations. Based on the physicochemical data, adsorption kinetics and colloid particle deposition measurements, probable adsorption mechanisms of fibrinogen on solid/electrolyte interfaces are defined.

  6. Clinical and prognostic significance of plasma fibrinogen in lung cancer

    Directory of Open Access Journals (Sweden)

    Chen YS

    2014-01-01

    Full Text Available Objectives: Hyperfibrinogenemia is a common problem associated with various carcinomas. The recent studies have shown that high plasma fibrinogen concentration is associated with invasion, growth and metastases of cancer. Furthermore, the recent studies focus on the prognostic significance of fibrinogen in the patients with advanced NSCLC (stage IIIB -IV. However, the prognostic significance of the plasma fibrinogen levels in early stage NSCLC patients (stage I -IIIA still remains unclear. In addition, it remains unclear whether or not chemotherapy-induced changes in fibrinogen level relate to the prognosis. The aims of this study were to 1 further explore the relationship between the plasma fibrinogen concentration and the stage and metastases of lung cancer 2 evaluate the prognostic significance of the basal plasma fibrinogen level in patients with lung cancer 3 explore the prognostic value of the change in fibrinogen levels between pre and post-chemotherapy. Methods: In this retrospective study, the data from 370 patients with lung cancer were enrolled into this study. The plasma fibrinogen levels were compared with the clinical and prognostic significance of lung cancer. The association between the plasma fibrinogen level and clinical-prognostic characteristics were analyzed using SPSS 17.0 software. Results: 1 The median pre-treatment plasma fibrinogen levels were 4.20g/L. Pre-treatment plasma fibrinogen levels correlated significantly with gender (p = 0.013. A higher plasma fibrinogen concentration was associated with squamous cell carcinoma versus adenocarcinoma (4.83±1.50 g/L versus 4.15±1.30 g/L; P<0.001, there was a significant association between plasma fibrinogen level and metastases of lung cancer, pointing a higher plasma fibrinogen level in lymph nodes or distant organ metastases (p < 0.001. 2 Patients with low plasma fibrinogen concentration demonstrates higher overall survival compared with those with high plasma fibrinogen

  7. Fibrinogen geneva II: a new congenitally abnormal fibrinogen alpha chain (Gly17Asp) with a review of similar mutations resulting in abnormal knob A.

    Science.gov (United States)

    Casini, Alessandro; De Maistre, Emmanuel; Casini-Stuppi, Virginie; Fontana, Pierre; Neerman-Arbez, Marguerite; de Moerloose, Philippe

    2014-04-01

    Congenital dysfibrinogenemias are characterized by biosynthesis of a structurally abnormal fibrinogen molecule that exhibits reduced functional levels compared with the level of fibrinogen antigen. To date a large number of mutations have been identified in patients with dysfibrinogenemia. Mutations occurring at the thrombin cleavage site (Arg16-Gly17 in the mature alpha-chain) at the amino-terminal end of the fibrinogen alpha chain are a common cause of the disease. These mutations causing abnormal fibrin polymerization are associated with different phenotypes. Here, we report the identification of a novel heterozygous missense mutation of Glycine 17 (Gly17Asp) in a female patient with mild bleeding manifestations, and compare it with other previously reported mutations also resulting in abnormal knob A.

  8. Characterization of the gene encoding a fibrinogen-related protein expressed in Crassostrea gigas hemocytes.

    Science.gov (United States)

    Skazina, M A; Gorbushin, A M

    2016-07-01

    Four exons of the CgFrep1 gene (3333 bp long) encode a putative fibrinogen-related protein (324 aa) bearing a single C-terminal FBG domain. Transcripts of the gene obtained from hemocytes of different Pacific oysters show prominent individual variation based on SNP and indels of tandem repeats resulted in polymorphism of N-terminus of the putative CgFrep1 polypeptide. The polypeptide chain bears N-terminal coiled-coil region potentially acting as inter-subunit interface in the protein oligomerization. It is suggested that CgFrep1 gene encodes the oligomeric lectin composed of at least two subunits.

  9. Origin of the Nonadhesive Properties of Fibrinogen Matrices Probed by Force Spectroscopy

    OpenAIRE

    Yermolenko, Ivan S.; Fuhrmann, Alexander; Magonov, Sergei N.; Lishko, Valeryi K.; Oshkadyerov, Stanislav P.; Ros, Robert; Ugarova, Tatiana P.

    2010-01-01

    The deposition of a multilayered fibrinogen matrix on various surfaces results in a dramatic reduction of integrin-mediated cell adhesion and outside-in signaling in platelets and leukocytes. The conversion of a highly adhesive, low density fibrinogen substrate into the nonadhesive high density fibrinogen matrix occurs within a very narrow range of fibrinogen coating concentrations. The molecular events responsible for this transition are not well understood. Herein, single-cell and molecular...

  10. Clinical and prognostic significance of plasma fibrinogen in lung cancer

    OpenAIRE

    Chen YS; Zeng DH; Li HR; Wu YL; Lin X.; Xu NL; Lin M

    2014-01-01

    Objectives: Hyperfibrinogenemia is a common problem associated with various carcinomas. The recent studies have shown that high plasma fibrinogen concentration is associated with invasion, growth and metastases of cancer. Furthermore, the recent studies focus on the prognostic significance of fibrinogen in the patients with advanced NSCLC (stage IIIB -IV). However, the prognostic significance of the plasma fibrinogen levels in early stage NSCLC patients (stage I -IIIA) still remains unclear. ...

  11. Involvement of fibrinogen specific binding in erythrocyte aggregation

    OpenAIRE

    Lominadze, David; DEAN, WILLIAM L.

    2002-01-01

    Increased fibrinogen concentration and erythrocyte aggregation are significant risk factors during various cardiovascular diseases and cerebrovascular disorders. Currently, fibrinogen-induced erythrocyte aggregation is thought to be caused by a non-specific binding mechanism. However, the published data on changes in erythrocyte aggregation during hypertension point to the possible existence of other mechanism(s). Therefore, we tested the hypothesis that specific binding of fibrinogen is invo...

  12. Origin of the nonadhesive properties of fibrinogen matrices probed by force spectroscopy.

    Science.gov (United States)

    Yermolenko, Ivan S; Fuhrmann, Alexander; Magonov, Sergei N; Lishko, Valeryi K; Oshkadyerov, Stanislav P; Ros, Robert; Ugarova, Tatiana P

    2010-11-16

    The deposition of a multilayered fibrinogen matrix on various surfaces results in a dramatic reduction of integrin-mediated cell adhesion and outside-in signaling in platelets and leukocytes. The conversion of a highly adhesive, low-density fibrinogen substrate to the nonadhesive high-density fibrinogen matrix occurs within a very narrow range of fibrinogen coating concentrations. The molecular events responsible for this transition are not well understood. Herein, single-cell and molecular force spectroscopy were used to determine the early steps in the formation of nonadhesive fibrinogen substrates. We show that the adsorption of fibrinogen in the form of a molecular bilayer coincides with a several-fold reduction in the adhesion forces generated between the AFM tip and the substrate as well as between a cell and the substrate. The subsequent deposition of new layers at higher coating concentrations of fibrinogen results in a small additional decrease in adhesion forces. The poorly adhesive fibrinogen bilayer is more extensible under an applied tensile force than is the surface-bound fibrinogen monolayer. Following chemical cross-linking, the stabilized bilayer displays the mechanical and adhesive properties characteristic of a more adhesive fibrinogen monolayer. We propose that a greater compliance of the bi- and multilayer fibrinogen matrices has its origin in the interaction between the molecules forming the adjacent layers. Understanding the mechanical properties of nonadhesive fibrinogen matrices should be of importance in the therapeutic control of pathological thrombosis and in biomaterials science.

  13. Fibrinogen binding sites P336 and Y338 of clumping factor A are crucial for Staphylococcus aureus virulence.

    Directory of Open Access Journals (Sweden)

    Elisabet Josefsson

    Full Text Available We have earlier shown that clumping factor A (ClfA, a fibrinogen binding surface protein of Staphylococcus aureus, is an important virulence factor in septic arthritis. When two amino acids in the ClfA molecule, P(336 and Y(338, were changed to serine and alanine, respectively, the fibrinogen binding property was lost. ClfAP(336Y(338 mutants have been constructed in two virulent S. aureus strains Newman and LS-1. The aim of this study was to analyze if these two amino acids which are vital for the fibrinogen binding of ClfA are of importance for the ability of S. aureus to generate disease. Septic arthritis or sepsis were induced in mice by intravenous inoculation of bacteria. The clfAP(336Y(338 mutant induced significantly less arthritis than the wild type strain, both with respect to severity and frequency. The mutant infected mice developed also a much milder systemic inflammation, measured as lower mortality, weight loss, bacterial growth in kidneys and lower IL-6 levels. The data were verified with a second mutant where clfAP(336 and Y(338 were changed to alanine and serine respectively. When sepsis was induced by a larger bacterial inoculum, the clfAP(336Y(338 mutants induced significantly less septic death. Importantly, immunization with the recombinant A domain of ClfAP(336SY(338A mutant but not with recombinant ClfA, protected against septic death. Our data strongly suggest that the fibrinogen binding activity of ClfA is crucial for the ability of S. aureus to provoke disease manifestations, and that the vaccine potential of recombinant ClfA is improved by removing its ability to bind fibrinogen.

  14. A comparative study of fibrinogen adsorption onto metal oxide thin films

    Science.gov (United States)

    Silva-Bermudez, P.; Muhl, S.; Rodil, S. E.

    2013-10-01

    One of the first events occurring upon foreign material-biological medium contact is the adsorption of proteins, which evolution greatly determines the cells response to the material. Protein-surface interactions are a complex phenomenon driven by the physicochemical properties of the surface, protein(s) and liquid medium involve in the interaction. In this article the adsorption of fibrinogen (Fbg) onto Ta2O5, Nb2O5, TiO2 and ZrO2 thin films is reported. The adsorption kinetics and characteristics of the adsorbed fibrinogen layer were studied in situ using dynamic and spectroscopic ellipsometry. The films wettability, surface energy (γLW/AB) and roughness were characterized aiming to elucidate their correlations with Fbg adsorption. The adsorption rate changed accordingly to the film; the fastest adsorption rate and highest Fbg surface mass concentration (Γ) was observed on ZrO2. The hydrophobic/hydrophilic character of the oxide highly influenced Fbg adsorption. On Ta2O5, Nb2O5 and TiO2, which were either hydrophilic or in the breaking-point between hydrophilicity and hydrophobicity, Γ was correlated to the polar component of γLW/AB and roughness of the surface. On ZrO2, clearly hydrophobic, Γ increased significantly off the correlation observed for the other films. The results indicated different adsorption dynamics and orientations of the Fbg molecules dependent on the surface hydrophobic/hydrophilic character.

  15. Bacteroides gingivalis and Bacteroides intermedius recognize different sites on human fibrinogen

    Energy Technology Data Exchange (ETDEWEB)

    Lantz, M.S.; Allen, R.D.; Bounelis, P.; Switalski, L.M.; Hook, M. (Univ. of Alabama, Birmingham (USA))

    1990-02-01

    Bacteroides (Porphyromonas) gingivalis and Bacteroides (Porphyromonas) intermedius have been implicated in the etiology of human periodontal diseases. These organisms are able to bind and degrade human fibrinogen, and these interactions may play a role in the pathogenesis of periodontal disease. In attempts to map the bacterial binding sites along the fibrinogen molecule, we have found that strains of B. gingivalis and B. intermedius, respectively, recognize spatially distant and distinct sites on the fibrinogen molecule. Isolated reduced and alkylated alpha-, beta-, and gamma-fibrinogen chains inhibited binding of 125I-fibrinogen to both Bacteroides species in a concentration-dependent manner. Plasmin fragments D and to some extent fragment E, however, produced a concentration-dependent inhibition of 125I-fibrinogen binding to B. intermedius strains but did not affect binding of 125I-fibrinogen to B. gingivalis strains. Radiolabeled fibrinogen chains and fragments were compared with 125I-fibrinogen with respect to specificity and reversibility of binding to bacteria. According to these criteria, gamma chain most closely resembled the native fibrinogen molecule in behavior toward B. gingivalis strains and fragments D most closely resembled fibrinogen in behavior toward B. intermedius strains. The ability of anti-human fibrinogen immunoglobulin G (IgG) to inhibit binding of 125I-fibrinogen to B. intermedius strains was greatly reduced by absorbing the IgG with fragments D. Absorbing the IgG with fragments D had no effect on the ability of the antibody to inhibit binding of 125I-fibrinogen to B. gingivalis strains. A purified staphylococcal fibrinogen-binding protein blocked binding of 125I-fibrinogen to B. intermedius strains but not to B. gingivalis strains.

  16. Modulation of Dental Pulp Stem Cell Odontogenesis in a Tunable PEG-Fibrinogen Hydrogel System.

    Science.gov (United States)

    Lu, Qiqi; Pandya, Mirali; Rufaihah, Abdul Jalil; Rosa, Vinicius; Tong, Huei Jinn; Seliktar, Dror; Toh, Wei Seong

    2015-01-01

    Injectable hydrogels have the great potential for clinical translation of dental pulp regeneration. A recently developed PEG-fibrinogen (PF) hydrogel, which comprises a bioactive fibrinogen backbone conjugated to polyethylene glycol (PEG) side chains, can be cross-linked after injection by photopolymerization. The objective of this study was to investigate the use of this hydrogel, which allows tuning of its mechanical properties, as a scaffold for dental pulp tissue engineering. The cross-linking degree of PF hydrogels could be controlled by varying the amounts of PEG-diacrylate (PEG-DA) cross-linker. PF hydrogels are generally cytocompatible with the encapsulated dental pulp stem cells (DPSCs), yielding >85% cell viability in all hydrogels. It was found that the cell morphology of encapsulated DPSCs, odontogenic gene expression, and mineralization were strongly modulated by the hydrogel cross-linking degree and matrix stiffness. Notably, DPSCs cultured within the highest cross-linked hydrogel remained mostly rounded in aggregates and demonstrated the greatest enhancement in odontogenic gene expression. Consistently, the highest degree of mineralization was observed in the highest cross-linked hydrogel. Collectively, our results indicate that PF hydrogels can be used as a scaffold for DPSCs and offers the possibility of influencing DPSCs in ways that may be beneficial for applications in regenerative endodontics.

  17. Modulation of Dental Pulp Stem Cell Odontogenesis in a Tunable PEG-Fibrinogen Hydrogel System

    Directory of Open Access Journals (Sweden)

    Qiqi Lu

    2015-01-01

    Full Text Available Injectable hydrogels have the great potential for clinical translation of dental pulp regeneration. A recently developed PEG-fibrinogen (PF hydrogel, which comprises a bioactive fibrinogen backbone conjugated to polyethylene glycol (PEG side chains, can be cross-linked after injection by photopolymerization. The objective of this study was to investigate the use of this hydrogel, which allows tuning of its mechanical properties, as a scaffold for dental pulp tissue engineering. The cross-linking degree of PF hydrogels could be controlled by varying the amounts of PEG-diacrylate (PEG-DA cross-linker. PF hydrogels are generally cytocompatible with the encapsulated dental pulp stem cells (DPSCs, yielding >85% cell viability in all hydrogels. It was found that the cell morphology of encapsulated DPSCs, odontogenic gene expression, and mineralization were strongly modulated by the hydrogel cross-linking degree and matrix stiffness. Notably, DPSCs cultured within the highest cross-linked hydrogel remained mostly rounded in aggregates and demonstrated the greatest enhancement in odontogenic gene expression. Consistently, the highest degree of mineralization was observed in the highest cross-linked hydrogel. Collectively, our results indicate that PF hydrogels can be used as a scaffold for DPSCs and offers the possibility of influencing DPSCs in ways that may be beneficial for applications in regenerative endodontics.

  18. Waste to Energy Potential - A High Concentration Anaerobic Bioreactor

    Science.gov (United States)

    2012-05-23

    REPORT DATE 23 MAY 2012 2. REPORT TYPE 3. DATES COVERED 00-00-2012 to 00-00-2012 4. TITLE AND SUBTITLE Waste to Energy Potential - A High...and fermentative bacteria break down organic carbon to VFAs Acetogens break down VFAs to CH3CO2 − and H2 + Acetoclastic methanogens break...s -999999 999999 7 481 su -999999 999999 0 .. -999999 999999 HCA8 pti Flo$&-tdgc Tan.\\ feed su -999999 999999 0 .. -999999 999999 A-l>o -999999

  19. Fibrinogen as a risk factor for premature myocardial infarction in Iranian patients: A case control study

    Directory of Open Access Journals (Sweden)

    Mohammad Shojaie

    2009-08-01

    Full Text Available Mohammad Shojaie, Morteza Pourahmad, Ahad Eshraghian, Hamid Reza Izadi, Farzan NaghshvarPeymanieh Hospital, Internal Medicine Department, Jahrom University of Medical Sciences, Jahrom, Fars, IranBackground: Premature myocardial infarction with life-threatening complications may become epidemic in some Asian and African countries and especially Iran. Fibrinogen is considered as one of the probable risk factors of myocardial infarction. The aim of our study was to assess fibrinogen levels as an etiology of premature myocardial infarction in young Iranian men.Findings: A case-control study was conducted between May 2005 and May 2007 to investigate the association between serum total fibrinogen level and myocardial infarction in men aged younger than 55 years admitted to the cardiac care units of Peymanieh and Motahari Hospitals affiliated to Jahrom University of Medical Sciences, Iran. The mean age of patients was 45.2 ± 4 years in patients with premature myocardial infarction and 47.06 ± 4.5 years in the control group (p = 0.085. There were no statistically significant relationships between the two groups in history of premature myocardial infarction in their first-degree relatives (p = 0.05, cigarette smoking (p = 0.46, diabetes (p = 0.49, or hypertension (p = 1. The mean plasma fibrinogen in patients (354.9 ± 60 mg/dL was elevated markedly compared with the control group (329 ± 73 mg/dL. Hyperfibrinogenemia (>340 mg/dL was detected in 81.8% of patients and 57.5% of controls (95% confidence interval, odds ratio = 3.3; p = 0.036.Conclusion: This study introduced fibrinogen as a risk factor for premature coronary artery disease in Iranian men.Keywords: myocardial infarction, cigarette, hypertension, diabetes, fibrinogen

  20. Comparison of /sup 125/I-fibrinogen kinetics and fibrinopeptide A in patients with disseminated neoplasias

    Energy Technology Data Exchange (ETDEWEB)

    Mombelli, G.; Roux, A.; Haeberli, A.; Straub, P.W.

    1982-08-01

    To provide more information on the pathways of fibrinogen catabolism in generalized cancer, the effect of heparin on fibrinopeptide A (fpA) and on /sup 125/I-fibrinogen kinetics was studied in 15 patients with disseminated neoplasia. Three patients had evidence of venous thrombosis and in 2 additional patients a low fibrinogen level together with increased amounts of FDP/fdp and a positive ethanol test indicated disseminated intravascular coagulation (DIC). The plasma levels of fpA were grossly elevated (4.6--20, mean 11.4 ng/ml, normal values 1.01 +/- 0.45 ng/ml) in patients with thrombosis or DIC, and normal to grossly elevated (0.4--10.4, mean 6.1 ng/ml) in the other patients. Intravenous heparin bolus lowered the fpA level in 11/11 patients, and continuous heparin treatment led to an impressive suppression or complete normalization of the plasma fpA in 5/6 patients. This finding is thought to reflect heparin suppression of thrombin activity on fibrinogen. In some cases, the fpA fall after heparin bolus was slow and/or incomplete, suggesting fpA generation at sites not easily accessible to heparin or insufficient heparin dosage. The /sup 125/I-fibrinogen kinetics were characterized by a significantly shorter half-life (t1/2: 2.5 days), increased catabolic rate constant (j: 0.44 days-1), and increased absolute turnover (68.9 mg fibrinogen/kg/day) as compared to 4 normal subjects (t1/2: 4.2 days; j: 0.26 days-1; turnover 21.7 mg fibrinogen/kg/day). As estimated from the fpA generation rates, intravascular thrombin action on fibrinogen contributed only in minor part to increase the turnover of /sup 125/I-fibrinogen. In particular, the turnover was greatly accelerated in heparin-treated patients despite impressive suppression or normalization of the fpA levels in 5/6 cases.

  1. Elemental concentrations in Triticale straw, a potential bioenergy feedstock

    Science.gov (United States)

    Triticale (X Triticosecale Wittmack) is produced on more than three million ha world wide including 344,000 ha in the USA. Straw resulting from triticale production could provide feedstock for bioenergy production in many regions of the world, but high concentrations of certain elements, including s...

  2. Fibrinogen Seoul (FGG Ala341Asp): a novel mutation associated with hypodysfibrinogenemia.

    Science.gov (United States)

    Song, Kyung Soon; Park, Noh Jin; Choi, Jong Rak; Doh, Hyun Joo; Chung, Kwang Hoe

    2006-07-01

    Dysfibrinogenemia is a coagulation disorder caused by a variety of structural abnormalities in the fibrinogen molecule that result in fibrinogen function. The molecular basis of hypodysfibrinogenemia was investigated in a 66-year-old woman with peripheral artery obstructive disease and in her family members. Plasma level of functional fibrinogen determined using the Clauss method was lower (75 mg/dL; normal, 140-460 mg/dL) than that measured with immunologic nephelometric assay (137 mg/dL; normal, 180-400 mg/dL). Similar results were also observed in two family members through two generations. DNA was extracted from whole blood, and the coding regions and intron/exon boundaries of gamma chain gene (FGG) were amplified. A novel (Fibrinogen Seoul) heterozygous FGG mutation (GCT->GAT, Ala341Asp) was identified in all three affected family members. Thrombin-catalyzed polymerization was found to be defective on the analysis of purified fibinogen from the propositus. Molecular modeling also showed a conformational change of fibrinogen structure.

  3. Effect of moderate alcohol consumption on fibrinogen levels in healthy volunteers is discordant with effects on C-reactive protein

    NARCIS (Netherlands)

    Sierksma, A.; Gaag, M.S. van der; Kluft, C.; Hendriks, H.F.J.

    2001-01-01

    In a diet-controlled, crossover trial with 10 middle-aged men and 9 postmenopausal women, baseline concentrations of fibrinogen influenced the magnitude of decrease of fibrinogen after moderate alcohol consumption. The mechanism of reduction is specific for fibrinogen and unrelated to a reduction in

  4. Evaluation of photo-crosslinked fibrinogen as a rapid and strong tissue adhesive.

    Science.gov (United States)

    Elvin, C M; Danon, S J; Brownlee, A G; White, J F; Hickey, M; Liyou, N E; Edwards, G A; Ramshaw, J A M; Werkmeister, J A

    2010-05-01

    Tissue adhesives and sealants are commonly used in surgery either as an adjunct to, or replacement for, sutures. Previously, we have shown that fibrinogen can be crosslinked rapidly to give a high-strength bond in the presence of a ruthenium(II) complex, a persulfate and irradiation with visible light, and that the crosslinked fibrinogen is nontoxic to cells in vitro. This approach addresses limitations to current fibrin sealants that typically have relatively slow curing times and low bond strengths. In the present study, we have evaluated the efficacy and safety of this new biological scaffold sealant in various animal models. When placed as solid implants into rats, the crosslinked fibrinogen persisted for at least 8 weeks but was fully resorbed by 18 weeks with minimal inflammatory responses. When used as a tissue adhesive for repair of skin incisions in rats or as an arterial haemostat in pig, the photo-crosslinked fibrinogen sealed tissue or arrested bleeding within 20 s of application. For the skin incisions, the fibrinogen sealant promoted rapid tissue vascularization and cellular infiltration with no adverse foreign body cell generation. New collagen deposition occurred and with time the matrix had remodelled to acquire large mature collagen fiber bundles which were accompanied by maximum regenerated tensile strength. This biomaterial system may find useful applications in surgical procedures where rapid curing and/or high strength tissue sealing is required.

  5. Electrochemical behavior of Ti-Ni shape memory alloy in fibrinogen solution

    Institute of Scientific and Technical Information of China (English)

    梁成浩; 郭海霞; 陈邦义

    2004-01-01

    Electrochemical behaviors of Ti-Ni shape memory alloy in fibrinogen solution were studied by electrochemical techniques. The results indicate that the addition of the fibrinogen has no obvious effect on the corrosion potential, but decreases the pitting potential markedly and increases the passive current densities. The analysis of energy-dispersive X-ray for samples adsorbing fibrinogen exhibits that the elements of O, C and N exist on the surface of Ti-Ni alloy. Furthermore, the scanning electron microscope micrographs confirm that the configuration of the adsorbing fibrinogen concentrating on surface defects is like cluster and the fibrinogen adsorption concentration is 96.67 mg/m2 through ultroviolet ray absorption method. Fibrinogen combined with Ti-Ni alloy surface by complex band and its electrochemical transfer accelerated the corrosion of alloy.

  6. Fibrinogen and FXIII dose response effects on albumin-induced coagulopathy.

    OpenAIRE

    Hanna, Jennifer; Winstedt, Dag; Schött, Ulf

    2013-01-01

    Objectives. Natural colloid albumin induces a lesser degree of dilutional coagulopathy than synthetic colloids. Fibrinogen concentrate has emerged as a promising strategy to treat coagulopathy, and factor XIII (FXIII) works synergistically with fibrinogen to correct coagulopathy following haemodilution with crystalloids. Our objectives were to examine the ability of fibrinogen and FXIII concentrates to reverse albumin-induced dilutional coagulopathy. Methods. High and low concentrations of bo...

  7. Role of Fibrinogen in Trauma Induced Coagulopathy

    Science.gov (United States)

    2010-01-01

    von Willebrand factor have also been reported. Hydroxyethyl starch (HES) solutions may increase haemor- rhagic tendency, particularly solutions with a...coagulation include impaired enzyme activity, depleted fibrinogen levels and platelet counts, prolonged clotting time, and increased bleeding time.16...decreased fibrinogen syn- thesis, with no effects on fibrinogen degradation (Fig. 1). Fibrinogen synthesis and degradation are regulated via different

  8. Congenital fibrinogen deficiency

    Science.gov (United States)

    ... brain (very rare) Bleeding in the joints Heavy bleeding after injury or surgery Nosebleeds that do not stop easily People with a reduced level of fibrinogen bleed less often and the bleeding is not as severe. Those with a problem ...

  9. Homocysteine, fibrinogen, and lipoprotein(a) levels are simultaneously reduced in patients with chronic renal failure treated with folic acid, pyridoxine, and cyanocobalamin.

    Science.gov (United States)

    Naruszewicz, M; Klinke, M; Dziewanowski, K; Staniewicz, A; Bukowska, H

    2001-02-01

    Ischemic heart disease and other complications of atherosclerosis are the usual cause of death in patients with chronic renal failure. Important factors associated with early onset of atherosclerosis in these patients are hyperhomocysteinemia, hyperfibrinogenemia, and elevated levels of lipoprotein(a) (Lp(a)). Folic acid (15 mg/d), pyridoxine (150 mg/d), and cyanocobalamin (1 mg/wk) were administered for 4 weeks in 21 patients receiving dialysis, and a simultaneous, statistically significant reduction in the concentration of homocysteine, fibrinogen, and Lp(a) was found. A positive correlation between decreasing homocysteine and fibrinogen levels was also noted. The parameters studied approached presupplementation values 6 months after vitamins were discontinued. The results suggest that vitamin supplementation has a favorable effect on risk factors of atherosclerosis in patients with renal failure and that interactions may exist between homocysteine, fibrinogen, and Lp(a).

  10. Fibrinogen salvage during DF Thermo using Evaflux-5A plasma fractionators.

    Science.gov (United States)

    Nakashima, Momoko; Yasui, Masahide; Ihara, Akira

    2012-10-01

    DF Thermo, a modified form of double-filtration plasmapheresis (DFPP), has been used for the treatment of various indications such as arteriosclerosis obliterans (ASO). In case of ASO, fibrinogen is a substance to be removed by DFPP. On the other hand, plasmapheresis for chronic viral hepatitis C became an insurance covered treatment in Japan in April 2008. Since then DFPP has also become a treatment of chronic viral hepatitis C as an adjunctive therapy for the purpose of improving the effect of medication. Therefore, there has been a growing concern in recent years about patients' low fibrinogen levels due to DFPP treatment. With the aim of improving fibrinogen retention by DF Thermo, we examined by in vitro trial, the effects when recirculating the filtrate and elevating its temperature. The trial was conducted using bovine plasma, run through experimental circuits with the same configuration as the clinical setting of the One-Way method and DF Thermo method. The DF Thermo circuit contained a thermostat, on which the temperature was set to 40°C. Two One-Way method circuits were prepared with different temperature settings, i.e., 20°C and 40°C. With these three different conditions, variance of the fibrinogen retention under different temperatures and the implementation of recirculation were compared. Results show that the DF Thermo circuit tends to have enhanced the fibrinogen retention compared to the One-Way method 20°C and 40°C. The explanation is likely as follows: viscosity of plasma reduces when warmed, which in turn helps maintain the permeability of membrane, and the recirculation of the plasma helps prevent membrane fouling, thus more fibrinogen is retained in the DF Thermo method.

  11. High-performance scaffolds on titanium surfaces: osteoblast differentiation and mineralization promoted by a globular fibrinogen layer through cell-autonomous BMP signaling.

    Science.gov (United States)

    Horasawa, Noriko; Yamashita, Teruhito; Uehara, Shunsuke; Udagawa, Nobuyuki

    2015-01-01

    Titanium has been widely used as a dental implant material. However, it takes several months for the implant body to bind with the jawbone. To develop new bioactive modification on titanium surfaces to achieve full osseointegration expeditiously, we used fibrinogen and fibronectin as bioactive scaffolds on the titanium plate, which are common extracellular matrix (ECM) proteins. We analyzed the features of the surface of ECM-modified titanium plates by atomic force microscopy and Fourier transform infrared spectrophotometry. We also evaluated the effect of ECM modification on promoting the differentiation and mineralization of osteoblasts on these surfaces. Fibrinogen had excellent adsorption on titanium surfaces even at low concentrations, due to the binding ability of fibrinogen via its RGD motif. The surface was composed of a fibrinogen monolayer, in which the ratio of β-sheets was decreased. Osteoblast proliferation on ECM-modified titanium surface was significantly promoted compared with titanium alone. Calcification on the modified surface was also accelerated. These ECM-promoting effects correlated with increased expression of bone morphogenetic proteins (BMPs) by the osteoblasts themselves and were inhibited by Noggin, a BMP inhibitor. These results suggest that the fibrinogen monolayer-modified titanium surface is recognized as bioactive scaffolds and promotes bone formation, resulting in the acceleration of osseointegration.

  12. A Meta-analysis of β-fibrinogen Gene-455G/A Polymorphism and Plasma Fibrinogen Level in Chinese Cerebral Infarction Patients

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    To evaluate the correlation between the β-fibrinogen gene-455G/A polymorphism and cerebral infarction in Chinese population by means of meta-analysis. Methods Genetic association studies on evaluating the β-fibrinogen gene -455G/A polymorphism and cerebral infarction involving Chinese population published before December 2005 were collected from database of PubMed, EMBASE, and CNKI. All the data in literature were abstracted based on the defined selection criteria by two independent investigators. Publication bias was tested by funnel plot and the odd ratios of all studies were combined dependent on the result of heterogeneity test among the individual studies. The software Review Manager (Version 4.2) was used for meta-analysis. Results Eleven studies including 1405 patients and 1600 controls met the selection criteria.There was no publication bias in 11 reviewed studies. Heterogeneity test of reviewed studies showed statistically significant differences (x2=24.58, P=0.006) among the ORs of individual studies. The combined OR of 11 studies of susceptibility to cerebral infarction in -455A allele carriers compared with the -455G/G wild homozygotes was 1.33 (95%CI 1.04-1.71, P=0.02).In the patients with cerebral infarction in 6 studies, the summarized average plasma fibrinogen level of allele A carrier was 0.29g/L (95%CI 0.14-0.44, P=0.0002) higher than that of -455G/G homozygous ones. Conclusions β-fibrinogen gene -455G/A polymorphism might contribute to susceptibility of cerebral infarction in Chinese population; allele A increases the individual susceptibility to the disease.

  13. Indications and Risks of Fibrinogen in Surgery and Trauma.

    Science.gov (United States)

    Spahn, Donat R; Spahn, Gabriela H; Stein, Philipp

    2016-03-01

    Fibrinogen has a central role in coagulation. Following trauma and perioperatively, low fibrinogen levels have been found to be risk factors for exaggerated bleeding, transfusion needs, and adverse outcome. Conversely, treatment with exogenous fibrinogen in critically bleeding patients with low fibrinogen levels has been shown to decrease transfusion needs. Because following trauma and in many perioperative situations fibrinogen is the first coagulation "element" to become critically low, it appears reasonable to target fibrinogen in clinical coagulation algorithms aiming at early specific and goal-directed treatment. A low fibrinogen can be a low plasma concentration or a low functional fibrinogen as assessed by point-of-care techniques such as thromboelastography (TEG) or thromboelastometry (ROTEM). This review summarizes the evidence base for perioperative algorithm-based fibrinogen administration, including the exact thresholds for fibrinogen administration used in the different algorithms. Algorithm-based individualized goal-directed use of fibrinogen resulted in highly significant reduction in transfusion needs, adverse outcomes, in certain studies even mortality, and where investigated reduced costs, with high safety levels at the same time. Best evidence exists in cardiac surgery, followed by trauma, postpartum hemorrhage, and liver transplantation. The introduction of these concepts is highly demanding and requires a tremendous educational effort to familiarize all health care workers with the necessary knowledge and the skills of how to run TEG/ROTEM tests. Future research is needed to compare the efficacy, safety, and costs of different algorithms. This, however, should not prevent us from introducing these expedient point-of-care-based algorithms clinically today.

  14. Silver nanoparticle labeled immunoresonance scattering spectral assay for trace fibrinogen

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Silver nanoparticles in size of 8.0 nm was prepared by the trisodium citrate and used to label goat anti-human fibrinogen. In the pH 5.8 Na2HPO4-NaH2O4 buffer solution (PBS) and in the presence of polyethylene glycol (PEG) and KCl, the immune reaction between silver-labeled goat anti-human fibrinogen and fibrinogen took place and led the resonance scattering intensity at 465 nm (I465) to decreasing. The I465 decreased intensity was linear to the fibrinogen concentration in the range from 0.067 to 1.67 μg/mL, with a detection limit of 0.024 μg/mL. This method was applied to determination of fibrinogen in human plasma, with satisfactory results.

  15. Silver nanoparticle labeled immunoresonance scattering spectral assay for trace fibrinogen

    Institute of Scientific and Technical Information of China (English)

    JIANG ZhiLiang; CHEN YuanYuan; LIANG AiHui; TAO HuiLin; TANG NingLi; ZHONG FuXin

    2007-01-01

    Silver nanoparticles in size of 8.0 nm was prepared by the trisodium citrate and used to label goat anti-human fibrinogen. In the pH 5.8 Na2HPO4-NaH2O4 buffer solution (PBS) and in the presence of polyethylene glycol (PEG) and KCI, the immune reaction between silver-labeled goat anti-human fibrinogen and fibrinogen took place and led the resonance scattering intensity at 465 nm (I465) to decreasing. The I465 decreased intensity was linear to the fibrinogen concentration in the range from 0.067to 1.67 μg/mL, with a detection limit of 0.024 μg/mL. This method was applied to determination of fibrinogen in human plasma, with satisfactory results.

  16. 455G/A polymorphism of the beta-fibrinogen gene is associated with the progression of coronary atherosclerosis in symptomatic men: Proposed role for an acute-phase reaction pattern of fibrinogen

    NARCIS (Netherlands)

    Maat, M.P.M. de; Kastelein, J.J.P.; Jukema, J.W.; Zwinderman, A.H.; Jansen, H.; Groenemeier, B.; Bruschke, A.V.G.; Kluft, C.

    1998-01-01

    Increased plasma fibrinogen levels have been identified as a risk indicator for myocardial infarction, stroke, and thrombosis. Both environmental and genetic factors make an important contribution to plasma fibrinogen levels in humans. In the present study we evaluated, in patients with serum choles

  17. Hepatic fibrinogen storage disease due to the fibrinogen γ375 Arg → Trp mutation "fibrinogen aguadilla" is present in Arabs

    Directory of Open Access Journals (Sweden)

    Abdulrahman Al-Hussaini

    2014-01-01

    Full Text Available The mutation γ375Arg → Trp (fibrinogen Aguadilla is one of four mutations (Brescia, Aguadilla, Angers, and AI duPont capable of causing hepatic storage of fibrinogen. It has been observed in four children from the Caribbean, Europe, and Japan, suffering from cryptogenic liver disease. We report the first case of hepatic fibrinogen storage disease in Arabs due to a mutation in the fibrinogen γ-chain gene in a 3-year-old Syrian girl presenting with elevated liver enzymes. The finding of an impressive accumulation of fibrinogen in liver cells raised the suspicion of endoplasmic reticulum storage disease. Sequencing of the fibrinogen genes revealed a γ375Arg → Trp mutation (fibrinogen Aguadilla in the child and in her father. In conclusion, when confronted with chronic hepatitis of unknown origin, one should check the plasma fibrinogen level and look carefully for the presence of hepatocellular intracytoplasmic globular inclusions to exclude hepatic fibrinogen storage disease.

  18. B:b interactions are essential for polymerization of variant fibrinogens with impaired holes 'a'.

    Science.gov (United States)

    Okumura, N; Terasawa, F; Haneishi, A; Fujihara, N; Hirota-Kawadobora, M; Yamauchi, K; Ota, H; Lord, S T

    2007-12-01

    Fibrin polymerization is mediated by interactions between knobs 'A' and 'B' exposed by thrombin cleavage, and holes 'a' and 'b' always present in fibrinogen. The role of A:a interactions is well established, but the roles of knob:hole interactions A:b, B:b or B:a remain ambiguous. To determine whether A:b or B:b interactions have a role in thrombin-catalyzed polymerization, we examined a series of fibrinogen variants with substitutions altering holes 'a': gamma364Ala, gamma364His or gamma364Val. We examined thrombin- and reptilase-catalyzed fibrinopeptide release by high-performance liquid chromatography, fibrin clot formation by turbidity, fibrin clot structure by scanning electron microscopy (SEM) and factor (F) XIIIa-catalyzed crosslinking by sodium dodecylsulfate polyacrylamide gel electrophoresis. Thrombin-catalyzed fibrinopeptide A release was normal, but fibrinopeptide B release was delayed for all variants. The variant fibrinogens all showed markedly impaired thrombin-catalyzed polymerization; polymerization of gamma364Val and gamma364His were more delayed than gamma364Ala. There was absolutely no polymerization of any variant with reptilase, which exposed only knobs 'A'. SEM showed that the variant clots formed after 24 h had uniform, ordered fibers that were thicker than normal. Polymerization of the variant fibrinogens was inhibited dose-dependently by the addition of either Gly-Pro-Arg-Pro (GPRP) or Gly-His-Arg-Pro (GHRP), peptides that specifically block holes 'a' and 'b', respectively. FXIIIa-catalyzed crosslinking between gamma-chains was markedly delayed for all the variants. These results demonstrate that B:b interactions are critical for polymerization of variant fibrinogens with impaired holes 'a'. Based on these data, we propose a model wherein B:b interactions participate in protofibril formation.

  19. Fibrinogen γ′ in ischemic stroke: A case-control study

    NARCIS (Netherlands)

    E.Y.L. Cheung (Elim); S.U. de Willige; H.L. Vos (Hans); F.W.G. Leebeek (Frank); D.W.J. Dippel (Diederik); R.M. Bertina (Rogier); M.P.M. de Maat (Moniek)

    2008-01-01

    textabstractBACKGROUND AND PURPOSE - To determine the contribution of fibrinogen γ′ levels and FGG haplotypes to ischemic stroke. METHODS - Associations between fibrinogen γ′ levels, fibrinogen γ′/total fibrinogen ratio, and FGG haplotypes with the risk of ischemic stroke were determined in 124 case

  20. Fibrinogen labelling with I-131

    Energy Technology Data Exchange (ETDEWEB)

    Seminario, C.; Capillo, T.; Montanez, J. (Instituto Peruano de Energia Nuclear, Lima)

    1983-05-01

    Of the different techniques of labelling liophylized human fibrinogen, the technique of mono-chloride with modified iodine was selected. The labelling of the molecule was performed in alkali media of buffalo glycine in which the solution of stable iodine will react as well as on a later stage will the radioactive isotope. The labelling processes which were undertaken with different activities had an efficiency of over 40%; when purification with resins amberlite was carried through, in none of the cases were the impurities over 5%. Daily controls till the seventh day showed that the average values of radiochemical purity decrease were lower than 1%. The specific activity as well as the concentration of I/sup 131/, the fibrinogen and other characteristics come up to the norms of the pharmacopoeia which are applied.

  1. Preoperative Plasma Fibrinogen Level as a Significant Prognostic Factor in Patients With Localized Renal Cell Carcinoma After Surgical Treatment.

    Science.gov (United States)

    Lee, Hakmin; Lee, Sang Eun; Byun, Seok-Soo; Kim, Hyeon Hoe; Kwak, Cheol; Hong, Sung Kyu

    2016-01-01

    We sought to investigate the association of preoperative fibrinogen levels with clinicopathologic outcomes after surgical treatment of nonmetastatic renal cell carcinoma. We reviewed the records of 1511 patients who had their fibrinogen levels measured preceding surgery. The associations between preoperative fibrinogen level and risk of adverse clinicopathologic outcomes were tested using the multivariate logistic regression and multiple Cox-proportional hazards model, respectively. Based on plasma fibrinogen levels, we stratified the patients into 2 groups with a cut-off value of 328  mg/dL. Kaplan-Meier analysis showed significantly inferior survival outcomes in progression-free (P fibrinogen level (≥328  mg/dL) was significantly related to a higher Fuhrman grade (hazard ratio [HR] 1.374, P = 0.006) and a larger tumor size (≥7  cm) (HR 2.364, P fibrinogen level is a significant predictor for poor disease progression (HR 1.857, P fibrinogen levels were significantly associated with poor pathological features and worse survival outcomes in patients with nonmetastatic renal cell carcinoma after surgical treatment. Further evaluations such as prospective randomized trials are needed to understand the underlying mechanism for these associations.

  2. Fibrinogen nitrotyrosination after ischemic stroke impairs thrombolysis and promotes neuronal death.

    Science.gov (United States)

    Ill-Raga, Gerard; Palomer, Ernest; Ramos-Fernández, Eva; Guix, Francesc X; Bosch-Morató, Mònica; Guivernau, Biuse; Tajes, Marta; Valls-Comamala, Victòria; Jiménez-Conde, Jordi; Ois, Angel; Pérez-Asensio, Fernando; Reyes-Navarro, Mario; Caballo, Carolina; Gil-Gómez, Gabriel; Lopez-Vilchez, Irene; Galan, Ana M; Alameda, Francesc; Escolar, Gines; Opazo, Carlos; Planas, Anna M; Roquer, Jaume; Valverde, Miguel A; Muñoz, Francisco J

    2015-03-01

    Ischemic stroke is an acute vascular event that compromises neuronal viability, and identification of the pathophysiological mechanisms is critical for its correct management. Ischemia produces increased nitric oxide synthesis to recover blood flow but also induces a free radical burst. Nitric oxide and superoxide anion react to generate peroxynitrite that nitrates tyrosines. We found that fibrinogen nitrotyrosination was detected in plasma after the initiation of ischemic stroke in human patients. Electron microscopy and protein intrinsic fluorescence showed that in vitro nitrotyrosination of fibrinogen affected its structure. Thromboelastography showed that initially fibrinogen nitrotyrosination retarded clot formation but later made the clot more resistant to fibrinolysis. This result was independent of any effect on thrombin production. Immunofluorescence analysis of affected human brain areas also showed that both fibrinogen and nitrotyrosinated fibrinogen spread into the brain parenchyma after ischemic stroke. Therefore, we assayed the toxicity of fibrinogen and nitrotyrosinated fibrinogen in a human neuroblastoma cell line. For that purpose we measured the activity of caspase-3, a key enzyme in the apoptotic pathway, and cell survival. We found that nitrotyrosinated fibrinogen induced higher activation of caspase 3. Accordingly, cell survival assays showed a more neurotoxic effect of nitrotyrosinated fibrinogen at all concentrations tested. In summary, nitrotyrosinated fibrinogen would be of pathophysiological interest in ischemic stroke due to both its impact on hemostasis - it impairs thrombolysis, the main target in stroke treatments - and its neurotoxicity that would contribute to the death of the brain tissue surrounding the infarcted area.

  3. Fibrinogen is not a prognostic factor for response to HELP-apheresis in sudden sensorineural hearing loss (SSHL).

    Science.gov (United States)

    Berger, T; Kaiser, T; Scholz, M; Bachmann, A; Ceglarek, U; Hesse, G; Hagemeyer, B; Stumvoll, M; Thiery, J; Dietz, A

    2015-12-01

    Higher levels of fibrinogen or cholesterol were associated with improved hearing recovery in SSHL patients after treatment with HELP-apheresis (Heparin-induced extracorporeal LDL precipitation apheresis). The present trial was performed to demonstrate HELP-related effects on relevant metabolic and inflammatory parameters in the context of SSHL treatment. In the framework of a single arm non-controlled trial, we investigated the variation of metabolic and inflammatory parameters using HELP-apheresis for a defined group of 100 patients with SSHL. Based on cut off inclusion criteria (Serum LDL-cholesterol >1.6 g/l and/or fibrinogen >2.0 g/l, SSHL in minimum three frequencies more than 30 dB, time after event not longer than 6 days), the protocol followed a strict time line with one single shot HELP-apheresis and follow-up monitoring including laboratory parameters at six defined time points. If HELP-apheresis could not effect improvement of hearing on day 5, additional corticosteroid treatment was applied. Concentration of anti-inflammatory IL-10 increased while other proinflammatory parameters declined. Serum levels of all measured sterols and apolipoproteins decreased significantly. None of the investigated parameters were suitable to predict hearing improvement of the patients. Levels of fibrinogen and LDL-cholesterol were not prognostic for outcome after HELP-apheresis. A significant (p apheresis was notable, while most of the proinflammatory parameters declined. Despite the limited validity of a single arm non-controlled trial, these alterations on immune modulating factors indicate possible secondary pleiotropic effects caused by HELP-apheresis.

  4. Prognostic Impact of Pretreatment Plasma Fibrinogen in Patients with Locally Advanced Oral and Oropharyngeal Cancer.

    Directory of Open Access Journals (Sweden)

    Daniel Holzinger

    Full Text Available We aimed to determine the prognostic significance of pretreatment plasma fibrinigen in patients with oral and oropharyngeal squamous cell carcinoma (OOSCC.A cohort of 183 patients with locally advanced OOSCC receiving preoperative chemoradiotherapy was retrospectively examined. Using ROC curve analysis, a pretreatment plasma fibrinogen cutoff value of 447mg/dL was determined. The primary endpoints were overall survival and recurrence-free survival. A secondary endpoint was to determine whether pretreatment plasma fibrinogen could predict treatment response to neoadjuvant chemoradiotherapy. Cox regression models and Kaplan-Meier curves were used for survival analyses.Seventy-one patients had an elevated pretreatment plasma fibrinogen (fibrinogen >447mg/dL. Patients with high fibrinogen showed significantly higher pathologic stages after neoadjuvant treatment than those with low fibrinogen (p = 0.037. In univariate analysis, elevated fibrinogen was associated with poor overall survival (p = 0.005 and recurrence-free survival (p = 0.008 Multivariate analysis revealed that elevated fibrinogen remained an independent risk factor for death (hazard ratio 1.78, 95% CI 1.09-2.90, p = 0.021 and relapse (hazard ratio 1.78, 95% CI 1.11-2.86, p = 0.016.Elevated pretreatment plasma fibrinogen is associated with lack of response to neoadjuvant chemoradiotherapy and reduced OS and RFS in patients with OOSCC. Thus, plasma fibrinogen may emerge as a novel prognostic indicator and a potential therapeutic target in OOSCC.

  5. A fibrinogen-binding lipoprotein contributes to the virulence of Haemophilus ducreyi in humans.

    Science.gov (United States)

    Bauer, Margaret E; Townsend, Carisa A; Doster, Ryan S; Fortney, Kate R; Zwickl, Beth W; Katz, Barry P; Spinola, Stanley M; Janowicz, Diane M

    2009-03-01

    A gene expression study of Haemophilus ducreyi identified the hypothetical lipoprotein HD0192, renamed here "fibrinogen binder A" (FgbA), as being preferentially expressed in vivo. To test the role played by fgbA in virulence, an isogenic fgbA mutant (35000HPfgbA) was constructed using H. ducreyi 35000HP, and 6 volunteers were experimentally infected with 35000HP or 35000HPfgbA. The overall pustule-formation rate was 61.1% at parent sites and 22.2% at mutant sites (P = .019). Papules were significantly smaller at mutant sites than at parent sites (13.3 vs. 37.9 mm(2); P = .002) 24 h after inoculation. Thus, fgbA contributed significantly to the virulence of H. ducreyi in humans. In vitro experiments demonstrated that fgbA encodes a fibrinogen-binding protein; no other fibrinogen-binding proteins were identified in 35000HP. fgbA was conserved among clinical isolates of both class I and II H. ducreyi strains, supporting the finding that fgbA is important for H. ducreyi infection.

  6. Biochemistry and measurement of fibrinogen

    NARCIS (Netherlands)

    Nieuwenhuizen, W.

    1995-01-01

    Fibrinogen is a large heterogeneous family of closely related molecules consisting of three pairs of non-identical polypeptide chains: two Aα-, two Bβ- and two γ-chains, held together by disulphide bridges. The heterogeneity of fibrinogen is due to heterogeneities in all three chains. Four main

  7. Biochemistry and measurement of fibrinogen

    NARCIS (Netherlands)

    Nieuwenhuizen, W.

    1995-01-01

    Fibrinogen is a large heterogeneous family of closely related molecules consisting of three pairs of non-identical polypeptide chains: two Aα-, two Bβ- and two γ-chains, held together by disulphide bridges. The heterogeneity of fibrinogen is due to heterogeneities in all three chains. Four main type

  8. Antibody functionalized graphene biosensor for label-free electrochemical immunosensing of fibrinogen, an indicator of trauma induced coagulopathy.

    Science.gov (United States)

    Saleem, Waqas; Salinas, Carlos; Watkins, Brian; Garvey, Gavin; Sharma, Anjal C; Ghosh, Ritwik

    2016-12-15

    An antibody, specific to fibrinogen, has been covalently attached to graphene and deposited onto screen printed electrodes using a chitosan hydrogel binder to prepare an inexpensive electrochemical fibrinogen biosensor. Fourier Transform Infrared (FT-IR) spectroscopy has been utilized to confirm the presence of the antibody on the graphene scaffold. Electrochemical Impedance Spectroscopy (EIS) has been utilized to demonstrate that the biosensor responds in a selective manner to fibrinogen in aqueous media even in the presence of plasminogen, a potentially interfering molecule in the coagulopathy cascade. Furthermore, the biosensor was shown to reliably sense fibrinogen in the presence of high background serum albumin levels. Finally, we demonstrated detection of clinically relevant fibrinogen concentrations (938-44,542μg/dL) from human serum and human whole blood samples using this biosensor. This biosensor can potentially be used in a point-of-care device to detect the onset of coagulopathy and monitor response following therapeutic intervention in trauma patients. Thus this biosensor may improve the clinical management of patients with trauma-induced coagulopathy.

  9. ON THE CONCENTRATION PROPERTIES FOR THE NONLINEAR SCHR(O)DINGER EQUATION WITH A STARK POTENTIAL

    Institute of Scientific and Technical Information of China (English)

    Zhu Shihui; Zhang Jian

    2011-01-01

    In this paper,we study blow-up solutions of the Cauchy problem to the L2 critical nonlinear Schr(o)dinger equation with a Stark potential.Using the variational characterization of the ground state for nonlinear Schr(o)dinger equation without any potential,we obtain some concentration properties of blow-up solutions,including that the origin is the blow-up point of the radial blow-up solutions,the phenomenon of L2-concentration and rate of L2-concentration of blow-up solutions.

  10. Contribution to the study of plasmatic fibrinogen and serum albumin: effects of irradiation; Contribution a l'etude du fibrinogene et de la serum-albumine plasmatiques - effets de l'irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Suscillon, M. [Commissariat a l' Energie Atomique, Centre d' Etudes Nucleaires de Grenoble, 38 (France)

    1967-07-01

    The author studies the modifications of properties and structure of serum albumin and fibrinogen solution when subjected to radiation of low energy (X rays). On the other hand, two original techniques are exposed: 1. Amperometric determination of fibrin stabilizing factor or factor XIII of hemostasis. 2. Spectrophotometric study of fibrin formation kinetics. Then showing off and quantitative determination of platelets fibrinogen is exposed. (author) [French] L'auteur etudie les modifications des proprietes et de la structure des molecules de serum-albumine et de fibrinogene en solution soumise a un flux de RX de basse energie. D'autre part deux techniques originales sont exposees : 1. Dosage amperometrique du facteur stabilisant de la fibrine. 2. Etude spectrophotometrique de la cinetique de la fibro-formation. Enfin une mise en evidence et un dosage du fibrinogene plaquettaire sont presentes. (auteur)

  11. The estimation of fibrinogen levels in animal plasmas by a simple refractometric method. A comparison with a biuret method.

    Science.gov (United States)

    Sutton, R H

    1977-05-01

    A comparison was made between a biuret (reference) method and a simple refractometric (test) method for measuring fibrinogen levels in 84 animal plasmas. Although the correlation between the two methods was high (4=0.90 P less than 0-001) there was considerable random variation in the refractometric results in relation to the biuret results. This was thought to be due in part to the fact that refractometric results could only be expressed in multiples of 2.4 g/litre. In spite of this limitation, the refractometric method, on the grounds of speen and simplicity, is considered to have worthwhile application for fibrinogen determinations in practice laboratory.

  12. Dynamics in serum of the inflammatory markers serum amyloid A (SAA), haptoglobin, fibrinogen and alpha2-globulins during induced noninfectious arthritis in the horse.

    Science.gov (United States)

    Hultén, C; Grönlund, U; Hirvonen, J; Tulamo, R-M; Suominen, M M; Marhaug, G; Forsberg, M

    2002-11-01

    Despite the importance of noninfectious joint diseases in equine medicine, little is known about the acute phase response which may be elicited if the local inflammatory process of noninfectious arthritis is sufficiently strong, Therefore the aim of this study was to monitor the systemic inflammatory response during experimentally-induced noninfectious arthritis by studying the dynamics in serum of the acute phase proteins serum amyloid A (SAA), haptoglobin, fibrinogen and alpha2-globulins. Twenty-four Standardbred horses, age 3-7 years, found healthy on thorough clinical, radiological, haematological and serum biochemical examination, were injected aseptically into the right midcarpal joint with amphotericin B. Blood samples were drawn before induction of arthritis (0 h), and at 8, 16, 24, 36 and 48 h postinduction and then on Days 3, 4, 5 and 15 postinduction. All horses developed lameness with joint effusion and joint heat as well as increased respiratory rate, heart rate and body temperature. The lameness started to decline after 24-36 h and, in most animals, systemic signs disappeared on Day 2 postinjection. The concentration of the acute phase proteins increased following induction of arthritis. The SAA concentrations were higher than baseline concentrations from 16 h postinduction and were maximal at 36-48 h (227 times baseline concentration). The haptoglobin concentrations were higher than baseline concentrations from 24 h and were maximal at 48-96 h (1.14 times baseline concentration). The maximal concentrations of fibrinogen were seen between 36-72 h postinjection and increased on average 0.87 times from baseline concentrations. The fibrinogen concentrations were higher than baseline concentrations from 24 h postinjection. Alpha2-globulins concentrations showed a minor increase and increased 0.55 times from baseline concentrations. The markers had returned to baseline concentrations by Day 15. Our results demonstrate that amphotericin B-induced arthritis

  13. The pretreatment platelet and plasma fibrinogen level correlate with tumor progression and metastasis in patients with pancreatic cancer.

    Science.gov (United States)

    Wang, Haiyan; Gao, Jinbiao; Bai, Ming; Liu, Rui; Li, Hongli; Deng, Ting; Zhou, Likun; Han, Rubing; Ge, Shaohua; Huang, Dingzhi; Ba, Yi

    2014-01-01

    Cancer patients frequently present with activated coagulation pathways and thrombocytosis, which are potentially associated with tumor progression and prognosis. However, the prognostic value of abnormal plasma fibrinogen and platelet levels for the treatment of pancreatic cancer is unclear. The purpose of our study was to evaluate the prognostic value of plasma fibrinogen and platelet levels in pancreatic cancer, and to devise a prognostic model to identify the patients with greatest risk for a poor overall survival. One hundred and twenty-five patients diagnosed with pancreatic ductal adenocarcinoma in our hospital between May 2000 and June 2005 were included in this study. The plasma fibrinogen and platelet levels were examined before treatment and analyzed along with patient clinicopathological parameters and overall survival. The foundation of prognostic model was based on the risk factors according to the Cox proportional hazard model. The incidence of hyperfibrinogenemia and thrombocytosis was 24.8% (31/125) and 15.2% (19/125), respectively. The mean fibrinogen concentration differed significantly between the early (I/II) and late (III/IV) stage patients (3.19 ± 0.70 vs. 3.65 ± 0.90 g/l, p = 0.008). Patients with a higher concentration of plasma fibrinogen and platelets had a worse prognosis (p fibrinogen/platelet levels and distant organ metastasis (p fibrinogen levels correlated significantly with platelet levels (p = 0.000). Multivariate analysis revealed that pretreatment plasma fibrinogen levels (p = 0.027), tumor stage (p = 0.026) and distant metastasis (p = 0.027) were independent prognostic factors. The median survival time for the low-, intermediate-, and high-risk groups was 9.6 months (95% CI 6.2-13.0), 3.8 months (95% CI 2.3-5.3), and 2.3 months (95% CI 0.9-3.7), respectively (p = 0.000). Pretreatment plasma fibrinogen and platelet levels closely correlated with tumor progression, metastasis and overall

  14. Non-peptide fibrinogen receptor antagonists. 2. Optimization of a tyrosine template as a mimic for Arg-Gly-Asp.

    Science.gov (United States)

    Egbertson, M S; Chang, C T; Duggan, M E; Gould, R J; Halczenko, W; Hartman, G D; Laswell, W L; Lynch, J J; Lynch, R J; Manno, P D

    1994-08-05

    Inhibitors of platelet-fibrinogen binding offer an opportunity to interrupt the final, common pathway for platelet aggregation. Small molecule inhibitors of the platelet fibrinogen receptor GPIIb/IIIa were prepared and evaluated for their ability to prevent platelet aggregation. Compound 23m (L-700,462/MK-383) inhibited in vitro platelet aggregation with an IC50 of 9 nM and demonstrated a selectivity of > 24,000-fold between platelet and human umbilical vein endothelial cell fibrinogen receptors. Dose-dependent inhibition of ex vivo platelet aggregation induced by ADP was achieved with i.v. infusions of 0.1-10 micrograms/kg/min of 23m in anesthetized dogs, with 10 micrograms/kg/min completely inhibiting platelet aggregation during the entire 6 h infusion protocol. Platelet aggregatability returned rapidly after the termination of the 23m infusions. These features suggest that 23m may be useful in the treatment of arterial occlusive disorders.

  15. A family of cell-adhering peptides homologous to fibrinogen C-termini

    Energy Technology Data Exchange (ETDEWEB)

    Levy-Beladev, Liron [Institute of Chemistry, Safra Campus, Givat Ram, The Hebrew University of Jerusalem, Jerusalem 91904 (Israel); Levdansky, Lilia; Gaberman, Elena [Lab. of Biotechnology and Radiobiology, Hadassah-Hebrew University Medical Center, P.O. Box 12000, Jerusalem 91120 (Israel); Friedler, Assaf [Institute of Chemistry, Safra Campus, Givat Ram, The Hebrew University of Jerusalem, Jerusalem 91904 (Israel); Gorodetsky, Raphael, E-mail: Rafi@hadassah.org.il [Lab. of Biotechnology and Radiobiology, Hadassah-Hebrew University Medical Center, P.O. Box 12000, Jerusalem 91120 (Israel)

    2010-10-08

    Research highlights: {yields} Cell-adhesive sequences homologous to fibrinogen C-termini exist in other proteins. {yields} The extended homologous cell-adhesive C-termini peptides family is termed Haptides. {yields} In membrane-like environment random coiled Haptides adopt a helical conformation. {yields} Replacing positively charged residues with alanine reduces Haptides activity. -- Abstract: A family of cell-adhesive peptides homologous to sequences on different chains of fibrinogen was investigated. These homologous peptides, termed Haptides, include the peptides C{beta}, preC{gamma}, and C{alpha}E, corresponding to sequences on the C-termini of fibrinogen chains {beta}, {gamma}, and {alpha}E, respectively. Haptides do not affect cell survival and rate of proliferation of the normal cell types tested. The use of new sensitive assays of cell adhesion clearly demonstrated the ability of Haptides, bound to inert matrices, to mediate attachment of different matrix-dependent cell types including normal fibroblasts, endothelial, and smooth muscle cells. Here we present new active Haptides bearing homologous sequences derived from the C-termini of other proteins, such as angiopoietin 1 and 2, tenascins C and X, and microfibril-associated glycoprotein-4. The cell adhesion properties of all the Haptides were found to be associated mainly with their 11 N-terminal residues. Mutated preC{gamma} peptides revealed that positively charged residues account for their attachment effect. These results suggest a mechanism of direct electrostatic interaction of Haptides with the cell membrane. The extended Haptides family may be applied in modulating adhesion of cells to scaffolds for tissue regeneration and for enhancement of nanoparticulate transfection into cells.

  16. Nutrition as a determinant of blood rheology and fibrinogen in athletes.

    Science.gov (United States)

    Gaudard, Aurélie; Varlet-Marie, Emmanuelle; Bressolle, Françoise; Mercier, Jacques; Brun, Jean-Frédéric

    2004-01-01

    Blood rheology is influenced by metabolism and nutrition. We investigated this issue in 41 elite athletes exercising 13+/-0.9 hr/wk (mean age: 23.9+/-0.67 yr; mean VO2max: 52.6+/-2.3 ml/min/kg body weight) with a standardised nutritional questionnaire suitable for sports medicine. Calorie intake (% of recommended intake) was negatively correlated with the RBC disaggregability threshold (r=-0.505, p=0.01). There were negative correlations between fibrinogen and protein intake (% of the total caloric intake r=-0.787, p=0.0008; amount in g/kg/day r=-0.597, p=0.03). Accordingly, the RBC disaggregability threshold was also correlated negatively with protein intake (r=-0.508, p=0.05). Lipid intake (g/kg/day) was negatively correlated with the RBC disaggregability threshold (r=-0.564, p=0.03) and positively to the hematocrit/viscosity ratio (r=0.531, p=0.03). Carbohydrate intake (g/kg/day) was positively correlated with whole blood viscosity (r=0.517, p=0.04) and negatively to the hematocrit/viscosity ratio (r=-0.4863, p=0.05). In addition fibrinogen was negatively correlated with hematocrit (r=-0.4129, p=0.036) and positively with a host of aggregation parameters (pnutritional status in athletes. Low protein intake appears to be associated with (mildly) raised fibrinogen and aggregability, and low calorie intake is associated with lower RBC disaggregability.

  17. A new approach to endocochlear potential and potassium ion concentration measures in mini pig models

    Institute of Scientific and Technical Information of China (English)

    Lili Ren a; Ling Zhang b; Weiwei Guo a; Wei Sun c; Shiming Yang a

    2014-01-01

    Mini pig models are large mammals and their ears are more similar with human beings in structure and development than other animals. However, the study on porcine ears is still in the initial stage and there is no description of an ideal operation approach to endocochlear potential and potassium ion concentration measurements. In this article, we describe a pre-auricular surgical approach to access the middle and inner ear for endocochlear potential and potassium ion concentration measures in mini pig models. Ten one-week old normal mini pigs were used in the study. The bulla of the temporal bone was accessed via a pre-auricular approach for endocochlear potential and potassium ion concentration measurements. The condition of the animals during the first posteexperiment 24 h was observed. One animal died during surgery. The pre-auricular approach improved protection and preservation of relevant nervous and vascular elements including the facial nerve and carotid ar-tery. So, the pre-auricular approach can be used for endocochlear potential and potassium ion concentration measurements with improved nerve and artery preservation mini pigs.

  18. Conformational changes of fibrinogen in dispersed carbon nanotubes

    Directory of Open Access Journals (Sweden)

    Park SJ

    2012-08-01

    Full Text Available Sung Jean Park,1 Dongwoo Khang21College of Pharmacy, Gachon University, Yeonsu-gu, Incheon, South Korea; 2School of Nano and Advanced Materials Science Engineering and Center for PRC and RIGET, Gyeongsang National University, Jinju, South KoreaAbstract: The conformational changes of plasma protein structures in response to carbon nanotubes are critical for determining the nanotoxicity and blood coagulation effects of carbon nanotubes. In this study, we identified that the functional intensity of carboxyl groups on carbon nanotubes, which correspond to the water dispersity or hydrophilicity of carbon nanotubes, can induce conformational changes in the fibrinogen domains. Also, elevation of carbon nanotube density can alter the secondary structures (ie, helices and beta sheets of fibrinogen. Furthermore, fibrinogen that had been in contact with the nanoparticle material demonstrated a different pattern of heat denaturation compared with free fibrinogen as a result of a variation in hydrophilicity and concentration of carbon nanotubes. Considering the importance of interactions between carbon nanotubes and plasma proteins in the drug delivery system, this study elucidated the correlation between nanoscale physiochemical material properties of carbon nanotubes and associated structural changes in fibrinogen.Keywords: carbon nanotubes, fibrinogen, nanotoxicity, conformational change, denaturation

  19. Plasminogen and fibrinogen plasma levels in coronary artery disease

    Science.gov (United States)

    Lima, Luciana Moreira; Carvalho, Maria das Graças; Sousa, Marinez de Oliveira

    2012-01-01

    Objective The formation of thrombi at the site of atherosclerotic lesions plays a central role in atherothrombosis. Impaired fibrinolysis may exacerbate pre-existing coronary artery disease and potentiate its evolution. While the fibrinogen plasma level has been strongly associated with the severity of coronary artery disease, its relevance in the evaluation of plasminogen in coronary artery disease patients remains unclear. This study evaluated fibrinogen and plasminogen levels in subjects with coronary artery disease as diagnosed by angiography. Methods This is a cross-sectional study. Blood samples obtained from 17 subjects with angiographically normal coronary arteries (controls), 12 with mild/moderate atheromatosis and 28 with severe atheromatosis were evaluated. Plasma plasminogen and fibrinogen levels were measured by chromogenic and coagulometric methods, respectively. Results Fibrinogen levels were significantly higher in the severe atheromatosis group compared to the other groups(p-value < 0.0001). A significant positive correlation was observed between the severity of coronary artery diseaseand increasing fibrinogen levels (r = 0.50; p-value < 0.0001) and between fibrinogen and plasminogen levels (r =0.46; p-value < 0.0001). There were no significant differences in the plasminogen levels between groups. Conclusion Plasma fibrinogen, but not plasminogen levels were higher in patients with coronary artery disease compared to angiographically normal subjects. The plasma fibrinogen levels also appear to be associated with the severity of the disease. The results of this study provide no evidence of a significant correlation between plasma plasminogen levels and the progress of coronary stenosis in the study population. PMID:23049444

  20. Urinary fibrinogen and renal tubulointerstitial fibrinogen deposition: Discriminating between primary FSGS and minimal change disease.

    Science.gov (United States)

    Wang, Yu; Zheng, Chunxia; Xu, Feng; Liu, Zhihong

    2016-09-23

    Primary focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) are common types of primary glomerular disease; they share numerous clinical and pathological similarities but have different treatment regimens and prognoses. It is therefore necessary to distinguish between them and to explore the mechanism underlying their differences. Fibrinogen is reportedly involved in podocyte damage and in renal fibrosis in vitro and in animal models of kidney disease. We thus tested urinary fibrinogen, serum fibrinogen, and renal fibrinogen deposition levels in a cohort comprising 50 patients with FSGS and 40 patients with MCD. Our results suggested that urinary fibrinogen and renal interstitial fibrinogen deposition levels were significantly higher in the FSGS patients than in the MCD patients, while serum fibrinogen levels did not differ between the groups. Receiver operating characteristic (ROC) curve analysis showed an excellent diagnostic ability for urinary fibrinogen and a fair diagnostic ability for tubulointerstitial fibrinogen deposition in differentiating FSGS from MCD. Additionally, we found that urinary fibrinogen levels were positively correlated with the 24-h urine protein levels in patients with FSGS but not in patients with MCD. In conclusion, urinary fibrinogen and renal interstitial fibrinogen deposition is elevated in primary FSGS compared to MCD, which may be relevant to both diagnosis and pathogenesis.

  1. Assessment of Diagnostic Efficiency of Lipoprotein (a, Homocysteine, High Sensitive C-Reactive Protein and Fibrinogen in Patients with Coronary Artery Disease

    Directory of Open Access Journals (Sweden)

    Ebru Dundar Yenilmez

    2013-08-01

    Full Text Available Backround: To evaluate the diagnostic value of major and other risk factors as lipoprotein (Lp (a, homocysteine (Hcy, high sensitive C-reactive protein (hs-CRP and fibrinogen in CAD patients. Methods: A total of 223 subjects (118 patients and 105 controls were included in the study according to their coronary angiographic results. Lipoprotein (a, Hcy, hs-CRP and fibrinogen levels were measured using immunoturbidometric, florescent polarization immunoassay and nefelometric methods, respectively. Fasting glucose and lipid parameters, except low density lipoprotein cholesterol (LDL-C, are determined by enzymatic colorimetric methods and the LDL-C levels were calculated by the Fridewald formula. Results: Logistic regression analysis showed that when the biochemical variables in placed in a model, the most important variables were Lp (a, Hcy, hs-CRP and fibrinogen. We showed that each unit of Lp (a, Hcy, hs-CRP and fibrinogen increases the risk of CAD 1.029, 1.177, 1.027 and 1.013 fold, respectively. Among these, fibrinogen level was the most sensitive and efficient parameter in prediction of CAD. Conclusion: Although Lp (a, Hcy, hs-CRP and fibrinogen are independent risk factors for CAD, fibrinogen was the most important one. Fibrinogen can be used as a reliable risk factor for CAD in clinical practice. [Cukurova Med J 2013; 38(4.000: 559-566

  2. Association of novel genetic loci with circulating fibrinogen levels a genome-wide association study in 6 population-based cohorts

    NARCIS (Netherlands)

    A. Dehghan (Abbas); Q. Yang (Qiong Fang); A. Peters (Annette); S. Basu (Saonli); J.C. Bis (Joshua); A.R. Rudnicka (Alicja); M. Kavousi (Maryam); M-H. Chen (Ming-Huei); J. Baumert (Jens); G.D.O. Lowe (Gordon); B. McKnight (Barbara); W. Tang (Weihong); M.P.M. de Maat (Moniek); M.G. Larson (Martin); S. Eyhermendy (Susana); W.L. McArdle (Wendy); T. Lumley (Thomas); J.S. Pankow (James); A. Hofman (Albert); J. Massaro (Joseph); F. Rivadeneira Ramirez (Fernando); M. Kolz (Melanie); K.D. Taylor (Kent); P. Tikka-Kleemola (Päivi); S. Kathiresan (Sekar); T. Illig (Thomas); Y.S. Aulchenko (Yurii); K.A. Volcik (Kelly); A.D. Johnson (Andrew); A.G. Uitterlinden (André); G.H. Tofler (Geoffrey); C. Gieger (Christian); B.M. Psaty (Bruce); D.J. Couper (David); E.A. Boerwinkle (Eric); W. Koenig (Wolfgang); C.J. O'Donnell (Christopher); J.C.M. Witteman (Jacqueline); D.P. Strachan (David); N.L. Smith (Nicholas); A.R. Folsom (Aaron)

    2009-01-01

    textabstractBackground: Fibrinogen is both central to blood coagulation and an acute-phase reactant. We aimed to identify common variants influencing circulation fibrinogen levels. Methods and Results: We conducted a genome-wide association analysis on 6 population-based studies, the Rotterdam Study

  3. Evidence of fibrinogen as a target of citrullination in IgM rheumatoid factor-positive polyarticular juvenile idiopathic arthritis

    Directory of Open Access Journals (Sweden)

    Dehlendorf Amanda B

    2011-03-01

    Full Text Available Abstract Background Several studies have noted the significance of measuring anti-cyclic citrullinated peptide (CCP antibodies in juvenile idiopathic arthritis (JIA as an important indicator for destructive disease, as is the case in rheumatoid arthritis (RA. While the role of anti-CCP antibodies in RA and JIA has become better understood, the identity of the target proteins of this modification has remained elusive. In this study, we evaluated serum from patients with various subtypes of JIA to investigate the presence of anti-deiminated (citrullinated fibrinogen and anti-citrullinated α-enolase antibodies, and their association with RF and anti-CCP antibody isotypes. Methods Sera were obtained from 96 JIA patients, 19 systemic lupus erythematosus (SLE patients, and 10 healthy children. All sera were measured for antibodies against citrullinated and native fibrinogen and α-enolase by an enzyme linked immunosorbent assay (ELISA. In addition, all sera were assayed for anti-CCP antibody isotypes and rheumatoid factor (RF isotypes by ELISA. The relationship between anti-citrullinated fibrinogen and anti-α-enolase antibodies and disease activity and joint damage were also investigated. All results were correlated with clinical and laboratory parameters using Spearman's rho correlation coefficient. Multiple logistic regression analysis was utilized to identify which variables were associated with joint erosions and diagnosis of JIA. Results Thirty-one JIA patients (32% demonstrated reactivity to citrullinated fibrinogen and 9 (9% to citrullinated α-enolase. Reactivity to citrullinated fibrinogen and α-enolase was predominantly found in IgM RF-positive polyarthritis patients. Fourteen JIA patients reacted with native α-enolase and a higher percentage of SLE patients reacted with citrullinated α-enolase when compared to JIA patients. Anti-citrullinated fibrinogen antibodies correlated with the presence of IgG anti-CCP antibodies and IgA and Ig

  4. Potential utilization of algal protein concentrate as a food ingredient in space habitats

    Science.gov (United States)

    Nakhost, Z.; Karel, M.

    1989-01-01

    Green alga Scenedesmus obliquus was studied as one of the potential sources of macronutrients in a space habitat. Algal protein concentrate (70.5% protein) was incorporated into a variety of food products such as bran muffins, fettuccine (spinach noodle imitation) and chocolate chip cookies. Food products containing 20 to 40% of incorporated algal proteins were considered. In the sensory analysis the greenish color of the bran muffins and cookies was not found to be objectional. The mild spinachy flavor (algae flavor) was less detectable in chocolate chip cookies than in bran muffins. The color and taste of the algae noodles were found to be pleasant and compared well with commercially available spinach noodles. Commercially available spray-dried Spirulina algae was also incorporated so the products can be compared with those containing Scenedesmus obliquus concentrate. Food products containing commercial algae had a dark green color and a "burnt after taste" and were less acceptable to the panelists.

  5. Modelisation of leukocyte adhesion on a fibrinogen coated surface in static conditions.

    Science.gov (United States)

    Labrador, V; Legrand, S; Muller, S; Carl, P; Senger, B; Voegel, J C; Latger-Cannard, V; Stoltz, J F

    1999-01-01

    The adhesion of polymorphonuclear leukocytes (PMNs) on the vascular endothelium is a complex process that occurs during biological and pathological events and involves a large family of molecules. This phenomenom could be approached by a modelisation study of the adhesion of PMNs on a biological substrate, fibrinogen. Two different physiological conditions were tested such as the activated state of PMNs with a synthetic pro-inflammatory activator (N-Formyl-Methionyl-Leucyl-Phenylalanine, FMLP). The activated state of PMNs was both quantified by flow cytometry and controlled by fluorescence microscopy. The results suggest that quiescent PMNs deposit in accordance with the ballistic deposition model. The preliminary results obtained with FMLP-stimulated PMNs show a different deposit process compared to quiescent PMNs but do not allow to determine exactly a deposition model.

  6. Quantifying the potential of III-V/Si partial concentrator by a statistical approach

    Science.gov (United States)

    Lee, Kan-Hua; Araki, Kenji; Ota, Yasuyuki; Nishioka, Kensuke; Yamaguchi, Masafumi

    2017-09-01

    We propose a theoretical framework for analyzing the energy yields of partial concentrators. A partial concentrator uses a concentrator cell to absorb the principal defracted or reflected light rays from its concentrator optics and a backplane cell to absorbs the diffused or defocused light. This concept can be applied to the concentrator system when accurate sun-tracking is not available, such as on a vehicle. This analysis framework provides a simplified way to describe the uncertainties of solar incidences dealt by partial concentrator. This help identified a clearer design criteria of partial concentrator in order to outperform the flat-panel PV or conventional CPV.

  7. Fibrinogen adsorption on blocked surface of albumin

    DEFF Research Database (Denmark)

    Holmberg, Maria; Hou, Xiaolin

    2011-01-01

    We have investigated the adsorption of albumin and fibrinogen onto PET (polyethylene terephthalate) and glass surfaces and how pre-adsorption of albumin onto these surfaces can affect the adsorption of later added fibrinogen. For materials and devices being exposed to blood, adsorption...... of fibrinogen is often a non-wanted event, since fibrinogen is part of the clotting cascade and unspecific adsorption of fibrinogen can have an influence on the activation of platelets. Albumin is often used as blocking agent for avoiding unspecific protein adsorption onto surfaces in devices designed to handle...... energies, the adsorption of both albumin and fibrinogen has been monitored simultaneously on the same sample. Information about topography and coverage of adsorbed protein layers has been obtained using AFM (Atomic Force Microscopy) analysis in liquid. Our studies show that albumin adsorbs in a multilayer...

  8. Enhancing Potentially Plant-Available Lead Concentrations in Contaminated Residential Soils Using a Biodegradable Chelating Agent

    Science.gov (United States)

    Andra, S.; Datta, R.; Sarkar, D.; Saminathan, S.

    2007-12-01

    Chelation of heavy metals is an important factor in enhancing metal solubility and, hence, metal availability to plants to promote phytoremediation. In the present study, we compared the effects of application of a biodegradable chelating agent, namely, ethylenediaminedisuccinic acid (EDDS) on enhancing plant available form of lead (Pb) in Pb-based paint contaminated residential soils compared to that of a more commonly used, but non-biodegradable chelate, i.e., ethylenediaminetetraacetic acid (EDTA). Development of a successful phytoremediation model for metals such as Pb depends on a thorough understanding of the physical and chemical properties of the soil, along with the optimization of a chelate treatment to mobilize Pb from `unavailable' pools to potentially plant available fraction. In this context, we set out to perform batch incubation experiments to investigate the effectiveness of the two aforementioned chelates in enhancing plant available Pb at four different concentrations (0, 5, 10 and 15 mM/kg soil) and three treatment durations (0, 10 and 30 days). We selected 12 contaminated residential soils from two major metropolitan areas (San Antonio, TX and Baltimore, MD) with varying soil physico-chemical properties - the soils from San Antonio were primarily alkaline and those from Baltimore were typically acidic. Total soil Pb concentrations ranged between 256 mg/kg and 4,182 mg/kg. Our results show that both chelates increased the solubility of Pb, otherwise occluded in the complex soil matrix. For both EDTA and EDDS, the exchangeable concentrations of soil Pb also increased with increase in chelate concentration and incubation time. The most effective treatment was 15 mM chelate kg-1 soil incubated for 30 days, which caused many fold increase in potentially plant available Pb (a combination of the soluble and exchangeable fractions) relative to the unamended controls. Step wise multiple linear regression analysis using chelate-extractable Pb and soil

  9. Recombinant γT305A fibrinogen indicates severely impaired fibrin polymerization due to the aberrant function of hole 'A' and calcium binding sites.

    Science.gov (United States)

    Ikeda, Minami; Kobayashi, Tamaki; Arai, Shinpei; Mukai, Saki; Takezawa, Yuka; Terasawa, Fumiko; Okumura, Nobuo

    2014-08-01

    We examined a 6-month-old girl with inherited fibrinogen abnormality and no history of bleeding or thrombosis. Routine coagulation screening tests showed a markedly low level of plasma fibrinogen determined by functional measurement and also a low level by antigenic measurement (functional/antigenic ratio=0.295), suggesting hypodysfibrinogenemia. DNA sequence analysis was performed, and γT305A fibrinogen was synthesized in Chinese hamster ovary cells based on the results. We then functionally analyzed and compared with that of nearby recombinant γN308K fibrinogen. DNA sequence analysis revealed a heterozygous γT305A substitution (mature protein residue number). The γT305A fibrinogen indicated markedly impaired thrombin-catalyzed fibrin polymerization both in the presence or absence of 1mM calcium ion compared with that of γN308K fibrinogen. Protection of plasmin degradation in the presence of calcium ion or Gly-Pro-Arg-Pro peptide (analogue for so-called knob 'A') and factor XIIIa-catalyzed fibrinogen crosslinking demonstrated that the calcium binding sites, hole 'a' and D:D interaction sites were all markedly impaired, whereas γN308Kwas impaired at the latter two sites. Molecular modeling demonstrated that γT305 is localized at a shorter distance than γN308 from the high affinity calcium binding site and hole 'a'. Our findings suggest that γT305 might be important for construction of the overall structure of the γ module of fibrinogen. Substitution of γT305A leads to both dysfibrinogenemic and hypofibrinogenemic characterization, namely hypodysfibrinogenemia. We have already reported that recombinant γT305A fibrinogen was synthesized normally and secreted slightly, but was significantly reduced. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Effects on fibrinogen, fibrin, and blood coagulation of proteolytic extracts from fruits of Pseudananas macrodontes, Bromelia balansae, and B. hieronymi (Bromeliaceae) in comparison with bromelain.

    Science.gov (United States)

    Errasti, María E; Prospitti, Anabela; Viana, Carolina A; Gonzalez, Mariana M; Ramos, Márcio V; Rotelli, Alejandra E; Caffini, Néstor O

    2016-06-01

    Extracts rich in cysteine proteases obtained from fruits of Pseudananas macrodontes (Pm), Bromelia balansae (Bb), and B. hieronymi (Bh) have previously shown an anti-inflammatory effect on animal models. Given the close relationship between hemostasis and inflammation, it is attractive to investigate therapeutic agents capable of modulating both systems. The aim of this work was to study the effect of Pm, Bb, and Bh on fibrin(ogen) and blood coagulation compared with stem bromelain (Bro). Action on fibrinogen was electrophoretically and spectrophotometrically evaluated, fibrinolytic activity was measured both electrophoretically and by the fibrin plate assay, and the effect on blood coagulation was studied by conventional coagulation tests (PT and APPT). All extracts showed the same proteolytic preference for fibrinogen subunits, that is Aα > Bβ, whereas γ was partially hydrolyzed by 100-fold concentration increase. Unlike Bro, cysteine proteases of Pm, Bb, and Bh increased absorbance at 540 nm of fibrinogen solution, suggesting thrombin-like activity, which was time-dependent and reached maximum values at lower concentration. All extracts showed the same proteolytic preference for fibrin subunits; however Pm, Bb, and Bh showed lower fibrinolytic activity than Bro at the assayed concentrations. Although Bb acted only as anticoagulant, Pm, Bh, and unexpectedly Bro showed dual action on blood coagulation: at low concentration showed procoagulant effect and at high concentration anticoagulant effect. Results reveal new plant species as potential sources of pharmacological agents for the treatment of a wide range of hemostatic disorders as well as to wound healing.

  11. Prognostic significance of preoperative fibrinogen in patients with colon cancer.

    Science.gov (United States)

    Sun, Zhen-Qiang; Han, Xiao-Na; Wang, Hai-Jiang; Tang, Yong; Zhao, Ze-Liang; Qu, Yan-Li; Xu, Rui-Wei; Liu, Yan-Yan; Yu, Xian-Bo

    2014-07-14

    To investigate the prognostic significance of preoperative fibrinogen levels in colon cancer patients. A total of 255 colon cancer patients treated at the Affiliated Tumor Hospital of Xinjiang Medical University from June 1(st) 2005 to June 1(st) 2008 were enrolled in the study. All patients received radical surgery as their primary treatment method. Preoperative fibrinogen was detected by the Clauss method, and all patients were followed up after surgery. Preoperative fibrinogen measurements were correlated with a number of clinicopathological parameters using the Student t test and analysis of variance. Survival analyses were performed by the Kaplan-Meier method and Cox regression modeling to measure 5-year disease-free survival (DFS) and overall survival (OS). The mean preoperative fibrinogen concentration of all colon cancer patients was 3.17 ± 0.88 g/L. Statistically significant differences were found between preoperative fibrinogen levels and the clinicopathological parameters of age, smoking status, tumor size, tumor location, tumor-node-metastasis (TNM) stage, modified Glasgow prognostic scores (mGPS), white blood cell (WBC) count, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and carcinoembryonic antigen (CEA) levels. Univariate survival analysis showed that TNM stage, tumor cell differentiation grade, vascular invasion, mGPS score, preoperative fibrinogen, WBC, NLR, PLR and CEA all correlated with both OS and DFS. Alpha-fetoprotein (AFP) and body mass index correlated only with OS. Kaplan-Meier analysis revealed that both OS and DFS of the total cohort, as well as of the stage II and III patients, were higher in the hypofibrinogen group compared to the hyperfibrinogen group (all P TNM stage, mGPS score, CEA, and AFP levels correlated with both OS and DFS. Preoperative fibrinogen levels can serve as an independent prognostic marker to evaluate patient response to colon cancer treatment.

  12. Using competitive protein adsorption to measure fibrinogen in undiluted human serum

    Science.gov (United States)

    Choi, Seokheun; Wang, Ran; Lajevardi-Khosh, Arad; Chae, Junseok

    2010-12-01

    We report a unique sensing mechanism based on competitive protein adsorption to measure fibrinogen, a cardiovascular biomarker, in undiluted human serum. The method uses physical adsorption of proteins to a surface rather than complex and time-consuming immobilization procedures. Two fibrinogen concentrations were differentiated in spiked in human serum [3.0 mg/ml (normal concentration) versus 3.2 mg/ml (abnormal concentration with heart disease)]. Real-time surface plasmon resonance signals were monitored as fibrinogen displaced a preadsorbed protein, IgM, on a hydrophobic gold surface. The relatively strong-affinity protein, IgM, was displaced primarily by fibrinogen and much less by other proteins in human serum.

  13. Diagnosis of congenital fibrinogen disorders.

    Science.gov (United States)

    Lebreton, Aurélien; Casini, Alessandro

    2016-08-01

    Congenital fibrinogen disorders comprise quantitative disorders defined by a complete absence (afibrinogenemia) or by a decreased level (hypofibrinogenemia) of circulating fibrinogen and qualitative disorders characterized by a discrepancy between the activity and the antigenic levels of fibrinogen (dysfibrinogenemia and hypodysfibrinogenemia). The biological diagnosis is based on a standard haemostasis assessment. All the coagulation tests that depend on the formation of fibrin as the end point are affected; although in dysfibrinogenemia the specificity and sensitivity of routine test depend on reagent and techniques. A genetic exploration permits to confirm the diagnosis and may enhance the prediction of the patient's phenotype. Homozygous or composite heterozygous null mutations are most often responsible for afibrinogenemia while hypofibrinogenemic patients are mainly heterozygous carrier of an afibrinogenemic allele. Heterozygous missense mutations are prevalent in dysfibrinogenemia, with two hot spot localized in exon 2 of the FGA and in the exon 8 of the FGG. The correlation between phenotype and genotype has been identified in some fibrinogen variants, including six mutations clustered in exons 8 and 9 of the FGG leading to hypofibrinogenemia with hepatic inclusions of abnormal fibrinogen aggregates as well as a few mutations associated with an increase risk of thrombotic events. A familial screening and additional functional assays should be carried out when possible.

  14. Concentrating solar power. Its potential contribution to a sustainable energy future

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2011-11-15

    This report summarises the findings and recommendations of a study of concentrating solar power (CSP). The study has examined the potential contribution of CSP in Europe, the Middle East and North Africa (the MENA region) over the period to 2050, and the scientific and technical developments that will be required to realise that potential. This study critically reviews existing work and describes the scientific consensus on the status and prospects of this technology. It also identifies key outstanding issues and where knowledge gaps need to be filled for CSP to fulfil its potential contribution in Europe and the MENA region. Based on these findings, the study makes recommendations on how to improve national and European support programmes for CSP development and deployment. Specific aims of the study have been the following: (1) to review the current status of CSP technologies and identify the technological developments and research and development (R and D) needed to achieve reliable operation and cost competitiveness with fossil fuelled electricity generation; (2) to consider how issues associated with the intermittent nature of CSP for electricity generation due to the daily pattern of insolation and the potential for cloudy days can best be addressed; (3) to identify the environmental impacts and infrastructure requirements of CSP, and comment on the significance of these in relation to other options for electricity supply; and, consequently, (4) to develop a view of the potential contribution that CSP located in Europe, the Middle East and North Africa could make to the energy mix in those regions by 2020 and 2050. This report focuses primarily on the generation of electricity from CSP, but it is recognised that there are other potentially significant 'products' from CSP such as process steam for industry, water desalination, alternative energy carriers such as hydrogen and syngas, and decontamination of water supplies. Although not discussed in

  15. Contribution of haplotypes across the fibrinogen gene cluster to variation in risk of myocardial infarction.

    Science.gov (United States)

    Mannila, Maria Nastase; Eriksson, Per; Lundman, Pia; Samnegård, Ann; Boquist, Susanna; Ericsson, Carl-Göran; Tornvall, Per; Hamsten, Anders; Silveira, Angela

    2005-03-01

    Fibrinogen has consistently been recognized as an independent predictor of myocardial infarction (MI). Multiple mechanisms link fibrinogen to MI; therefore disentangling the factors underlying variation in plasma fibrinogen concentration is essential. Candidate regions in the fibrinogen gamma (FGG), alpha (FGA) and beta (FGB) genes were screened for single nucleotide polymorphisms (SNPs). Several novel SNPs were detected in the FGG and FGA genes in addition to the previously known SNPs in the fibrinogen genes. Tight linkage disequilibrium extending over various physical distances was observed between most SNPs. Consequently, eight SNPs were chosen and determined in 377 postinfarction patients and 387 healthy individuals. None of the SNPs were associated with plasma fibrinogen concentration or MI. Haplotype analyses revealed a consistent pattern of haplotypes associated with variation in risk of MI. Of the four haplotypes inferred using the FGA -58G>A and FGG 1299 +79T>C SNPs, the most frequent haplotype, FGG-FGA*1 (prevalence 46.6%), was associated with increased risk of MI (OR 1.51; 95%CI 1.18, 1.93), whereas the least frequent haplotype, FGG-FGA*4 (11.8%), was associated with lower risk of MI (OR 0.79 95%CI 0.64, 0.98). In conclusion, fibrinogen haplotypes, but not SNPs in isolation, are associated with variation in risk of MI.

  16. Effects of low frequency ultrasound on some properties of fibrinogen and its plasminolysis

    Directory of Open Access Journals (Sweden)

    Cherniavsky Eugene A

    2011-11-01

    Full Text Available Abstract Background Pharmacological thrombolysis with streptokinase, urokinase or tissue activator of plasminogen (t-PA, and mechanical interventions are frequently used in the treatment of both arterial and venous thrombotic diseases. It has been previously reported that application of ultrasound as an adjunct to thrombolytic therapy offers unique potential to improve effectiveness. However, little is known about effects of the ultrasound on proteins of blood coagulation and fibrinolysis. Here, we investigated the effects of the ultrasound on fibrinogen on processes of coagulation and fibrinogenolysis in an in vitro system. Results Our study demonstrated that low frequency high intensity pulse ultrasound (25.1 kHz, 48.4 W/cm2, duty 50% induced denaturation of plasminogen and t-PA and fibrinogen aggregates formation in vitro. The aggregates were characterized by the loss of clotting ability and a greater rate of plasminolysis than native fibrinogen. We investigated the effect of the ultrasound on individual proteins. In case of plasminogen and t-PA, ultrasound led to a decrease of the fibrinogenolysis rate, while it increased the fibrinogenolysis rate in case of fibrinogen. It has been shown that upon ultrasound treatment of mixture fibrinogen or fibrin with plasminogen, t-PA, or both, the rate of proteolytic digestion of fibrin(ogen increases too. It has been shown that summary effect on the fibrin(ogen proteolytic degradation under the conditions for combined ultrasound treatment is determined exclusively by effect on fibrin(ogen. Conclusions The data presented here suggest that among proteins of fibrinolytic systems, the fibrinogen is one of the most sensitive proteins to the action of ultrasound. It has been shown in vitro that ultrasound induced fibrinogen aggregates formation, characterized by the loss of clotting ability and a greater rate of plasminolysis than native fibrinogen in different model systems and under different mode of

  17. LIPOPOLYSACCHARIDE INDUCES EXPOSURE OF FIBRINOGEN RECEPTORS ON HUMAN PLATELETS

    Institute of Scientific and Technical Information of China (English)

    于希春; 吴其夏

    1995-01-01

    The effect of lipopolysaccharide (LPS) on the exposure of platelet fibrinogen receptors was investigated.The results showed that:1)LPS increased the binding of fibrinogen-gold complexes to platelets and the labels were primarily limited to shape-changed platelets;2)LPS caused a dose-dependent rise in intracellular Ca2+ concentration in platelets;3)LPS induced the activation of platelet protein kinase C(PKC) and the phosphorylation of glycoprotein llla (GP llla) which was inhibited by H-7.All these results suggest that stimulation of platelets with LPS causes a conformational change in glycoprotein llb/Illa (GPllb/llla) through platelet shape change and/or phosphorylation of GPllla via PKC,which serves to expose the fibrinogen binding sites of GPllb/llla on human platelets.

  18. Whitings as a Potential Mechanism for Controlling Atmospheric Carbon Dioxide Concentrations – Final Project Report

    Energy Technology Data Exchange (ETDEWEB)

    Brady D. Lee; William A. Apel; Michelle R. Walton

    2006-03-01

    Species of cyanobacteria in the genera Synechococcus and Synechocystis are known to be the catalysts of a phenomenon called "whitings", which is the formation and precipitation of fine-grained CaCO3 particles. Whitings occur when the cyanobacteria fix atmospheric CO2 through the formation of CaCO3 on their cell surfaces which leads to precipitation to the ocean floor and subsequent entombment in mud. Whitings represent one potential mechanism for CO2 sequestration. Research was performed to determine the ability of various strains of Synechocystis and Synechococcus to calcify when grown in microcosms amended with 2.5 mM HCO3- and 3.4 mM Ca2+. Results indicated that while all strains tested have the ability to calcify, only two, Synechococcus species, strains PCC 8806 and PCC 8807, were able to calcify to the extent that CaCO3 was precipitated. Enumeration of the cyanobacterial cultures during testing indicated that cell density did not appear to have an effect on calcification. Factors that had the greatest effect on calcification were CO2 removal and subsequent generation of alkaline pH. As CO2 was removed, growth medium pH increased and soluble Ca2+ was removed from solution. The largest increases in growth medium pH occurred when CO2 levels dropped below 400 ppmv. Precipitation of CaCO3 catalyzed by the growth and physiology of cyanobacteria in the Genus Synechococcus represents a potential mechanism for sequestration of atmospheric CO2 produced during the burning of coal for power generation. Synechococcus sp. strain PCC 8806 and Synechococcus sp. strain PCC 8807 were tested in microcosm experiments for their ability to calcify when exposed to a fixed calcium concentration of 3.4 mM and dissolved inorganic carbon concentrations of 0.5, 1.25 and 2.5 mM. Synechococcus sp. strain PCC 8806 removed calcium continuously over the duration of the experiment producing approximately 18.6 mg of solid-phase calcium. Calcium removal occurred over a two-day time period when

  19. Physiological functions and clinical implications of fibrinogen-like 2: A review

    Science.gov (United States)

    Yang, Genyan; Hooper, W Craig

    2015-01-01

    Fibrinogen-like 2 (FGL2) encompasses a transmembrane (mFGL2) and a soluble (sFGL2) form with differential tertiary structure and biological activities. Typically, mFGL2 functions as prothrombinase that is capable of initiating coagulation in tissue without activation of the blood clotting cascade, whereas sFGL2 largely acts as an immunosuppressor that can repress proliferation of alloreactive T lymphocytes and maturation of bone marrow dendritic cells. Protein sequences of FGL2 exhibit evolutionary conservation across wide variety of species, especially at the carboxyl terminus that contains fibrinogen related domain (FRED). The FRED of FGL2 confers specificity and complexity in the action of FGL2, including receptor recognition, calcium affiliation, and substrate binding. Constitutive expression of FGL2 during embryogenesis and in mature tissues suggests FGL2 might be physiologically important. However, excessive induction of FGL2 under certain medical conditions (e.g., pathogen invasion) could trigger complement activation, inflammatory response, cellular apoptosis, and immune dysfunctions. On the other hand, complete absence of FGL2 is also detrimental as lack of FGL2 can cause autoimmune glomerulonephritis and acute cellular rejection of xenografts. All these roles involve mFGL2, sFGL2, or their combination. Although it is not clear how mFGL2 is cleaved off its host cells and secreted into the blood, circulating sFGL2 has been found correlated with disease severity and viral loading among patients with human hepatitis B virus or hepatitis C virus infection. Further studies are warranted to understand how FGL2 expression is regulated under physiological and pathological conditions. Even more interesting is to determine whether mFGL2 can fulfill an immunoregulatory role through its FRED at carboxyl end of the molecule and, and vice versa, whether sFGL2 is procoagulant upon binding to a target cell. Knowledge in this area should shed light on development of sFGL2

  20. Role of Serum Fibrinogen Levels in Patients with Rotator Cuff Tears

    Directory of Open Access Journals (Sweden)

    Umile Giuseppe Longo

    2014-01-01

    Full Text Available Although rotator cuff (RC tendinopathy is a frequent pathology of the shoulder, the real understanding of its aetiopathogenesis is still unclear. Several studies showed that RC tendinopathy is more frequent in patients with hyperglycemia, diabetes, obesity, or metabolic syndrome. This paper aims to evaluate the serum concentration of fibrinogen in patients with RC tears. Metabolic disorders have been related to high concentration of serum fibrinogen and the activity of fibrinogen has been proven to be crucial in the development of microvascular damage. Thus, it may produce progression of RC degeneration by reducing the vascular supply of tendons. We report the results of a cross-sectional frequency-matched case-control study comparing the serum concentration of fibrinogen of patients with RC tears with that of a control group of patients without history of RC tears who underwent arthroscopic meniscectomy. We choose to enrol in the control group patients with pathology of the lower limb with a likely mechanic, not metabolic, cause, different from tendon pathology. We found no statistically significant differences in serum concentration of fibrinogen when comparing patients with RC tears and patients who underwent arthroscopic meniscectomy (P = 0.5. Further studies are necessary to clarify the role of fibrinogen in RC disease.

  1. Trimeric autotransporter DsrA is a major mediator of fibrinogen binding in Haemophilus ducreyi.

    Science.gov (United States)

    Fusco, William G; Elkins, Christopher; Leduc, Isabelle

    2013-12-01

    Haemophilus ducreyi is the etiologic agent of the sexually transmitted genital ulcer disease chancroid. In both natural and experimental chancroid, H. ducreyi colocalizes with fibrin at the base of the ulcer. Fibrin is obtained by cleavage of the serum glycoprotein fibrinogen (Fg) by thrombin to initiate formation of the blood clot. Fg binding proteins are critical virulence factors in medically important Gram-positive bacteria. H. ducreyi has previously been shown to bind Fg in an agglutination assay, and the H. ducreyi Fg binding protein FgbA was identified in ligand blotting with denatured proteins. To better characterize the interaction of H. ducreyi with Fg, we examined Fg binding to intact, viable H. ducreyi bacteria and identified a novel Fg binding protein. H. ducreyi bound unlabeled Fg in a dose-dependent manner, as measured by two different methods. In ligand blotting with total denatured cellular proteins, digoxigenin (DIG)-Fg bound only two H. ducreyi proteins, the trimeric autotransporter DsrA and the lectin DltA; however, only the isogenic dsrA mutant had significantly less cell-associated Fg than parental strains in Fg binding assays with intact bacteria. Furthermore, expression of DsrA, but not DltA or an empty vector, rendered the non-Fg-binding H. influenzae strain Rd capable of binding Fg. A 13-amino-acid sequence in the C-terminal section of the passenger domain of DsrA appears to be involved in Fg binding by H. ducreyi. Taken together, these data suggest that the trimeric autotransporter DsrA is a major determinant of Fg binding at the surface of H. ducreyi.

  2. Quantitative assessment of fibrinogen cross-linking by epsilon aminocaproic acid in patients with end-stage liver disease.

    Science.gov (United States)

    Quach, Thien; Tippens, Melissa; Szlam, Fania; Van Dyke, Rebecca; Levy, Jerrold H; Csete, Marie

    2004-01-01

    Analysis of the effectiveness of antifibrinolytic therapy for liver transplant recipients is hampered by lack of quantitative assays for assessing drug effects. We adapted chemical engineering tools used in polymerization studies to quantify fibrinogen cross-linking by plasma from liver transplant patients obtained before and after epsilon aminocaproic acid (EACA) therapy. A target fluorescein isothiocyanate-fibrinogen (FITC-fibrinogen) molecule was constructed; it fluoresces in a quantifiable pattern when in solution, and undergoes cross-linking in the presence of plasmin inhibitors. Cross-linking quenches the fluorescent signal, and the quenching is a quantifiable endpoint. Thus fluorescence from this reporter molecule can be used to assess functional improvement in fibrinogen cross-linking as a result of antifibrinolytic therapies, and it is sensitive to picomolar amounts of plasmin inhibitors and activators. Cross-linking of FITC-fibrinogen by patient plasma, before and after EACA therapy, was assessed using fluorescence spectrometry. Fluorescence patterns from FITC-fibrinogen indicated no significant cross-linking of the target fibrinogen as a consequence of EACA in posttreatment plasma. When the fibrinogen-FITC target was assayed without plasma in the presence of EACA at concentrations that bracket therapeutic levels (100 and 400 microg/ml), significant fluorescence quenching (target FITC-fibrinogen cross-linking) was achieved. These results suggest that fibrinogen-FITC fluorescence is sensitive enough to detect EACA activity in clinically relevant ranges, but that EACA given in usual doses is insufficient to promote fibrinogen cross-linking in patients with end-stage liver disease.

  3. Molecular characterization of 7 patients affected by dys- or hypo-dysfibrinogenemia: Identification of a novel mutation in the fibrinogen Bbeta chain causing a gain of glycosylation.

    Science.gov (United States)

    Asselta, Rosanna; Robusto, Michela; Platé, Manuela; Santoro, Cristina; Peyvandi, Flora; Duga, Stefano

    2015-07-01

    Fibrinogen is a hexameric glycoprotein consisting of two sets of three polypeptides (the Aα, Bβ, and γ chains, encoded by the three genes FGA, FGB, and FGG). It is involved in the final phase of the coagulation process, being the precursor of the fibrin monomers necessary for the formation of the hemostatic plug. Rare inherited fibrinogen disorders can manifest as quantitative deficiencies, qualitative defects, or both. In particular, dysfibrinogenemia and hypo-dysfibrinogenemia are characterized by reduced functional activity associated with normal or reduced antigen levels, and are usually determined by heterozygous mutations affecting any of the three fibrinogen genes. In this study, we investigated the genetic basis of dys- and hypo-dysfibrinogenemia in seven unrelated patients. Mutational screening disclosed six different variants, two of which novel (FGB-p.Asp185Asn and FGG-p.Asn230Lys). The molecular characterization of the FGG-p.Asn230Lys mutation, performed by transient expression experiments of the recombinant mutant protein, demonstrated that it induces an almost complete impairment in fibrinogen secretion, according to a molecular mechanism often associated with quantitative fibrinogen disorders. Conversely, the FGB-p.Asp185Asn variant was demonstrated to be a gain-of-glycosylation mutation leading to a hyperglycosylation of the Bβ chain, not affecting fibrinogen assembly and secretion. To our knowledge, this is the second gain-of-glycosylation mutation involving the FGB gene.

  4. Plasma fibrinogen in NIDDM - The Rotterdam Study

    NARCIS (Netherlands)

    Missov, RM; Stolk, RP; vanderBom, JG; Hofman, A; Bots, ML; Pols, HAP; Grobbee, DE

    1996-01-01

    OBJECTIVE - To compare plasma fibrinogen levels across groups of subjects with and without NIDDM with respect to diabetes therapy and to evaluate the influence of metabolic control and other selected factors. RESEARCH DESIGN AND METHODS - In a cross-sectional study, plasma fibrinogen was measured in

  5. Sulfur in foraminiferal calcite as a potential proxy for seawater carbonate ion concentration

    Science.gov (United States)

    van Dijk, I.; de Nooijer, L. J.; Boer, W.; Reichart, G.-J.

    2017-07-01

    Sulfur (S) incorporation in foraminiferal shells is hypothesized to change with carbonate ion concentration [CO32-], due to substitution of sulfate for carbonate ions in the calcite crystal lattice. Hence S/Ca values of foraminiferal carbonate shells are expected to reflect sea water carbonate chemistry. To generate a proxy calibration linking the incorporation of S into foraminiferal calcite to carbonate chemistry, we cultured juvenile clones of the larger benthic species Amphistegina gibbosa and Sorites marginalis over a 350-1200 ppm range of pCO2 values, corresponding to a range in [CO32-] of 93 to 211 μmol/kg. We also investigated the potential effect of salinity on S incorporation by culturing juvenile Amphistegina lessonii over a large salinity gradient (25-45). Results show S/CaCALCITE is not impacted by salinity, but increases with increasing pCO2 (and thus decreasing [CO32-] and pH), indicating S incorporation may be used as a proxy for [CO32-]. Higher S incorporation in high-Mg species S. marginalis suggests a superimposed biomineralization effect on the incorporation of S. Microprobe imaging reveals co-occurring banding of Mg and S in Amphistegina lessonii, which is in line with a strong biological control and might explain higher S incorporation in high Mg species. Provided a species-specific calibration is available, foraminiferal S/Ca values might add a valuable new tool for reconstructing past ocean carbonate chemistry.

  6. CORRELATION BETWEEN FIBRINOGEN LEVEL AND CEREBRAL INFARCTION

    Institute of Scientific and Technical Information of China (English)

    Yi-cheng Zhu; Li-ying Cui; Bao-lai Hua; Jia-qi Pan

    2006-01-01

    Objective To investigate the correlation between plasma fibrinogen level and cerebral infarction (CI) as well as the difference of fibrinogen among subtypes of CI.Methods A case-controlled study was conducted with 131 cases of CI and 148 controls. Plasma fibrinogen levels were detected by the Clauss method.Results High fibrinogen level (3.09±0.94 g/L) was correlated with CI (OR=2.47, 95% CI:1.51-4.04,P<0.005) at the onset stage of the disease. Persistent high fibrinogen level (3.14±0.81 g/L) at 6-month after stroke onset was detected and correlated with CI (OR=4.34, 95% CI: 1.80-10. 51,P=0.001). Higher fibrinogen level was correlated with total anterior circulation infarction (TACI), partial anterior circulation infarction (PACI), and posterior circulation infarction (POCI) (OR = 4.008, P<0.001). Higher fibrinogen level was correlated with extracranial atherosclerosis (OR=3.220, P<0.05), but not with intracranial atherosclerosis.Conclusion Fibrinogen level may be a risk factor of CI and probably correlates with subtypes of CI and distributions of atherosclerosis.

  7. Fibrinogen Is at the Interface of Host Defense and Pathogen Virulence in Staphylococcus aureus Infection

    Science.gov (United States)

    Ko, Ya-Ping; Flick, Matthew J.

    2017-01-01

    Fibrinogen not only plays a pivotal role in hemostasis but also serves key roles in antimicrobial host defense. As a rapidly assembled provisional matrix protein, fibrin(ogen) can function as an early line of host protection by limiting bacterial growth, suppressing dissemination of microbes to distant sites, and mediating host bacterial killing. Fibrinogen-mediated host antimicrobial activity occurs predominantly through two general mechanisms, namely, fibrin matrices functioning as a protective barrier and fibrin(ogen) directly or indirectly driving host protective immune function. The potential of fibrin to limit bacterial infection and disease has been countered by numerous bacterial species evolving and maintaining virulence factors that engage hemostatic system components within vertebrate hosts. Bacterial factors have been isolated that simply bind fibrinogen or fibrin, promote fibrin polymer formation, or promote fibrin dissolution. Staphylococcus aureus is an opportunistic gram-positive bacterium, the causative agent of a wide range of human infectious diseases, and a prime example of a pathogen exquisitely sensitive to host fibrinogen. Indeed, current data suggest fibrinogen serves as a context-dependent determinant of host defense or pathogen virulence in Staphylococcus infection whose ultimate contribution is dictated by the expression of S. aureus virulence factors, the path of infection, and the tissue microenvironment. PMID:27056151

  8. Fibrinogen Availability and Coagulation Function After Hemorrhage and Resuscitation in Pigs

    Science.gov (United States)

    2011-08-01

    next morning (24 h after hemor- rhage and resuscitation), the pigs were tranquilized with diazepam (0.5 mg/kg intramuscular [IM]) before being trans...2008) Efficacy and tolerability of human fibrinogen concentrate ad- ministration to patients with acquired fibrinogen deficiency and active or in...is indicative of transfusion requirements in pa- tients with penetrating injuries. J. Trauma. 64:S64–8. 15. Nuttall GA, et al. (2001) Efficacy of a

  9. Targeted deletion of fibrinogen like protein 1 reveals a novel role in energy substrate utilization.

    Directory of Open Access Journals (Sweden)

    Valeriy Demchev

    Full Text Available Fibrinogen like protein 1(Fgl1 is a secreted protein with mitogenic activity on primary hepatocytes. Fgl1 is expressed in the liver and its expression is enhanced following acute liver injury. In animals with acute liver failure, administration of recombinant Fgl1 results in decreased mortality supporting the notion that Fgl1 stimulates hepatocyte proliferation and/or protects hepatocytes from injury. However, because Fgl1 is secreted and detected in the plasma, it is possible that the role of Fgl1 extends far beyond its effect on hepatocytes. In this study, we show that Fgl1 is additionally expressed in brown adipose tissue. We find that signals elaborated following liver injury also enhance the expression of Fgl1 in brown adipose tissue suggesting that there is a cross talk between the injured liver and adipose tissues. To identify extra hepatic effects, we generated Fgl1 deficient mice. These mice exhibit a phenotype suggestive of a global metabolic defect: Fgl1 null mice are heavier than wild type mates, have abnormal plasma lipid profiles, fasting hyperglycemia with enhanced gluconeogenesis and exhibit differences in white and brown adipose tissue morphology when compared to wild types. Because Fgl1 shares structural similarity to Angiopoietin like factors 2, 3, 4 and 6 which regulate lipid metabolism and energy utilization, we postulate that Fgl1 is a member of an emerging group of proteins with key roles in metabolism and liver regeneration.

  10. Fibrinogen adsorption on zinc oxide nanoparticles: a Micro-Differential Scanning Calorimetry analysis.

    Science.gov (United States)

    Lousinian, S; Missopolinou, D; Panayiotou, C

    2013-04-01

    Understanding the interactions between proteins and surfaces (nanoparticles or films) is crucial for the fabrication and improvement of biomedical devices in direct contact with human blood. The aim of this work is the study of the interaction of fibrinogen (Fib) with zinc oxide nanoparticles. The nanoparticles were either synthesized chemically or were commercially available, having different size. Zinc oxide nanoparticles are known for their antibacterial properties, and Fib adsorption is studied in view of combining the antibacterial and desirable clotting behavior of a single material. The thermal properties of the Fib solution were studied by Micro-Differential Scanning Calorimetry. For the consideration of the compositional and structural properties of the nanoparticles, Fourier Transform Infrared Spectroscopy and Scanning Electron Microscopy were employed, respectively. Through the changes of the thermal properties of Fib upon adsorption that were observed by microDSC, the mechanisms of the protein adsorption were revealed. It seems that electrostatic (for the D and E domains) and hydrophobic interactions (for the aC chains) were responsible for the adsorption and the protein structural changes caused by it. The discrepancy between the Fib adsorption percentages on homemade and commercially available zinc oxide nanoparticles can be attributed to their different size. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Trimeric Autotransporter DsrA Is a Major Mediator of Fibrinogen Binding in Haemophilus ducreyi

    OpenAIRE

    William G. Fusco; Elkins, Christopher; Leduc, Isabelle

    2013-01-01

    Haemophilus ducreyi is the etiologic agent of the sexually transmitted genital ulcer disease chancroid. In both natural and experimental chancroid, H. ducreyi colocalizes with fibrin at the base of the ulcer. Fibrin is obtained by cleavage of the serum glycoprotein fibrinogen (Fg) by thrombin to initiate formation of the blood clot. Fg binding proteins are critical virulence factors in medically important Gram-positive bacteria. H. ducreyi has previously been shown to bind Fg in an agglutinat...

  12. Homozygosity for the E526V Mutation in Fibrinogen A Alpha-Chain Amyloidosis: The First Report

    Directory of Open Access Journals (Sweden)

    Isabel Tavares

    2015-01-01

    Full Text Available Systemic hereditary amyloidoses are autosomal dominant diseases associated with mutations in genes encoding ten different proteins. The clinical phenotype has implications on therapeutic approach, but it is commonly variable and largely dependent on the type of mutation. Except for rare cases involving gelsolin or transthyretin, patients are heterozygous for the amyloidogenic variants. Here we describe the first patient identified worldwide as homozygous for a nephropathic amyloidosis, involving the fibrinogen variant associated with the fibrinogen alpha-chain E526V (p.Glu545Val mutation. In 1989, a 44-year-old woman presented with hypertension, hepatosplenomegaly, nephrotic syndrome, and renal failure. She started hemodialysis in 1990 and 6 years later underwent isolated kidney transplantation from a deceased donor. Graft function and clinical status were unremarkable for 16 years, despite progressively increased left ventricular mass on echocardiography. In 2012, 4 months before death, she deteriorated rapidly with severe heart failure, precipitated by Clostridium difficile colitis and urosepsis. Affected family members developed nephropathy, on average, nearly three decades later, which may be explained by the gene dosage effects on the phenotype of E526V (p.Glu545Val fibrinogen A alpha-chain amyloidosis.

  13. Postmortem distribution of guaifenesin concentrations reveals a lack of potential for redistribution.

    Science.gov (United States)

    McIntyre, Iain M; Navarrete, Aylmer; Mena, Othon

    2014-12-01

    Therapeutic (or non-toxic) postmortem guaifenesin blood and liver concentrations have not been previously described. Peripheral blood guaifenesin concentrations were compared to central blood and liver concentrations in eight medical examiner cases. Specimens were initially screened for alcohol and simple volatiles, drugs of abuse, alkaline, and acid/neutral drugs. Guaifenesin, when detected by the acid/neutral drug screen, was subsequently confirmed and quantified by a high performance liquid chromatography procedure. Data suggest that postmortem guaifenesin peripheral blood concentrations may be considered non-toxic to at least 5.4mg/L with liver concentrations to at least 7.0mg/kg. Overall, guaifenesin concentrations ranged from 1.9 to 40mg/L in peripheral blood, 2.2-150mg/L in central blood, and 2.6-36mg/kg in liver. The median guaifenesin central blood to peripheral blood ratio was 1.1 (N=8). Similarly, liver to peripheral blood ratios showed a median value of 0.9L/kg (N=5). Given that a liver to peripheral blood ratio less than 5L/kg is consistent with little to no propensity for postmortem redistribution, these data suggest that guaifenesin is not prone to substantial postmortem redistribution. Published by Elsevier Ireland Ltd.

  14. Low dose BMP-2 treatment for bone repair using a PEGylated fibrinogen hydrogel matrix.

    Science.gov (United States)

    Ben-David, Dror; Srouji, Samer; Shapira-Schweitzer, Keren; Kossover, Olga; Ivanir, Eran; Kuhn, Gisela; Müller, Ralph; Seliktar, Dror; Livne, Erella

    2013-04-01

    Bone repair strategies utilizing resorbable biomaterial implants aim to stimulate endogenous cells in order to gradually replace the implant with functional repair tissue. These biomaterials should therefore be biodegradable, osteoconductive, osteoinductive, and maintain their integrity until the newly formed host tissue can contribute proper function. In recent years there has been impressive clinical outcomes for this strategy when using osteoconductive hydrogel biomaterials in combination with osteoinductive growth factors such as human recombinant bone morphogenic protein (hrBMP-2). However, the success of hrBMP-2 treatments is not without risks if the factor is delivered too rapidly and at very high doses because of a suboptimal biomaterial. Therefore, the aim of this study was to evaluate the use of a PEGylated fibrinogen (PF) provisional matrix as a delivery system for low-dose hrBMP-2 treatment in a critical size maxillofacial bone defect model. PF is a semi-synthetic hydrogel material that can regulate the release of physiological doses of hrBMP-2 based on its controllable physical properties and biodegradation. hrBMP-2 release from the PF material and hrBMP-2 bioactivity were validated using in vitro assays and a subcutaneous implantation model in rats. Critical size calvarial defects in mice were treated orthotopically with PF containing 8 μg/ml hrBMP-2 to demonstrate the capacity of these bioactive implants to induce enhanced bone formation in as little as 6 weeks. Control defects treated with PF alone or left empty resulted in far less bone formation when compared to the PF/hrBMP-2 treated defects. These results demonstrate the feasibility of using a semi-synthetic biomaterial containing small doses of osteoinductive hrBMP-2 as an effective treatment for maxillofacial bone defects.

  15. Nanostructuring of PEG-fibrinogen polymeric scaffolds.

    Science.gov (United States)

    Frisman, Ilya; Seliktar, Dror; Bianco-Peled, Havazelet

    2010-07-01

    Recent studies have shown that nanostructuring of scaffolds for tissue engineering has a major impact on their interactions with cells. The current investigation focuses on nanostructuring of a biocompatible, biosynthetic polymeric hydrogel scaffold made from crosslinked poly(ethylene glycol)-fibrinogen conjugates. Nanostructuring was achieved by the addition of the block copolymer Pluronic F127, which self-assembles into nanometric micelles at certain concentrations and temperatures. Cryo-transmission electron microscopy experiments detected F127 micelles, both embedded within PEGylated fibrinogen hydrogels and in solution. The density of the F127 micelles, as well as their ordering, increased with increasing block copolymer concentration. The mechanical properties of the nanostructured hydrogels were investigated using stress-sweep rheological testing. These tests revealed a correlation between the block copolymer concentration and the storage modulus of the composite hydrogels. In vitro cellular assays confirmed that the increased modulus of the hydrogels did not limit the ability of the cells to form extensions and become spindled within the three-dimensional (3-D) hydrogel culture environment. Thus, altering the nanostructure of the hydrogel may be used as a strategy to control cellular behavior in 3-D through changes in mechanical properties of the environment.

  16. Fibrinogen concentration and risk of ischemic stroke and acute coronary events in 5113 patients with transient ischemic attack and minor ischemic stroke

    NARCIS (Netherlands)

    Rothwell, PM; Howard, SC; Power, DA; Gutnikov, SA; Algra, A; van Gijn, J; Clark, TG; Murphy, MFG; Warlow, CP

    2004-01-01

    Background and Purpose - Fibrinogen is an independent risk factor for coronary events in population-based studies and in patients with coronary heart disease, but there is uncertainty about prediction of stroke, particularly in secondary prevention. Methods - We studied unpublished data from 3 prosp

  17. Fibrinogen concentration and risk of ischemic stroke and acute coronary events in 5113 patients with transient ischemic attack and minor ischemic stroke

    NARCIS (Netherlands)

    Rothwell, PM; Howard, SC; Power, DA; Gutnikov, SA; Algra, A; van Gijn, J; Clark, TG; Murphy, MFG; Warlow, CP

    2004-01-01

    Background and Purpose - Fibrinogen is an independent risk factor for coronary events in population-based studies and in patients with coronary heart disease, but there is uncertainty about prediction of stroke, particularly in secondary prevention. Methods - We studied unpublished data from 3 prosp

  18. Fibrinogen concentration and risk of ischemic stroke and acute coronary events in 5113 patients with transient ischemic attack and minor ischemic stroke

    NARCIS (Netherlands)

    Rothwell, PM; Howard, SC; Power, DA; Gutnikov, SA; Algra, A; van Gijn, J; Clark, TG; Murphy, MFG; Warlow, CP

    2004-01-01

    Background and Purpose - Fibrinogen is an independent risk factor for coronary events in population-based studies and in patients with coronary heart disease, but there is uncertainty about prediction of stroke, particularly in secondary prevention. Methods - We studied unpublished data from 3

  19. A regenerative label-free fiber optic sensor using surface plasmon resonance for clinical diagnosis of fibrinogen

    Directory of Open Access Journals (Sweden)

    Nguyen TT

    2015-08-01

    Full Text Available Tan Tai Nguyen,1 Sun Oh Bea,1 Dong Min Kim,2 Won Jung Yoon,3 Jin-Won Park,4 Seong Soo A An,1 Heongkyu Ju1,5,6 1Department of Bionano Technology, College of Bionano Technology, Gachon University, Seongnam, 2Department of Materials Science and Engineering, Hongik University, Sejong City, 3Department of Chemical and Bio Engineering, Gachon University, Seongnam, 4Department of Chemical and Biomolecular Engineering, College of Energy and Biotechnology, Seoul National University of Science and Technology, Seoul, 5Department of Nanophysics, College of Bionano Technology, Gachon University, Seongnam, 6Neuroscience Institute, Gil Hospital, Incheon, South Korea Purpose: We present the regenerative label-free fiber optical biosensor that exploits surface plasmon resonance for quantitative detection of fibrinogen (Fbg extracted from human blood plasma.Materials and methods: The sensor head was made up of a multimode optical fiber with its polymer cladding replaced by metal composite of nanometer thickness made of silver, aluminum, and nickel. The Ni layer coated allowed a direct immobilization of histidine-tagged peptide (HP on its metal surface without an additional cross-linker in between. On the coated HP layer, immunoglobulin G was then immobilized for specific capturing of Fbg.Results: We demonstrated a real-time quantitative detection of Fbg concentrations with limit of detection of ~10 ng/mL. The fact that the HP layer could be removed by imidazole with acid also permitted us to demonstrate the regeneration of the outermost metal surface of the sensor head for the sensor reusability.Conclusion: The sensor detection limit was estimated to be ~10 pM, which was believed to be sensitive enough for detecting Fbg during the clinical diagnosis of cardiovascular diseases, myocardial infarction, strokes, and Alzheimer’s diseases. Keywords: SPR, real-time assay, histidine-tagged peptide, protein sensing

  20. A statistical evaluation of the influence of housing characteristics and geogenic radon potential on indoor radon concentrations in France.

    Science.gov (United States)

    Demoury, C; Ielsch, G; Hemon, D; Laurent, O; Laurier, D; Clavel, J; Guillevic, J

    2013-12-01

    Radon-222 is a radioactive natural gas produced by the decay of radium-226, known to be the main contributor to natural background radiation exposure. Effective risk management needs to determine the areas in which the density of buildings with high radon levels is likely to be highest. Predicting radon exposure from the location and characteristics of a dwelling could also contribute to epidemiological studies. Beginning in the nineteen-eighties, a national radon survey consisting in more than 10,000 measurements of indoor radon concentrations was conducted in French dwellings by the Institute for Radiological Protection and Nuclear Safety (IRSN). Housing characteristics, which may influence radon accumulation in dwellings, were also collected. More recently, the IRSN generated a French geogenic radon potential map based on the interpretation of geological features. The present study analyzed the two datasets to investigate the factors influencing indoor radon concentrations using statistical modeling and to determine the optimum use of the information on geogenic radon potential that showed the best statistical association with indoor radon concentration. The results showed that the variables associated with indoor radon concentrations were geogenic radon potential, building material, year of construction, foundation type, building type and floor level. The model, which included the surrounding geogenic radon potential (i.e. the average geogenic radon potential within a disc of radius 20 km centered on the indoor radon measurement point) and variables describing house-specific factors and lifestyle explained about 20% of the overall variability of the logarithm of radon concentration. The surrounding geogenic radon potential was fairly closely associated with the local average indoor radon concentration. The prevalence of exposure to radon above specific thresholds and the average exposures to radon clearly increased with increasing classes of geogenic radon

  1. Influence of fibrinogen β-chain gene variations on risk of myocardial infarction in a Chinese Han population

    Institute of Scientific and Technical Information of China (English)

    LU Xiang-feng; YU Hong-jiang; ZHOU Xiao-yang; WANG Lai-yuan; HUANG Jian-feng; GU Dong-feng

    2008-01-01

    Background Although the role of fibrinogen as a predictor of acute myocardial infarction(MI)has been well-established,the association of genetic polymorphisms in the fibrinogen gene with MI is still controversial.This study was conducted to elucidate the association between the genetic polymorphisms of the fibrinogen β-chain(FGB)gene and MI in Chinese Han population.Methods The occurrence of 3 common polymorphisms(i.e.-455G/A,R448K and 8558C/G)in a case-control study including 508 patients with MI and 503 healthy controls was investigated. Results Analyses of single polymorphisms showed that individuals carrying the rare alleles for the 3 polymorphisms were significantly associated with a decreased risk of MI.Logistic regression analysis indicated that R448K remained independently associated with MI after adjustment for environmental risk factors(adjusted odds ratio(OR)=0.71 for KK/RK versus RR.P=0.023).The three polymorphisms were found to be in strong linkage disequilibrium.Haplotype analyses showed that the A-K-G haplotype(-455A,448K,8558G)was associated with a protective effect against MI.Compared with the common haplotype G-R-C,the adjusted OR for A-K-G was 0.68(95% CI,0.51-0.90;P=0.006). Conclusion These data indicate that individuals carrying the FGB 448K allele may be protective against having MI in this population.

  2. Genetic variation in estrogen receptor, C-reactive protein and fibrinogen does not predict the plasma levels of inflammation markers after longterm hormone replacement therapy

    DEFF Research Database (Denmark)

    de Maat, Moniek P M; Madsen, Jonna Skov; Langdahl, Bente

    2007-01-01

    Markers of inflammation, such as C-reactive protein (CRP) and fibrinogen, are associated with the risk of atherothrombosis. Plasma levels of these markers of inflammation are affected by hormone replacement therapy (HRT) and modulated by smoking. We studied whether genetic variation in the estrogen......). The effect of HRT, smoking and genetic variations in ESR1 (PvuII and XbaI), CRP (1444C/T) and fibrinogen-beta (FGB, -455G/A) were determined. The plasma concentration of CRP was higher in the HRT group than in the control group (2.03 mg/l and 1.41 mg/l, respectively; p ... concentration (n.s.). Genetic polymorphisms in ESR1, CRP and fibrinogen were not associated with an effect of HRT on the CRP and fibrinogen plasma levels, and no significant interaction with smoking was observed. In conclusion, higher plasma levels of CRP and lower plasma levels of fibrinogen were observed...

  3. Fibrinogen functionality in black South Africans : the PURE study / Christina Magrietha Kotzé

    OpenAIRE

    Kotzé, Christina Magrietha

    2014-01-01

    INTRODUCTION AND AIM Black South Africans are experiencing an increase in the prevalence of cardiovascular disease (CVD). Fibrinogen functionality, including total and gamma prime (y’) fibrinogen concentration, as well as fibrin network structure, play an important role in CVD development and events. Several genetic and environmental factors influence fibrinogen functionality, and in turn, known CVD risk factors associated with total and y’ fibrinogen concentration have also been associate...

  4. Elevated Fibrinogen Levels Associate with Risk of Pulmonary Embolism, but not with Deep Venous Thrombosis

    DEFF Research Database (Denmark)

    Klovaite, Jolanta; Nordestgaard, Børge G; Tybjærg-Hansen, Anne;

    2013-01-01

    RATIONALE: It is unclear whether elevated plasma fibrinogen associates with both deep venous thrombosis(DVT) and its complication pulmonary embolism(PE), and whether elevated fibrinogen is a direct cause of these disorders. OBJECTIVES: We tested the hypotheses that elevated plasma fibrinogen...... relationship using a Mendelian randomization approach, we genotyped for FGB(rs1800790; rs4220) encoding fibrinogen beta chain. MEASUREMENTS AND MAIN RESULTS: Increasing plasma fibrinogen quintiles associated with increased risk of PE in combination with DVT(P-trend...

  5. Propofol Breath Monitoring as a Potential Tool to Improve the Prediction of Intraoperative Plasma Concentrations

    NARCIS (Netherlands)

    Colin, Pieter; Eleveld, Douglas J; van den Berg, Johannes P; Vereecke, Hugo E M; Struys, Michel M R F; Schelling, Gustav; Apfel, Christian C; Hornuss, Cyrill

    2015-01-01

    INTRODUCTION: Monitoring of drug concentrations in breathing gas is routinely being used to individualize drug dosing for the inhalation anesthetics. For intravenous anesthetics however, no decisive evidence in favor of breath concentration monitoring has been presented up until now. At the same tim

  6. Evaluación del efecto de la ingesta de una alta carga de ácidos grasos saturados sobre los niveles séricos de la proteína C reactiva, alfa1-antitripsina, fibrinógeno y alfa1-glicoproteína ácida en mujeres obesas Effect of a high saturated fatty acids load on serum concentrations of C-reactive protein, alpha1-antitrypsin, fibrinogen and alpha1-acid glycoprotein in obese women

    Directory of Open Access Journals (Sweden)

    M.ª M. Ramírez Alvarado

    2010-02-01

    en mujeres obesas. Los niveles séricos de PCR y fibrinógeno están incrementados en mujeres obesas y se correlacionan positivamente con el IMC.Obesity is associated with increased inflammation. Creactive protein (CRP and inflammation-sensitive plasma protein (ISPs are inflammatory markers. Proinflammatory process may be influenced by high saturated fatty acid intake. Objective: The aim of the present study was to evaluate the role of saturated fatty acids load on postprandial circulating levels of PCR and ISPs (alpha1-antitrypsin, alpha1-acid glucoprotein, and fibrinogen in obese women. Design: A total of 15 obese women (age = 31,7 ± 4,5 years, BMI = 37,9 ± 7,3 kg/m² and 15 lean controls women (age = 30,6 ± 4,6 years, BMI = 20,6 ± 2,6 kg/m² were recruited for this study. After and overnight fast subjects ate the fat load consisted of 75 g of fat (100% saturated fatty acid, 0% cholesterol, 5 g of carbohydrates, and 6 g of protein per m2 body surface area. Postprandial serum levels of CRP, alpha1-antitrypsin, alpha1-acid glucoprotein, and fibrinogen were measured. Anthropometry and blood biochemical parameters were measured in both groups. Results: The obese women had fasting serum PCR levels higher (p = 0,013 and fibrinogen (p = 0,04 than those of control women. Serum CRP and fibrinogen levels was positively related to body mass index (BMI in obese group. There weren't differences in fasting serum alpha1- antitrypsin levels (p = 0,40, and alpha1-acid glucoprotein (p = 0,28 levels in obese group in comparison to lean control group. Serum CRP, alpha1-antitrypsin, alpha1-acid glucoprotein, and fibrinogen did not change postprandially (p = > 0,05 difference to fasting levels. Conclusion: A high-saturated fatty acids load is not associated with serum CRP, alpha1-antitrypsin, alpha1-acid glucoprotein, and fibrinogen levels increase. Serum alpha1-antitripsin and alpha1-acid glucoprotein levels are not increased in obese women. Serum PCR and fibrinogen levels are

  7. Fibrinogen variant B[beta]D432A has normal polymerization but does not bind knob 'B'

    Energy Technology Data Exchange (ETDEWEB)

    Bowley, Sheryl R.; Lord, Susan T.; (UNC)

    2009-10-23

    Fibrinogen residue B{beta}432Asp is part of hole 'b' that interacts with knob 'B,' whose sequence starts with Gly-His-Arg-Pro-amide (GHRP). Because previous studies showed B{beta}D432A has normal polymerization, we hypothesized that B{beta}432Asp is not critical for knob 'B' binding and that new knob-hole interactions would compensate for the loss of this Asp residue. To test this hypothesis, we solved the crystal structure of fragment D from B{beta}D432A. Surprisingly, the structure (rfD-B{beta}D432A+GH) showed the peptide GHRP was not bound to hole 'b.' We then re-evaluated the polymerization of this variant by examining clot turbidity, clot structure, and the rate of FXIIIa cross-linking. The turbidity and the rate of - dimer formation for B{beta}D432A were indistinguishable compared with normal fibrinogen. Scanning electron microscopy showed no significant differences between the clots of B{beta}D432A and normal, but the thrombin-derived clots had thicker fibers than clots obtained from batroxobin, suggesting that cleavage of FpB is more important than 'B:b' interactions. We conclude that hole 'b' and 'B:b' knob-hole binding per se have no influence on fibrin polymerization.

  8. A novel peptide can mimic extracellular fibrinogen-binding protein to block the activation of complement system.

    Science.gov (United States)

    Gao, Ya-ping; Dong, Jie; Zhang, Xin; Liu, Yu; Lu, Qiang; Feng, Jian-nan; Tan, Xiao-rong; Yang, Guang

    2013-07-01

    Extracellular fibrinogen-binding protein (Efb) of Staphylococcus aureus (S. aureus) is a bi-functional protein, which can specifically bind fibrinogen with its N terminus and inhibit deposition of C3b on the surface of S. aureus with its C terminus. Here, we screened the epitopes of Efb using phage display. Four peptides with consensus motif were screened. This consensus motif was identical to C terminus (161-164) of Efb. In the further investigation, it was found the synthesized peptide EC1 (154-165aa of Efb) could specifically bind C3/C3b and subsequently to block the activation of complement. Meanwhile, EC1 could inhibit the interaction between Efb and C3/C3b. Moreover, the interaction between the mutant protein of EmC1 (Efb without EC1) and C3 was decreased. And, the effect on the complement system of the mutant protein was dramatically declined compared with Efb. Our finding suggested that the peptide EC1 could mimic Efb to block complement system activation via binding C3.

  9. A computer program for estimating instream travel times and concentrations of a potential contaminant in the Yellowstone River, Montana

    Science.gov (United States)

    McCarthy, Peter M.

    2006-01-01

    The Yellowstone River is very important in a variety of ways to the residents of southeastern Montana; however, it is especially vulnerable to spilled contaminants. In 2004, the U.S. Geological Survey, in cooperation with Montana Department of Environmental Quality, initiated a study to develop a computer program to rapidly estimate instream travel times and concentrations of a potential contaminant in the Yellowstone River using regression equations developed in 1999 by the U.S. Geological Survey. The purpose of this report is to describe these equations and their limitations, describe the development of a computer program to apply the equations to the Yellowstone River, and provide detailed instructions on how to use the program. This program is available online at [http://pubs.water.usgs.gov/sir2006-5057/includes/ytot.xls]. The regression equations provide estimates of instream travel times and concentrations in rivers where little or no contaminant-transport data are available. Equations were developed and presented for the most probable flow velocity and the maximum probable flow velocity. These velocity estimates can then be used to calculate instream travel times and concentrations of a potential contaminant. The computer program was developed so estimation equations for instream travel times and concentrations can be solved quickly for sites along the Yellowstone River between Corwin Springs and Sidney, Montana. The basic types of data needed to run the program are spill data, streamflow data, and data for locations of interest along the Yellowstone River. Data output from the program includes spill location, river mileage at specified locations, instantaneous discharge, mean-annual discharge, drainage area, and channel slope. Travel times and concentrations are provided for estimates of the most probable velocity of the peak concentration and the maximum probable velocity of the peak concentration. Verification of estimates of instream travel times and

  10. A Review of Heavy Metal Concentration and Potential Health Implications of Beverages Consumed in Nigeria

    Directory of Open Access Journals (Sweden)

    Sylvester Chibueze Izah

    2016-12-01

    Full Text Available Beverages are consumed in Nigeria irrespective of age, sex, and socioeconomic status. Beverages may be alcoholic (wine, spirits, and beers or non-alcoholic (soft drink, energy drinks, candies, chocolates, milks. Notwithstanding, most beverages are packed in cans, bottles, and plastics. This paper reviews the concentration of heavy metals from some commercially-packaged beverages consumed in Nigeria. The study found that heavy metal concentrations, including iron, mercury, tin, antimony, cadmium, zinc, copper, chromium, lead, and manganese, seldom exceed the maximum contaminant level recommended by the Standard Organization of Nigeria (SON and the World Health Organization (WHO as applicable to drinking water resources. The occurrence of heavy metals in the beverages could have resulted from the feedstocks and water used in their production. Consumption of beverages high in heavy metal could be toxic and cause adverse effect to human health, depending on the rate of exposure and accumulation dosage. This study concludes by suggesting that heavy metal concentration in the feedstocks and water should be monitored by producers, and its concentration in beverages should also be monitored by appropriate regulatory agencies.

  11. Adsorption of fibrinogen on a biomedical-grade stainless steel 316LVM surface: a PM-IRRAS study of the adsorption thermodynamics, kinetics and secondary structure changes.

    Science.gov (United States)

    Desroches, Marie-Josee; Omanovic, Sasha

    2008-05-14

    Polarization-modulation infrared reflection-absorption spectroscopy (PM-IRRAS) was employed to investigate the interaction of serum protein fibrinogen with a biomedical-grade 316LVM stainless steel surface, in terms of the adsorption thermodynamics, kinetics and secondary structure changes of the protein. Apparent Gibbs energy of adsorption values indicated a highly spontaneous and strong adsorption of fibrinogen onto the surface. The kinetics of fibrinogen adsorption were successfully modeled using a pseudo first-order kinetic model. Deconvolution of the amide I bands indicated that the adsorption of fibrinogen on 316LVM results in significant changes in the protein's secondary structure that occur predominantly within the first minute of adsorption. Among the investigated structures, the alpha-helix structure undergoes the smallest changes, while the beta-sheet and beta-turns structures undergo significant changes. It was shown that lateral interactions between the adsorbed molecules do not play a role in controlling the secondary structure changes. An increase in temperature induced changes in the secondary structure of the protein, characterized by a loss of the alpha-helical content and its transformation into the beta-turns structure.

  12. Platelet glycoproteins and fibrinogen in recovery from idiopathic sudden hearing loss.

    Directory of Open Access Journals (Sweden)

    Daniel Weiss

    Full Text Available BACKGROUND: The pathomechanism and location of idiopathic sudden sensorineural hearing loss (ISSHL is unclear. In a previous case-control study, we found elevated fibrinogen concentrations and a higher prevalence of T allele carriers of the glycoprotein (Gp Ia C807T polymorphism in ISSHL patients. METHODOLOGY: 127 patients with ISSHL (mean age 53.3 years, 48.8% females, who underwent a standard therapy with high dose steroids, pentoxifyllin and sterofundine over 8 days were included. We examined the influence of GpIa genotype and fibrinogen (BclI-, A312-, HaeIII- genotype and fibrinogen plasma levels on hearing recovery after 8 weeks (change from baseline: 0 dB  =  no recovery, >0 to 10 dB = moderate recovery, >10 dB = good recovery. In a subsample of 59 patients with ISSHL, we further studied the association of platelet glycoprotein GpIa, Ib and IIIa densities on hearing recovery as well as the possible effect-modification of platelet glycoproteins on hearing recovery by plasma fibrinogen. RESULTS: In univariate analysis, neither the GpIa genotype nor fibrinogen genotype (all p>0.1 but lower fibrinogen levels (p = 0.029, less vertigo (p = 0.002 and lower GpIIIa receptor density (p = 0.037, n = 59 were associated with hearing recovery. In multivariate analysis, fibrinogen significantly modified the effect of GPIa receptor density on good hearing recovery (effect-modification on multiplicative scale OR = 0.45 (95% confidence interval (0.21-0.94, p = 0.03. GPIb receptor density below the mean was associated with a 2-fold increase in good hearing recovery both in patients with fibrinogen levels above (p = 0.04 as well as in patients with fibrinogen levels below the mean (p = 0.06. There was no indication for an effect-modification (p = 0.97. CONCLUSIONS: The findings suggest a vascular/rheological origin of ISSHL with unique features of thrombosis in the inner ear artery that may include complex

  13. ESTUDO COMPARATIVO ENTRE AS TÉCNICAS DE SCHALM E DE CLAUSS NA DETERMINAÇÃO DA CONCENTRAÇÃO PLASMÁTICA DO FIBRINOGÊNIO EM EQÜINOS HÍGIDOS E COM CÓLICA COMPARATIVE STUDY BETWEEN PLASMA FIBRINOGEN CONCENTRATIONS DETERMINED BY SCHALM AND CLAUSS TECHNIQUES IN COLIC AND HEALTHY HORSES

    Directory of Open Access Journals (Sweden)

    Aureo Evangelista Santana

    2009-12-01

    Full Text Available

    Foram comparadas, em oito diferentes momentos, duas técnicas de determinação da concentração plasmática do fibrinogênio em equinos hígidos (GI=20 e com cólica (GII=10: a técnica de Schalm, fundamentada na precipitação térmica do fibrinogênio a 56oC, e a técnica de Clauss, que envolve a polimerização da molécula de fibrinogênio. Em ambos os grupos e em todos os momentos de avaliação os valores médios obtidos por intermédio da técnica de Schalm foram superiores (P<0,05 àqueles obtidos pela técnica de Clauss. A diferença observada entre os dois métodos avaliados deve-se à interferência de inúmeros fatores inibidores do processo cinético atuantes no procedimento de Clauss. A hiperfibrinogenemia apresentada pelos animais com cólica (GII entre o segundo e o quinto dias pós-operatório deve-se não somente ao trauma cirúrgico, mas também ao processo inflamatório e infeccioso da ferida cirúrgica. A análise seriada do fibrinogênio contribui de forma positiva e precoce no diagnóstico de processos inflamatórios e infecciosos em equinos com cólica. Diante de tais observações, recomenda-se o método de Schalm na determinação do fibrinogênio em equinos hígidos e com cólica, por ser de um procedimento simples, de fácil execução, baixo custo e com resultados coerentes.

    PALAVRAS-CHAVES: Cólica, comparação de técnicas, equinos, fibrinogênio.

    Two different techniques for the determination of fibrinogen plasma concentration were compared during eight time points. Twenty healthy horses (GI and ten horses with colic (GII were included in this study. The Schalm´s technique was compared to the Clauss´s technique. The first one is based on the thermal precipitation of the fibrinogen at 56oC. The second involves the polymerization of the fibrinogen molecule. Both groups of horses during all time points had mean values of plasmatic fibrinogen higher

  14. Homocysteine and its thiolactone-mediated modification of fibrinogen affect blood platelet adhesion.

    Science.gov (United States)

    Malinowska, Joanna; Olas, Beata

    2012-01-01

    Homocysteine (Hcys) and homocysteine thiolactone (HTL) concentrations in organism are correlated with a number of serious pathologies. In the literature, there are few papers describing studies on the effects of homocysteine on proteins that participate in blood coagulation and fibrinolysis in human. However, mechanisms involved in the relationship between hyperhomocysteinemia and hemostatic process are still unclear. The role of N- or S-homocysteinylation (induced by Hcys and its derivatives) of different hemostatic proteins, including fibrinogen is also still poorly known. The aim of this study was to establish the functional changes of the fibrinogen molecule induced by Hcys (at final doses of 10-100 µM) and the most reactive form of Hcys - its cyclic thioester, homocysteine thiolactone (0.1-1 µM), and to examine the effects of these changes on the capability of fibrinogen to interact with human blood platelets (by measuring the platelet adhesion). Our present results demonstrated that Hcys-treated fibrinogen in comparison with native molecule had a distinct capability to mediate platelet adhesion. Both, unstimulated and thrombin-activated platelets showed a reduced ability to adhere to Hcys-mediated fibrinogen. HTL (at all tested concentrations) had similar properties when we used thrombin-activated platelets. In conclusion, the results reported in this study could be useful for a better understanding of changes in hemostasis during hyperhomocysteinemia.

  15. Urinary leukotriene E4 concentrations as a potential marker of inflammation in dogs with inflammatory bowel disease.

    Science.gov (United States)

    Im Hof, M; Schnyder, M; Hartnack, S; Stanke-Labesque, F; Luckschander, N; Burgener, I A

    2012-01-01

    Inflammatory bowel disease (IBD) and food-responsive diarrhea (FRD) are chronic enteropathies of dogs (CCE) that currently can only be differentiated by their response to treatment after exclusion of other diseases. In humans, increased urinary concentrations of leukotriene E4 (LTE4) have been associated with active IBD. To evaluate urinary LTE4 concentrations in dogs with IBD, FRD, and healthy controls, and to assess correlation of urinary LTE4 concentrations with the canine IBD activity index (CIBDAI) scores. Eighteen dogs with IBD, 19 dogs with FRD, and 23 healthy control dogs. In this prospective study, urine was collected and CIBDAI scores were calculated in client-owned dogs with IBD and those with FRD. Quantification of LTE4 in urine was performed by liquid chromatography-tandem mass spectrometry and corrected to creatinine. Urinary LTE4 concentrations were highest in dogs with IBD (median 85.2 pg/mg creatinine [10th-90th percentiles 10.9-372.6]) followed by those with FRD (median 31.2 pg/mg creatinine [10th-90th percentiles 6.2-114.5]) and control dogs (median 21.1 pg/mg creatinine [10th-90th percentiles 9.1-86.5]). Urinary LTE4 concentrations were higher in dogs with IBD than in control dogs (P = .011), but no significant difference between IBD and FRD was found. No correlation was found between urinary LTE4 concentrations and CIBDAI. The higher urinary LTE4 concentrations in dogs with IBD suggest that cysteinyl leukotriene pathway activation might be a component of the inflammatory process in canine IBD. Furthermore, urinary LTE4 concentrations are of potential use as a marker of inflammation in dogs with CCE. Copyright © 2012 by the American College of Veterinary Internal Medicine.

  16. Pilot Randomized trial of Fibrinogen in Trauma Haemorrhage (PRooF- iTH)

    DEFF Research Database (Denmark)

    Steinmetz, Jacob; Henriksen, Hanne Hee; Sørensen, Anne Marie

    2016-01-01

    Background: Haemorrhage remains a leading cause of morbidity and mortality in trauma patients. Fibrinogen is an essential endogenous component of haemostasis and the plasma level is associated with bleeding, transfusion and outcome. Fibrinogen concentrate is widely used to correct acquired...... hypofibrinogenaemia, recommended by several international guidelines for the treatment of trauma patients, but evidence is lacking regarding the treatment safety and efficacy.We aim to assess the efficacy and safety of an immediate pre-emptive first-line treatment with fibrinogen concentrate in patients with trauma...... to the Level 1 Trauma Centre at Rigshospitalet in Copenhagen, with immediate need for blood transfusion on arrival and an expected need for haemostatic resuscitation with multiple transfusions during the initial resuscitation. Patients will receive either pre-emptive administration of a bolus dose of 60–70 mg...

  17. Study on the correlation of plasma fibrinogen levels and Fg Bβ-455A gene polymorphisms to the acute cerebral infarction%急性脑梗死与血浆Fg水平以及FgBβ-455G/A多态性的相关性研究

    Institute of Scientific and Technical Information of China (English)

    张海霞; 杨美荣; 张江; 陈乃耀; 王大力

    2011-01-01

    Objective To investigate the correlation of plasma fibrinogen level and Fg Bβ-455 A gene polymorphisms with the acute cerebral infarction. Methods A total of 90 patients with acute cerebral infarction and 102 healthy subjects as case-control group were selected. The plasma fibrinogen levels in the two groups were compared, and the relationship analysis was performed among the plasma fibrinogen levels, the Fg Bβ-455A gene polymorphisms and the acute cerebral infarction. Results The plasma fibrinogen level in the acute cerebral infarction group was higher than that in control group (P < 0.05 ). The plasma fibrinogen level in gene-455A carrier, gene-455AA especially, was significantly higher than that in gene-455G carrier. Through Logisitic analysis, the increasing of fibrinogen concentrations and Fg Bβ-455G/A were independent risk factors in the acute cerebral infarction. Conclusion The alleles of Fg Bβ-455A are associated with fibrinogen concentrations. The increasing of fibrinogen concentrations and Fg Bβ-455G/A are independent risk factors of cerebral infarction.%目的 探讨急性脑梗死与血浆纤维蛋白原(Fg)水平及Fg Bβ-455G/A多态性的相关性.方法 选择急性脑梗死患者90例及同期门诊体检的健康者102例,比较两组间血浆Fg水平,对血浆Fg、Fg Bβ-455G/A基因多态性与急性脑梗死做相关性分析.结果 病例组血浆Fg水平高于对照组;突变基因-455A(AA、GA基因型)携带者的血浆Fg水平均高于非-455A携带者(GG型);以脑梗死为因变量经过多因素非条件的Logistic回归分析显示,血浆Fg水平、-455GA+AA进入回归方程.结论 Fg Bβ-455G/A多态性与血浆Fg水平具有相关性,血浆Fg浓度、FgBβ-455G/A是急性脑梗死发生的独立危险因素.

  18. Label-Free Quantitative Immunoassay of Fibrinogen in Alzheimer Disease Patient Plasma Using Fiber Optical Surface Plasmon Resonance

    Science.gov (United States)

    Kim, Jisoo; Kim, SeJin; Nguyen, Tan Tai; Lee, Renee; Li, Tiehua; Yun, Changhyun; Ham, Youngeun; An, Seong Soo A.; Ju, Heongkyu

    2016-05-01

    We present a real-time quantitative immunoassay to detect fibrinogen in the blood plasma of Alzheimer's disease patients using multimode fiber optical sensors in which surface plasmon resonance (SPR) was employed. Nanometer-thick bimetals including silver and aluminum were coated onto the core surface of the clad-free part (5 cm long) of the fiber for SPR excitation at the He-Ne laser wavelength of 632.8 nm. The histidine-tagged peptide was then coated on the metal surface to immobilize the fibrinogen antibody for the selective capture of fibrinogen among the proteins in the patient blood plasma. The SPR fiber optical sensor enabled quantitative detection of concentrations of fibrinogen from the different human patient blood at a detection limit of ˜20 ng/ml. We also observed a correlation in the fibrinogen concentration measurement between enzyme-linked immunosorbent assay and our SPR fiber-based sensors. This suggests that the presented SPR fiber-based sensors that do not rely on the use of labels such as fluorophores can be used for a real-time quantitative assay of a specific protein such as fibrinogen in a human blood that is known to contain many other kinds of proteins together.

  19. mRNA expression of genes involved in inflammation and haemostasis in equine fibroblast-like synoviocytes following exposure to lipopolysaccharide, fibrinogen and thrombin

    DEFF Research Database (Denmark)

    Andreassen, Stine Mandrup; Berg, Lise Charlotte; Nielsen, Søren Saxmose;

    2015-01-01

    to lipopolysaccharide (LPS), fibrinogen and thrombin. Synovial membranes were collected from metacarpo-phalangeal joints of 6 skeletally mature horses euthanized for non-orthopaedic reasons. Passage 4 fibroblast-like synoviocytes were left non-treated or treated with either 0.1 μ g/ml LPS, 5 mg/ml fibrinogen or 5 U...... in increased mRNA expression of SAA, IL-6, MCP-1 and PAI-1, and a decreased PAR-1 expression compared to non-treated cells. The fibrinogen-treated synoviocytes showed significantly increased mRNA expression of IL-6, MCP-1, TF and PAI-1, and decreased PAR-1 expression compared to non-treated cells. Conclusion......: LPS, fibrinogen and thrombin induced an increased gene expression of inflammatory markers in isolated equine fibroblast-like synoviocytes. LPS caused changes in gene expression promoting increased fibrinolysis, while fibrinogen and thrombin changed the gene expression resulting potentially in reduced...

  20. Regulation of fibrinogen receptor expression on human platelets

    Energy Technology Data Exchange (ETDEWEB)

    Shattil, S.J.; Motulsky, H.J.; Insel, P.A.; Brass, L.F.

    1986-03-01

    Platelet aggregation requires the binding of fibrinogen to specific receptors on the plasma membrane glycoprotein IIb-IIIa complex. Although the IIb-IIIa complex is identifiable on the surface of resting platelets, the fibrinogen receptor is expressed only after platelet activation. The authors have developed a monoclonal anti-IIb-IIIa antibody (PAC-1) that binds only to stimulated platelets and only in the presence of Ca. In order to better understand the steps leading to platelet aggregation, the authors used radiolabeled PAC-1 and fibrinogen to examine the effect of the ..cap alpha../sub 2/-adrenergic agonist, epinephrine, on the expression and function of the fibrinogen receptor. The addition of epinephrine to unstirred platelets caused and immediate increase in PAC-1 and fibrinogen binding that was associated with platelet aggregation once the platelets were stirred. Even after prolonged incubation of the platelets with epinephrine, fibrinogen receptor expression could be reversed by adding EGTA, PGl/sub 2/, or the ..cap alpha../sub 2/-adrenergic antagonist, phentolamine. When unstirred platelets were exposed to epinephrine for more than 10 min, the extent of aggregation caused by subsequent stirring was decreased by 70%. Surprisingly, these desensitized platelets bound PAC-1 and fibrinogen normally, indicating that the loss of aggregation was not due to a decrease in fibrinogen receptor expression or function. These studies demonstrate that: (1) fibrinogen receptor expression is dependent on extracellular CA; (2) induction of the fibrinogen receptor by epinephrine requires the continued presence of the agonist; and (3) prolonged stimulation of the platelet by epinephrine can lead to a reduced aggregation response by a mechanism that does not involve a loss of either fibrinogen recepor expression or fibrinogen binding.

  1. The role of fibrinogen and haemostatic assessment in postpartum haemorrhage

    DEFF Research Database (Denmark)

    Wikkelsø, Anne Juul

    2015-01-01

    Pregnancy is a state of hypercoagulobility that might be an evolutionary way of protecting parturients from exsanguination following child birth. Observational studies suggest an association between a low level of fibrinogen (coagulation factor I) at the start of postpartum haemorrhage (PPH....... Paper III was based on two national Danish registries evaluating the predictability of postpartum blood transfusion. Prediction was found difficult. However, retained placental parts seemed to be the strongest predictor. Since this diagnosis is made very late and often in association with the onset...... of bleeding, tools to perform an early diagnosis is highly warranted. Paper IV includes recommendations of the European Society of Anaesthesiology regarding the use of fibrinogen concentrate in PPH, and is based on very weak (GRADE 2) evidence and low confidence in estimates of effect (GRADE C). Paper V...

  2. Genetic polymorphism of β-fibrinogen gene-455G/A can contribute to the risk of ischemic stroke.

    Science.gov (United States)

    Gu, Lian; Wu, Guangliang; Su, Li; Yan, Yan; Long, Jianxiong; Tan, Jinjing; Liang, Baoyun; Guo, Xiaojing; Huang, Guihua

    2014-02-01

    Many studies have investigated the association between the β-fibrinogen gene-455G/A (FGβ-455G/A) polymorphism and the risk of ischemic stroke. However, these evidences were inadequate to provide stronger conclusions because most studies were generally small. To shed light on these inconclusive findings, we conducted a large sample size meta-analysis of studies relating to the FGβ-455G/A polymorphism and the risk of ischemic stroke. Odds ratios with a 95 % confidence interval were used to investigate the association between FGβ-455G/A polymorphism and ischemic stroke. Publication bias was tested by Egger's test and funnel plot. Inconsistency index and Cochran's Q statistic were used to check heterogeneity. Cumulative and recursive cumulative meta-analyses were performed to provide a framework for updating a genetic effect from all of the included studies. Twenty-six independent publications with 4,070 cases and 4,649 controls were included in this meta-analysis. Results showed that the β-fibrinogen-455G/A polymorphism was significantly associated with the risk of ischemic stroke. The FGβ-455G/A polymorphism was found to be a risk factor for ischemic stroke in Asians and adults, while association was not observed for Caucasians and juveniles based on the small size and it may be necessary to conduct larger studies on them to investigate the association in the future. The cumulative meta-analysis indicated a decline from 1998 to 2003, and the results remained stable during the period 2004-2012. The results indicate that FGβ-455G/A polymorphism may be a susceptible predictor of ischemic stroke. More studies are needed to elucidate the relationship further.

  3. [Fibrinogen/fibrin-specific enzymes from copperhead (Agkistrodon halys halys) and cobra (Naja oxiana eichwald) snake venoms].

    Science.gov (United States)

    Yunusova, E S; Sadykov, E S; Sultanalieva, N M; Shkinev, A V

    2016-03-01

    Ability of fractions of cobra's (Naja oxiana Eichwald) and copperhead snake's (Agkistrodon halys halys) venoms to hydrolyze fibrinogen/fibrin was studied. In cobra's snake a component with molecular mass of nearly 60 kDa was found to hydrolyze a-chain of fibrinogen but failed to hydrolyze casein/azocasein and fibrin. A fibrinogen-specific metalloproteinase, the enzyme was inhibited by EDTA. Cobra's venom reduced the mass of donor's fresh blood clots. The copperhead snake's venom and the fractions obtained by gel-filtration (HW-50) and ion exchange chromatography (DEAE-650) were found to hydrolyze casein/azocasein, a- and b-chains of fibrinogen/fibrin and donor's blood clots. The results from the study of the venom and proteolytically active fractions are the evidence for a thrombolytic potential in a copperhead snake's venom.

  4. Mechanisms of fibrinogen adsorption at solid substrates at lower pH.

    Science.gov (United States)

    Cieśla, Michał; Adamczyk, Zbigniew; Barbasz, Jakub; Wasilewska, Monika

    2013-06-11

    Adsorption of fibrinogen was theoretically studied using the three-dimensional random sequential adsorption (RSA) model. Fibrinogen molecule shape was approximated by the bead model considering the presence of flexible side arms. Various cases were considered inter alia, the side-on adsorption mechanisms and the simultaneous side-on/end-on adsorption mechanism. The latter mechanisms is pertinent to fibrinogen adsorption at lower pH (below isoelectric point of 5.8) where the entire molecule is positively charged. Extensive calculations enabled one to determine the jamming surface concentration (coverage) of molecules adsorbed under the side-on and end-on orientations as well as the total coverage. For the simultaneous side-on/end-on model the maximum surface concentration was 7.29 × 10(3) μm(-2) corresponding to the protein coverage of 4.12 mg m(-2) (without considering hydration). Additionally, the surface blocking functions for different adsorption regimes were determined and analytically approximated for the entire range of coverage by the interpolating polynomials. Using these blocking functions, fibrinogen adsorption kinetics for diffusion controlled transport conditions was evaluated. Comparison of these theoretical results with experimental data was made. It was demonstrated that the simultaneous side-on/end-on model properly reflects the maximum coverage of fibrinogen adsorbed on latex particles determined via the electrokinetic (electrophoretic mobility) and AFM measurements. Also, streaming potential measurements of fibrinogen adsorption kinetics on mica were successfully interpreted in terms of this model. The theoretical results derived in this work have implications for basic science providing information on mechanisms of anisotropic protein adsorption.

  5. Recurrence of the 'deep-intronic' FGG IVS6-320A>T mutation causing quantitative fibrinogen deficiency in the Italian population of Veneto.

    Science.gov (United States)

    Platè, Manuela; Duga, Stefano; Castaman, Giancarlo; Rodeghiero, Francesco; Asselta, Rosanna

    2009-07-01

    Quantitative fibrinogen deficiency is a rare bleeding disorder characterized by abnormally low levels of fibrinogen in plasma, generally due to mutations in one of the three fibrinogen genes: FGA, FGB, and FGG, coding for A alpha, B beta, and gamma chain, respectively. Although the partial defect (hypofibrinogenemia) is due to mutations occurring in the heterozygous state, homozygosity or compound heterozygosity for the same genetic defects give rise to the more severe afibrinogenemia. Mutations responsible for these conditions are scattered throughout the three fibrinogen genes, with only few sites representing relative mutational hot spots. In this study, we report the identification of the FGG IVS6-320A>T mutation in an Italian hypofibrinogenemic patient from Veneto (a region of North-Eastern Italy). This 'deep-intronic' mutation, which would go unnoticed by using conventional mutational screening strategies was previously reported in an afibrinogenemic family from Vicenza (a province of Veneto). The geographic clustering of patients carrying the FGG IVS6-320A>T mutation and the results of haplotype analysis suggest the existence of a common founder. This information will be useful to direct future genetic screenings in patients coming from the same geographic area.

  6. Genetic variation in the fibrinogen gamma gene increases the risk for deep venous thrombosis by reducing plasma fibrinogen gamma' levels.

    Science.gov (United States)

    Uitte de Willige, Shirley; de Visser, Marieke C H; Houwing-Duistermaat, Jeanine J; Rosendaal, Frits R; Vos, Hans L; Bertina, Rogier M

    2005-12-15

    We investigated the association between haplotypes of fibrinogen alpha (FGA), beta (FGB), and gamma (FGG), total fibrinogen levels, fibrinogen gamma' (gammaA/gamma' plus gamma'/gamma') levels, and risk for deep venous thrombosis. In a population-based case-control study, the Leiden Thrombophilia Study, we typed 15 haplotype-tagging single nucleotide polymorphisms (htSNPs) in this gene cluster. None of these haplotypes was associated with total fibrinogen levels. In each gene, one haplotype increased the thrombosis risk approximately 2-fold. After adjustment for linkage disequilibrium between the genes, only FGG-H2 homozygosity remained associated with risk (odds ratio [OR], 2.4; 95% confidence interval [95% CI], 1.5-3.9). FGG-H2 was also associated with reduced fibrinogen gamma' levels and reduced ratios of fibrinogen gamma' to total fibrinogen. Multivariate analysis showed that reduced fibrinogen gamma' levels and elevated total fibrinogen levels were both associated with an increased risk for thrombosis, even after adjustment for FGG-H2. A reduced fibrinogen gamma' to total fibrinogen ratio (less than 0.69) also increased the risk (OR, 2.4; 95% CI, 1.7-3.5). We propose that FGG-H2 influences thrombosis risk through htSNP 10034C/T [rs2066865] by strengthening the consensus of a CstF site and thus favoring the formation of gammaA chain above that of gamma' chain. Fibrinogen gamma' contains a unique high-affinity, nonsubstrate binding site for thrombin, which seems critical for the expression of the antithrombin activity that develops during fibrin formation (antithrombin 1).

  7. Influence of a salt marsh plant (Halimione portulacoides) on the concentrations and potential mobility of metals in sediments.

    Science.gov (United States)

    Almeida, C Marisa R; Mucha, Ana P; Bordalo, A A; Vasconcelos, M Teresa S D

    2008-09-15

    Influence of Halimione portulacoides, commonly found in temperate salt marshes, on sediment metal contents, speciation and potential mobility in case of sediment re-suspension was evaluated. Both colonized and non-colonized sediments were studied for total Cd, Cu, Pb and Zn contents and metal fraction exchangeable to water collected in situ. Sediment elutriates, prepared with water collected from each site, were used to simulate a sediment re-suspension phenomenon. As the characteristics and degree of contamination of sediments may influence system behaviour, salt marshes of two Portuguese estuaries, Cavado (NW coast) and Sado (SW coast), were studied. Cu, Pb and Zn contents higher than ERL (quality guideline, effect range-low) were observed, indicating potential risks for living organisms. Strong Cu-complexing organic ligands, also determined in both water and elutriates, were higher in rhizosediment elutriates, at concentrations similar, or even higher, to those of Cu. Such ligands condition metals speciation in the water column and probably also metal bioavailability. From rhizosediment significant amounts of Cu and Zn were transferred to the aqueous phase, concentrations 2-8 times higher than concentrations present in water. In contrast, elutriates of non-colonized sediment removed metals from water, Cu and Zn levels in elutriates being 2-6 times lower than initial ones. Cd and Pb levels in water and elutriates were not measurable in most cases. Results clearly indicate that metals potential solubility in the rhizosphere of plants was markedly higher than that in the surrounding sediment. The obtained results indicated that H. portulacoides presence (and probably other salt marsh plants) may cause a marked increase in metals concentrations in dissolved phase (pore water or even water column if rhizosediment is re-suspended). As salt marsh plants may be abundant in temperate and subtropical estuaries and costal lagoons, this phenomenon should not be disregard in

  8. Fibrinogen Yecheon: congenital dysfibrinogenemia with gamma methionine-310 to threonine substitution.

    Science.gov (United States)

    Park, Eunkyung; Park, Geumbore; Park, Rojin; Kim, Hee-Jin; Lee, Sang Jae; Cha, Young Joo

    2009-12-01

    This case study reports a rare fibrinogen variant, gamma Met310Thr mutation, for the first time in Korea. The case shows a point mutation from T to C in the 1,007th nucleotide of the FGG gene. This report describes a variant fibrinogen, hereinafter called "fibrinogen Yecheon", using the name after the town where the patient was living at the time of diagnosis. Fibrinogen Yecheon has a de novo heterozygous point mutation of FGG resulting in gamma Met310Thr and subsequent extra N-glycosylation at gamma Asn308. Extra N-glycosylated fibrinogen is considered a main inhibitor of normal fibrinogen activity.

  9. Demonstration of extracellular peptidylarginine deiminase (PAD) activity in synovial fluid of patients with rheumatoid arthritis using a novel assay for citrullination of fibrinogen

    DEFF Research Database (Denmark)

    Damgaard, Dres; Senolt, Ladislav; Nielsen, Michael Friberg

    2014-01-01

    INTRODUCTION: Members of the peptidylarginine deiminase (PAD) family catalyse the posttranslational conversion of peptidylarginine to peptidylcitrulline. Citrullination of proteins is well described in rheumatoid arthritis (RA), and hypercitrullination of proteins may be related to inflammation...... in general. PAD activity has been demonstrated in various cell lysates, but so far not in synovial fluid. We aimed to develop an assay for detection of PAD activity, if any, in synovial fluid from RA patients. METHODS: An enzyme-linked immunosorbent assay using human fibrinogen as the immobilized substrate...... for citrullination and anti-citrullinated fibrinogen antibody as the detecting agent were used for measurement of PAD activity in synovial fluid samples from five RA patients. The concentrations of PAD2 and calcium were also determined. RESULTS: Approximately 150 times lower levels of recombinant human PAD2 (rhPAD2...

  10. A meta-analysis of relationship between β-fibrinogen gene -148C/T polymorphism and susceptibility to cerebral infarction in Han Chinese

    Institute of Scientific and Technical Information of China (English)

    CHEN Xiao-chao; XU Ming-tong; ZHOU Wu; HAN Chun-li; CHEN Wei-qing

    2007-01-01

    Objective The results of studies on association between -148C/T polymorphism in promoter region of β-fibrinogen gene and susceptibility to cerebral infarction in Chinese population are controversial. In this study, we summarize the results of published works in this field by a meta-analysis.Data sources Genetic association studies evaluating the β-fibrinogen gene -148C/T polymorphisms and cerebral infarction involving Chinese population published before December 2005 were collected from PubMed, EMBASE and CNKI.Study selection Case control studies involving unrelated, Han subjects aged from 18 to 80 years, and the internationally recognized diagnostic standard of cerebral infarction and genotype frequencies in control group consistent with Hardy-Weinberg equilibrium were used. Publication bias was tested by funnel plot and the odds ratios of all studies were combined dependent on the result of heterogeneity test among the individual studies. The software Review Manager (Version 4.2) was used for meta-analysis.Results Eleven studies including 1223 patients and 1433 controls met the selection criteria. There was no heterogeneity among the odds ratios (ORs) of individual studies (x2=17.82, P=0.06). The combined OR of susceptibility to cerebral infarction in -148T allele carriers compared to the wild homozygote was 1.32 (95%C/1.12 to 1.55, P=0.0008).In the patients with cerebral infarction, the average plasma fibrinogen level of allele T carrier was 0.42 g/L (95%CI 0.29 to 0.54, P<0.001), higher than that of -148C/C homozygous ones.Conclusions β-fibrinogen gene -148C/T polymorphism might contribute to susceptibility to cerebral infarction in Han Chinese. To reach a definitive conclusion, further gene to gene and gene to environment interactions studies on β-fibrinogen polymorphisms and cerebral infarction with large sample size are required.

  11. Mechanisms of fibrinogen-acebutolol interactions: Insights from DSC, CD and LS.

    Science.gov (United States)

    Hassan, Natalia; Ruso, Juan M; Somasundaran, P

    2011-02-01

    The complex formed due to the interaction of the amphiphilic betablocker acebutolol with fibrinogen in a buffer solution (50mN glycine, pH of 8.5) has been investigated using a multipronged physicochemical approach. Differential scanning calorimetry measurements of the complexes have shown no reversibility of thermal denaturation as indicated by the three observed peaks and the opposite role that acebutolol plays in the folding different domains of the fibrinogen molecule and the stability of such domains. While circular dichroism measurements have revealed that interaction of acebutolol with fibrinogen affects the protein secondary structure to a different extent depending on the temperature and drug concentration, dynamic light scattering analysis showed evidence for protein aggregation mainly to tetramers and dimers.

  12. Plasma circulating fibrinogen stability and moderate beer consumption.

    Science.gov (United States)

    Gorinstein, Shela; Caspi, Abraham; Zemser, Marina; Libman, Imanuel; Goshev, Ivan; Trakhtenberg, Simon

    2003-12-01

    MODERATE BEER CONSUMPTION (MBC) IS CARDIOPROTECTIVE: it positively influences plasma lipid levels and plasma antioxidant activity in beer-consuming individuals. The connection between MBC and blood coagulation is not clearly defined. Forty-two volunteers were equally divided into experimental (EG) and control (CG) groups following coronary bypass surgery. For 30 consecutive days, only patients of the EG consumed 330 mL of beer per day (about 20 g of alcohol). A comprehensive clinical investigation of 42 patients was done. Blood samples were collected before and after the investigation for a wide range of laboratory tests. The plasma fibrinogen was denatured with 8 M urea and intrinsic fluorescence (IF), hydrophobicity and differential scanning calorimetry (DSC) were used to reveal possible qualitative changes. After 30 days of moderate beer consumption, positive changes in the plasma lipid levels, plasma anticoagulant and plasma antioxidant activities were registered in patients of the EG group. In 17 out of 21 patients of the same group, differences in plasma circulating fibrinogen's (PCF), secondary and tertiary structures were found. The stability of fibrinogen, expressed in thermodynamic parameters, has shown that the loosening of the structure takes place under ethanol and urea denaturation. Also fluorescence stability of PCF was decreased. No changes in the lipid levels, anticoagulant and antioxidant activity or changes in PCF were detected in patients of CG. In conclusion, for the first time after a short term of moderate beer consumption some qualitative changes in the plasma circulating fibrinogen were detected: differences in the emission peak response, fluorescence intensity and all thermodynamic data. Together, with the decrease in the PCF concentration it may lead to an elevation of the blood anticoagulant activity.

  13. Impact of changing DOC concentrations on the potential distribution of acid sensitive biota in a boreal stream network

    Directory of Open Access Journals (Sweden)

    H. Laudon

    2007-09-01

    Full Text Available DOC concentrations have increased in many surface waters in Europe and North America over the past few decades. As DOC exerts a strong influence on pH this DOC increase could have detrimental effects on acid sensitive biota in many streams and lakes. To investigate the potential implications of changes in the DOC concentration on stream water biota, we have used a mesoscale boreal stream network in northern Sweden as a case study. The network was sampled for stream water chemistry at 60 locations during both winter base flow and spring flood periods, representing the extremes experienced annually in these streams both in terms of discharge and acidity. The effect of changing DOC on pH was modeled for all sampling locations using an organic acid model, with input DOC concentrations for different scenarios adjusted by between –30% and +50% from measured present concentrations. The resulting effect on pH was then used to quantify the proportion of stream length in the catchment with pH below the acid thresholds of pH 5.5 and pH 5.0. The results suggest that a change in stream water DOC during base flow would have only a limited effect on pH and hence on the stream length with pH below the acid thresholds. During the spring flood on the other hand a change in DOC would strongly influence pH and the stream length with pH below the acid thresholds. For example an increase in DOC concentration of 30% at all sites would increase the proportion of stream length with pH below 5.5 from 37% to 65%, and the proportion of stream length with pH below 5.0 would increase from 18% to 27%. The results suggest that in poorly-buffered high DOC waters, even a marginal change in the DOC concentration could impact acid sensitive biota in a large portion of the aquatic landscape.

  14. Impact of changing DOC concentrations on the potential distribution of acid sensitive biota in a boreal stream network

    Directory of Open Access Journals (Sweden)

    H. Laudon

    2008-03-01

    Full Text Available DOC concentrations have increased in many surface waters in Europe and North America over the past few decades. As DOC exudes a strong influence on pH this DOC increase could have detrimental effects on acid sensitive biota in many streams and lakes. To investigate the potential implications of changes in the DOC concentration on stream water biota, we have used a mesoscale boreal stream network in northern Sweden as a case study. The network was sampled for stream water chemistry at 60 locations during both winter base flow and spring flood periods, representing the extremes experienced annually in these streams both in terms of discharge and acidity. The effect of changing DOC on pH was modeled for all sampling locations using an organic acid model, with input DOC concentrations for different scenarios adjusted by between −30% and +50% from measured present concentrations. The resulting effect on pH was then used to quantify the proportion of stream length in the catchment with pH below the acid thresholds of pH 5.5 and pH 5.0. The results suggest that a change in stream water DOC during base flow would have only a limited effect on pH and hence on the stream length with pH below the acid thresholds. During the spring flood on the other hand a change in DOC would strongly influence pH and the stream length with pH below the acid thresholds. For example an increase in DOC concentration of 30% at all sites would increase the proportion of stream length with pH below 5.5 from 37% to 65%, and the proportion of stream length with pH below 5.0 would increase from 18% to 27%. The results suggest that in high DOC waters, even a marginal change in the DOC concentration could impact acid sensitive biota in a large portion of the aquatic landscape.

  15. Iron modulates the alpha chain of fibrinogen.

    Science.gov (United States)

    Nielsen, Vance G; Jacobsen, Wayne K

    2016-04-01

    Iron-bound fibrinogen has been noted to accelerate plasmatic coagulation in patients with divergent conditions involving upregulation of heme oxygenase activity, including hemodialysis, Alzheimer's disease, sickle cell anemia, and chronic migraine. Our goal was to determine if a site of iron-fibrinogen interaction was on the alpha chain. Using thrombelastography, we compared the coagulation kinetic profiles of plasma exposed to 0-10 µM ferric chloride after activation of coagulation with thrombin generated by contact activation of plasma with the plastic sample cup or by exposure to 1 µg/ml of Calloselasma rhodostoma venom (rich in ancrod activity), which causes coagulation via polymerization of alpha chain monomers. Venom mediated coagulation always occurred before thrombin activated thrombus formation, and ferric chloride always diminished the time of onset of coagulation and increased the velocity of clot growth. Iron enhances plasmatic coagulation kinetics by modulating the alpha chain of fibrinogen.

  16. Neprilysin Inhibits Coagulation through Proteolytic Inactivation of Fibrinogen.

    Directory of Open Access Journals (Sweden)

    Matthew Burrell

    Full Text Available Neprilysin (NEP is an endogenous protease that degrades a wide range of peptides including amyloid beta (Aβ, the main pathological component of Alzheimer's disease (AD. We have engineered NEP as a potential therapeutic for AD but found in pre-clinical safety testing that this variant increased prothrombin time (PT and activated partial thromboplastin time (APTT. The objective of the current study was to investigate the effect of wild type NEP and the engineered variant on coagulation and define the mechanism by which this effect is mediated. PT and APTT were measured in cynomolgus monkeys and rats dosed with a human serum albumin fusion with an engineered variant of NEP (HSA-NEPv as well as in control plasma spiked with wild type or variant enzyme. The coagulation factor targeted by NEP was determined using in vitro prothrombinase, calibrated automated thrombogram (CAT and fibrin formation assays as well as N-terminal sequencing of fibrinogen treated with the enzyme. We demonstrate that HSA-NEP wild type and HSA-NEPv unexpectedly impaired coagulation, increasing PT and APTT in plasma samples and abolishing fibrin formation from fibrinogen. This effect was mediated through cleavage of the N-termini of the Aα- and Bβ-chains of fibrinogen thereby significantly impairing initiation of fibrin formation by thrombin. Fibrinogen has therefore been identified for the first time as a substrate for NEP wild type suggesting that the enzyme may have a role in regulating fibrin formation. Reductions in NEP levels observed in AD and cerebral amyloid angiopathy may contribute to neurovascular degeneration observed in these conditions.

  17. Potentially clinically toxic concentrations of whole blood manganese in a patient fed enterally with a high tea consumption.

    Science.gov (United States)

    Ross, Colleen; O'Reilly, Dennis St J; McKee, Ruth

    2006-05-01

    This report describes a 37-year-old female patient who after seven years on intermittent overnight enteral feeding supplementation was noted to have an increased whole blood manganese concentration. Manganese toxicity is well documented after pathological absorption through inhalation via the lungs, or after intravenous administration to patients on long-term total parenteral nutrition. A dietary history revealed high tea consumption. The association between high blood manganese concentrations and enteral/oral nutrition does not appear to have previously been described.

  18. Nasogastric feeding tubes from a neonatal department yield high concentrations of potentially pathogenic bacteria- even 1 d after insertion

    DEFF Research Database (Denmark)

    Petersen, Sandra Meinich; Greisen, Gorm; Krogfelt, Karen Angeliki

    2016-01-01

    probiotic administration through the tube. RESULTS: Out of the 94 NG-tubes, 89% yielded more than 1,000 colony-forming units (CFU)/ml bacteria, and 55% yielded the potentially pathogenic Enterobacteriaceae and/or Staphylococcus aureus. The mean concentration in the yield was 5.3 (SD: 2.1, maximum 9.4) log10......BACKGROUND: Preterm infants are vulnerable to pathogens and at risk of developing necrotizing enterocolitis (NEC) or sepsis. Nasogastric feeding tubes (NG-tubes) might contaminate feeds given through them due to biofilm formation. We wanted to determine if there is a rationale in replacing NG-tubes...... more often to reduce contamination. METHODS: We conducted an observational study of used NG-tubes from a tertiary neonatal department. After removal, we flushed a 1-ml saline solution through the tube, determined the density of bacteria by culture, and related it to the duration of use and any...

  19. CORRELATION OF PLASMA FIBRINOGEN WITH BLOOD PRESSURE, BMI, LIPID PROFILE AND GLYCEMIC STATUS IN TYPE II D M

    Directory of Open Access Journals (Sweden)

    Suresh

    2014-12-01

    Full Text Available BACKGROUND: Diabetes is the most common metabolic disorder all over the world3.The incidence of diabetes is showing an alarming rise in developing countries, particularly in India. Type 2 diabetes is the most prevalent form in India and constitutes more than 95% of the cases.9 During the past decade, the potential role of haemostatic factors particularly fibrinogen in various disorders and their complication has gained considerable interest. Plasma fibrinogen is a important marker in type 2 Diabetes, but its correlation with smoking, age, sex, hypertension, obesity, family history lipids, has not been evaluated in large studies. In view of paucity of data from Indian studies, we attempt to correlate plasma fibrinogen with blood pressure, BMI, lipid profile and glycemic status in type 2 diabetes mellitus. METHODS: A total of 100, known and newly detected type-2 diabetic patients with and without associated hypertension of more than 40 years of age belonging to both sexes were included. All these patients were registered cases in Basaveshwar Teaching & General Hospital, Gulbarga as outpatients and in-patients. Type-2 diabetic patients associated with myocardial infarction, stroke, chronic inflammatory diseases, tuberculosis, malignancy, secondary hypertension and pregnancy were excluded from this study. After a detailed clinical examination, the following investigations were done: For diabetes mellitus: Random blood sugar, fasting blood sugar, post-prandial blood sugar and glycosylated haemoglobin (ERBA Kit. Renal profile: Blood urea and serum creatinine. Serum lipids: Cholesterol, triglyceride (TG, high density lipoprotein (HDL and low density lipoprotein (LDL by commercially available kits (ERBA Kit. Routine urine examination: Sugar and albumin. Estimation of plasma fibrinogen: The plasma fibrinogen was estimated by thrombin-clotting method by using FIBROQUANT KIT [Tulip Diagnostics (P Ltd.]. OBJECTIVES: To know the fibrinogen levels in patients

  20. Uncertainty quantification in MD simulations of concentration driven ionic flow through a silica nanopore. II. Uncertain potential parameters.

    Science.gov (United States)

    Rizzi, F; Jones, R E; Debusschere, B J; Knio, O M

    2013-05-21

    This article extends the uncertainty quantification analysis introduced in Paper I for molecular dynamics (MD) simulations of concentration driven ionic flow through a silica nanopore. Attention is now focused on characterizing, for a fixed pore diameter of D = 21 Å, the sensitivity of the system to the Lennard-Jones energy parameters, ɛ(Na(+)) and ɛ(Cl(-)), defining the depth of the potential well for the two ions Na(+) and Cl(-), respectively. A forward propagation analysis is applied to map the uncertainty in these parameters to the MD predictions of the ionic fluxes. Polynomial chaos expansions and Bayesian inference are exploited to isolate the effect of the intrinsic noise, stemming from thermal fluctuations of the atoms, and properly quantify the impact of parametric uncertainty on the target MD predictions. A Bayes factor analysis is then used to determine the most suitable regression model to represent the MD noisy data. The study shows that the response surface of the Na(+) conductance can be effectively inferred despite the substantial noise level, whereas the noise partially hides the underlying trend in the Cl(-) conductance data over the studied range. Finally, the dependence of the conductances on the uncertain potential parameters is analyzed in terms of correlations with key bulk transport coefficients, namely, viscosity and collective diffusivities, computed using Green-Kubo time correlations.

  1. Association between Plasma Fibrinogen Levels and Mortality in Acute-on-Chronic Hepatitis B Liver Failure

    OpenAIRE

    Zhexin Shao; Ying Zhao; Limin Feng; Guofang Feng; Juanwen Zhang; Jie Zhang

    2015-01-01

    Acute-on-chronic liver failure (AoCLF) is the most common type of liver failure and is associated with high mortality. Fibrinogen is critical in maintaining primary and secondary hemostasis. Therefore, we prospectively analyzed the association between fibrinogen and outcomes in AoCLF patients. Plasma fibrinogen was measured in 169 AoCLF, 173 chronic hepatitis B (CHB), and 171 healthy patients using a coagulation method. The predictive ability of fibrinogen for 3-month mortality in AoCLF patie...

  2. A hemocyte-expressed fibrinogen-related protein gene (LvFrep) from the shrimp Litopenaeus vannamei: Expression analysis after microbial infection and during larval development.

    Science.gov (United States)

    Coelho, Jaqueline da Rosa; Barreto, Cairé; Silveira, Amanda da Silva; Vieira, Graziela Cleusa; Rosa, Rafael Diego; Perazzolo, Luciane Maria

    2016-09-01

    Fibrinogen-related proteins (FREPs) comprise a large family of microbial recognition proteins involved in many biological functions in both vertebrate and invertebrate animals. By taking advantage of publicly accessible databases, we have identified a FREP-like homolog in the most cultivated penaeid shrimp, Litopenaeus vannamei (LvFrep). The obtained sequence showed a conserved fibrinogen-related domain (FReD) and displayed significant similarities to FREP-like proteins from other invertebrates and to ficolins from crustaceans. The expression of LvFrep appeared to be limited to circulating hemocytes. Interestingly, LvFrep gene expression was induced in shrimp hemocytes only in response to a Vibrio infection but not to the White spot syndrome virus (WSSV). Moreover, LvFrep transcript levels were detected early in fertilized eggs, suggesting the participation of this immune-related gene in the antimicrobial defenses during shrimp development.

  3. Signal transduction pathways in erythrocyte nitric oxide metabolism under high fibrinogen levels

    Science.gov (United States)

    Saldanha, Carlota; Freitas, T.; Lopez de Almeida, J. P.; Silva-Herdade, A.

    2014-05-01

    Previous studies show that the fibrinogen molecule modulates the metabolism of nitric oxide (NO) in erythrocyte. The in vitro induced hiperfibrinogenemia interferes in the metabolism of the NO in the erythrocyte in dependence of the phosphorylation degree of the band 3. The soluble form of fibrinogen binds into CD47 protein present in the erythrocyte membrane. The soluble thrombomodulin is an inflammatory marker that binds to the erythrocyte CD47 in a site with a sequence peptide known as 4N1K. A study done in vitro shows that when hiperfibrinogenemia was induced in the presence of the peptide 4N1K agonist of CD47 it were observed variations in the efflux of NO from erythrocyte and an increase in the concentrations of GSNO, peroxinitrite, nitrite and nitrate of the erythrocytes. The aim of this work was to study the influence of the peptide 4N1K, on the metabolism of NO in the erythrocyte under high fibrinogen concentration and in the presence of inhibitors of the status of phosphorylation of protein band 3. In this in vitro study, whole blood samples were harvested from healthy subjects and NO, peroxynitrite, nitrite, nitrate and S-nitro-glutathione (GSNO) were determined in presence of 4N1K, calpeptine, Syk inhibitor and under high fibrinogen concentrations. The results obtained in erythrocytes under high fibrinogen levels when 4N1K is present with the Syk inhibitor or with calpeptine, showed in relation to the control samples increased significant concentrations of efflux of NO and of peroxynitrite, nitrite, nitrate and GSNO. In conclusion it was verified that in the in vitro model of hiperfibrinogenemia the peptide 4N1K, agonist of CD47, induces mobilization of NO in the erythrocyte in dependence of the status of phosphorylation of protein band 3.

  4. Membrane potential and Ca2+ concentration dependence on pressure and vasoactive agents in arterial smooth muscle: A model.

    Science.gov (United States)

    Karlin, Arthur

    2015-07-01

    Arterial smooth muscle (SM) cells respond autonomously to changes in intravascular pressure, adjusting tension to maintain vessel diameter. The values of membrane potential (Vm) and sarcoplasmic Ca(2+) concentration (Ca(in)) within minutes of a change in pressure are the results of two opposing pathways, both of which use Ca(2+) as a signal. This works because the two Ca(2+)-signaling pathways are confined to distinct microdomains in which the Ca(2+) concentrations needed to activate key channels are transiently higher than Ca(in). A mathematical model of an isolated arterial SM cell is presented that incorporates the two types of microdomains. The first type consists of junctions between cisternae of the peripheral sarcoplasmic reticulum (SR), containing ryanodine receptors (RyRs), and the sarcolemma, containing voltage- and Ca(2+)-activated K(+) (BK) channels. These junctional microdomains promote hyperpolarization, reduced Ca(in), and relaxation. The second type is postulated to form around stretch-activated nonspecific cation channels and neighboring Ca(2+)-activated Cl(-) channels, and promotes the opposite (depolarization, increased Ca(in), and contraction). The model includes three additional compartments: the sarcoplasm, the central SR lumen, and the peripheral SR lumen. It incorporates 37 protein components. In addition to pressure, the model accommodates inputs of α- and β-adrenergic agonists, ATP, 11,12-epoxyeicosatrienoic acid, and nitric oxide (NO). The parameters of the equations were adjusted to obtain a close fit to reported Vm and Ca(in) as functions of pressure, which have been determined in cerebral arteries. The simulations were insensitive to ± 10% changes in most of the parameters. The model also simulated the effects of inhibiting RyR, BK, or voltage-activated Ca(2+) channels on Vm and Ca(in). Deletion of BK β1 subunits is known to increase arterial-SM tension. In the model, deletion of β1 raised Ca(in) at all pressures, and these

  5. A comparison of methods used to calculate normal background concentrations of potentially toxic elements for urban soil

    Energy Technology Data Exchange (ETDEWEB)

    Rothwell, Katherine A., E-mail: k.rothwell@ncl.ac.uk; Cooke, Martin P., E-mail: martin.cooke@ncl.ac.uk

    2015-11-01

    To meet the requirements of regulation and to provide realistic remedial targets there is a need for the background concentration of potentially toxic elements (PTEs) in soils to be considered when assessing contaminated land. In England, normal background concentrations (NBCs) have been published for several priority contaminants for a number of spatial domains however updated regulatory guidance places the responsibility on Local Authorities to set NBCs for their jurisdiction. Due to the unique geochemical nature of urban areas, Local Authorities need to define NBC values specific to their area, which the national data is unable to provide. This study aims to calculate NBC levels for Gateshead, an urban Metropolitan Borough in the North East of England, using freely available data. The ‘median + 2MAD’, boxplot upper whisker and English NBC (according to the method adopted by the British Geological Survey) methods were compared for test PTEs lead, arsenic and cadmium. Due to the lack of systematically collected data for Gateshead in the national soil chemistry database, the use of site investigation (SI) data collected during the planning process was investigated. 12,087 SI soil chemistry data points were incorporated into a database and 27 comparison samples were taken from undisturbed locations across Gateshead. The SI data gave high resolution coverage of the area and Mann–Whitney tests confirmed statistical similarity for the undisturbed comparison samples and the SI data. SI data was successfully used to calculate NBCs for Gateshead and the median + 2MAD method was selected as most appropriate by the Local Authority according to the precautionary principle as it consistently provided the most conservative NBC values. The use of this data set provides a freely available, high resolution source of data that can be used for a range of environmental applications. - Highlights: • The use of site investigation data is proposed for land contamination studies

  6. Moderate alcohol consumption reduces plasma C-reactive protein and fibrinogen levels : a randomized, diet-controlled intervention study

    NARCIS (Netherlands)

    Sierksma, A.; Gaag, M.S. van der; Kluft, C.; Hendriks, H.F.J.

    2002-01-01

    Objective: To evaluate the effect of moderate alcohol consumption on the acute phase proteins C-reactive protein and fibrinogen. Design: Randomized, diet-controlled, cross-over study. Setting: The study was performed at TNO Nutrition and Food Research, Zeist, The Netherlands. Subjects: Ten middle-ag

  7. Geographic Concentration and Development Potential of Poultry Microenterprises and Value Chain: A Study Based on Suitable Sites in Gazipur, Bangladesh

    Directory of Open Access Journals (Sweden)

    Syeda Khaleda

    2013-08-01

    Full Text Available In Bangladesh, many poultry microenterprises (MEs have flourished through the lending of microcredit to the poor. These MEs are linked to the value chain and play a significant role in poverty reduction. Not all of these MEs are located in favorable places. Almost all are developed utilizing homestead lands, which results in poor input supply and marketing facilities, and causes higher costs and less profit. This paper tries to uncover the constraints in value chain development, mainly those related to its physical and infrastructural environment; verify the potential of MEs through an analysis of their geographic concentration in sites with different suitability levels; and make recommendations as to how to overcome the constraints, with a view to ensuring higher profit levels for vulnerable poor. The suitability of sites was delineated through Geographic Information System (GIS. The analysis—a combination of field survey data with a site suitability map of farms/MEs concentration—is important, because it helps to validate the GIS analysis-based results of sites’ suitability, helps supporters to design interventions in areas where the farms exist, and thus, helps farmers in vulnerable sites to lift themselves out of poverty.

  8. Evaluation of Fibrinogen Self-assembly: Role of its alphaC Region

    Energy Technology Data Exchange (ETDEWEB)

    J Koo; M Rafailovich; L Medved; G Tsurupa; B Kudryk; y Liu; D Galanakis

    2011-12-31

    Background: Exposure of cryptic, functional sites on fibrinogen upon its adsorption to hydrophobic surfaces of biomaterials has been linked to an inflammatory response and fibrosis. Such adsorption also induces ordered fibrinogen aggregation which is poorly understood. Objective: To investigate hydrophobic surface-induced fibrinogen aggregation. Methods: Contact and lateral force scanning probe microscopy, yielding topography, image dimensions and fiber elastic modulus measurements were used along with transmission and scanning electron microscopy. Fibrinogen aggregation was induced under non-enzymatic conditions by adsorption on a trioctyl-surface monolayer (trioctylmethylamine) grafted onto silica clay plates. Results: A more than one molecule thick coating was generated by adsorption on the plate from 100 to 200 {mu}g mL{sup -1} fibrinogen solutions, and three-dimensional networks formed from 4 mg mL{sup -1} fibrinogen incubated with uncoated or fibrinogen-coated plates. Fibrils appeared laterally assembled into branching and overlapping fibers whose heights from the surface ranged from approximately 3 to 740 nm. The elastic modulus of fibrinogen fibers was 1.55 MPa. No fibrils formed when fibrinogen lacking {alpha}C-domains was used as a coating or was incubated with intact fibrinogen-coated plates, or when the latter plates were sequentially incubated with anti-A{alpha}529-539 mAb and intact fibrinogen. When an anti-A{alpha}241-476 mAb was used instead, fine, long fibers formed. Similarly, sequential incubations of fibrinogen-coated plates with recombinant {alpha}C-domain (A{alpha}392-610 fragment) or {alpha}C-connector (A{alpha}221-372 fragment) and fibrinogen resulted in distinctly fine fiber networks. Conclusions: Adsorption-induced fibrinogen self-assembly is initiated by a more than one molecule-thick surface layer and eventuates in three-dimensional networks whose formation requires fibrinogen with intact {alpha}C-domains.

  9. Genetic variation in estrogen receptor, C-reactive protein and fibrinogen does not predict the plasma levels of inflammation markers after longterm hormone replacement therapy

    DEFF Research Database (Denmark)

    de Maat, Moniek P M; Madsen, Jonna Skov; Langdahl, Bente Lomholt;

    2007-01-01

    Markers of inflammation, such as C-reactive protein (CRP) and fibrinogen, are associated with the risk of atherothrombosis. Plasma levels of these markers of inflammation are affected by hormone replacement therapy (HRT) and modulated by smoking. We studied whether genetic variation in the estrogen...... receptor- 1 (ESR1), CRP and fibrinogen-beta genes influences the plasma levels of inflammation markers after HRT. Plasma CRP and fibrinogen were measured after five years follow-up in healthy postmenopausal women (per-protocol group) who were randomised to hormone therapy (n=187) or no treatment (n=249......). The effect of HRT, smoking and genetic variations in ESR1 (PvuII and XbaI), CRP (1444C/T) and fibrinogen-beta (FGB, -455G/A) were determined. The plasma concentration of CRP was higher in the HRT group than in the control group (2.03 mg/l and 1.41 mg/l, respectively; p

  10. Risk Factors for Postoperative Fibrinogen Deficiency after Surgical Removal of Intracranial Tumors.

    Science.gov (United States)

    Wei, Naili; Jia, Yanfei; Wang, Xiu; Zhang, Yinian; Yuan, Guoqiang; Zhao, Baotian; Wang, Yao; Zhang, Kai; Zhang, Xinding; Pan, Yawen; Zhang, Jianguo

    2015-01-01

    Higher levels of fibrinogen, a critical element in hemostasis, are associated with increased postoperative survival rates, especially for patients with massive operative blood loss. Fibrinogen deficiency after surgical management of intracranial tumors may result in postoperative intracranial bleeding and severely worsen patient outcomes. However, no previous studies have systematically identified factors associated with postoperative fibrinogen deficiency. In this study, we retrospectively analyzed data from patients who underwent surgical removal of intracranial tumors in Beijing Tiantan Hospital date from 1/1/2013to12/31/2013. The present study found that patients with postoperative fibrinogen deficiency experienced more operative blood loss and a higher rate of postoperative intracranial hematoma, and they were given more blood transfusions, more plasma transfusions, and were administered larger doses of hemocoagulase compared with patients without postoperative fibrinogen deficiency. Likewise, patients with postoperative fibrinogen deficiency had poorer extended Glasgow Outcome Scale (GOSe), longer hospital stays, and greater hospital expenses than patients without postoperative fibrinogen deficiency. Further, we assessed a comprehensive set of risk factors associated with postoperative fibrinogen deficiency via multiple linear regression. We found that body mass index (BMI), the occurrence of postoperative intracranial hematoma, and administration of hemocoagulasewere positively associated with preoperative-to-postoperative plasma fibrinogen consumption; presenting with a malignant tumor was negatively associated with fibrinogen consumption. Contrary to what might be expected, intraoperative blood loss, the need for blood transfusion, and the need for plasma transfusion were not associated with plasma fibrinogen consumption. Considering our findings together, we concluded that postoperative fibrinogen deficiency is closely associated with postoperative

  11. Evaluation of Fibrinogen Self-assembly: Role of its αC Region

    Science.gov (United States)

    Koo, Jaseung; Rafailovich, Miriam H.; Medved, Leonid; Tsurupa, Galina; Kudryk, Bohdan J.; Liu, Ying; Galanakis, Dennis K.

    2010-01-01

    SUMMARY Background Exposure of cryptic, functional sites on fibrinogen upon its adsorption to hydrophobic surfaces of biomaterials have been linked to inflammatory response and fibrosis. Such adsorption also induces ordered fibrinogen aggregation which is poorly understood. Objective To investigate hydrophobic surface-induced fibrinogen aggregation. Methods: Contact and lateral force scanning probe microscopy, yielding topography, image dimensions, and fiber elastic modulus measurements were used along with transmission and scanning electron microscopy. Fibrinogen aggregation was induced under non-enzymatic conditions by adsorption on a trioctyl-surface monolayer (trioctylmethylamine) grafted onto silica clay plates. Results A more than one molecule thick coating was generated by adsorption on the plate from 100–200 μg/ml fibrinogen solutions, and three-dimensional networks formed from 4 mg/ml fibrinogen incubated with uncoated or fibrinogen-coated plates. Fibrils appeared laterally assembled into branching and overlapping fibers whose heights from surface ranged from ~3 to 740 nm. The elastic modulus of fibrinogen fibers was 1.55 MPa. No fibrils formed when fibrinogen lacking αC-domains was used as coating or was incubated with intact fibrinogen-coated plates, or when the latter plates were sequentially incubated with anti-Aα529–539 mAb and intact fibrinogen. When an anti-Aα241–476 mAb was used instead, fine, long fibers formed. Similarly, sequential incubations of fibrinogen-coated plates with recombinant αC-domain (Aα392–610 fragment) or αC-connector (Aα221–372 fragment) and fibrinogen resulted in distinctly fine fiber networks. Conclusions Adsorption-induced fibrinogen self-assembly is initiated by a more than one molecule-thick surface layer and eventuates in three-dimensional networks whose formation requires fibrinogen with intact αC-domains. PMID:20880206

  12. Modelling of a solar stove: small scale concentrating system with heat storage: potential for cooking in rural areas, Zimbabwe

    Energy Technology Data Exchange (ETDEWEB)

    Chikukwa, Actor

    2007-10-15

    The central objective of the present research is to serve as an in-depth technical introduction to small-scale concentrating systems tailored for application especially in rural areas in Africa located outside the national electricity grids. For example, MSc and doctoral-students recently matriculated on NUFU-sponsorship at some universities in Africa (i.e Mozambique, Uganda, Tanzania, South Africa and Ethiopia) for research in solar-concentrator technologies will find most of the material in this work quite useful. Chapter 1 discusses the premise on which this research is based. It essentially highlights the gravity of the energy crisis as experienced by the impoverished masses living in most parts of Africa. The situation in Zimbabwe was discussed in detail (for case-studies1) because it is a suitable example added to the convenience of being the country of the author's origin. The second chapter is thus a detailed study on the solar energy resource situation in Zimbabwe. It describes the availability and patterns of solar energy based on the existing solar radiation data obtained from meteorological stations scattered throughout the country. These results were necessary for assessing the potential of the proposed system in Zimbabwe, and can also be extended for use in other solar energy projects. Chapter 3 focuses on the collection of solar radiation using parabolic concentrators. Major determinants that include errors and optical sensitivity of parabolic solar collectors, the correlation between receiver configuration and the parabolic collector are expounded. Arguments for and the main principle on how-to incorporate a mechanical solar tracking device are also laid-out in this part of the thesis. A very critical component of the concentrating system: the volumetric fibrous receiver, is described in the 4th chapter. Here, the theory on which one of the major computer programmes developed in this research, is given an in-depth treatment. The gist of this

  13. Genetic variation in estrogen receptor, C-reactive protein and fibrinogen does not predict the plasma levels of inflammation markers after longterm hormone replacement therapy

    DEFF Research Database (Denmark)

    de Maat, Moniek P M; Madsen, Jonna Skov; Langdahl, Bente;

    2007-01-01

    ). The effect of HRT, smoking and genetic variations in ESR1 (PvuII and XbaI), CRP (1444C/T) and fibrinogen-beta (FGB, -455G/A) were determined. The plasma concentration of CRP was higher in the HRT group than in the control group (2.03 mg/l and 1.41 mg/l, respectively; p ... receptor- 1 (ESR1), CRP and fibrinogen-beta genes influences the plasma levels of inflammation markers after HRT. Plasma CRP and fibrinogen were measured after five years follow-up in healthy postmenopausal women (per-protocol group) who were randomised to hormone therapy (n=187) or no treatment (n=249...... concentration (n.s.). Genetic polymorphisms in ESR1, CRP and fibrinogen were not associated with an effect of HRT on the CRP and fibrinogen plasma levels, and no significant interaction with smoking was observed. In conclusion, higher plasma levels of CRP and lower plasma levels of fibrinogen were observed...

  14. Developmental expression and organisation of fibrinogen genes in the zebrafish.

    Science.gov (United States)

    Fish, Richard J; Vorjohann, Silja; Béna, Frédérique; Fort, Alexandre; Neerman-Arbez, Marguerite

    2012-01-01

    The zebrafish is a model organism for studying vertebrate development and many human diseases. Orthologues of the majority of human coagulation factors are present in zebrafish, including fibrinogen. As a first step towards using zebrafish to model human fibrinogen disorders, we cloned the zebrafish fibrinogen cDNAs and made in situ hybridisations and quantitative reverse transcription-polymerase chain reactions (qRT-PCR) to detect zebrafish fibrinogen mRNAs. Prior to liver development or blood flow we detected zebrafish fibrinogen expression in the embryonic yolk syncytial layer and then in the early cells of the developing liver. While human fibrinogen is encoded by a three-gene, 50 kilobase (kb) cluster on chromosome 4 ( FGB-FGA-FGG ), recent genome assemblies showed that the zebrafish fgg gene appears distanced from fga and fgb , which we confirmed by in situ hybridisation. The zebrafish fibrinogen Bβ and γ protein chains are conserved at over 50% of amino acid positions, compared to the human polypeptides. The zebrafish Aα chain is less conserved and its C-terminal region is nearly 200 amino acids shorter than human Aα. We generated transgenic zebrafish which express a green fluorescent protein reporter gene under the control of a 1.6 kb regulatory region from zebrafish fgg . Transgenic embryos showed strong fluorescence in the developing liver, mimicking endogenous fibrinogen expression. This regulatory sequence can now be used for overexpression of transgenes in zebrafish hepatocytes. Our study is a proof-of-concept step towards using zebrafish to model human disease linked to fibrinogen gene mutations.

  15. The recombinant LIC10508 is a plasma fibronectin, plasminogen, fibrinogen and C4BP-binding protein of Leptospira interrogans.

    Science.gov (United States)

    Siqueira, Gabriela H; Teixeira, Aline F; Fernandes, Luis G; de Souza, Gisele O; Kirchgatter, Karin; Romero, Eliete C; Vasconcellos, Silvio A; Vieira, Monica L; Nascimento, Ana Lucia T O

    2016-03-01

    Leptospirosis is a zoonosis caused by pathogenic Leptospira spp. In this study, we report that the recombinant proteins LIC10507, LIC10508 and LIC10509 are recognized by confirmed leptospirosis serum samples at both phases of the disease. The recombinant rLIC10508 and rLIC10507 are plasminogen (PLG)-binding proteins, capable of generating plasmin in the presence of a PLG activator. The proteins bind to PLG in a dose-dependent and saturable manner, fulfilling host-ligand interaction. Furthermore, rLIC10508 interacts with fibrinogen (Fg), plasma fibronectin and C4b binding protein (C4BP). The binding of rLIC10508 to Fg decreases the fibrin clotting in a thrombin-catalyzed reaction. The incubation with 4 μM of protein promoted 40% inhibition upon clotting formation. C4BP bound to rLIC10508 retained its cofactor activity for factor I promoting the cleavage of C4b protein, which may reduce the membrane attack complex formation. Although these proteins have high amino acid sequence similarity, rLIC10508 is the most talented of the three, a behavior that might be explained by its unique putative 3D structure, whereas structures of rLIC10507 and rLIC10509 are very similar. Plasmin generation (rLIC10507 and rLIC10508), together with decreasing fibrin clot formation (rLIC10508) and impairment of the complement system (rLIC10508) may help the bacteria to overcome host defense, facilitating the infection process.

  16. Preoperative CA125 and fibrinogen in patients with endometrial cancer: a risk model for predicting lymphovascular space invasion

    Science.gov (United States)

    2017-01-01

    Objective The aim of this study was to build a model to predict the risk of lymphovascular space invasion (LVSI) in women with endometrial cancer (EC). Methods From December 2010 to June 2013, 211 patients with EC undergoing surgery at Shanghai First Maternity and Infant Hospital were enrolled in this retrospective study. Those patients were divided into a positive LVSI group and a negative LVSI group. The clinical and pathological characteristics were compared between the two groups; logistic regression was used to explore risk factors associated with LVSI occurrence. The threshold values of significant factors were calculated to build a risk model and predict LVSI. Results There were 190 patients who were negative for LVSI and 21 patients were positive for LVSI out of 211 patients with EC. It was found that tumor grade, depth of myometrial invasion, number of pelvic lymph nodes, and International Federation of Gynecology and Obstetrics (FIGO) stage (p0.05) were not associated with LVSI. Receiver operating characteristic (ROC) curves revealed that the threshold values of the following factors were correlated with positive LVSI: 28.1 U/mL of CA19-9, 21.2 U/mL of CA125, 2.58 mg/dL of fibrinogen (Fn), 1.84 U/mL of carcinoembryonic antigen (CEA) and (6.35×109)/L of white blood cell (WBC). Logistic regression analysis indicated that CA125 ≥21.2 (p=0.032) and Fn ≥2.58 mg/dL (p=0.014) were significantly associated with LVSI. Conclusion Positive LVSI could be predicted by CA125 ≥21.2 U/mL and Fn ≥2.58 mg/dL in women with EC. It could help gynecologists better adapt surgical staging and adjuvant therapies. PMID:27894164

  17. Homocysteine influences blood clot properties alone and in combination with total fibrinogen but not with fibrinogen γ' in Africans.

    Science.gov (United States)

    Nienaber-Rousseau, Cornelie; de Lange, Zelda; Pieters, Marlien

    2015-06-01

    Simultaneously increased fibrinogen and homocysteine (Hcy) in blood are believed to elevate the risk of cardiovascular disease mortality. However, the pathophysiological mechanisms involved are unknown. We sought to determine whether Hcy or its genetic determinants influence blood clot properties alone or in combination with fibrinogen. In addition, we investigated, for the first time, the gamma prime (γ') isoform of fibrinogen with Hcy in relation to clot architecture and lysis. Single-nucleotide polymorphisms, Hcy and hemostatic variables, including clot lysis, determined with a global fibrinolytic assay [giving lag time, slope, maximum absorbance and clot lysis time (CLT)], were measured in 1867 healthy black South Africans and cross-sectionally analyzed. Increasing Hcy did not affect fiber cross-sectional area (maximum absorbance). However, it decreased the time needed to initiate the coagulation cascade and for fibrin fibers to grow (lag time), it increased the tempo of lateral aggregation (slope) and reduced CLT. None of the single-nucleotide polymorphisms measured had effects on clot properties. Combined effects were observed between Hcy and total fibrinogen in predicting CLT. Fibrinogen γ', which affected markers of the fibrinolytic assay, did not have conjoint effects with Hcy. We believe that there is value in recognizing the combined effects of Hcy and fibrinogen, but not its γ' isoform in relation to clot structure and lysis. The enhanced fibrinolysis rate observed in patients with low fibrinogen and high Hcy may have adverse consequences for health if it disturbs hemostasis and results in a bleeding tendency.

  18. Fibrinogen in trauma, an evaluation of thrombelastography and rotational thromboelastometry fibrinogen assays

    DEFF Research Database (Denmark)

    Meyer, Martin A S; Ostrowski, Sisse R; Sørensen, Anne Marie

    2015-01-01

    BACKGROUND: Identifying hypofibrinogenemia in trauma is important. The optimal method of fibrinogen determination is unknown. We therefore evaluated fibrinogen levels determined by two whole blood viscoelastic hemostatic assays, thrombelastography functional fibrinogen (FF) and rotational thrombo...

  19. The fibrous form of intracellular inclusion bodies in recombinant variant fibrinogen-producing cells is specific to the hepatic fibrinogen storage disease-inducible variant fibrinogen.

    Science.gov (United States)

    Arai, Shinpei; Ogiwara, Naoko; Mukai, Saki; Takezawa, Yuka; Sugano, Mitsutoshi; Honda, Takayuki; Okumura, Nobuo

    2017-06-01

    Fibrinogen storage disease (FSD) is a rare disorder that is characterized by the accumulation of fibrinogen in hepatocytes and induces liver injury. Six mutations in the γC domain (γG284R, γT314P, γD316N, the deletion of γG346-Q350, γG366S, and γR375W) have been identified for FSD. Our group previously established γ375W fibrinogen-producing Chinese hamster ovary (CHO) cells and observed aberrant large granular and fibrous forms of intracellular inclusion bodies. The aim of this study was to investigate whether fibrous intracellular inclusion bodies are specific to FSD-inducible variant fibrinogen. Thirteen expression vectors encoding the variant γ-chain were stably or transiently transfected into CHO cells expressing normal fibrinogen Aα- and Bβ-chains or HuH-7 cells, which were then immunofluorescently stained. Six CHO and HuH-7 cell lines that transiently produced FSD-inducible variant fibrinogen presented the fibrous (3.2-22.7 and 2.1-24.5%, respectively) and large granular (5.4-25.5 and 7.7-23.9%) forms of intracellular inclusion bodies. Seven CHO and HuH-7 cell lines that transiently produced FSD-non-inducible variant fibrinogen only exhibit the large granular form. These results demonstrate that transiently transfected variant fibrinogen-producing CHO cells and inclusion bodies of the fibrous form may be useful in non-invasive screening for FSD risk factors for FSD before its onset.

  20. An investigation of serum concentration of apoM as a potential MODY3 marker using a novel ELISA.

    Science.gov (United States)

    Cervin, C; Axler, O; Holmkvist, J; Almgren, P; Rantala, E; Tuomi, T; Groop, L; Dahlbäck, B; Karlsson, E

    2010-03-01

    To investigate the fitness of serum apolipoprotein M (apoM) concentration as a marker for maturity-onset diabetes of the young 3 (MODY3). This study consisted of two parts. A family study included 71 carriers of the P291fsinsC mutation in hepatocyte nuclear factor-1alpha (HNF-1alpha) from the Finnish Botnia study, 53 of whom were diabetic, and 75 matched family controls. A second, case-control study included 24 MODY3 patients, 17 healthy MODY3 mutation carriers, 11 MODY1 patients, 18 type 2 diabetes patients and 19 healthy control individuals. Subjects in the case-control study were recruited from the Botnia study or the Clinic of Endocrinology, Malmö University Hospital. Serum apoM levels were measured using a novel ELISA based on two monoclonal apoM antibodies. In the family study, mean serum apoM was 10% lower in female carriers of the P291fsinsC mutation compared to the family controls (P = 0.0058), a difference which remained significant after adjustment for diabetes status. There was no observed difference between groups for men. In the case-control study, no significant difference in apoM concentration was observed between MODY3 and type 2 diabetes patients, neither before nor after adjustment for total cholesterol. Female carriers of the P291fsinsC mutation in HNF-1alpha displayed slightly lower apoM serum levels. This difference is too small for apoM to be reliably employed as a biomarker for HNF-1alpha mutation status.

  1. [Study on the selective removal of plasma low-density lipoprotein and fibrinogen by degraded carrageenan].

    Science.gov (United States)

    Cong, Haixia; Yin, Liang; Fang, Bo; Du, Longbing; Zhao, Hui; Chen, Jingling; You, Chao

    2010-08-01

    The selective removal of low density lipoprotein (LDL) and fibrinogen (Fib) by degraded carrageenan was studied by the present authors. Degraded carrageenan was prepared by acid with carrageenan as the main material. The effects of acid conditions on the molecular weight were investigated, and the proper reaction conditions were ascertained. The results of infrared spectrometry indicated that the degraded carrageenan is a heparin-like polysaccharide. Then the selective removal of LDL/Fibrinogen by degraded carrageenan was studied. When molecular weight was about 10,000, pH was 5.10 and the concentration of degraded carrageenan was 800 mg/L, the average reduction percentages were 60.0% for total cholesterol(TC), 79.4% for LDL and very low-density lipoprotein (VLDL), and 93.8% for fibrinogen. There were no significant changes with relation to the level of high-density lipoprotein (HDL) and total protein (TP). So, degraded carrageenan was shown to be of good selectivity on plasma LDL/Fibrinogen apheresis.

  2. Subtoxic concentrations of allergenic haptens induce LC migration and maturation in a human organotypic skin explant culture model: A novel method for identifying potential contact allergens

    NARCIS (Netherlands)

    Lehé, C.L.; Jacobs, J.J.L.; Hua, C.M.; Courtellemont, P.; Elliott, G.R.; Das, P.K.

    2006-01-01

    The accelerated migration of Langerhans cells (LCs) out of the epidermis and up-regulation of maturation markers, upon treatment with subtoxic concentrations of chemicals, were used as the criteria to determine the potential of allergenic chemicals capable of inducing a hapten-specific delayed-type

  3. Fibrinogen depletion in trauma: early, easy to estimate and central to trauma-induced coagulopathy

    OpenAIRE

    Davenport, Ross; Brohi, Karim

    2013-01-01

    Fibrinogen is fundamental to hemostasis and falls rapidly in trauma hemorrhage, although levels are not routinely measured in the acute bleeding episode. Prompt identification of critically low levels of fibrinogen and early supplementation has the potential to correct trauma-induced coagulation and improve outcomes. Early estimation of hypofibrinogenemia is possible using surrogate markers of shock and hemorrhage; for example, hemoglobin and base excess. Rapid replacement with fibrinogen con...

  4. A framework to estimate concentrations of potentially unknown substances by semi-quantification in liquid chromatography electrospray ionization mass spectrometry

    DEFF Research Database (Denmark)

    Pieke, Eelco Nicolaas; Granby, Kit; Trier, Xenia

    2017-01-01

    screening. The method was successfully applied to an extract of food contact material containing over 300 unknown substances. Without identification and authentic standards, the method was able to estimate the concentration of a virtually unlimited number of compounds thereby providing valuable data...

  5. Immunohistochemical evaluation of tissue factor, fibrin/fibrinogen and D-dimers in canine gliomas.

    Science.gov (United States)

    de la Fuente, Cristian; Pumarola, Martí; Blasco, Ester; Fernández, Francisco; Viu, Judit; Añor, Sònia

    2014-06-01

    In human gliomas, tissue factor (TF) is overexpressed, associated with the grade of malignancy and influences tumour biology. Intra-tumoural fibrin/fibrinogen deposition and activation of the fibrinolytic system also play a role in tumour cell proliferation and angiogenesis. The first aim of the present study was to investigate TF expression and the presence of fibrin/fibrinogen and D-dimers in canine glioma biopsies, graded according to the World Health Organization (WHO) classification of tumours of the central nervous system. The second aim was to investigate the occurrence of intravascular thrombosis (IVT) in canine gliomas, as a potential histological marker of glioma type or grade of malignancy. An immunohistochemical study using antibodies against TF, fibrin/fibrinogen and D-dimers was performed with 24 glioma samples, including 15 oligodendrogliomas, 6 astrocytomas and 3 mixed gliomas. Immunohistochemical data were statistically analysed to determine whether there was any relationship between glioma type and grade of malignancy. All gliomas were moderate to strongly positive for TF and the staining score was significantly higher (P = 0.04) in high-grade (III or IV) than in low-grade (II) gliomas. Intra-tumoural fibrin/fibrinogen deposition was detected in all tumour biopsies assessed, and D-dimers were detected in 17/24 gliomas. IVT was a frequent finding, but was not linked to a specific glioma type or malignancy grade. TF expression, fibrin/fibrinogen deposition, extravascular fibrinolytic system activation and IVT occur in canine gliomas. Canine glioma might be a suitable model for studying coagulation and fibrinolysis as potential therapeutic targets for human gliomas.

  6. UafB is a serine-rich repeat adhesin of Staphylococcus saprophyticus that mediates binding to fibronectin, fibrinogen and human uroepithelial cells.

    Science.gov (United States)

    King, Nathan P; Beatson, Scott A; Totsika, Makrina; Ulett, Glen C; Alm, Richard A; Manning, Paul A; Schembri, Mark A

    2011-04-01

    Staphylococcus saprophyticus is an important cause of urinary tract infection (UTI), particularly among young women, and is second only to uropathogenic Escherichia coli as the most frequent cause of UTI. The molecular mechanisms of urinary tract colonization by S. saprophyticus remain poorly understood. We have identified a novel 6.84 kb plasmid-located adhesin-encoding gene in S. saprophyticus strain MS1146 which we have termed uro-adherence factor B (uafB). UafB is a glycosylated serine-rich repeat protein that is expressed on the surface of S. saprophyticus MS1146. UafB also functions as a major cell surface hydrophobicity factor. To characterize the role of UafB we generated an isogenic uafB mutant in S. saprophyticus MS1146 by interruption with a group II intron. The uafB mutant had a significantly reduced ability to bind to fibronectin and fibrinogen. Furthermore, we show that a recombinant protein containing the putative binding domain of UafB binds specifically to fibronectin and fibrinogen. UafB was not involved in adhesion in a mouse model of UTI; however, we observed a striking UafB-mediated adhesion phenotype to human uroepithelial cells. We have also identified genes homologous to uafB in other staphylococci which, like uafB, appear to be located on transposable elements. Thus, our data indicate that UafB is a novel adhesin of S. saprophyticus that contributes to cell surface hydrophobicity, mediates adhesion to fibronectin and fibrinogen, and exhibits tropism for human uroepithelial cells.

  7. Revealing fibrinogen monolayer conformations at different pHs: electrokinetic and colloid deposition studies.

    Science.gov (United States)

    Nattich-Rak, Małgorzata; Adamczyk, Zbigniew; Wasilewska, Monika; Sadowska, Marta

    2015-07-01

    Adsorption mechanism of human fibrinogen on mica at different pHs is studied using the streaming potential and colloid deposition measurements. The fibrinogen monolayers are produced by a controlled adsorption under diffusion transport at pH of 3.5 and 7.4. Initially, the electrokinetic properties of these monolayers and their stability for various ionic strength are determined. It is shown that at pH 3.5 fibrinogen adsorbs irreversibly on mica for ionic strength range of 4×10(-4) to 0.15 M. At pH 7.4, a partial desorption is observed for ionic strength below 10(-2) M. This is attributed to the desorption of the end-on oriented molecules whereas the side-on adsorbed molecules remain irreversibly bound at all ionic strengths. The orientation of molecules and monolayer structure is evaluated by the colloid deposition measurements involving negatively charged polystyrene latex microspheres, 820 nm in diameter. An anomalous deposition of negative latex particles on substrates exhibiting a negative zeta potential is observed. At pH 3.5 measurable deposition of latex is observed even at low ionic strength where the approach distance of latex particles exceeded 70 nm. At pH 7.4 this critical distance is 23 nm. This confirms that fibrinogen monolayers formed at both pHs are characterized by the presence of the side-on and end-on oriented molecules that prevail at higher coverage range. It is also shown that positive charge is located at the end parts of the αA chains of the adsorbed fibrinogen molecules. Therefore, it is concluded that the colloid deposition method is an efficient tool for revealing protein adsorption mechanisms at solid/electrolyte interfaces.

  8. Molecular weight fibrinogen variants determine angiogenesis rate in a fibrin matrix in vitro and in vivo

    NARCIS (Netherlands)

    Kaijzel, E.L.; Koolwijk, P.; Erck, M.G.M. van; Hinsbergh, V.W.M. van; Maat, M.P.M. de

    2006-01-01

    Background: During wound repair, fibrin acts both as a barrier to prevent blood loss and as a temporary matrix for the invasion and ingrowth of endothelial and tissue cells. A well-controlled angiogenesis process in the fibrinous exudate matrix is crucial for optimal wound healing. The composition a

  9. Development of a Fibrinogen-Specific Sandwich Enzyme-Linked Immunosorbent Assay Microarray Assay for Distinguishing Between Blood Plasma and Serum Samples

    Energy Technology Data Exchange (ETDEWEB)

    Gonzales, Rachel M.; Zhang, Qibin; Zangar, Richard C.; Smith, Richard D.; Metz, Thomas O.

    2011-07-01

    We have developed a fibrinogen-specific sandwich ELISA microarray assay for use in qualitatively distinguishing between blood plasma and serum samples. Three capture antibodies, 49D2, HPA001900, and F8512, were evaluated in conjunction with 1D6 as detection antibody, and the data show that 49D2 and, to a lesser extent, F8512 successfully identify previously unknown plasma and serum samples based upon a ~28-fold difference in signal intensity between the sample types. This assay has utility in rapidly identifying previously archived clinical samples with incomplete annotation in a high throughput manner prior to proteomics analyses.

  10. Familial dysfibrinogenemia and thrombophilia - Report on a study of the SSC subcommittee on fibrinogen

    NARCIS (Netherlands)

    Haverkate, F.; Samama, M.

    1995-01-01

    Approximately 250 cases of dysfibrinogenemia have been reported; 55% were asymptomatic (detected by chance), 25% had a tendency to bleeding, and 20% were reported to have a tendency to thrombosis. To establish a possible association between familial dysfibrinogenemia and thrombophilia, data on cases

  11. Familial dysfibrinogenemia and thrombophilia - Report on a study of the SSC subcommittee on fibrinogen

    NARCIS (Netherlands)

    Haverkate, F.; Samama, M.

    1995-01-01

    Approximately 250 cases of dysfibrinogenemia have been reported; 55% were asymptomatic (detected by chance), 25% had a tendency to bleeding, and 20% were reported to have a tendency to thrombosis. To establish a possible association between familial dysfibrinogenemia and thrombophilia, data on cases

  12. Lack of a 5.9 kDa peptide C-terminal fragment of fibrinogen α chain precedes fibrosis progression in patients with liver disease.

    Directory of Open Access Journals (Sweden)

    Santiago Marfà

    Full Text Available Early detection of fibrosis progression is of major relevance for the diagnosis and management of patients with liver disease. This study was designed to find non-invasive biomarkers for fibrosis in a clinical context where this process occurs rapidly, HCV-positive patients who underwent liver transplantation (LT. We analyzed 93 LT patients with HCV recurrence, 41 non-LT patients with liver disease showing a fibrosis stage F≥1 and 9 patients without HCV recurrence who received antiviral treatment before LT, as control group. Blood obtained from 16 healthy subjects was also analyzed. Serum samples were fractionated by ion exchange chromatography and their proteomic profile was analyzed by SELDI-TOF-MS. Characterization of the peptide of interest was performed by ion chromatography and electrophoresis, followed by tandem mass spectrometry identification. Marked differences were observed between the serum proteome profile of LT patients with early fibrosis recurrence and non-recurrent LT patients. A robust peak intensity located at 5905 m/z was the distinguishing feature of non-recurrent LT patients. However, the same peak was barely detected in recurrent LT patients. Similar results were found when comparing samples of healthy subjects with those of non-LT fibrotic patients, indicating that our findings were not related to either LT or HCV infection. Using tandem mass-spectrometry, we identified the protein peak as a C-terminal fragment of the fibrinogen α chain. Cell culture experiments demonstrated that TGF-β reduces α-fibrinogen mRNA expression and 5905 m/z peak intensity in HepG2 cells, suggesting that TGF-β activity regulates the circulating levels of this protein fragment. In conclusion, we identified a 5.9 kDa C-terminal fragment of the fibrinogen α chain as an early serum biomarker of fibrogenic processes in patients with liver disease.

  13. The basis for fibrinogen Cedar Rapids ({gamma}R275C) fibrin network structure

    Energy Technology Data Exchange (ETDEWEB)

    DiOrio, J.P. [Baxter Healthcare Corp., Round Lake, IL (United States); Mosesson, M.W.; Siebenlist, K.R. [Univ. Wisconsin Medical School-Milwaukee Clinic Campus, WI (United States)] [and others

    1996-12-31

    Fibrinogen `Cedar Rapids` is a heterozygous dysfibrinogenemia characterized by delayed and abnormal fibrin polymerization. The specific molecular defect ({gamma}R275C) is relatively common, but in only one case, fibrinogen Tokyo II, has the ultrastructural basis for defective clot formation been determined. This report reflects similar structural studies on Cedar Rapids fibrinogen and fibrin. Crosslinked fibrinogen molecules and fibrils, were prepared at 1 mg/ml in the presence of factor XIIIa (100 u/ml). When {gamma} chains had become {approximately}10 to 20% crosslinked to {gamma} dimers, samples were diluted with Hepes buffered saline, pH 7, to a fibrinogen concentrated of 5 to 10 {mu}g/ml. Three {mu}l was then injected into 3 {mu}l buffer on a carbon-coated EM grid, the specimen allowed to attach for one minute, fluid-exchanged several times with 150 mM NH{sub 4} acetate solution, frozen in liquid nitrogen, freeze-dried, and imaged at the Brookhaven STEM facility using a 40 kv probe focused at 0.25 nm. Fibrin for scanning EM (SEM) was formed directly on carbon-formvar coated gold grids. Clots that had formed overnight were fixed with 2.5% glutaraldehyde in 0.1 M Hepes, pH 7 buffer containing 0.2% tannic acid, washed with buffer, dehydrated, CO{sub 2} critical point dried, coated with 7.5 nm platinum, and imaged in a JOEL Field Emission SEM operated at 5 kV.

  14. A potential dating technique using 228Th/228Ra ratio for tracing the chronosequence of elemental concentrations in plants.

    Science.gov (United States)

    Chao, J H; Niu, H; Chiu, C Y; Lin, C

    2007-06-01

    We propose a radiometric method based on measurement of the radioactivity of the naturally occurring radionuclides (228)Ra and 228)Th and the derived (228)Th/(228)Ra ratios in plant samples to estimate plant age and the corresponding nutritional conditions in a field-growing fern, Dicranopteris linearis. Plant age (tissue age) was associated with the (228)Th/(228)Ra ratio in fronds, which implies the accumulation time of immobile elements in the plant tissue or the life span of the fronds. Results indicated that the accumulation of alkaline earth elements in D. linearis is relatively constant with increased age, while the K concentration is reversed with age because of translocation among plant tissues. Estimation of dating uncertainty based on measurement conditions revealed that the radiometric technique can be applied to trace chronosequential changes of elemental concentrations and environmental pollutants in plants with ages of less than 10-15 years.

  15. Oral fibrinogen-depleting agent lumbrokinase for secondary ischemic stroke prevention: results from a multicenter, randomized, parallel-group and controlled clinical trial

    Institute of Scientific and Technical Information of China (English)

    CAO Yong-jun; ZHANG Xia; WANG Wan-hua; ZHAI Wan-qing; QIAN Ju-fen; WANG Jian-sheng; CHEN Jun

    2013-01-01

    Background Elevated fibrinogen (Fg) level is a known risk factor for ischemic stroke.There are few clinical trials on oral fibrinogen-depleting therapies for secondary ischemic stroke prevention.We aimed to assess the effects of one-year therapy with oral lumbrokinase enteric-coated capsules on secondary ischemic stroke prevention.Methods This is a multicenter,randomized,parallel group and controlled study that began treatment in hospitalized patients with ischemic stroke and continued for 12 months.Patients were randomized to either the control group that received the standard stroke treatment or the fibrinogen-depleting group that received the standard stroke treatment plus enteric-coated lumbrokinase capsules.The NIH Stroke Scale scores (NIHSSs) and plasma Fg level were recorded.The carotid artery intima-media thickness (IMT) and status of plaques were examined through carotid ultrasound examination.Primary outcomes included all-cause mortality,any event of recurrent ischemic stroke/transient ischemic attack (TIA),hemorrhagic stroke,myocardial infarction and angina,and other noncerebral ischemia or hemorrhage.Kaplan-Meier survival analysis and the Long-rank test were used to compare total vascular end point incidence between the two groups.Comparison of median values between two groups was done by the Student t test,one-way analysis of variance (ANOVA),or non-parametric rank sum test.Results A total of 310 patients were enrolled,192 patients in the treatment group and 118 patients in the control group.Compared to the control group,the treatment group showed favorable outcomes in the Fg level,carotid IMT,the detection rate of vulnerable plaques,the volume of carotid plaques,NIHSS scores,and incidence of total vascular (6.78% and 2.08%,respectively) and cerebral vascular events (5.93% and 1.04%,respectively) (P <0.05).In the treatment group,the volume of carotid plaques was significantly related to the carotid IMT,the plaque diameter,width and number (P

  16. Sensitive Immunoassays of Nitrated Fibrinogen in Human Biofluids

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Zhiwen; Wu, Hong; Du, Dan; Wang, Jun; Wang, Hua; Qian, Weijun; Bigelow, Diana J.; Pounds, Joel G.; Smith, Richard D.; Lin, Yuehe

    2010-05-05

    Three new sandwich immunoassays for detection of nitrated biomarker have been established with potential applications in biomedical studies and clinical practice. In this study, nitrated human fibrinogen, a potential oxidative stress biomarker for several pathologies, was chosen as the target. To improve the sensitivity and overcome the interference caused by the complexity of human biofluids, we developed three sandwich strategies using various combinations of primary antibody and secondary antibody. All three strategies demonstrated high sensitivity and selectivity towards nitrated forms of fibrinogen in buffer, but their performances were dramatically reduced when tested with human plasma and serum samples. Systematically optimizations were carried out to investigate the effects of numerous factors, including sampling, coating, blocking, and immunoreactions. Our final optimization results indicate that two of these strategies retain sufficient sensitivity and selectivity for use as assays in human physiological samples. Specifically, detection limits reached the pM level and the linear response ranges were up to nM level with a correlation coefficient > 0.99. To our best knowledge, this is the first example of using an electrochemical immunoassay for a nitrated biomarker in a physiological fluid. This novel approach provides a rapid, sensitive, selective, cost efficient and robust bioassay for detection of oxidative stress in pathology and for clinical applications. Moreover, the sandwich strategies developed in this paper can be readily used to establish effective methods targeting other nitration biomarkers.

  17. Follicular fluid oocyte/cumulus-free DNA concentrations as a potential biomolecular marker of embryo quality and IVF outcome.

    Science.gov (United States)

    Dimopoulou, M; Anifandis, G; Messini, C I; Dafopoulos, K; Kouris, S; Sotiriou, S; Satra, M; Vamvakopoulos, N; Messinis, I E

    2014-01-01

    The present prospective study examined the follicular fluid oocyte/cumulus-free DNA concentrations (ff o/c-free DNA) during ovarian stimulation and the possible association between ff o/c-free DNA and embryological results such as embryo quality and pregnancy rate. Eighty-three women undergoing IV/ICSI-ET treatments were prospectively included in this study. ff o/c-free DNA was determined by conventional quantitative real time PCR-Sybr green detection approach. The 83 ff samples were categorized in two groups: group 1 (n = 62) with cumulus oocytes complexes (CoCs) ≥2 and group 2 (n = 21) with CoCs = 1. Group 1 revealed significant higher embryo quality in terms of mean score of embryo transfer (MSET), but lower ff o/c-free DNA concentrations compared to group 2. The two groups showed comparable pregnancy rates (positive hCG and clinical pregnancy). The higher the ff o/c-free DNA concentration, the lower the number of produced oocytes. ff o/c-free DNA did not seem to have any direct role in the IVF outcome. Further research is required to clarify whether ff o/c-free DNA is a biomolecular marker of embryo quality and IVF outcome.

  18. Elevated plasma fibrinogen associated with reduced pulmonary function and increased risk of chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Dahl, Morten; Tybjaerg-Hansen, A; Vestbo, J

    2001-01-01

    We tested whether increased concentrations of the acute-phase reactant fibrinogen correlate with pulmonary function and rate of chronic obstructive pulmonary disease (COPD) hospitalization. We measured plasma fibrinogen and forced expiratory volume in 1 s (FEV(1)), and assessed prospectively COPD...

  19. Impact of plasma fibrinogen levels in benign and malignant soft tissue tumors.

    Science.gov (United States)

    Asanuma, Kunihiro; Matsumine, Akihiko; Nakamura, Tomoki; Matsubara, Takao; Asanuma, Yumiko; Oi, Toru; Goto, Mikinobu; Okuno, Kazuma; Kakimoto, Takuya; Yada, Yuuki; Sudo, Akihiro

    2016-01-01

    Fibrinogen, a 340 kDa glycoprotein synthesized in the liver, is known to be involved in tumor angiogenesis, enlargement, and metastasis. Elevated plasma fibrinogen levels are associated with tumor progression in many cancer patients. However, there are no reports about differences in fibrinogen levels between benign and malignant soft tissue tumors. The purpose of this study was to clarify whether preoperative plasma fibrinogen levels can be used for differential diagnosis of benign or malignant soft tissue tumors. The plasma fibrinogen levels from 102 primary soft tissue tumor patients were measured before biopsy or treatment. Fibrinogen levels were analyzed and compared to various clinical parameters. According to receiver operating characteristic (ROC) curve analysis, a threshold of serum fibrinogen of 315 mg/dL identified malignant patients with 60.9% sensitivity and 87.5% specificity. The diagnostic accuracy was evaluated by area under the curve (AUC: 0.805). Over 315 mg/dL of fibrinogen was associated with a significantly increased risk of malignancy by multiple logistic regression analysis (OR: 6.452, p= 0.0004). We demonstrated that plasma fibrinogen levels have a relationship with tumor malignancy of soft tissue tumors. High fibrinogen levels can be a helpful subsidiary tool for the prediction of malignant soft tissue tumors with other diagnostic tools.

  20. Complementary effect of fibrinogen and rFVIIa on clotting ex vivo in Bernard-Soulier syndrome and combined use during three deliveries

    DEFF Research Database (Denmark)

    Palsson, Ragnar; Vidarsson, Brynjar; Gudmundsdottir, Brynja R

    2014-01-01

    coagulation profile of a pregnant woman with BSS before and after spiking ex vivo with different concentrations of recombinant activated factor VII (rFVIIa) and fibrinogen. As experiments suggested improved clotting with clinically applicable concentrations of both agents in a complementary manner...

  1. Surface characterization and AFM imaging of mixed fibrinogen-surfactant films.

    Science.gov (United States)

    Hassan, Natalia; Maldonado-Valderrama, Julia; Gunning, A Patrick; Morris, Victor J; Ruso, Juan M

    2011-05-19

    This study describes the adsorption behavior of mixed protein/surfactant systems at the air-water interface: specifically fibrinogen and the fluorinated and hydrogenated surfactants (C(8)FONa, C(8)HONa, and C(12)HONa). Surface tension techniques and atomic force microscopy (AFM) have been combined to investigate the adsorption behavior of these mixed systems. Interfacial rheology showed that fibrinogen has a low dilatational modulus at the air-water interface when compared to other proteins, suggesting the formation of a weak surface network. Fluorinated and hydrogenated surfactants severely decreased the dilatational modulus of the adsorbed fibrinogen film at the air-water interface. These measurements suggest the progressive displacement of fibrinogen from the air-water interface by both types of surfactants. However, in the case of fibrinogen/fluorinated surfactant systems, surface tension and dilatational rheology measurements suggest the formation of complexes with improved surface activity. AFM imaging of fibrinogen in the presence and absence of surfactants provided new information on the structure of mixed surface films, and revealed new features of the interaction of fibrinogen with hydrogenated and fluorinated surfactants. These studies suggest complexes formed between fibrinogen and fluorinated surfactants which are more surface active than fibrinogen, while the absence of interaction between fibrinogen and hydrogenated surfactants (C(8)HONa and C(12)HONa) results in compaction of the surface layer.

  2. Association between plasma fibrinogen levels and mortality in acute-on-chronic hepatitis B liver failure.

    Science.gov (United States)

    Shao, Zhexin; Zhao, Ying; Feng, Limin; Feng, Guofang; Zhang, Juanwen; Zhang, Jie

    2015-01-01

    Acute-on-chronic liver failure (AoCLF) is the most common type of liver failure and is associated with high mortality. Fibrinogen is critical in maintaining primary and secondary hemostasis. Therefore, we prospectively analyzed the association between fibrinogen and outcomes in AoCLF patients. Plasma fibrinogen was measured in 169 AoCLF, 173 chronic hepatitis B (CHB), and 171 healthy patients using a coagulation method. The predictive ability of fibrinogen for 3-month mortality in AoCLF patients was assessed using receiver operating characteristic (ROC) curve and multivariable logistic regression analyses. Plasma fibrinogen was significantly lower in nonsurvivor AoCLF patients compared with survivor AoCLF, CHB, and control patients. The sensitivity, specificity, and area under the ROC curve of 1/fibrinogen predicting mortality in AoCLF patients were 66.7%, 72.5%, and 0.746 (95% confidence interval (CI): 0.672-0.820, P fibrinogen cutoff value was 0.90 g/L. On multivariate logistic regression analysis, low fibrinogen was an independent factor predicting mortality (odds ratio: 0.304; 95% CI: 0.094-0.983; P = 0.047). Nonsurvivor AoCLF patients had significantly decreased fibrinogen levels, suggesting that low plasma fibrinogen may be a useful predictor of poor prognosis in AoCLF patients.

  3. Interaction of fibrinogen and albumin with titanium dioxide nanoparticles of different crystalline phases

    Science.gov (United States)

    Marucco, Arianna; Fenoglio, Ivana; Turci, Francesco; Fubini, Bice

    2013-04-01

    TiO2 nanoparticles (NPs) are contained in different kinds of industrial products including paints, self-cleaning glasses, sunscreens. TiO2 is also employed in photocatalysis and it has been proposed for waste water treatment. Micrometric TiO2 is generally considered a safe material, while there is concern on the possible health effects of nanometric titania. Due to their small size NPs may migrate within the human body possibly entering in the blood stream. Therefore studies on the interaction of NPs with plasma proteins are needed. In fact, the interaction with proteins is believed to ultimately influences the NPs biological fate. Fibrinogen and albumin are two of the most abundant plasma proteins. They are involved in several important physiological functions. Furthermore, fibrinogen is known to trigger platelet adhesion and inflammation. For these reasons the study of the interaction between these protein and nanoparticles is an important step toward the understanding of the behavior of NPs in the body. In this study we investigated the interaction of albumin and fibrinogen with TiO2 nanoparticles of different crystal phases (rutile and anatase) using an integrated set of techniques. The amount of adsorbed fibrinogen and albumin for each TiO2 surface was investigated by using the bicinchoninic acid assay (BCA). The variation of the surface charge of the NP-protein conjugates respect to the naked NPs was used to indirectly estimate both surface coverage and reversibility of the adsorption upon dilution. Surface charge was monitored by measuring the ζ potential with a conventional electrophoretic light scattering (ELS) system. The extent of protein deformation was evaluated by Raman Spectroscopy. We found that both proteins adsorb irreversibly against electrostatic repulsion, likely undergoing conformational changes or selective orientation upon adsorption. The size of primary particles and the particles aggregation rather than the crystal phase modulate the

  4. Fibrinogen interaction of CHO cells expressing chimeric αIIb/αvβ3 integrin

    Institute of Scientific and Technical Information of China (English)

    Juan-juan CHEN; Xiao-yu SU; Xiao-dong XI; Li-ping LIN; Jian DING; He LU

    2008-01-01

    Aim: The molecular mechanisms of the affinity regulation of αvβ3 integrin are important in tumor development, wound repairing, and angiogenesis. It has been established that the cytoplasmic domains of αvβ3 integrin play an important role in integrin-ligand affinity regulation. However, the relationship of structure-func-tion within these domains remains unclear. Methods: The extracellular and trans-membrane domain of αⅡb was fused to the αv integrin cytoplasmic domain, and the chimeric α subunit was coexpressed in Chinese hamster ovary (CHO) cells with the wild-type β3 subunit or with 3 mutant 133 sequences bearing truncations at the positions of T741, Y747, and F754, respectively. The CHO cells expressing these recombinant integrins were tested for soluble fibrinogen binding and the cell adhesion and spreading on immobilized fibrinogen. Results: All 4 types of integrins bound soluble fibrinogen in the absence of agonist stimulation, and only the cells expressing the chimeric α subunit with the wild-type β3 subunit, but not those with truncated β3, could adhere to and spread on immobilized fibrinogen. Conclusion: The substitution αⅡb at the cytoplasmic domain with the ctv cyto-plasmic sequence rendered the extracellular αⅡbβ3 a constitutively activated con-formation for ligands without the need of "inside-out" signals. Our results also indicated that the COOH-terminal sequence of β3 might play a key role in integrin αⅡb/αvβ3-mediated cell adhesion and spreading on immobilized fibrinogen. The cells expressing αⅡb/αvβ3 have enormous potential for facilitating drug screen-ing for antagonists either to αvβ3 intracellular interactions or to αⅡbβ3 receptor functions.

  5. Plasma Fibrinogen Qualification as a Drug Development Tool in Chronic Obstructive Pulmonary Disease. Perspective of the Chronic Obstructive Pulmonary Disease Biomarker Qualification Consortium.

    Science.gov (United States)

    Miller, Bruce E; Tal-Singer, Ruth; Rennard, Stephen I; Furtwaengler, Armin; Leidy, Nancy; Lowings, Michael; Martin, Ubaldo J; Martin, Thomas R; Merrill, Debora D; Snyder, Jeffrey; Walsh, John; Mannino, David M

    2016-03-15

    The COPD Foundation Biomarker Qualification Consortium (CBQC) is a unique public-private partnership established in 2010 between the COPD Foundation, the pharmaceutical industry, and academic chronic obstructive pulmonary disease (COPD) experts with advisors from the U.S. NHLBI and the Food and Drug Administration (FDA). This was a direct response to the 2009 publication of a guidance on qualification of drug development tools by the FDA. Although data were believed to be available from publicly funded and industry-funded studies that could support qualification of several tools, the necessary data resided in disparate databases. The initial intent of the CBQC was to integrate these data and submit a dossier for the qualification. This led to the FDA qualification of plasma fibrinogen as a prognostic or enrichment biomarker for all-cause mortality and COPD exacerbations in July 2015. It is the first biomarker drug development tool qualified for use in COPD under the FDA's drug development tool qualification program. This perspective summarizes the FDA's qualification process, the formation of the CBQC, and the effort that led to a successful outcome for plasma fibrinogen and discusses implications for future biomarker qualification efforts.

  6. A new fibrinogen-related protein from Argopecten irradians (AiFREP-2) with broad recognition spectrum and bacteria agglutination activity.

    Science.gov (United States)

    Yang, Chuanyan; Wang, Leilei; Zhang, Huan; Wang, Lingling; Huang, Mengmeng; Sun, Zhibin; Sun, Ying; Song, Linsheng

    2014-05-01

    Fibrinogen-related proteins (FREPs) are a kind of pattern recognition receptors (PRRs) containing fibrinogen-like (FBG) domains, and they play curial roles in the innate immune response. In the present study, a new FREP protein was identified from bay scallop Argopecten irradians (designated as AiFREP-2). The full-length cDNA of AiFREP-2 was of 1299 bp with an open reading frame of 762 bp encoding a polypeptide of 253 amino acids, including a signal sequence and an FBG domain. The FBG domain in AiFREP-2 was highly similar to those of ficolins, tenascins and other FREPs. The mRNA expression of AiFREP-2 could be detected in all the examined tissues with the highest level in gill. The mRNA expression of AiFREP-2 in hemocytes was significantly up-regulated post the stimulation of lipopolysaccharide (LPS), peptidoglycan (PGN) and β-glucan (GLU) (P agglutination activity towards Gram-negative bacteria V. anguillarum and Gram positive bacteria S. aureus. The results indicated that AiFREP-2 was involved in the immune response against Gram-negative bacteria, Gram-positive bacteria and fungus as a PRR in bay scallop, and the information was helpful to understand the innate immune defense mechanisms of mollusks.

  7. Influence of Ficoll on urea induced denaturation of fibrinogen

    Science.gov (United States)

    Sankaranarayanan, Kamatchi; Meenakshisundaram, N.

    2016-03-01

    Ficoll is a neutral, highly branched polymer used as a molecular crowder in the study of proteins. Ficoll is also part of Ficoll-Paque used in biology laboratories to separate blood to its components (erythrocytes, leukocytes etc.,). Role of Ficoll in the urea induced denaturation of protein Fibrinogen (Fg) has been analyzed using fluorescence, circular dichroism, molecular docking and interfacial studies. Fluorescence studies show that Ficoll prevents quenching of Fg in the presence of urea. From the circular dichroism spectra, Fg shows conformational transition to random coil with urea of 6 M concentration. Ficoll helps to shift this denaturation concentration to 8 M and thus constraints by shielding Fg during the process. Molecular docking studies indicate that Ficoll interacts favorably with the protein than urea. The surface tension and shear viscosity analysis shows clearly that the protein is shielded by Ficoll.

  8. 纤维蛋白原γ链Arg275His突变所致的遗传性异常纤维蛋白原血症家系分析%Analysis of a family with congenital dysfibrinogenemia caused by an Arg275His mutation in the gamma chain of fibrinogen

    Institute of Scientific and Technical Information of China (English)

    闫婕; 邓东红; 邓雪连; 罗美玲; 程鹏; 廖林; 林发全

    2016-01-01

    Objective To explore the clinical phenotype of a family affected with congenital dysfibrinogenemia and potential mutations underlying the disease.Methods Coagulation testing and hepatorenal function testing were conducted on 18 individuals fromthree generations.Plasma fibrinogen was extracted and analyzed with SDS-PAGE electrophoresis.All of the exons and flanking sequences of fibrinogen FGA,FGB,FGG genes were analyzed by PCR,and the products were subjected to Sanger sequencing.Results Hepatorenal function,prothrombin time and activated partial thromboplastin time of the proband were all normal.However,his thrombin time was significantly prolonged.Fibrinogen activity was decreased,while the concentration of antigen was in the normal range.The results of his mother,brother,and nephew were similar.DNA sequencing has confirmed that the proband,his mother,brother,and nephew have all carried a g.5877G> A mutation in the exon 8 of the FGG gene,which resultedin replacement of arginine (Arg) by histidine (His) at position 275.Conclusion The Arg275His mutation of the fibrinogen γ chain probably underlies the pathogenesis of congenital dysfibrinogenemia in this family.%目的 对1个遗传性异常纤维蛋白原血症家系进行临床表型和基因型研究,了解其分子遗传学发病机制.方法 抽取家系18名成员外周血,进行凝血指标检测;提取血浆纤维蛋白原,进行SDS-PAGE电泳;PCR扩增纤维蛋白原FGA、FGB、FGG基因所有外显子以及侧翼序列.PCR扩增产物进行测序,确定突变位点.结果 先证者肝肾功能、凝血酶原时间与活化部分凝血活酶时间均正常,但凝血酶时间显著延长.纤维蛋白原活性明显降低,而抗原浓度在正常范围,先证者母亲、弟弟及侄子的表型检测结果与其相似.基因测序结果显示,先证者及其母亲、弟弟及侄子FGG基因第8外显子发生了g.5877G>A杂合突变,导致275位的精氨酸(Arg)被组氨酸(His)取代.FGG基因第8

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

    DEFF Research Database (Denmark)

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

    1995-01-01

    .6 micrograms/min): Coagulation factors: blood platelet count and mean volume, plasma Factor VII antigen concentration and coagulant activity, and plasma concentrations of prothrombin fragment 1 + 2, thrombin-antithrombin III complexes, fibrinogen, and fibrinopeptide A; fibrinolytic and endothelial factors...

  10. Association of β-fibrinogen gene -148C/T and -455G/A polymorphisms and coronary artery disease in Chinese population: A Meta analysis

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The purpose of our study was to evaluate the correlation between the β-fibrinogen gene –148C/T and –455G/A polymorphisms and susceptibility to coronary artery disease in the Chinese population using a meta–analytic approach. Eligible studies about this correlation were identified by searching the PubMed, EMBASE, and CNKI databases. Of the 13 identified, 7 (with 1488 cases and 1234 controls) involved the –148C/T polymorphism and 9 (with 1023 cases and 1081 controls) involved the –455G/A polymorphism. No publication bias was detectable and heterogeneity testing found significant differ-ences between the ORs for both groups of studies. The combined OR for the 7 studies on susceptibility to coronary artery disease in –148T allele carriers compared to the –148C/C wild-type homozygotes was 1.31 (95%CI: 0.94-1.84, P=0.11). The combined OR for the 9 studies on susceptibility to coronary artery disease in –455A allele carriers compared to the –455G/G wild-type homozygotes was 1.75 (95%CI: 1.24-2.46, P=0.001). Our results suggest the absence of an association between the β-fibrinogen gene –148C/T polymorphism and susceptibility to coronary artery disease and the possibility that –455G/A polymorphism (in particular, allele A) increases susceptibility to this disease in the Chinese population.

  11. Elevation of urinary adipsin in preeclampsia: correlation with urine protein concentration and the potential use for a rapid diagnostic test.

    Science.gov (United States)

    Wang, Tao; Zhou, Rong; Gao, Linbo; Wang, Yanyun; Song, Changping; Gong, Yunhui; Jia, Jin; Xiong, Wei; Dai, Li; Zhang, Lin; Hu, Huaizhong

    2014-10-01

    Early diagnosis and treatment of preeclampsia are essential for prevention of seizure development and fetus maturation. Although various methods have been developed for predicting or monitoring the onset of preeclampsia, a simple assay that can be used as a home or point of care test remains unavailable. We attempted to find a urinary protein that could be used as a biomarker for developing such a test. Urinary samples were collected from 124 preeclampsia and 135 healthy pregnant women for screening using a protein array technology and quantification by ELISA. A urinary protein, adipsin, was found significantly increased, and the adipsin creatinine ratio was closely correlated with the urinary 24-hour protein in patients with preeclampsia. When combined with the increased diastolic blood pressure (≥90 mm Hg), the sensitivity was 90.3% and the specificity reached 100.0% for preeclampsia diagnosis. We then developed a laminar flow immunoassay for rapid diagnosis, and the sensitivity and specificity were 89.04% and 100%, respectively, when combined with increased diastolic blood pressure. Because of the easiness of sample collection, assay conduction, and result interpretation, this urine test can be potentially used as a home test for monitoring preeclampsia onset for high-risk pregnant women and as a rapid test for a preliminary diagnosis for emergency patients at hospitals.

  12. The mechanical properties of dry, electrospun fibrinogen fibers

    Energy Technology Data Exchange (ETDEWEB)

    Baker, Stephen; Sigley, Justin; Helms, Christine C. [Department of Physics, Wake Forest University, Winston-Salem, NC 27109 (United States); Stitzel, Joel [Department of Biomedical Engineering, Wake Forest University Health Sciences, Winston-Salem, NC, 27157 (United States); Berry, Joel; Bonin, Keith [Department of Physics, Wake Forest University, Winston-Salem, NC 27109 (United States); Guthold, Martin, E-mail: gutholdm@wfu.edu [Department of Physics, Wake Forest University, Winston-Salem, NC 27109 (United States)

    2012-02-01

    Due to their low immunogenicity, biodegradability and native cell-binding domains, fibrinogen fibers may be good candidates for tissue engineering scaffolds, drug delivery vehicles and other medical devices. We used a combined atomic force microscope (AFM)/optical microscope technique to study the mechanical properties of individual, electrospun fibrinogen fibers in dry, ambient conditions. The AFM was used to stretch individual fibers suspended over 13.5 {mu}m wide grooves in a transparent substrate. The optical microscope, located below the sample, was used to monitor the stretching process. Electrospun fibrinogen fibers (diameter, 30-200 nm) can stretch to 74% beyond their original length before rupturing at a stress of 2.1 GPa. They can stretch elastically up to 15% beyond their original length. Using incremental stress-strain curves the viscoelastic behavior of these fibers was determined. The total stretch modulus was 4.2 GPa while the relaxed elastic modulus was 3.7 GPa. When held at constant strain, fibrinogen fibers display stress relaxation with a fast and slow relaxation time of 1.2 s and 11 s. In comparison to native and electrospun collagen fibers, dry electrospun fibrinogen fibers are significantly more extensible and elastic. In comparison to wet electrospun fibrinogen fibers, dry fibers are about 1000 times stiffer. - Highlights: Black-Right-Pointing-Pointer Fabricated dry, electrospun, fibrinogen fibers; average diameter, D{sub avg.} = 95 nm. Black-Right-Pointing-Pointer Determined mechanical properties with combined atomic force/optical microscope. Black-Right-Pointing-Pointer Fibers are very extensible ({epsilon}{sub max} = 74%) and elastic ({epsilon}{sub elastic} = 15%). Black-Right-Pointing-Pointer Fiber total modulus, E{sub tot.} = 4.2 GPa; elastic modulus, E{sub el.} = 3.7 GPa. Black-Right-Pointing-Pointer Fiber stress relaxation times: {tau}{sub 1} = 1.2 s and {tau}{sub 2} = 11 s.

  13. Changes in fibrinogen availability and utilization in an animal model of traumatic coagulopathy

    DEFF Research Database (Denmark)

    Hagemo, Jostein S; Jørgensen, Jørgen; Ostrowski, Sisse R

    2013-01-01

    Impaired haemostasis following shock and tissue trauma is frequently detected in the trauma setting. These changes occur early, and are associated with increased mortality. The mechanism behind trauma-induced coagulopathy (TIC) is not clear. Several studies highlight the crucial role of fibrinogen...... in posttraumatic haemorrhage. This study explores the coagulation changes in a swine model of early TIC, with emphasis on fibrinogen levels and utilization of fibrinogen....

  14. No evidence for genome-wide interactions on plasma fibrinogen by smoking, alcohol consumption and body mass index: results from meta-analyses of 80,607 subjects.

    Directory of Open Access Journals (Sweden)

    Jens Baumert

    Full Text Available Plasma fibrinogen is an acute phase protein playing an important role in the blood coagulation cascade having strong associations with smoking, alcohol consumption and body mass index (BMI. Genome-wide association studies (GWAS have identified a variety of gene regions associated with elevated plasma fibrinogen concentrations. However, little is yet known about how associations between environmental factors and fibrinogen might be modified by genetic variation. Therefore, we conducted large-scale meta-analyses of genome-wide interaction studies to identify possible interactions of genetic variants and smoking status, alcohol consumption or BMI on fibrinogen concentration. The present study included 80,607 subjects of European ancestry from 22 studies. Genome-wide interaction analyses were performed separately in each study for about 2.6 million single nucleotide polymorphisms (SNPs across the 22 autosomal chromosomes. For each SNP and risk factor, we performed a linear regression under an additive genetic model including an interaction term between SNP and risk factor. Interaction estimates were meta-analysed using a fixed-effects model. No genome-wide significant interaction with smoking status, alcohol consumption or BMI was observed in the meta-analyses. The most suggestive interaction was found for smoking and rs10519203, located in the LOC123688 region on chromosome 15, with a p value of 6.2 × 10(-8. This large genome-wide interaction study including 80,607 participants found no strong evidence of interaction between genetic variants and smoking status, alcohol consumption or BMI on fibrinogen concentrations. Further studies are needed to yield deeper insight in the interplay between environmental factors and gene variants on the regulation of fibrinogen concentrations.

  15. Concentration of polybrominated diphenyl ethers (PBDEs) in house hold dust from various countries. Inhalation a potential route of human exposure

    Energy Technology Data Exchange (ETDEWEB)

    Sjoedin, A. [Centers for Disease Control and Prevention (CDC), Atlanta, GA (United States); Paepke, O. [ERGO Research, Hamburg (Germany); McGahee III, E. [Centers for Disease Control and Prevention (CDC), Atlanta, GA (US)] (and others)

    2004-09-15

    Polybrominated diphenyl ethers (PBDEs) are congeners of a class of environmental contaminants that have been present in the environment for decades. PBDEs were first identified in the River Viskan in Sweden and have since then been recognized as an environmental contaminant with a global distribution as shown by the detection of this compound class in aquatic and terrestrial environments in Europe and North America. However, PBDEs will still be present in consumer products sold prior to the phase out of pentaBDE and octaBDE for decades to come. Hence it is of utmost importance to identify the exposure routes to humans especially in the Unites States where much higher levels of PBDEs have been observed in people. An average level of 34 ng/g lipid has been observed in human serum pools collected in 2002 and values in the range of 2.9-272 ng lipid (average 41ng/g lipid) have been observed in human milk. This can be contrasted to levels observed in Swedish milk pools (2.3 ng/g lipid) collected in 1997. Human exposure to persistent chemicals like polychlorinated biphenyls has traditionally been considered to be mainly through food consumption. Other direct exposure routes such as inhalation and/or dermal exposure are only of quantitatively more importance in the case of occupational exposures. However, this may or may not be true for PBDEs which are still being used in the modern indoor environment. This is further supported by the relatively low concentrations recently reported in foodstuffs sampled in the United States.

  16. Formation and cell translocation of carbon nanotube-fibrinogen protein corona

    Science.gov (United States)

    Chen, Ran; Radic, Slaven; Choudhary, Poonam; Ledwell, Kimberley G.; Huang, George; Brown, Jared M.; Chun Ke, Pu

    2012-09-01

    The binding of plasma fibrinogen with both single-walled and multi-walled carbon nanotubes (SWNTs and MWNTs) has been examined. Specifically, our absorbance study indicated that MWNTs were coated with multi-layers of fibrinogen to render a "hard protein corona," while SWNTs were adsorbed with thin layers of the protein to precipitate out of the aqueous phase. In addition, static quenching as a result of energy transfer from fluorescently labeled fibrinogen to their nanotube substrates was revealed by Stern-Volmer analysis. When exposed to HT-29 cells, the nanotubes and fibrinogen could readily dissociate, possibly stemming from their differential affinities for the amphiphilic membrane bilayer.

  17. The impact of elevated CO2 concentration on the quality of algal starch as a potential biofuel feedstock.

    Science.gov (United States)

    Tanadul, Orn-U-Ma; VanderGheynst, Jean S; Beckles, Diane M; Powell, Ann L T; Labavitch, John M

    2014-07-01

    Cultured microalgae are viewed as important producers of lipids and polysaccharides, both of which are precursor molecules for the production of biofuels. This study addressed the impact of elevated carbon dioxide (CO2) on Chlorella sorokiniana production of starch and on several properties of the starch produced. The production of C. sorokiniana biomass, lipid and starch were enhanced when cultures were supplied with 2% CO2. Starch granules from algae grown in ambient air and 2% CO2 were analyzed by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The granules from algae grown in 2% CO2 were disk-shaped and contained mainly stromal starch; granules from cultures grown in ambient air were cup-shaped with primarily pyrenoid starch. The granules from cells grown in 2% CO2 had a higher proportion of the accumulated starch as the highly branched, amylopectin glucan than did granules from cells grown in air. The rate of hydrolysis of starch from 2% CO2-grown cells was 1.25 times greater than that from air-grown cells and 2-11 times higher than the rates of hydrolysis of starches from cereal grains. These data indicate that culturing C. sorokiniana in elevated CO2 not only increases biomass yield but also improves the structure and composition of starch granules for use in biofuel generation. These modifications in culture conditions increase the hydrolysis efficiency of the starch hydrolysis, thus providing potentially important gains for biofuel production.

  18. Fibrinogen γ' increases the sensitivity to activated protein C in normal and factor V Leiden plasma.

    Science.gov (United States)

    Omarova, Farida; Uitte de Willige, Shirley; Simioni, Paolo; Ariëns, Robert A S; Bertina, Rogier M; Rosing, Jan; Castoldi, Elisabetta

    2014-08-28

    Activated protein C (APC) resistance, often associated with the factor V (FV) Leiden mutation, is the most common risk factor for venous thrombosis. We observed increased APC resistance in carriers of fibrinogen γ gene (FGG) haplotype 2, which is associated with reduced levels of the alternatively spliced fibrinogen γ' chain. This finding prompted us to study the effects of fibrinogen and its γ' chain on APC resistance. Fibrinogen, and particularly the γA/γ' isoform, improved the response of plasma to added APC in the thrombin generation-based assay. Similarly, a synthetic peptide mimicking the C-terminus of the fibrinogen γ' chain, which binds thrombin and inhibits its activities, greatly increased the APC sensitivity of normal and FV Leiden plasma, likely due to its ability to inhibit thrombin-mediated activation of FV and FVIII. Although the fibrinogen γ' peptide also inhibited protein C activation by the thrombin/thrombomodulin complex, it still increased the sensitivity of plasma to endogenously formed APC when thrombin generation was measured in the presence of soluble thrombomodulin. We conclude that fibrinogen, and particularly fibrinogen γ', increases plasma APC sensitivity. The fibrinogen γ' peptide might form the basis for pharmacologic interventions to counteract APC resistance. © 2014 by The American Society of Hematology.

  19. Increased fibrinogen levels at diagnosis are associated with adverse outcome in patients with acute myeloid leukemia.

    Science.gov (United States)

    Berger, Martin D; Heini, Alexander D; Seipel, Katja; Mueller, Beatrice; Angelillo-Scherrer, Anne; Pabst, Thomas

    2016-06-15

    Increased plasma fibrinogen levels are associated with shortened overall survival (OS) in some solid tumor types. In contrast, the prognostic significance of varying fibrinogen levels in acute myeloid leukemia (AML) at diagnosis is unknown. In this study, we assessed the prognostic significance of fibrinogen levels in AML patients. In a comprehensive retrospective single-center study, we determined the survival rates of 375 consecutive AML patients undergoing at least one cycle of intensive chemotherapy induction treatment. Patients were dichotomized between low (high fibrinogen levels (≥4.1 g/L) at diagnosis of AML before initiation of treatment. Subsequently, quartile ranges were applied to analyze the association of varying fibrinogen levels on survival. We observed that the rates of complete remission, early death, and admission to intensive care unit were equal in the low versus high fibrinogen group. However, OS was significantly better in the low fibrinogen group (27.3 vs 13.5 months; p = 0.0009) as well as progression-free survival (12.3 vs 7.8 months; p = 0.0076). This survival difference remained significant in the multivariate analysis (p = 0.003). Assessing quartiles of fibrinogen values, we further confirmed this observation. Our data suggest that high fibrinogen levels at diagnosis of AML are associated with unfavorable OS and progression-free survival but not with increased mortality during induction treatment. Copyright © 2016 John Wiley & Sons, Ltd.

  20. Elevated plasma fibrinogen : Cause or consequence of cardiovascular disease?

    NARCIS (Netherlands)

    Bom, J.G. van der; Maat, M.P.M. de; Bots, M.L.; Haverkate, F.; Jong, P.T.V.M. de; Hofman, A.; Kluft, C.; Grobbee, D.E.

    1998-01-01

    An association between increased plasma fibrinogen and an increased risk for myocardial infarction (MI) is well established, but the nature of this association is subject to debate. Our aim was to shed light on the potentially causal nature of this association. We examined whether increased plasma f

  1. Polimorfismo genético do fibrinogênio na doença arterial periférica Genetic polymorphisms of fibrinogen in peripheral artery disease

    Directory of Open Access Journals (Sweden)

    Antônio C. Brandão

    2004-01-01

    Full Text Available O objetivo do presente estudo foi analisar freqüências alélicas e genotípicas para o gene codificador da cadeia beta do fibrinogênio em pacientes com doença arterial periférica (DAP. Foram estudados 44 pacientes caucasóides do sexo masculino com sintomas clínicos e comprovação angiográfica de DAP, com idade entre 38 e 79 anos (62±8,6 anos. Entre eles, 22 apresentaram obstrução aterosclerótica nas artérias ilíacas, femorais e/ou carótidas e 22 tinham aneurisma de aorta torácica, abdominal ou tóraco-abdominal. O grupo controle foi constituído por 56 indivíduos, sem história clínica de DAP ou alterações ao exame clínico, com idades variando de 43 a 80 anos (59±9,2 anos. Foram excluídos os indivíduos com doença renal, doença hepática ou diabetes mellitus. A análise do polimorfismo genético da cadeia do fibrinogênio foi realizada por PCR (polimerase chain reaction e RFLP (restriction fragment lenght polimorphism com a endonuclease Bcl I, identificando-se três genótipos: B1/B1, B1/B2 e B2/B2. A análise estatística incluiu teste exato de Fisher, calculo do odds ratio, teste de Kruskal Wallis e análise de variância (ANOVA. Admitiu-se erro a igual a 5%, com nível de significância para PThe objective of this study was to analyze the frequencies of the alleles and genotypes of the gene encoder of the fibrinogen b-chain in patients suffering from peripheral artery disease. A total of 62 male Caucasoid patients with ages varying from 38 to 79 years old were studied. All the patients had clinical symptoms of peripheral artery disease, which was later confirmed by angiography. Forty of the patients had atherosclerotic obstructions of the iliac, femoral or carotid arteries and 22 suffered from aneurysms of the thoracic, abdominal or thoracoabdominal aortas. All the patients were submitted to surgery. A control group was formed of 62 individuals, with ages ranging from 43 to 80 years old, without clinical histories or

  2. Triglyceride concentration and waist circumference influence alcohol-related plasminogen activator inhibitor-1 activity increase in black South Africans

    NARCIS (Netherlands)

    Pieters, Marlien; de Lange, Zelda; Hoekstra, Tiny; Ellis, Suria M.; Kruger, Annamarie

    2010-01-01

    We investigated the association between alcohol consumption and plasminogen activator inhibitor-1 activity (PAI-1(act)) and fibrinogen concentration in a black South African population presenting with lower PAI-1(act) and higher fibrinogen than what is typically observed in white populations. We, fu

  3. Effect of Fibrinogen on Platelet Reactivity Measured by the VerifyNow P2Y12 Assay.

    Science.gov (United States)

    Dobrovolsky, A B; Laguta, P S; Guskova, E V; Yarovaya, E B; Titaeva, E V; Storozhilova, A N; Panchenko, E P

    2016-05-01

    The VerifyNow assay is based upon the ability of activated platelets to cross-link beads coated with fibrinogen. However, fibrinogen is an abundant protein of blood, and therefore it may affect test results by competing with fibrinogen of beads for binding to platelets. To test this assumption, we assessed the influence of artificial alteration of fibrinogen level in blood samples obtained from donors (n = 9) and patients on clopidogrel therapy (n = 8) on the results of the VerifyNow P2Y12 assay. Fibrinogen level was altered by adding to blood samples 1/10 volume of fibrinogen solution (10.56 g/liter) or corresponding buffer. Relative to baseline, addition of buffer significantly increased platelet reactivity, whereas addition of fibrinogen decreased it. Analysis of the relationship between change in platelet reactivity values (dBase and dPRU) and change in fibrinogen concentration (dFg) revealed strong negative correlations: dBase = -63.3 × dFg - 27.1 (r = -0.924, p fibrinogen strongly influences results of the VerifyNow P2Y12 assay, and (ii) correcting for fibrinogen effect may be needed to improve the accuracy of the test in the measuring of antiplatelet effect of clopidogrel therapy.

  4. A high intake of dietary fiber influences C-reactive protein and fibrinogen, but not glucose and lipid metabolism, in mildly hypercholesterolemic subjects.

    Science.gov (United States)

    Johansson-Persson, Anna; Ulmius, Matilda; Cloetens, Lieselotte; Karhu, Toni; Herzig, Karl-Heinz; Onning, Gunilla

    2014-02-01

    The aim of the study was to investigate how a diet high in dietary fiber, with several fiber sources included, modulates glucose and lipid metabolism and the inflammatory response in humans. Subjects (n = 25) aged 58.6 (1.1) years (mean and SD) with a BMI of 26.6 (0.5) kg/m(2) and a total cholesterol (TC) of 5.8 (0.1) mmol/L (mean and SEM) were given a high fiber (HF) and low fiber (LF) diet, in a randomized controlled 5-week crossover intervention, separated by a 3-week washout. The HF diet consisted of oat bran, rye bran, and sugar beet fiber incorporated into test food products; one bread roll, one ready meal, and two beverages consumed daily. Equivalent food products, without added fibers, were provided in the LF diet. Total dietary fiber intake was 48.0 g and 30.2 g per day for the HF and LF diet, respectively. Significant reduction in C-reactive protein (CRP) was observed between the diets (P = 0.017) and a significant reduction in fibrinogen within the HF diet (P = 0.044). There were no significant effects in other measured circulating cytokines or in glucose, insulin, and lipid levels. Our study suggests that a 5-week high dietary fiber intake of oat bran, rye bran, and sugar beet fiber might reduce the low-grade inflammatory response measured as CRP which could, together with reduced fibrinogen, help to prevent the risk of cardiovascular disease.

  5. The Enterococcus faecalis EbpA Pilus Protein: Attenuation of Expression, Biofilm Formation, and Adherence to Fibrinogen Start with the Rare Initiation Codon ATT

    Science.gov (United States)

    Montealegre, Maria Camila; La Rosa, Sabina Leanti; Roh, Jung Hyeob; Harvey, Barrett R.

    2015-01-01

    ABSTRACT The endocarditis and biofilm-associated pili (Ebp) are important in Enterococcus faecalis pathogenesis, and the pilus tip, EbpA, has been shown to play a major role in pilus biogenesis, biofilm formation, and experimental infections. Based on in silico analyses, we previously predicted that ATT is the EbpA translational start codon, not the ATG codon, 120 bp downstream of ATT, which is annotated as the translational start. ATT is rarely used to initiate protein synthesis, leading to our hypothesis that this codon participates in translational regulation of Ebp production. To investigate this possibility, site-directed mutagenesis was used to introduce consecutive stop codons in place of two lysines at positions 5 and 6 from the ATT, to replace the ATT codon in situ with ATG, and then to revert this ATG to ATT; translational fusions of ebpA to lacZ were also constructed to investigate the effect of these start codons on translation. Our results showed that the annotated ATG does not start translation of EbpA, implicating ATT as the start codon; moreover, the presence of ATT, compared to the engineered ATG, resulted in significantly decreased EbpA surface display, attenuated biofilm, and reduced adherence to fibrinogen. Corroborating these findings, the translational fusion with the native ATT as the initiation codon showed significantly decreased expression of β-galactosidase compared to the construct with ATG in place of ATT. Thus, these results demonstrate that the rare initiation codon of EbpA negatively regulates EbpA surface display and negatively affects Ebp-associated functions, including biofilm and adherence to fibrinogen. PMID:26015496

  6. Quantitative Determination of Fibrinogen of Patients with Coronary Heart Diseases through Piezoelectric Agglutination Sensor

    Directory of Open Access Journals (Sweden)

    Ming Chen

    2010-03-01

    Full Text Available Fibrinogen can transform fibrin through an agglutination reaction, finally forming fibrin polymer with grid structure. The density and viscosity of the reaction system changes drastically during the course of agglutination. In this research, we apply an independently-developed piezoelectric agglutination sensor to detect the fibrinogen agglutination reaction in patients with coronary heart diseases. The terminal judgment method of determining plasma agglutination reaction through piezoelectric agglutination sensor was established. In addition, the standard curve between plasma agglutination time and fibrinogen concentration was established to determinate fibrinogen content quantitatively. The results indicate the close correlation between the STAGO paramagnetic particle method and the method of piezoelectric agglutination sensor for the detection of Fibrinogen. The correlation coefficient was 0.91 (γ = 0.91. The determination can be completed within 10 minutes. The fibrinogen concentration in the coronary heart disease group was significantly higher than that of the healthy control group (P < 0.05. The results reveal that high fibrinogen concentration is closely correlated to the incurrence, development and prognosis of coronary heart diseases. Compared with other traditional methods, the method of piezoelectric agglutination sensor has some merits such as operation convenience, small size, low cost, quick detecting, good precision and the common reacting agents with paramagnetic particle method.

  7. Quantitative determination of fibrinogen of patients with coronary heart diseases through piezoelectric agglutination sensor.

    Science.gov (United States)

    Chen, Qinghai; Hua, Xing; Fu, Weiling; Liu, Dongbo; Chen, Ming; Cai, Guoru

    2010-01-01

    Fibrinogen can transform fibrin through an agglutination reaction, finally forming fibrin polymer with grid structure. The density and viscosity of the reaction system changes drastically during the course of agglutination. In this research, we apply an independently-developed piezoelectric agglutination sensor to detect the fibrinogen agglutination reaction in patients with coronary heart diseases. The terminal judgment method of determining plasma agglutination reaction through piezoelectric agglutination sensor was established. In addition, the standard curve between plasma agglutination time and fibrinogen concentration was established to determinate fibrinogen content quantitatively. The results indicate the close correlation between the STAGO paramagnetic particle method and the method of piezoelectric agglutination sensor for the detection of Fibrinogen. The correlation coefficient was 0.91 (γ = 0.91). The determination can be completed within 10 minutes. The fibrinogen concentration in the coronary heart disease group was significantly higher than that of the healthy control group (P high fibrinogen concentration is closely correlated to the incurrence, development and prognosis of coronary heart diseases. Compared with other traditional methods, the method of piezoelectric agglutination sensor has some merits such as operation convenience, small size, low cost, quick detecting, good precision and the common reacting agents with paramagnetic particle method.

  8. Heavy metal concentrations in two populations of Mopane worms (Imbrasia belina) in the Kruger National Park pose a potential human health risk.

    Science.gov (United States)

    Greenfield, R; Akala, N; van der Bank, F H

    2014-09-01

    Metal concentrations in Mopane worms from Phalaborwa and Shangoni sites in the Kruger National Park were determined. Metal concentrations were evaluated by inductively coupled plasma optical emission spectroscopy (ICP-OES) and ICP-MS spectrometry after microwave digestion. The results indicate a substantial bioaccumulation of metals in Mopane worms. In Phalaborwa Cd concentrations were 15 times and Cu two times higher than the EU and UK recommended legal limits for human consumption, Zn levels were tolerable. Likewise, Cd, Cu and Zn concentrations at the Shangoni site were 26, 2.5 and 0.4 times over the EU and UK approved limits. Manganese concentrations were 20 and 67 times higher than FDA standards respectively. During the study the condition factor of the worms was determined. No significant difference between the condition factors indicated the worms at both sites are in similar condition. Potential sources of metals in the worms are either from the food they eat or pollution settling on the leaves.

  9. Combined single cell AFM manipulation and TIRFM for probing the molecular stability of multilayer fibrinogen matrices

    Energy Technology Data Exchange (ETDEWEB)

    Christenson, W. [Department of Physics, Arizona State University, Tempe, AZ 85287 (United States); Center for Biological Physics, Arizona State University, Tempe, AZ 85287 (United States); Yermolenko, I. [Department of Physics, Arizona State University, Tempe, AZ 85287 (United States); School of Life Sciences, Arizona State University, Tempe, AZ 85287 (United States); Plochberger, B. [Department of Physics, Arizona State University, Tempe, AZ 85287 (United States); Camacho-Alanis, F.; Ros, A. [Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287 (United States); Ugarova, T.P. [School of Life Sciences, Arizona State University, Tempe, AZ 85287 (United States); Ros, R., E-mail: Robert.Ros@asu.edu [Department of Physics, Arizona State University, Tempe, AZ 85287 (United States); Center for Biological Physics, Arizona State University, Tempe, AZ 85287 (United States)

    2014-01-15

    Adsorption of fibrinogen on various surfaces produces a nanoscale multilayer matrix, which strongly reduces the adhesion of platelets and leukocytes with implications for hemostasis and blood compatibility of biomaterials. The nonadhesive properties of fibrinogen matrices are based on their extensibility, ensuing the inability to transduce strong mechanical forces via cellular integrins and resulting in weak intracellular signaling. In addition, reduced cell adhesion may arise from the weaker associations between fibrinogen molecules in the superficial layers of the matrix. Such reduced stability would allow integrins to pull fibrinogen molecules out of the matrix with comparable or smaller forces than required to break integrin–fibrinogen bonds. To examine this possibility, we developed a method based on the combination of total internal reflection fluorescence microscopy, single cell manipulation with an atomic force microscope and microcontact printing to study the transfer of fibrinogen molecules out of a matrix onto cells. We calculated the average fluorescence intensities per pixel for wild-type HEK 293 (HEK WT) and HEK 293 cells expressing leukocyte integrin Mac-1 (HEK Mac-1) before and after contact with multilayered matrices of fluorescently labeled fibrinogen. For contact times of 500 s, HEK Mac-1 cells show a median increase of 57% of the fluorescence intensity compared to 6% for HEK WT cells. The results suggest that the integrin Mac-1-fibrinogen interactions are stronger than the intermolecular fibrinogen interactions in the superficial layer of the matrix. The low mechanical stability of the multilayer fibrinogen surface may contribute to the reduced cell adhesive properties of fibrinogen-coated substrates. We anticipate that the described method can be applied to various cell types to examine their integrin-mediated adhesion to the extracellular matrices with a variable protein composition. - Highlights: • We present a method combining

  10. Potential impact of low-concentration silver nanoparticles on predator-prey interactions between predatory dragonfly nymphs and Daphnia magna as a prey.

    Science.gov (United States)

    Pokhrel, Lok R; Dubey, Brajesh

    2012-07-17

    This study investigated the potential impacts of low-concentration citrate-coated silver nanoparticles (citrate-nAg; 2 μg L(-1) as total Ag) on the interactions of Daphnia magna Straus (as a prey) with the predatory dragonfly ( Anax junius : Odonata) nymph using the behavioral, survival, and reproductive end points. Four different toxicity bioassays were evaluated: (i) horizontal migration; (ii) vertical migration; (iii) 48 h survival; and (iv) 21 day reproduction; using four different treatment combinations: (i) Daphnia + citrate-nAg; (ii) Daphnia + predator; (iii) Daphnia + citrate-nAg + predator; and (iv) Daphnia only (control). Daphnia avoided the predators using the horizontal and vertical movements, indicating that Daphnia might have perceived a significant risk of predation. However, with citrate-nAg + predator treatment, Daphnia response did not differ from control in the vertical migration test, suggesting that Daphnia were unable to detect the presence of predator with citrate-nAg treatment and this may have potential implication on daphnids population structure owing to predation risk. The 48 h survival test showed a significant mortality of Daphnia individuals in the presence of predators, with or without citrate-nAg, in the test environment. Average reproduction of daphnids increased by 185% with low-concentration citrate-nAg treatment alone but was severely compromised in the presence of predators (decreased by 91.3%). Daphnia reproduction was slightly enhanced by approximately 128% with citrate-nAg + predator treatment. Potential mechanisms of these differential effects of low-concentration citrate-nAg, with or without predators, are discussed. Because silver dissolution was minimal, the observed toxicity could not be explained by dissolved Ag alone. These findings offer novel insights into how exposure to low-concentration silver nanoparticles could influence predator-prey interactions in the fresh water systems.

  11. High Fibrinogen in Peripheral Blood Correlates with Poorer Hearing Recovery in Idiopathic Sudden Sensorineural Hearing Loss

    Science.gov (United States)

    Kanzaki, Sho; Sakagami, Masafumi; Hosoi, Hiroshi; Murakami, Shingo; Ogawa, Kaoru

    2014-01-01

    Objectives We used hearing tests and peripheral blood sample analyses to characterize the pathology of idiopathic sudden sensorineural hearing loss (ISSNHL) and to identify possible prognostic factors for predicting recovery of hearing loss. Study Design A retrospective, multicenter trial was conducted. Methods Two hundred three patients examined within 7 days after the onset of ISSNHL received prednisone with lipo-prostaglandin E1. Pure-tone auditory tests were performed before and after treatment with these drugs. Blood tests were performed on blood samples collected during the patients’ initial visit to our clinic. Results In all patients, elevated white blood cell (WBC) counts, fasting blood sugar levels, HgbA1c, and erythrocyte sedimentation rate (ESR) significantly correlated with high hearing threshold measurements obtained on the initial visit. High fibrinogen levels, WBC counts, ESR, and low concentrations of fibrinogen degradation products (FDP) were associated with lower hearing recovery rates. Additionally, different audiogram shapes correlated with different blood test factors, indicating that different pathologies were involved. Conclusions High fibrinogen levels measured within seven days after ISSNHL onset correlated with poorer hearing recovery. This may be a consequence of ischemia or infections in the inner ear. The high WBC counts also observed may therefore reflect an immune response to inner ear damage induced by ischemic changes or infections. Our data indicate that therapeutic strategies should be selected based on the timing of initial treatment relative to ISSNHL onset. PMID:25166620

  12. High fibrinogen in peripheral blood correlates with poorer hearing recovery in idiopathic sudden sensorineural hearing loss.

    Directory of Open Access Journals (Sweden)

    Sho Kanzaki

    Full Text Available OBJECTIVES: We used hearing tests and peripheral blood sample analyses to characterize the pathology of idiopathic sudden sensorineural hearing loss (ISSNHL and to identify possible prognostic factors for predicting recovery of hearing loss. STUDY DESIGN: A retrospective, multicenter trial was conducted. METHODS: Two hundred three patients examined within 7 days after the onset of ISSNHL received prednisone with lipo-prostaglandin E1. Pure-tone auditory tests were performed before and after treatment with these drugs. Blood tests were performed on blood samples collected during the patients' initial visit to our clinic. RESULTS: In all patients, elevated white blood cell (WBC counts, fasting blood sugar levels, HgbA1c, and erythrocyte sedimentation rate (ESR significantly correlated with high hearing threshold measurements obtained on the initial visit. High fibrinogen levels, WBC counts, ESR, and low concentrations of fibrinogen degradation products (FDP were associated with lower hearing recovery rates. Additionally, different audiogram shapes correlated with different blood test factors, indicating that different pathologies were involved. CONCLUSIONS: High fibrinogen levels measured within seven days after ISSNHL onset correlated with poorer hearing recovery. This may be a consequence of ischemia or infections in the inner ear. The high WBC counts also observed may therefore reflect an immune response to inner ear damage induced by ischemic changes or infections. Our data indicate that therapeutic strategies should be selected based on the timing of initial treatment relative to ISSNHL onset.

  13. Fibrinogen assays: a collaborative study of six different methods. C.I.S.M.E.L. Comitato Italiano per la Standardizzazione dei Metodi in Ematologia e Laboratorio.

    Science.gov (United States)

    Palareti, G; Maccaferri, M; Manotti, C; Tripodi, A; Chantarangkul, V; Rodeghiero, F; Ruggeri, M; Mannucci, P M

    1991-05-01

    This collaborative study, organized by the Hemostasis Subcommittee of C.I.S.M.E.L., evaluated the accuracy, precision, and comparability of the following six widely used fibrinogen assays: total clottable fibrinogen (Blombäck and Blombäck), clotting time (Von Clauss), turbidimetry (Ellis and Stransky), Chromotime System, prothrombin time (PT)-derived, and radial immunodiffusion (RID). The same frozen samples, with normal and high contents of fibrinogen, were examined in four laboratories. The methods were calibrated with an internal standard whose fibrinogen content was determined gravimetrically. Both the Von Clauss and the RID methods were reliable, accurate, and precise, if adequate calibration was used. The PT-derived method was highly reproducible, but had some problems with accuracy. We demonstrate that an adequate calibration procedure is indispensable for reliable fibrinogen measurements whatever method is used. Because neither the calibration procedures proposed by the manufacturers nor the use of lyophilized commercial plasmas is adequate for this purpose, we urge that an international standard for fibrinogen measurement be promptly established.

  14. Encapsulation of factor IX-engineered mesenchymal stem cells in fibrinogen-alginate microcapsules enhances their viability and transgene secretion.

    Science.gov (United States)

    Sayyar, Bahareh; Dodd, Megan; Wen, Jianping; Ma, Shirley; Marquez-Curtis, Leah; Janowska-Wieczorek, Anna; Hortelano, Gonzalo

    2012-01-01

    Cell microencapsulation holds significant promise as a strategy for cellular therapies; however, inadequate survival and functionality of the enclosed cells limit its application in hemophilia treatment. Here, we evaluated the use of alginate-based microcapsules to enhance the viability and transgene secretion of human cord blood-derived mesenchymal stem cells in three-dimensional cultures. Given the positive effects of extracellular matrix molecules on mesenchymal stem cell growth, we tested whether fibrinogen-supplemented alginate microcapsules can improve the efficiency of encapsulated factor IX-engineered mesenchymal stem cells as a treatment of hemophilia B. We found that fibrinogen-supplemented alginate microcapsules (a) significantly enhanced the viability and proliferation of factor IX-engineered mesenchymal stem cells and (b) increased factor IX secretion by mesenchymal stem cells compared to mesenchymal stem cells in nonsupplemented microcapsules. Moreover, we observed the osteogenic, but not chondrogenic or adipogenic, differentiation capability of factor IX-engineered cord blood mesenchymal stem cells and their efficient factor IX secretion while encapsulated in fibrinogen-supplemented alginate microcapsules. Thus, the use of engineered mesenchymal stem cells encapsulated in fibrinogen-modified microcapsules may have potential application in the treatment of hemophilia or other protein deficiency diseases.

  15. Predictive Role of Intraoperative Plasma Fibrinogen for Postoperative Portal Venous Flow in Living Donor Liver Transplantation.

    Science.gov (United States)

    Chae, Min Suk; Park, Chul Soo; Oh, Su A; Hong, Sang Hyun

    2017-02-14

    BACKGROUND Previous studies have reported poor graft regeneration after living donor liver transplantation (LDLT) due to inappropriate portal venous flow (PVF). In this study, we investigated the perioperative factors affecting postoperative PVF after LDLT. MATERIAL AND METHODS The perioperative data of 366 LDLT patients were retrospectively reviewed. The average PVF on postoperative days 1, 3, and 5 was measured and dichotomized at a cut-off value for patient survival of 1,477 mL/min. Perioperative variables, including coagulation profiles, were compared between high and low postoperative PVF groups. The factors potentially significant (plow postoperative PVF were evaluated in a univariate analysis, followed by the development of a predictive model for a low postoperative PVF. RESULTS A low post-LDLT PVF was determined in 113 patients (30.9%). The univariate analysis identified systemic hypertension, LDLT duration, average mean blood pressure, and insulin administration as the significantly related factors. Other significant factors were a plasma fibrinogen, at the anhepatic phase and 1 h after graft reperfusion, as well as the platelet count at the anhepatic phase. After multivariate adjustment, plasma fibrinogen 1 h after graft reperfusion against a recipient background of systemic hypertension was independently associated with a low mean postoperative PVF. CONCLUSIONS A low mean PVF during the early post-LDLT period was independently related to the plasma fibrinogen level 1 h after graft reperfusion, and to a history of systemic hypertension. Thus, the practice of aggressive supplementation of plasma fibrinogen during the immediate post-reperfusion period merits serious consideration.

  16. Modelling and measurements of fibrinogen adsorption on positively charged microspheres

    Directory of Open Access Journals (Sweden)

    P. Zeliszewska

    2016-02-01

    Full Text Available Adsorption of fibrinogen on positively charged microspheres was theoretically and experimentally studied. The structure of monolayers and the maximum coverage were determined by applying the experimental measurements at pH = 3.5 and 9.7 for NaCl concentration in the range of 10^{-3} - 0.15 M. The maximum coverage of fibrinogen on latex particles was precisely determined by the AFM method. Unexpectedly, at pH = 3.5, where both fibrinogen molecule and the latex particles were positively charged, the maximum coverage varied between 0.9 mg m^{-2} and 1.1 mg m^{-2} for 10^{-2} and 0.15 M NaCl, respectively. On the other hand, at pH = 9.7, the maximum coverage of fibrinogen was larger, varying between 1.8 mg m^{-2} and 3.4 mg m^{-2} for 10^{-2} and 0.15 M NaCl, respectively. The experimental results were quantitatively interpreted by the numerical simulations.

  17. Molecular weight fibrinogen variants alter gene expression and functional characteristics of human endothelial cells.

    NARCIS (Netherlands)

    Weijers, E.M.; Wijhe, M.H. van; Joosten, L.; Horrevoets, A.J.; Maat, M.P. de; Hinsbergh, V.W.H. van; Koolwijk, P.

    2010-01-01

    BACKGROUND: Fibrin is a temporary matrix that not only seals a wound, but also provides a temporary matrix structure for invading cells during wound healing. Two naturally occurring fibrinogen variants, high molecular weight (HMW) and low molecular weight (LMW) fibrinogen, display different properti

  18. Gender-related association between β-fibrinogen genotype and plasma fibrinogen levels and linkage disequilibrium at the fibrinogen locus in Greenland Inuit

    NARCIS (Netherlands)

    Maat, M.P.M. de; Knijff, P. de; Green, F.R.; Thomas, A.E.; Jespersen, J.; Kluft, C.

    1995-01-01

    Elevated plasma fibrinogen levels represent an increased risk for cardiovascular diseased, but the mechanism explaining this association is still not clear. Genetic differences may play a role, because it has been shown that individuals who carry the rare alleles of polymorphisms in the genes for th

  19. Strongly increased levels of fibrinogen elastase degradation products in patients with ischemic stroke

    NARCIS (Netherlands)

    Lau, L.M.L. de; Cheung, E.Y.L.; Kluft, C.; Leebeek, F.W.G.; Meijer, P.; Laterveer, R.; Dippel, D.W.J.; Maat, M.P.M.de

    2008-01-01

    Ischemic stroke is associated with leucocyte activation. Activated leucocytes release elastase, an enzyme that can degrade fibrinogen. Fibrinogen elastase degradation products (FgEDP) may serve as a specific marker of elastase proteolytic activity. In a case-control study of 111 ischemic stroke pati

  20. Fibrinogen polymorphisms are not associated with the risk of myocardial infarction

    NARCIS (Netherlands)

    Doggen, C.J.M.; Bertina, R.M.; Manger Cats, V.; Rosendaal, F.R.

    2000-01-01

    In the Study of Myocardial Infarctions Leiden, we investigated the prevalence of three polymorphisms in the α- and β-fibrinogen genes among 560 patients with a myocardial infarction and 646 control subjects. Secondly, we studied the relationships between these polymorphisms and fibrinogen activity a

  1. Strongly increased levels of fibrinogen elastase degradation products in patients with ischemic stroke

    NARCIS (Netherlands)

    Lau, L.M.L. de; Cheung, E.Y.L.; Kluft, C.; Leebeek, F.W.G.; Meijer, P.; Laterveer, R.; Dippel, D.W.J.; Maat, M.P.M.de

    2008-01-01

    Ischemic stroke is associated with leucocyte activation. Activated leucocytes release elastase, an enzyme that can degrade fibrinogen. Fibrinogen elastase degradation products (FgEDP) may serve as a specific marker of elastase proteolytic activity. In a case-control study of 111 ischemic stroke pati

  2. Future changes in global warming potentials under representative concentration pathways

    Energy Technology Data Exchange (ETDEWEB)

    Reisinger, Andy [New Zealand Agricultural Greenhouse Gas Research Centre, PO Box 10002, Wellington 6143 (New Zealand); Meinshausen, Malte [Earth System Analysis, Potsdam Institute for Climate Impact Research (Germany); Manning, Martin, E-mail: andy.reisinger@nzagrc.org.nz [Climate Change Research Institute, Victoria University of Wellington (New Zealand)

    2011-04-15

    Global warming potentials (GWPs) are the metrics currently used to compare emissions of different greenhouse gases under the United Nations Framework Convention on Climate Change. Future changes in greenhouse gas concentrations will alter GWPs because the radiative efficiencies of marginal changes in CO{sub 2}, CH{sub 4} and N{sub 2}O depend on their background concentrations, the removal of CO{sub 2} is influenced by climate-carbon cycle feedbacks, and atmospheric residence times of CH{sub 4} and N{sub 2}O also depend on ambient temperature and other environmental changes. We calculated the currently foreseeable future changes in the absolute GWP of CO{sub 2}, which acts as the denominator for the calculation of all GWPs, and specifically the GWPs of CH{sub 4} and N{sub 2}O, along four representative concentration pathways (RCPs) up to the year 2100. We find that the absolute GWP of CO{sub 2} decreases under all RCPs, although for longer time horizons this decrease is smaller than for short time horizons due to increased climate-carbon cycle feedbacks. The 100-year GWP of CH{sub 4} would increase up to 20% under the lowest RCP by 2100 but would decrease by up to 10% by mid-century under the highest RCP. The 100-year GWP of N{sub 2}O would increase by more than 30% by 2100 under the highest RCP but would vary by less than 10% under other scenarios. These changes are not negligible but are mostly smaller than the changes that would result from choosing a different time horizon for GWPs, or from choosing altogether different metrics for comparing greenhouse gas emissions, such as global temperature change potentials.

  3. Distributed vasculogenesis from modular agarose-hydroxyapatite-fibrinogen microbeads.

    Science.gov (United States)

    Rioja, Ana Y; Daley, Ethan L H; Habif, Julia C; Putnam, Andrew J; Stegemann, Jan P

    2017-06-01

    Critical limb ischemia impairs circulation to the extremities, causing pain, disrupted wound healing, and potential tissue necrosis. Therapeutic angiogenesis seeks to repair the damaged microvasculature directly to restore blood flow. In this study, we developed modular, micro-scale constructs designed to possess robust handling qualities, allow in vitro pre-culture, and promote microvasculature formation. The microbead matrix consisted of an agarose (AG) base to prevent aggregation, combined with cell-adhesive components of fibrinogen (FGN) and/or hydroxyapatite (HA). Microbeads encapsulating a co-culture of human umbilical vein endothelial cells (HUVEC) and fibroblasts were prepared and characterized. Microbeads were generally 80-100µm in diameter, and the size increased with the addition of FGN and HA. Addition of HA increased the yield of microbeads, as well as the homogeneity of distribution of FGN within the matrix. Cell viability was high in all microbead types. When cell-seeded microbeads were embedded in fibrin hydrogels, HUVEC sprouting and inosculation between neighboring microbeads were observed over seven days. Pre-culture of microbeads for an additional seven days prior to embedding in fibrin resulted in significantly greater HUVEC network length in AG+HA+FGN microbeads, as compared to AG, AG+HA or AG+FGN microbeads. Importantly, composite microbeads resulted in more even and widespread endothelial network formation, relative to control microbeads consisting of pure fibrin. These results demonstrate that AG+HA+FGN microbeads support HUVEC sprouting both within and between adjacent microbeads, and can promote distributed vascularization of an external matrix. Such modular microtissues may have utility in treating ischemic tissue by rapidly re-establishing a microvascular network. Critical limb ischemia (CLI) is a chronic disease that can lead to tissue necrosis, amputation, and death. Cell-based therapies are being explored to restore blood flow and

  4. Loss of fibrinogen in zebrafish results in symptoms consistent with human hypofibrinogenemia.

    Directory of Open Access Journals (Sweden)

    Andy H Vo

    Full Text Available Cessation of bleeding after trauma is a necessary evolutionary vertebrate adaption for survival. One of the major pathways regulating response to hemorrhage is the coagulation cascade, which ends with the cleavage of fibrinogen to form a stable clot. Patients with low or absent fibrinogen are at risk for bleeding. While much detailed information is known about fibrinogen regulation and function through studies of humans and mammalian models, bleeding risk in patients cannot always be accurately predicted purely based on fibrinogen levels, suggesting an influence of modifying factors and a need for additional genetic models. The zebrafish has orthologs to the three components of fibrinogen (fga, fgb, and fgg, but it hasn't yet been shown that zebrafish fibrinogen functions to prevent bleeding in vivo. Here we show that zebrafish fibrinogen is incorporated into an induced thrombus, and deficiency results in hemorrhage. An Fgb-eGFP fusion protein is incorporated into a developing thrombus induced by laser injury, but causes bleeding in adult transgenic fish. Antisense morpholino knockdown results in intracranial and intramuscular hemorrhage at 3 days post fertilization. The observed phenotypes are consistent with symptoms exhibited by patients with hypo- and afibrinogenemia. These data demonstrate that zebrafish possess highly conserved orthologs of the fibrinogen chains, which function similarly to mammals through the formation of a fibrin clot.

  5. Modulation of plasma fibrinogen levels by ticlopidine in healthy volunteers and patients with stable angina pectoris

    NARCIS (Netherlands)

    Maat, M.P.M. de; Arnold, A.E.R.; Buuren, S. van; Paul Wilson, J.H.; Kluft, C.

    1996-01-01

    Elevated plasma fibrinogen levels represent an increased risk for cardiac events. Ticlopidine is a drug that inhibits the ADP-induced aggregation of blood platelets and it also has been described that ticlopidine can decrease the plasma fibrinogen level in patients with vascular diseases. The

  6. Modulation of plasma fibrinogen levels by ticlopidine in healthy volunteers and patients with stable angina pectoris

    NARCIS (Netherlands)

    Maat, M.P.M. de; Arnold, A.E.R.; Buuren, S. van; Wilson, J.H.P.; Kluft, C.

    1996-01-01

    Elevated plasma fibrinogen levels are associated with an increased risk for cardiac events. Ticlopidine is a drug that inhibits the ADP-induced aggregation of blood platelets and it also has been described that ticlopidine can decrease the plasma fibrinogen level in patients with vascular diseases.

  7. Modulation of plasma fibrinogen levels by ticlopidine in healthy volunteers and patients with stable angina pectoris

    NARCIS (Netherlands)

    Maat, M.P.M. de; Arnold, A.E.R.; Buuren, S. van; Paul Wilson, J.H.; Kluft, C.

    1996-01-01

    Elevated plasma fibrinogen levels represent an increased risk for cardiac events. Ticlopidine is a drug that inhibits the ADP-induced aggregation of blood platelets and it also has been described that ticlopidine can decrease the plasma fibrinogen level in patients with vascular diseases. The mechan

  8. Binding of Efb from Staphylococcus aureus to fibrinogen blocks neutrophil adherence

    Science.gov (United States)

    In addition to its pivotal role in hemostasis, fibrinogen (Fg) and provisional fibrin matrices play important roles in inflammation and regulate innate immune responses by interacting with leukocytes. Efb (the extracellular fibrinogen-binding protein) is a secreted Staphylococcus aureus protein that...

  9. Modulation of plasma fibrinogen levels by ticlopidine in healthy volunteers and patients with stable angina pectoris

    NARCIS (Netherlands)

    Maat, M.P.M. de; Arnold, A.E.R.; Buuren, S. van; Wilson, J.H.P.; Kluft, C.

    1996-01-01

    Elevated plasma fibrinogen levels are associated with an increased risk for cardiac events. Ticlopidine is a drug that inhibits the ADP-induced aggregation of blood platelets and it also has been described that ticlopidine can decrease the plasma fibrinogen level in patients with vascular diseases.

  10. Fibrinogen polymorphisms are not associated with the risk of myocardial infarction

    NARCIS (Netherlands)

    Doggen, Catharina Jacoba Maria; Bertina, R.M.; Manger Cats, V.; Rosendaal, F.R.

    2000-01-01

    In the Study of Myocardial Infarctions Leiden, we investigated the prevalence of three polymorphisms in the α- and β-fibrinogen genes among 560 patients with a myocardial infarction and 646 control subjects. Secondly, we studied the relationships between these polymorphisms and fibrinogen activity

  11. Fibrinogen

    Science.gov (United States)

    ... during pregnancy if the placenta separates from its attachment to the uterus wall ( placenta abruptio ). Risks There ... most often performed on people who have bleeding disorders. The risk of excessive bleeding is slightly greater ...

  12. SERUM FIBRINOGEN LEVELS AND ITS RELATION TO DIABETIC RETINOPATHY

    Directory of Open Access Journals (Sweden)

    Adil Majeed

    2015-11-01

    Full Text Available BACKGROUND Elevation of plasma fibrinogen is thought to be one of the major risk factors associated with increase in blood viscosity in patients with diabetic retinopathy. Diabetic retinopathy being a microangiopathy, the study was done with the aim to assess the relationship between serum fibrinogen levels in patients with and without diabetic retinopathy. MATERIALS AND METHODS This study was conducted at Government Medical College, Srinagar, in which 101 diabetic patients with and without retinopathy were evaluated. These patients were classified into two groups: 1 Patients with diabetic retinopathy, which included 50 patients. 2 Patients without diabetic retinopathy, which included 51 patients. Each patient was subjected to a comprehensive ocular examination and the results were recorded and analyzed in detail. RESULTS Our study which was prospective, non-randomized hospital based study was undertaken for the period of 18 months to see the association between fibrinogen levels in the blood and the development of diabetic retinopathy. Our study included 101 patients with type-2 diabetes. Among this Group-1 included 50 patients with diabetic retinopathy and Group-2 included 51 patients without diabetic retinopathy. In our study, total number of female patients were 65 (64.35% and males were 36 (35.64%. The mean age for males and females was 57.5 and 54.6 years respectively. Mean duration of diabetes in patients with retinopathy and without retinopathy was 10.9 and 5.7 years respectively. It was observed in our study that most of the patients with diabetic retinopathy had compromised visual acuity in one or both eyes, i.e., Vn>6/60. We found that out of 50 patients with diabetic retinopathy, 36 (72% patients were having raised serum fibrinogen levels, while as out of 51 patients without diabetic retinopathy 17 (33.33% patients were having raised serum fibrinogen levels, and mean serum fibrinogen levels in patients with and without retinopathy

  13. Arterial and venous thrombus imaging using Ga-67 DFO-DAS-fibrinogen. Its clinical applicability

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Teruyasu; Torizuka, Kanji; Horiuchi, Kazuko; Yokoyama, Akira.

    1987-10-01

    The purpose of this study was the clinical application of /sup 67/Ga-DFO-DAS-fibrinogen /sup 67/Ga-fibrinogen in normal volunteers and patients with arterial or venous therombus, or bypass graft. DFO-DAS-fibrinogen was available as a lyophilized product and easily labeled by simple mixing with /sup 67/Ga-fibrinogen solution (2 mCi/2 ml). Images were taken by a scintillation camera 72 hours after the venous injection of /sup 67/Ga-fibrinogen (2 mCi). Ga-67 fibrinogen accumulated well in the liver and kidney innormal volunteers at the early stage, and radioactivity in the kidney, lung, and heart decreased after noticeably after 48 hours postinjection. Ga-67 fibrinogen clearly visualized fresh and old arterial thrombi localized in the thorax or abdomen of all patients suffering aneurysm, and in occlusive bypass graft, contrary to past observations with labeled fibrinogen. In venous thrombus, with the pulmonary artery included, visualization was limited to fresh thrombi of up to one month old. No adverse side effects were observed in any case.

  14. Fibrinogen adsorption mechanisms at the gold substrate revealed by QCM-D measurements and RSA modeling.

    Science.gov (United States)

    Kubiak, Katarzyna; Adamczyk, Zbigniew; Cieśla, Michał

    2016-03-01

    Adsorption kinetics of fibrinogen at a gold substrate at various pHs was thoroughly studied using the QCM-D method. The experimental were interpreted in terms of theoretical calculations performed according to the random sequential adsorption model (RSA). In this way, the hydration functions and water factors of fibrinogen monolayers were quantitatively evaluated at various pHs. It was revealed that for the lower range of fibrinogen coverage the hydration function were considerably lower than previously obtained for the silica sensor [33]. The lower hydration of fibrinogen monolayers on the gold sensor was attributed to its higher roughness. However, for higher fibrinogen coverage the hydration functions for both sensors became identical exhibiting an universal behavior. By using the hydration functions, the fibrinogen adsorption/desorption runs derived from QCM-D measurements were converted to the Γd vs. the time relationships. This allowed to precisely determine the maximum coverage that varied between 1.6mgm(-2) at pH 3.5 and 4.5mgm(-2) at pH 7.4 (for ionic strength of 0.15M). These results agree with theoretical eRSA modeling and previous experimental data derived by using ellipsometry, OWLS and TIRF. Various fibrinogen adsorption mechanisms were revealed by exploiting the maximum coverage data. These results allow one to develop a method for preparing fibrinogen monolayers of well-controlled coverage and molecule orientation. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Changes in fibrin D-dimer, fibrinogen, and protein S during pregnancy

    DEFF Research Database (Denmark)

    Hansen, Anette Tarp; Andreasen, Birgitte Horst; Salvig, Jannie Dalby

    2010-01-01

    Background. Pregnancy is a hypercoagulable state with a 5- to 10- fold higher risk of venous thromboembolism. Existing reference intervals for fibrin D-dimer (D-dimer), functional fibrinogen (fibrinogen) and protein S, free antigen (protein S) are based on non-pregnant patients and reference...... intervals for pregnant patients are warranted. Objectives. The aim of the present study was to contribute to the establishment of reference intervals for D-dimer, fibrinogen and protein S during pregnancy and to discuss the use of the analyses during pregnancy. Methods. We included 55 healthy pregnant women....... Changes during pregnancy in plasma D-dimer, protein S and fibrinogen were confirmed. Further clinical studies are needed to clarify a clinical useful cut-off point for D-dimer in pregnancy. We suggest careful attention to a low peripartum fibrinogen, since it indicates an increased bleeding risk. We...

  16. Modulation of plasma fibrinogen levels by medication

    NARCIS (Netherlands)

    Maat, M.P.M. de; Kodex, M.; Kastelein, J.J.P.

    1996-01-01

    Elevated plasma fibrinogen levels represent an increased risk for cardiac events. This has enhanced the interest in identifying agents that can normalize elevated plasma fibrinogen levels. Agents that have this capacity are the lipid lowering fibric acid derivatives (e.g. ciprofibrate) and the plate

  17. DNA methylation profiling of the fibrinogen gene landscape in human cells and during mouse and zebrafish development.

    Science.gov (United States)

    Vorjohann, Silja; Pitetti, Jean-Luc; Nef, Serge; Gonelle-Gispert, Carmen; Buhler, Leo; Fish, Richard J; Neerman-Arbez, Marguerite

    2013-01-01

    The fibrinogen genes FGA, FGB and FGG show coordinated expression in hepatocytes. Understanding the underlying transcriptional regulation may elucidate how their tissue-specific expression is maintained and explain the high variability in fibrinogen blood levels. DNA methylation of CpG-poor gene promoters is dynamic with low methylation correlating with tissue-specific gene expression but its direct effect on gene regulation as well as implications of non-promoter CpG methylation are not clear. Here we compared methylation of CpG sites throughout the fibrinogen gene cluster in human cells and mouse and zebrafish tissues. We observed low DNA methylation of the CpG-poor fibrinogen promoters and of additional regulatory elements (the liver enhancers CNC12 and PFE2) in fibrinogen-expressing samples. In a gene reporter assay, CpG-methylation in the FGA promoter reduced promoter activity, suggesting a repressive function for DNA methylation in the fibrinogen locus. In mouse and zebrafish livers we measured reductions in DNA methylation around fibrinogen genes during development that were preceded by increased fibrinogen expression and tri-methylation of Histone3 lysine4 (H3K4me3) in fibrinogen promoters. Our data support a model where changes in hepatic transcription factor expression and histone modification provide the switch for increased fibrinogen gene expression in the developing liver which is followed by reduction of CpG methylation.

  18. DNA methylation profiling of the fibrinogen gene landscape in human cells and during mouse and zebrafish development.

    Directory of Open Access Journals (Sweden)

    Silja Vorjohann

    Full Text Available The fibrinogen genes FGA, FGB and FGG show coordinated expression in hepatocytes. Understanding the underlying transcriptional regulation may elucidate how their tissue-specific expression is maintained and explain the high variability in fibrinogen blood levels. DNA methylation of CpG-poor gene promoters is dynamic with low methylation correlating with tissue-specific gene expression but its direct effect on gene regulation as well as implications of non-promoter CpG methylation are not clear. Here we compared methylation of CpG sites throughout the fibrinogen gene cluster in human cells and mouse and zebrafish tissues. We observed low DNA methylation of the CpG-poor fibrinogen promoters and of additional regulatory elements (the liver enhancers CNC12 and PFE2 in fibrinogen-expressing samples. In a gene reporter assay, CpG-methylation in the FGA promoter reduced promoter activity, suggesting a repressive function for DNA methylation in the fibrinogen locus. In mouse and zebrafish livers we measured reductions in DNA methylation around fibrinogen genes during development that were preceded by increased fibrinogen expression and tri-methylation of Histone3 lysine4 (H3K4me3 in fibrinogen promoters. Our data support a model where changes in hepatic transcription factor expression and histone modification provide the switch for increased fibrinogen gene expression in the developing liver which is followed by reduction of CpG methylation.

  19. Fibrinopeptides A and B release in the process of surface fibrin formation

    OpenAIRE

    Riedel, Tomas; Suttnar, Jiri; Brynda, Eduard; Houska, Milan; Medved, Leonid; Jan E. Dyr

    2011-01-01

    Fibrinogen adsorption on a surface results in the modification of its functional characteristics. Our previous studies revealed that fibrinogen adsorbs onto surfaces essentially in 2 different orientations depending on its concentration in the solution: “side-on” at low concentrations and “end-on” at high concentrations. In the present study, we analyzed the thrombin-mediated release of fibrinopeptides A and B (FpA and FpB) from fibrinogen adsorbed in these orientations, as well as from surfa...

  20. Development of a high performance liquid chromatography/mass spectroscopy method for the determination of strychnine concentrations in insects used to assess potential risks to insectivores.

    Science.gov (United States)

    Stahl, Randal S; Arjo, Wendy M; Wagner, Kim K; Furcolow, Carol; Nolte, Dale L; Johnston, John J

    2004-11-25

    A high performance liquid chromatography/mass spectrometry (HPLC/MS) method was developed in support of a study to assess potential tertiary risks posed to insectivores by strychnine baited pocket gophers (Thomomys sp.). Necropholous insects are primary consumers of pocket gopher carcasses. A field study was conducted to collect insects from strychnine-baited and control pocket gopher carcasses. The majority of the insects collected were from the orders Diptera (flies, assayed separately as adults and larvae), Coleoptera (beetles), and Hymenoptera (ants and wasps, assayed separately). Samples (0.5 g) were extracted in acetic acid (2%) and analyzed with the mass spectrometer configured for tandem mass spectrometry. For most of the samples the strychnine concentrations were less than the method limit of detection. However, strychnine concentrations as high as 0.338, 0.341, 0.698, and 0.034 microg/g were detected in ants, fly adults, fly larvae, and beetles, respectively. This information collected with the HPLC/MS method is critical for assessing potential non-target hazards for insectivores.

  1. Scaling of flat band potential and dielectric constant as a function of Ta concentration in Ta-TiO2 epitaxial films

    Directory of Open Access Journals (Sweden)

    Y. L. Zhao

    2011-06-01

    Full Text Available Electrochemical impedance spectroscopy measurements of pulsed laser deposited single crystal anatase TiO2 thin films with various concentrations of Ta substituting for Ti were carried out. The qualities of the films were characterized by X-ray diffraction and Rutherford back scattering-channeling measurements. UV-visible measurements show a systematic increase of the bandgap with Ta incorporation. Corresponding Mott-Schottky plot was applied to obtain a continuous shift of the flat band potential with increasing free charge carrier (provided by Ta concentration. This was verified theoretically by ab initio calculation which shows that extra Ta d-electrons occupy Ti t2g orbital with increasing Ta concentration, thereby pushing up the Fermi level. The Mott-Schottky results were consistent when compared with Hall effect and temperature dependent resistivity measurements. From the measured deviation of carrier densities from Hall and Mott-Schottky measurements we have estimated the static dielectric constant of the TiO2 as a function of Ta incorporation, not possible from capacitive measurements.

  2. Comparative prognostic value of C-reactive protein & fibrinogen in patients with coronary artery disease

    Directory of Open Access Journals (Sweden)

    Gjin Ndrepepa

    2014-01-01

    Full Text Available Background & objectives: The comparative prognostic value of C-reactive protein (CRP and fibrinogen for cardiovascular events has been inconclusively investigated. t0 his study was carried out to compare the prognostic value of CRP versus fibrinogen in patients with coronary artery disease (CAD. Methods: The study included 13,100 patients with coronary angiography-confirmed CAD. Plasma CRP and fibrinogen levels were measured before angiography in all patients. The levels of CRP>3 mg/l and fibrinogen>350 mg/dl were considered as elevated. The primary outcome was 1-year all-cause mortality. Results: Patients were divided into four groups: patients with CRP≤3 mg/l and fibrinogen ≤350 mg/dl (n=4206; patients with CRP≤3 mg/l and fibrinogen >350 mg/dl (n=3132; patients with CRP>3 mg/l and fibrinogen ≤ 350 mg/dl (n=1273 and CRP >3 mg/l and patients with fibrinogen >350 mg/dl (n=4489. There were 634 deaths: 75 deaths in patients with CRP ≤3 mg/l and fibrinogen ≤350 mg/dl, 91 deaths in patients with CRP ≤3 mg/l and fibrinogen >350 mg/dl, 87 deaths in patients with CRP >3 mg/l and fibrinogen ≤350 mg/dl and 381 deaths in patients with CRP >3 mg/l and fibrinogen >350 mg/dl (Kaplan-Meier estimates of all-cause mortality, 1.8, 3.0, 7.0 and 8.7 %, log-rank test P<0.001. The multivariate analysis showed that CRP [adjusted hazard ratio (HR=1.31, 95% confidence interval (CI 1.18-1.45, for each standard deviation increase in the logarithmic scale] but not fibrinogen [adjusted HR=0.99 (0.90-1.09, for each standard deviation increase in the logarithmic scale] was an independent correlate of mortality. Interpretation & conclusions: The findings indicated that in patients with CAD, CRP was a better predictor of mortality than fibrinogen and offered prognostic information beyond that provided by the conventional cardiovascular risk factors.

  3. Relation of C-reactive protein, fibrinogen, and cardiorespiratory fitness to risk of systemic hypertension in men.

    Science.gov (United States)

    Jae, Sae Young; Kurl, Sudhir; Laukkanen, Jari A; Lee, Chong-Do; Choi, Yoon-Ho; Fernhall, Bo; Franklin, Barry A

    2015-06-15

    We investigated the relation between inflammation and incident hypertension, independent of obesity, and tested the associations of cardiorespiratory fitness (fitness) and indexes of inflammation for the development of hypertension in 2,475 normotensive men. Inflammatory markers were C-reactive protein (CRP) and fibrinogen. Fitness was directly measured by peak oxygen uptake during sign/symptom-limited treadmill exercise testing to volitional fatigue; 266 men (10.7%) developed hypertension during an average of 4 years follow-up. After adjusting for potential confounding variables, the relative risk (RR) and 95% confidence interval (CI) for incident hypertension in those in the upper tertile versus lower tertile were 1.55 (95% CI 1.15 to 2.09) for CRP and 1.51 (95% CI 1.10 to 2.06) for fibrinogen. Although the association between fibrinogen and incident hypertension persisted after adjusting for body mass index (p = 0.049), the relation between CRP and incident hypertension was no longer statistically significant (p = 0.08). Fit men had a 27% decreased (RR 0.73, 95% CI 0.56 to 0.94) risk of incident hypertension compared with unfit men in a multivariable adjusted model. In the joint analysis, unfit men with upper CRP had 1.81 times (95% CI 1.21 to 2.70) and unfit men with upper fibrinogen had 2.03 times (95% CI 1.33 to 3.12) greater risks of incident hypertension compared with fit men with low CRP and fibrinogen, respectively. However, these risks did not significantly increase in fit men with upper CRP (RR 1.12, 95% CI 0.76 to 1.63) and fibrinogen (RR 1.26, 95% CI 0.86 to 1.85) groups. In conclusion, these results suggest that heightened levels of fibrinogen, but not CRP, are associated with incident hypertension, independent of body weight, and that high fitness attenuates the risk of incident hypertension across upper levels of inflammatory markers in men.

  4. Impaired Protofibril Formation in Fibrinogen γN308K Is Due to Altered D:D and "A:a" Interactions

    Energy Technology Data Exchange (ETDEWEB)

    Bowley, S.; Okumura, N; Lord, S

    2009-01-01

    'A:a' knob-hole interactions and D:D interfacial interactions are important for fibrin polymerization. Previous studies with recombinant ?N308K fibrinogen, a substitution at the D:D interface, showed impaired polymerization. We examined the molecular basis for this loss of function by solving the crystal structure of ?N308K fragment D. In contrast to previous fragment D crystals, the ?N308K crystals belonged to a tetragonal space group with an unusually long unit cell (a = b = 95 Angstroms, c = 448.3 Angstroms). Alignment of the normal and ?N308K structures showed the global structure of the variant was not changed and the knob 'A' peptide GPRP was bound as usual to hole 'a'. The substitution introduced an elongated positively charged patch in the D:D region. The structure showed novel, symmetric D:D crystal contacts between ?N308K molecules, indicating the normal asymmetric D:D interface in fibrin would be unstable in this variant. We examined GPRP binding to ?N308K in solution by plasmin protection assay. The results showed weaker peptide binding, suggesting that 'A:a' interactions were altered. We examined fibrin network structures by scanning electron microscopy and found the variant fibers were thicker and more heterogeneous than normal fibers. Considered together, our structural and biochemical studies indicate both 'A:a' and D:D interactions are weaker. We conclude that stable protofibrils cannot assemble from ?N308K monomers, leading to impaired polymerization.

  5. Crystal structure of the tetrameric fibrinogen-like recognition domain of Fibrinogen C domain containing 1 (FIBCD1)

    DEFF Research Database (Denmark)

    Shrive, Annette K; Moeller, Jesper B; Burns, Ian;

    2014-01-01

    The high-resolution crystal structures of a recombinant fragment of the C-terminal fibrinogen-like recognition domain of FIBCD1, a vertebrate receptor that binds chitin, have been determined. The overall tetrameric structure shows similarity in structure and aggregation to the horseshoe crab innate...

  6. Binding of Human Fibrinogen to MRP Enhances Streptococcus suis Survival in Host Blood in a αXβ2 Integrin-dependent Manner.

    Science.gov (United States)

    Pian, Yaya; Li, Xueqin; Zheng, Yuling; Wu, Xiaohong; Yuan, Yuan; Jiang, Yongqiang

    2016-05-27

    The Gram-positive bacterium Streptococcus suis serotype 2 (S. suis 2), an important zoonotic pathogen, induces strong systemic infections in humans; sepsis and meningitis are the most common clinical manifestations and are often accompanied by bacteremia. However, the mechanisms of S. suis 2 survival in human blood are not well understood. In our previous study, we identified muramidase-released protein (MRP), a novel human fibrinogen (hFg)-binding protein (FBP) in S. suis 2 that is an important epidemic infection marker with an unknown mechanism in pathogenesis. The present study demonstrates that the N-terminus of MRP (a.a. 283-721) binds to both the Aα and Bβ chains of the D fragment of hFg. Strikingly, the hFg-MRP interaction improved the survival of S. suis 2 in human blood and led to the aggregation and exhaustion of polymorphonuclear neutrophils (PMNs) via an αXβ2 integrin-dependent mechanism. Other Fg-binding proteins, such as M1 (GAS) and FOG (GGS), also induced PMNs aggregation; however, the mechanisms of these FBP-hFg complexes in the evasion of PMN-mediated innate immunity remain unclear. MRP is conserved across highly virulent strains in Europe and Asia, and these data shed new light on the function of MRP in S. suis pathogenesis.

  7. Synergistic effect of vitamin D and low concentration of transforming growth factor beta 1, a potential role in dermal wound healing.

    Science.gov (United States)

    Ding, Jie; Kwan, Peter; Ma, Zengshuan; Iwashina, Takashi; Wang, Jianfei; Shankowsky, Heather A; Tredget, Edward E

    2016-09-01

    Dermal wound healing, in which transforming growth factor beta 1 (TGFβ1) plays an important role, is a complex process. Previous studies suggest that vitamin D has a potential regulatory role in TGFβ1 induced activation in bone formation, and there is cross-talk between their signaling pathways, but research on their effects in other types of wound healing is limited. The authors therefore wanted to explore the role of vitamin D and its interaction with low concentration of TGFβ1 in dermal fibroblast-mediated wound healing through an in vitro study. Human dermal fibroblasts were treated with vitamin D, TGFβ1, both, or vehicle, and then the wound healing functions of dermal fibroblasts were measured. To further explore possible mechanisms explaining the synergistic effect of vitamin D and TGFβ1, targeted gene silencing of the vitamin D receptor was performed. Compared to either factor alone, treatment of fibroblasts with both vitamin D and low concentration of TGFβ1 increased gene expression of TGFβ1, connective tissue growth factor, and fibronectin 1, and enhanced fibroblast migration, myofibroblast formation, and collagen production. Vitamin D receptor gene silencing blocked this synergistic effect of vitamin D and TGFβ1 on both collagen production and myofibroblast differentiation. Thus a synergistic effect of vitamin D and low TGFβ1 concentration was found in dermal fibroblast-mediated wound healing in vitro. This study suggests that supplementation of vitamin D may be an important step to improve wound healing and regeneration in patients with a vitamin D deficiency. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

  8. An in silico approach to understand the structure-function properties of a serine protease (Bacifrinase) from Bacillus cereus and experimental evidence to support the interaction of Bacifrinase with fibrinogen and thrombin.

    Science.gov (United States)

    Bora, Bandana; Biswas, Akash Deep; Gurung, Arun Bahadur; Bhattacharjee, Atanu; Mattaparthi, Venkata Satish Kumar; Mukherjee, Ashis K

    2017-02-01

    Microbial fibrinogenolytic serine proteases find therapeutic applications in the treatment of thrombosis- and hyperfibrinogenemia-associated disorders. However, analysis of structure-function properties of an enzyme is utmost important before its commercial application. In this study, an attempt has been made to understand the structure of a fibrinogenolytic protease enzyme, "Bacifrinase" from Bacillus cereus strain AB01. From the molecular dynamics trajectory analysis, the modelled three-dimensional structure of the protease was found to be stable and the presence of a catalytic triad made up of Asp102, His83 and Ser195 suggests that it is a serine protease. To understand the mechanism of enzyme-substrate and enzyme-inhibitor interactions, the equilibrated protein was docked with human fibrinogen (the physiological substrate of this enzyme), human thrombin and with ten selective protease inhibitors. The Bacifrinase-chymostatin interaction was the strongest among the selected protease inhibitors. The serine protease inhibitor phenyl methane sulphonyl fluoride was found to interact with the Ser134 residue of Bacifrinase. Furthermore, protein-protein docking study revealed the fibrinogenolytic property of Bacifrinase and its interaction with Aα-, Bβ- and Cγ-chains human fibrinogen to a different extent. However, biochemical analysis showed that Bacifrinase did not hydrolyse the γ-chain of fibrinogen. The in silico and spectrofluorometric studies also showed interaction of Bacifrinase with thrombin as well as fibrinogen with a Kd value of 16.5 and .81 nM, respectively. Our findings have shed light on the salient structural features of Bacifrinase and confirm that it is a fibrinogenolytic serine protease.

  9. Relationship between the -455G/A and -148C/T polymorphisms in the beta-fibrinogen gene and cerebral infarction in the Xinjiang Uygur and Han Chinese populations

    Institute of Scientific and Technical Information of China (English)

    Xiaoning Zhang; Yanyun Li; Xuebing Guo; Lei Du; Jianhua Ma

    2012-01-01

    We sought to investigate the correlation between the -455G/A and -148C/T polymorphisms of the β-fibrinogen gene and plasma fibrinogen levels in patients with cerebral infarction and in healthy subjects among the Xinjiang Uygur and Han Chinese populations, by using polymerase chain reaction-restriction enzyme digestion analysis.Results showed that there were no statistically significant differences in the distributions of the -455G/A genotype and allele frequency between the Uygurs and the Han.Plasma fibrinogen levels in cerebral infarction patients among the Uygurs and the Han were higher than those among healthy subjects.In particular, the frequencies of the -455G/A AA and -148C/T TT genotypes were significantly higher than in healthy subjects.Individuals carrying the A or T allele had a higher incidence of cerebral infarction compared with those carrying the G or C allele.Our experimental findings indicate that the -148C/T and -455G/A polymorphisms are associated with cerebral infarction in Xinjiang Uygur and Han Chinese subjects.The susceptibility- conferring alleles are -148T and -455A, and the susceptibility-conferring genotype is -455G/A + AA.

  10. Food preservative potential of gassericin A-containing concentrate prepared from a cheese whey culture supernatant from Lactobacillus gasseri LA39.

    Science.gov (United States)

    Nakamura, Kiyoshi; Arakawa, Kensuke; Kawai, Yasushi; Yasuta, Narimi; Chujo, Takahiro; Watanabe, Masamichi; Iioka, Hiroyuki; Tanioka, Masashi; Nishimura, Junko; Kitazawa, Haruki; Tsurumi, Koichi; Saito, Tadao

    2013-02-01

    Gassericin A (GA) is a circular bacteriocin produced by Lactobacillus gasseri LA39. In this study, GA-containing concentrate was prepared using a cross-flow membrane filtration device (30 kDa cut-off) from the culture supernatant of Lb. gasseri LA39 cultivated in a cheese whey-based food-grade medium. The bacteriocin activity titer in the concentrate was 16 times as high as that of the culture supernatant and was completely maintained through each incubation at 4°C for 3 months, 37°C for 2 months, 60°C for 5 h, and 100°C for 30 min. The GA-containing concentrate was used with glycine powder to make custard creams, and then four representative strains of custard cream spoilage bacteria (Bacillus cereus, Lactococcus lactis subsp. lactis, Achromobacter denitrificans and Pseudomonas fluorescens) were individually inoculated at c. 10(3) colony forming units/g in the custard creams. Throughout 30 days of incubation at 30°C, all of the inoculated bacteria were completely inhibited by the combination of 5% (w/w) of the GA-containing concentrate and 0.5% (w/w) glycine. This is the first highly practical application of GA to foods as a biopreservative, and the concentration method and the bacteriocin concentrate would contribute to biopreservation of several foods.

  11. Concentration, composition, bioavailability, and N-nitrosodimethylamine formation potential of particulate and dissolved organic nitrogen in wastewater effluents: A comparative study.

    Science.gov (United States)

    Hu, Haidong; Ma, Haijun; Ding, Lili; Geng, Jinju; Xu, Ke; Huang, Hui; Zhang, Yingying; Ren, Hongqiang

    2016-11-01

    Wastewater-derived organic nitrogen (org-N) can act as both nutrients and carcinogenic nitrogenous disinfection byproduct precursors. In this study, the concentration, composition, bioavailability, and N-nitrosodimethylamine (NDMA) formation potential of particulate organic nitrogen (PON) from three different municipal wastewater treatment plants were characterized and compared with that of effluent dissolved organic nitrogen (DON). The average effluent PON and DON concentrations ranged from 0.09 to 0.55mgN/L and from 0.91 to 1.88mgN/L, respectively. According to principal component analysis, org-N composition and characterization differed in PON and DON samples (n=20). Compared with DON, PON tended to be enriched in protein and nucleic acids, and showed a more proteinaceous character. Composition of org-N functional groups estimated from the X-ray photoelectron spectroscopy N 1s spectra indicate no significant differences in the molecular weight distribution of the protein-like materials between PON and DON. Moreover, PON exhibited a significantly higher bioavailability (61.0±13.3%) compared to DON (38.5±12.4%, p˂0.05, t-test) and a significantly higher NDMA yields (791.4±404.0ng/mg-N) compared to DON (374.8±62.5ng/mg-N, p˂0.05, t-test). Accordingly, PON contributed to approximately 12.3-41.7% of the total bioavailable org-N and 22.0-38.4% of the total NDMA precursors in wastewater effluents. Thus, the potential adverse effects of PON on wastewater discharge and reuse applications should not be overlooked, even though it only accounted for 7.4-26.8% of the total effluent org-N.

  12. Three cases of congenital dysfibrinogenemia in unrelated Chinese families: heterozygous missense mutation in fibrinogen alpha chain Argl6His.

    Science.gov (United States)

    Luo, Meiling; Deng, Donghong; Xiang, Liqun; Cheng, Peng; Liao, Lin; Deng, Xuelian; Yan, Jie; Lin, Faquan

    2016-09-01

    Congenital dysfibrinogenemia (CD) is a qualitative fibrinogen disorder caused by an abnormal fibrinogen molecule structure, leading to dysfunctional blood coagulation. This study describes 3 cases of dysfibrinogenemia identified in the unrelated Chinese pedigrees.Routine coagulation screening tests were performed on the probands and their families. The antigens and functionality of fibrinogen was measured using an immunoturbidimetry assay and the Clauss method, respectively. To identify the genetic mutation responsible for these dysfibrinogens, genomic DNA extracted from the blood was analyzed using PCR amplification and direct sequencing. The presence of the mutant chains was determined using matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectroscopy. Purified plasma fibrinogen of 3 probands was analyzed using SDS-PAGE, fibrinogen clottability, fibrin polymerization, fibrinopeptide release, and scanning electron microscopy (SEM).The 3 probands had a long thrombin time. Levels of functional fibrinogen were found to be very low, while the fibrinogen antigen was within the normal range. DNA sequencing revealed a heterozygous Arg16His substitution in the fibrinogen Aα chain (FGA). The mutant chains were found to be expressed using MALDI-TOF mass spectroscopy. SDS-PAGE did not reveal any difference in the molecular weights of 3 polypeptide chains between normal and abnormal fibrinogens. Fibrinogen clottability showed a slower fibrin clot formation than the healthy control. Fibrin polymerization, after addition of thrombin, showed a prolonged lag phase and decreased final turbidity. The kinetics of fibrinopeptides release revealed a decreased amount of the released fibrinopeptide A. SEM of the patient's fibrin clot was found to be abnormal.Results indicate that the 3 probands with dysfibrinogenemia were caused by mutations of Aα chain Arg16His. Mutation of this fibrinogen induced dysfunction of plasma fibrinogen.

  13. Albumin and fibrinogen adsorption on boron nitride and carbon-based thin films

    Energy Technology Data Exchange (ETDEWEB)

    Lousinian, S.; Kalfagiannis, N. [Laboratory for Thin Films - Nanosystems and Nanometrology (LTFN), Department of Physics, Aristotle University of Thessaloniki, GR-54124 Thessaloniki (Greece); Logothetidis, S. [Laboratory for Thin Films - Nanosystems and Nanometrology (LTFN), Department of Physics, Aristotle University of Thessaloniki, GR-54124 Thessaloniki (Greece)], E-mail: logot@auth.gr

    2008-08-25

    The haemocompatibility (in the sense of the least possibility of thrombus formation/thrombogenicity potential) of homogeneous and amorphous BN (a-BN) thin films through the adsorption of two basic blood plasma proteins, human serum albumin (HSA) and fibrinogen (Fib) is explored in this work. A comparative study of the thrombogenicity potential of BN, amorphous carbon (a-C) and amorphous hydrogenated carbon thin films (a-C:H) is also presented. a-BN and a-C thin films were produced by radio frequency (RF) magnetron sputtering onto c-Si (1 0 0) substrates under various values of substrate bias voltage. a-C:H thin films were developed by RF Reactive MS, with various values of substrate bias voltage and under different values of H{sub 2} partial pressure during deposition. For the consideration of the optical, compositional and structural properties of the films Spectroscopic Ellipsometry in the energy region of 1.5-6.5 eV was used, while for the study of surface topography and wetting properties Atomic Force Microscopy and Contact Angle measurements were additionally employed. The properties of the thin films were correlated with their thrombogenicity, through the estimation of the ratio of HSA/Fib surface concentration. a-BN films exhibit the smallest possibility of clot formation, with their wetting properties determining the thickness of the Fib layer formed on them as well as the ratio of HSA/Fib surface concentration. In the case of a-C thin films, the increase of % sp{sup 3} content is crucial, while the value of the fundamental gap seems to influence the possibility for clot formation on a-C:H thin films.

  14. Improved fibronectin-immobilized fibrinogen microthreads for the attachment and proliferation of fibroblasts

    Directory of Open Access Journals (Sweden)

    Rajangam T

    2013-03-01

    Full Text Available Thanavel Rajangam, Seong Soo A AnDepartment of Bionanotechnology, Gachon University, Seongnam, South KoreaAbstract: The aim of this study was to fabricate fibrinogen (Fbg microfibers with different structural characteristics for the development of 3-D tissue-engineering scaffolds. Fabricated Fbg microfibers were investigated for their biomolecule encapsulation, cell adhesion, and proliferations. Microfibers with three different concentrations of Fbg (5, 10, and 15 wt% were prepared by a gel solvent-extraction method using a silicone rubber tube. Fbg microfibers were covalently modified with fibronectin (FN by using water-soluble 1-ethyl-3-(3-dimethylaminopropyl carbodiimide as the cross-linking agent. Fbg microfibers were characterized by their FN cross-linking properties, structural morphology, and in vitro degradation. Furthermore, FN/Fbg microfibers were evaluated for cell attachment and proliferation. The biocompatibility and cell proliferation of the microfibers were assessed by measuring adenosine triphosphate activity in C2C12 fibroblast cells. Cell attachment and proliferation on microfibers were further examined using fluorescence and scanning electron microscopic images. FN loading on the microfibers was confirmed by fluorescence and infrared spectroscopy. Surface morphology was characterized by scanning electron microscopy, and showed highly aligned nanostructures for fibers made with 15 wt% Fbg, a more porous structure for fibers made with 10 wt% Fbg, and a less porous structure for those made with 5 wt% Fbg. Controlled biodegradation of the fiber was observed for 8 weeks by using an in vitro proteolytic degradation assay. Fbg microfibers with highly aligned nanostructures (15 wt% showed enhanced biomolecule encapsulation, as well as higher cell adhesion and proliferation than another two types of FN/Fbg fibers (5 and 10 wt% and unmodified Fbg fibers. The promising results obtained from the present study reveal that optimal structure

  15. Concentration, ozone formation potential and source analysis of volatile organic compounds (VOCs) in a thermal power station centralized area: A study in Shuozhou, China.

    Science.gov (United States)

    Yan, Yulong; Peng, Lin; Li, Rumei; Li, Yinghui; Li, Lijuan; Bai, Huiling

    2017-04-01

    Volatile organic compounds (VOCs) from two sampling sites (HB and XB) in a power station centralized area, in Shuozhou city, China, were sampled by stainless steel canisters and measured by gas chromatography-mass selective detection/flame ionization detection (GC-MSD/FID) in the spring and autumn of 2014. The concentration of VOCs was higher in the autumn (HB, 96.87 μg/m(3); XB, 58.94 μg/m(3)) than in the spring (HB, 41.49 μg/m(3); XB, 43.46 μg/m(3)), as lower wind speed in the autumn could lead to pollutant accumulation, especially at HB, which is a new urban area surrounded by residential areas and a transportation hub. Alkanes were the dominant group at both HB and XB in both sampling periods, but the contribution of aromatic pollutants at HB in the autumn was much higher than that of the other alkanes (11.16-19.55%). Compared to other cities, BTEX pollution in Shuozhou was among the lowest levels in the world. Because of the high levels of aromatic pollutants, the ozone formation potential increased significantly at HB in the autumn. Using the ratio analyses to identify the age of the air masses and analyze the sources, the results showed that the atmospheric VOCs at XB were strongly influenced by the remote sources of coal combustion, while at HB in the spring and autumn were affected by the remote sources of coal combustion and local sources of vehicle emission, respectively. Source analysis conducted using the Positive Matrix Factorization (PMF) model at Shuozhou showed that coal combustion and vehicle emissions made the two largest contributions (29.98% and 21.25%, respectively) to atmospheric VOCs. With further economic restructuring, the influence of vehicle emissions on the air quality should become more significant, indicating that controlling vehicle emissions is key to reducing the air pollution.

  16. Oxidation reduction potential as a parameter to regulate micro-oxygen injection into anaerobic digester for reducing hydrogen sulphide concentration in biogas.

    Science.gov (United States)

    Nghiem, Long D; Manassa, Patrick; Dawson, Marcia; Fitzgerald, Shona K

    2014-12-01

    This study aims to evaluate the use of oxidation reduction potential (ORP) to regulate the injection of a small amount of oxygen into an anaerobic digester for reducing H2S concentration in biogas. The results confirm that micro-oxygen injection can be effective for controlling H2S formation during anaerobic digestion without disturbing the performance of the digester. Biogas production, composition, and the removal of volatile solids (VS) and chemical oxygen demand (COD) were monitored to assessment the digester's performance. Six days after the start of the micro-oxygen injection, the ORP values increased to between -320 and -270 mV, from the natural baseline value of -485 mV. Over the same period the H2S concentration in the biogas decreased from over 6000 ppm to just 30 ppm. No discernible changes in the VS and COD removal rates, pH and alkalinity of the digestate or in the biogas production or composition were observed.

  17. Ionic charge, radius, and potential control root/soil concentration ratios of fifty cationic elements in the organic horizon of a beech (Fagus sylvatica) forest podzol.

    Science.gov (United States)

    Tyler, Germund

    2004-08-15

    The root/organic soil concentration ratio; R/S) of 50 cationic mineral elements was related to their ionic properties, including ionic radius (r), ionic charge (z), and ionic potential (z/r or z2/r). The materials studied were ectomycorrhizal beech (Fagus sylvatica L.) roots and their almost purely organic soil substrate, the O-horizon (mor; raw humus) of a Podzol in South Sweden, developed in a site which has been untouched by forestry or other mechanical disturbance since at least 50 years and located in an area with no local sources of pollution. Elements determined by ICP-AES were aluminium, barium, calcium, iron, potassium, magnesium, manganese, sodium and strontium. Determined by ICP-MS were silver, beryllium, bismuth, cadmium, cerium, cobalt, chromium, caesium, copper, dysprosium, erbium, europium, gallium, gadolinium, hafnium, mercury, holmium, indium, lanthanum, lithium, lutetium, niobium, neodymium, nickel, lead, praseodymium, rubidium, scandium, samarium, tin, terbium, thorium, titanium, thallium, thulium, uranium, vanadium, yttrium, ytterbium, zinc and zirconium. The R/S ratios were most clearly related to the ionic potential of the cationic elements studied, which accounted for approximately 60% of the variability in R/S among elements. The ionic charge of an element was more important than the ionic radius. Elements with high ionic charge had low R/S ratios and vice versa. No clear differences in R/S between essential and non-essential plant nutrients were observed, especially when ions of similar charge were compared.

  18. Lipids, lipoproteins, fibrinogen and fibrinolytic activity in angiographically assessed coronary heart disease.

    Science.gov (United States)

    Lipinska, I; Gurewich, V; Meriam, C M; Kosowsky, B D; Ramaswamy, K; Philbin, E; Losordo, D

    1987-01-01

    Plasma lipids, lipoproteins, fibrinogen and fibrinolytic activity (FA) were measured in 202 consecutive patients undergoing coronary angiography. Twenty-one patients, 13 men and 8 women with a mean age of 52.8 years and 56.7 years respectively, were found to be angiographically free of coronary artery disease (CAD) and served as the principal control group. Since this group contained a disproportionate number of subjects with risk factors such as family history, hypertension and smoking, a second control group of clinically healthy subjects selected for age was also tested. Their laboratory results were not used in the statistical calculations. The group with angiographic CAD consisted of 130 men (mean age 57.6 years) and 51 women (mean age 61.5 years). Abnormal angiograms were graded according to the number of major vessels with more than 50% stenosis involved. The laboratory variables which were significantly (p less than .01-.001) associated with the presence of CAD were: High density lipoprotein (HDL) when determined by polyacrylamide gel electrophoresis (PAGE) and expressed as a percentage of total lipoproteins rather than concentration, presence of Intermediate Density Lipoprotein (IDL), percent of Very Low Density Lipoprotein (VLDL), fibrinogen concentration and FA. The HDL2 subfraction was significantly inversely correlated only in women. The total plasma cholesterol was normal and virtually identical in both groups. Within the CAD group, only two of the laboratory results were significantly correlated with the extent of disease. By univariate analysis, the FA showed the closest association with the score for severity of CAD (p less than .001) followed by the presence of IDL (p less than .01). In conclusion, lipoprotein analysis by a method which measures not only HDL, but also LDL, VLDL and IDL, together with the determination of fibrinogen and FA provides information useful in the identification of individuals at risk for CAD.

  19. Fibrinogen-Induced Streptococcus mutans Biofilm Formation and Adherence to Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Telma Blanca Lombardo Bedran

    2013-01-01

    Full Text Available Streptococcus mutans, the predominant bacterial species associated with dental caries, can enter the bloodstream and cause infective endocarditis. The aim of this study was to investigate S. mutans biofilm formation and adherence to endothelial cells induced by human fibrinogen. The putative mechanism by which biofilm formation is induced as well as the impact of fibrinogen on S. mutans resistance to penicillin was also evaluated. Bovine plasma dose dependently induced biofilm formation by S. mutans. Of the various plasma proteins tested, only fibrinogen promoted the formation of biofilm in a dose-dependent manner. Scanning electron microscopy observations revealed the presence of complex aggregates of bacterial cells firmly attached to the polystyrene support. S. mutans in biofilms induced by the presence of fibrinogen was markedly resistant to the bactericidal effect of penicillin. Fibrinogen also significantly increased the adherence of S. mutans to endothelial cells. Neither S. mutans cells nor culture supernatants converted fibrinogen into fibrin. However, fibrinogen is specifically bound to the cell surface of S. mutans and may act as a bridging molecule to mediate biofilm formation. In conclusion, our study identified a new mechanism promoting S. mutans biofilm formation and adherence to endothelial cells which may contribute to infective endocarditis.

  20. Clinical and molecular characterisation of 21 patients affected by quantitative fibrinogen deficiency.

    Science.gov (United States)

    Asselta, Rosanna; Platè, Manuela; Robusto, Michela; Borhany, Munira; Guella, Ilaria; Soldà, Giulia; Afrasiabi, Abdolreza; Menegatti, Marzia; Shamsi, Tahir; Peyvandi, Flora; Duga, Stefano

    2015-03-01

    Fibrinogen is a plasma glycoprotein mainly synthesised by hepatocytes and circulating as a 340-kDa hexamer consisting of two sets of three different polypeptide chains (Aα, Bβ, and γ, encoded by the FGA, FGB, and FGG gene, respectively). Congenital afibrinogenaemia and hypofibrinogenaemia are rare bleeding disorders characterised by abnormally low levels of functional and immunoreactive fibrinogen in plasma, associated with haemorrhagic manifestations of variable severity. While afibrinogenaemia is caused by mutations in the homozygous or compound heterozygous state in one of the three fibrinogen genes, hypofibrinogenaemia is generally due to heterozygous mutations, and is usually characterised by a milder phenotype. The mutational spectrum of these quantitative fibrinogen disorders includes large deletions, point mutations causing premature termination codons, and missense mutations often affecting fibrinogen assembly and/or secretion. Here we report the clinical and molecular characterisation of 13 unrelated afibrinogenaemic and eight hypofibrinogenaemic patients, leading to the identification of 17 different mutations (10 hitherto unknown). All the newly-identified missense and splicing mutations werein vitro expressed to verify their pathogenic role. Our data increase the number of mutations causing quantitative fibrinogen deficiencies by about 7 %. The high number of private mutations identified in the analysed probands indicates that the full mutational screening of the three fibrinogen genes is still required for molecular diagnosis.

  1. Association between polymorphisms in the fibrinogen α- and β-genes on the post-trauma fibrinogen increase

    NARCIS (Netherlands)

    Ferrer-Antunes, C.; Maat, M.P.M. de; Palmeiro, A.; Pimentel, J.; Fernandes, V.

    1998-01-01

    Fibrinogen is an acute phase reactant, and there, fore its plasma levels increase after severe injury. Polymorphisms in the fibrinogen α and β genes have been found to be associated with plasma levels of fibrinogen, and it has also been suggested that they are associated with the fibrinogen increase

  2. Association between polymorphisms in the fibrinogen α- and β-genes on the post-trauma fibrinogen increase

    NARCIS (Netherlands)

    Ferrer-Antunes, C.; Maat, M.P.M. de; Palmeiro, A.; Pimentel, J.; Fernandes, V.

    1998-01-01

    Fibrinogen is an acute phase reactant, and there, fore its plasma levels increase after severe injury. Polymorphisms in the fibrinogen α and β genes have been found to be associated with plasma levels of fibrinogen, and it has also been suggested that they are associated with the fibrinogen increase

  3. Deposition of fibrinogen on the surface of in vitro thrombi prevents platelet adhesion.

    Science.gov (United States)

    Owaynat, Hadil; Yermolenko, Ivan S; Turaga, Ramya; Lishko, Valeryi K; Sheller, Michael R; Ugarova, Tatiana P

    2015-12-01

    The initial accumulation of platelets after vessel injury is followed by thrombin-mediated generation of fibrin which is deposited around the plug. While numerous in vitro studies have shown that fibrin is highly adhesive for platelets, the surface of experimental thrombi in vivo contains very few platelets suggesting the existence of natural anti-adhesive mechanisms protecting stabilized thrombi from platelet accumulation and continuous thrombus propagation. We previously showed that adsorption of fibrinogen on pure fibrin clots results in the formation of a nonadhesive matrix, highlighting a possible role of this process in surface-mediated control of thrombus growth. However, the deposition of fibrinogen on the surface of blood clots has not been examined. In this study, we investigated the presence of intact fibrinogen on the surface of fibrin-rich thrombi generated from flowing blood and determined whether deposited fibrinogen is nonadhesive for platelets. Stabilized fibrin-rich thrombi were generated using a flow chamber and the time that platelets spend on the surface of thrombi was determined by video recording. The presence of fibrinogen and fibrin on the surface of thrombi was analyzed by confocal microscopy using specific antibodies. Examination of the spatial distribution of two proteins revealed the presence of intact fibrinogen on the surface of stabilized thrombi. By manipulating the surface of thrombi to display either fibrin or intact fibrinogen, we found that platelets adhere to fibrin- but not to fibrinogen-coated thrombi. These results indicate that the fibrinogen matrix assembled on the outer layer of stabilized in vitro thrombi protects them from platelet adhesion.

  4. Adsorption of human fibrinogen and albumin onto hydrophobic and hydrophilic Ti6Al4V powder

    Science.gov (United States)

    Rodríguez-Sánchez, Jesús; Gallardo-Moreno, Amparo M.; Bruque, José M.; González-Martín, M. Luisa

    2016-07-01

    Adsorption of proteins on solid surfaces has been widely studied because of its importance in various biotechnological, medical and technical applications, such as medical implants or biosensors. One of the main problems is the adsorption-induced conformational changes because they often modify the biological activity of the proteins, which is believed to be a key factor on the subsequent cellular adhesion. The aim of this work is the study of the adsorption of human fibrinogen (Fg) and human serum albumin (HSA) onto Ti6Al4V particles, commercially available on different size, that are used to elaborate scaffolds to provide structural support to cell proliferation, promoting tissue development and bone regeneration among others. The study was done through the analysis of the adsorption isotherms and the electrical characterization of surfaces after adsorption in terms of the zeta potential (ζ). From this analysis it seems that Fg adsorbs preferentially vertically oriented (end-on) and HSA moves sequentially over the surface of the Ti6Al4V particles through dimmer formation, allowing adsorption progress over this initial bilayer. The zeta potential values of both proteins remain constant when the monolayer is formed. The study also extends the analysis of both adsorption behaviour and ζ potential characterization factors to the influence of the substrate hydrophobicity as this property can be modified for the Ti6Al4V by irradiating it with ultraviolet light (UV-C) without changes on its chemical composition [1,2]. Differences at low protein concentrations were found for both isotherms and zeta-potential values.

  5. Adsorption of human fibrinogen and albumin onto hydrophobic and hydrophilic Ti6Al4V powder

    Energy Technology Data Exchange (ETDEWEB)

    Rodríguez-Sánchez, Jesús; Gallardo-Moreno, Amparo M.; Bruque, José M.; González-Martín, M. Luisa, E-mail: mlglez@unex.es

    2016-07-15

    Adsorption of proteins on solid surfaces has been widely studied because of its importance in various biotechnological, medical and technical applications, such as medical implants or biosensors. One of the main problems is the adsorption-induced conformational changes because they often modify the biological activity of the proteins, which is believed to be a key factor on the subsequent cellular adhesion. The aim of this work is the study of the adsorption of human fibrinogen (Fg) and human serum albumin (HSA) onto Ti6Al4V particles, commercially available on different size, that are used to elaborate scaffolds to provide structural support to cell proliferation, promoting tissue development and bone regeneration among others. The study was done through the analysis of the adsorption isotherms and the electrical characterization of surfaces after adsorption in terms of the zeta potential (ζ). From this analysis it seems that Fg adsorbs preferentially vertically oriented (end-on) and HSA moves sequentially over the surface of the Ti6Al4V particles through dimmer formation, allowing adsorption progress over this initial bilayer. The zeta potential values of both proteins remain constant when the monolayer is formed. The study also extends the analysis of both adsorption behaviour and ζ potential characterization factors to the influence of the substrate hydrophobicity as this property can be modified for the Ti6Al4V by irradiating it with ultraviolet light (UV-C) without changes on its chemical composition [1,2]. Differences at low protein concentrations were found for both isotherms and zeta-potential values.

  6. The N-terminal domain of the thermo-regulated surface protein PrpA of Enterococcus faecium binds to fibrinogen, fibronectin and platelets.

    Science.gov (United States)

    Guzmán Prieto, Ana M; Urbanus, Rolf T; Zhang, Xinglin; Bierschenk, Damien; Koekman, C Arnold; van Luit-Asbroek, Miranda; Ouwerkerk, Janneke P; Pape, Marieke; Paganelli, Fernanda L; Wobser, Dominique; Huebner, Johannes; Hendrickx, Antoni P A; Bonten, Marc J M; Willems, Rob J L; van Schaik, Willem

    2015-12-17

    Enterococcus faecium is a commensal of the mammalian gastrointestinal tract, but is also found in non-enteric environments where it can grow between 10 °C and 45 °C. E. faecium has recently emerged as a multi-drug resistant nosocomial pathogen. We hypothesized that genes involved in the colonization and infection of mammals exhibit temperature-regulated expression control and we therefore performed a transcriptome analysis of the clinical isolate E. faecium E1162, during mid-exponential growth at 25 °C and 37 °C. One of the genes that exhibited differential expression between 25 °C and 37 °C, was predicted to encode a peptidoglycan-anchored surface protein. The N-terminal domain of this protein is unique to E. faecium and closely related enterococci, while the C-terminal domain is homologous to the Streptococcus agalactiae surface protein BibA. This region of the protein contains proline-rich repeats, leading us to name the protein PrpA for proline-rich protein A. We found that PrpA is a surface-exposed protein which is most abundant during exponential growth at 37 °C in E. faecium E1162. The heterologously expressed and purified N-terminal domain of PrpA was able to bind to the extracellular matrix proteins fibrinogen and fibronectin. In addition, the N-terminal domain of PrpA interacted with both non-activated and activated platelets.

  7. Quantitative analysis of aggregation in dilute solutions of effectively rigid biomacromolecules via the combination of oscillatory flow birefringence and viscoelasticity measurements: example study of aggregation of bovine fibrinogen in aqueous glycerol, and detection of a large aggregate formed on addition of guanidine hydrochloride.

    Science.gov (United States)

    Miller, J W; Nestler, F H M; Schrag, J L

    2004-12-20

    Oscillatory flow birefringence (OFB) properties have been measured for dilute solutions of bovine fibrinogen in 65-68% aqueous glycerol with the Miller-Schrag Thin Fluid Layer (TFL) apparatus employing either titanium or stainless steel surfaces in contact with the solutions. The shearing frequency range was 1 to 2500 Hz, the concentrations ranged from 4 to 8 mg/ml, and measurement temperatures were 9.9, 10.0, and 15.8 degrees C. The data showed evidence of significant amounts of aggregation that apparently is caused by the presence of glycerol; contributions from the various aggregates were readily detected since the staggered half-overlap aggregation in this system results in substantial differences in the rotational relaxation times of the various effectively rigid aggregates. The combination of oscillatory flow birefringence and viscoelasticity (VE) data provided sensitive and precise characterization of aggregation in these example systems; all aggregates exhibited the expected positive optical anisotropy. The length of unaggregated fibrinogen in solution was found to be that obtained via electron microscopy. Addition of guanidine hydrochloride to hopefully reduce aggregation did so but also resulted in formation of a very large (2800 to 3500 A), apparently nearly monodisperse, negatively birefringent aggregate, suggesting that this new species might be formed by lateral aggregation.

  8. Ozone-induced oxidative modification of fibrinogen: role of the D regions.

    Science.gov (United States)

    Rosenfeld, Mark A; Shchegolikhin, Alexander N; Bychkova, Anna V; Leonova, Vera B; Biryukova, Marina I; Kostanova, Elizaveta A

    2014-12-01

    Native fibrinogen is a key blood plasma protein whose main function is to maintain hemostasis by virtue of producing cross-linked fibrin clots under the influence of thrombin and fibrin-stabilizing factor (FXIIIa). The aim of this study was to investigate mechanisms of impairment of both the molecular structure and the spatial organization of fibrinogen under ozone-induced oxidation. FTIR analysis showed that ozone treatment of the whole fibrinogen molecule results in the growth of hydroxyl, carbonyl, and carboxyl group content. A similar analysis of fibrinogen D and E fragments isolated from the oxidized protein also revealed transformation of distinct important functional groups. In particular, a remarkable decay of N-H groups within the peptide backbone was observed along with a lowering of the content of C-H groups belonging to either the aromatic moieties or the aliphatic chain CH2 and CH3 units. The model experiments performed showed that the rather unexpected decay of the aliphatic CH units might be caused by the action of hydroxyl radicals, these being produced in the water solution from ozone. The observed dissimilarities in the shapes of amide I bands of the fibrinogen D and E fragments before and after ozone treatment are interpreted in terms of feasible local conformational changes affecting the secondary structure of the protein. Taken as a whole, the FTIR data suggests that the terminal D fragments of fibrinogen are markedly more susceptible to the ozone-induced oxidation than the central E fragment. The data on elastic and dynamic light scattering provide evidence that, in the presence of FXIIIa, both the unoxidized and the oxidized fibrinogen molecules bind to one another in an "end-to-end" fashion to form the flexible covalently cross-linked fibrinogen homopolymers. The γ and α polypeptide chains of the oxidized fibrinogen proved to be involved in the enzymatic cross-linking more readily than those of unaffected fibrinogen. The experimental data

  9. Fibrinogen Vicenza and Genova II: two new cases of congenital dysfibrinogenemia with isolated defect of fibrin monomer polymerization and inhibitory activity on normal coagulation.

    Science.gov (United States)

    Rodeghiero, F; Castaman, G C; Dal Belin Peruffo, A; Dini, E; Galletti, A; Barone, E; Gastaldi, G

    1987-06-01

    Two new cases of congenital dysfibrinogenemia are presented in which defective fibrin monomer polymerization and inhibitory activity on normal coagulation were observed. They have been tentatively called fibrinogen Vicenza and Genova II. The first was discovered in a family with mild bleeding diathesis, the second in an asymptomatic family. In almost all reported cases of fibrinogens with defective fibrin monomer polymerization, additional functional or structural defects have been detected. In our cases, on the contrary, detailed investigations failed to show any other abnormality. Fibrinogen Genova II is apparently identical to fibrinogen Baltimore IV, whereas fibrinogen Vicenza is similar to fibrinogen Troyes and Genova I, but also exerts an evident inhibitory activity on normal coagulation and differs from fibrinogen Genova II and Baltimore IV showing a different kinetic pattern of fibrin monomer polymerization.

  10. Combination of recombinant factor VIIa and fibrinogen corrects clot formation in primary immune thrombocytopenia at very low platelet counts

    DEFF Research Database (Denmark)

    Larsen, Ole H; Stentoft, Jesper; Radia, Deepti

    2013-01-01

    Haemostatic treatment modalities alternative to platelet transfusion are desirable to control serious acute bleeds in primary immune thrombocytopenia (ITP). This study challenged the hypothesis that recombinant activated factor VII (rFVIIa) combined with fibrinogen concentrate may correct whole b...

  11. Dual role of G-runs and hnRNP F in the regulation of a mutation-activated pseudoexon in the fibrinogen gamma-chain transcript.

    Directory of Open Access Journals (Sweden)

    Valeria Rimoldi

    Full Text Available Most pathological pseudoexon inclusion events originate from single activating mutations, suggesting that many intronic sequences are on the verge of becoming exons. However, the precise mechanisms controlling pseudoexon definition are still largely unexplored. Here, we investigated the cis-acting elements and trans-acting regulatory factors contributing to the regulation of a previously described fibrinogen gamma-chain (FGG pseudoexon, which is activated by a deep-intronic mutation (IVS6-320A>T. This pseudoexon contains several G-run elements, which may be bound by heterogeneous nuclear ribonucleoproteins (hnRNPs F and H. To explore the effect of these proteins on FGG pseudoexon inclusion, both silencing and overexpression experiments were performed in eukaryotic cells. While hnRNP H did not significantly affect pseudoexon splicing, hnRNP F promoted pseudoexon inclusion, indicating that these two proteins have only partially redundant functions. To verify the binding of hnRNP F and the possible involvement of other trans-acting splicing modulators, pulldown experiments were performed on the region of the pseudoexon characterized by both a G-run and enrichment for exonic splicing enhancers. This 25-bp-long region strongly binds hnRNP F/H and weakly interacts with Serine/Arginine-rich protein 40, which however was demonstrated to be dispensable for FGG pseudoexon inclusion in overexpression experiments. Deletion analysis, besides confirming the splicing-promoting role of the G-run within this 25-bp region, demonstrated that two additional hnRNP F binding sites might instead function as silencer elements. Taken together, our results indicate a major role of hnRNP F in regulating FGG pseudoexon inclusion, and strengthen the notion that G-runs may function either as splicing enhancers or silencers of the same exon.

  12. Dual role of G-runs and hnRNP F in the regulation of a mutation-activated pseudoexon in the fibrinogen gamma-chain transcript.

    Science.gov (United States)

    Rimoldi, Valeria; Soldà, Giulia; Asselta, Rosanna; Spena, Silvia; Stuani, Cristiana; Buratti, Emanuele; Duga, Stefano

    2013-01-01

    Most pathological pseudoexon inclusion events originate from single activating mutations, suggesting that many intronic sequences are on the verge of becoming exons. However, the precise mechanisms controlling pseudoexon definition are still largely unexplored. Here, we investigated the cis-acting elements and trans-acting regulatory factors contributing to the regulation of a previously described fibrinogen gamma-chain (FGG) pseudoexon, which is activated by a deep-intronic mutation (IVS6-320A>T). This pseudoexon contains several G-run elements, which may be bound by heterogeneous nuclear ribonucleoproteins (hnRNPs) F and H. To explore the effect of these proteins on FGG pseudoexon inclusion, both silencing and overexpression experiments were performed in eukaryotic cells. While hnRNP H did not significantly affect pseudoexon splicing, hnRNP F promoted pseudoexon inclusion, indicating that these two proteins have only partially redundant functions. To verify the binding of hnRNP F and the possible involvement of other trans-acting splicing modulators, pulldown experiments were performed on the region of the pseudoexon characterized by both a G-run and enrichment for exonic splicing enhancers. This 25-bp-long region strongly binds hnRNP F/H and weakly interacts with Serine/Arginine-rich protein 40, which however was demonstrated to be dispensable for FGG pseudoexon inclusion in overexpression experiments. Deletion analysis, besides confirming the splicing-promoting role of the G-run within this 25-bp region, demonstrated that two additional hnRNP F binding sites might instead function as silencer elements. Taken together, our results indicate a major role of hnRNP F in regulating FGG pseudoexon inclusion, and strengthen the notion that G-runs may function either as splicing enhancers or silencers of the same exon.

  13. 二种纤维蛋白原测定方法的评价%The Study of Two Different Methods of Fibrinogen Assays

    Institute of Scientific and Technical Information of China (English)

    杨绍信; 熊玮平; 王飙

    2001-01-01

    Aim A preliminary study was made to evaluate two fibrinogen determination methods:Von clauss method and Prothrombin time derived method.Methods Three level of control plasma were determined repeatly to evaluate the precision of two methods.The result that obtained by two methods from daily work sample were statistically evaluated.Result There hadn't statistically significant difference by t-test (P<0.05) only when the concentration of fibrinogen is between 2 and 3g/L.For plasma with lower (<2g/L) or with high fibrinogen concentration (>3g/L ),the values had statistically significant difference. The PT-derived method tend to overestimate the fibrinogen results compared to the Von clauss method.Conclusion In daily work,PT-der method should not replace the Von clauss method in the fibrinogen assay.%目的对Von clauss法和PT衍算法(PT-der法)定量测定纤维蛋白原(Fbg)进行实验评价。方法低、中、高值质控血浆的批内精密度实验,对临床样本测定的统计学分析。结果 Von clauss法和PT-der法对样本的测定只有Fbg含量在2~3 g/L时,测定结果才无统计学差异,在2 g/L>Fbg>3 g/L时均有显著性差异,PT-der法测得的结果偏高。结论建议在临床应用中不要以PT-der法代替Von clauss法进行Fbg测定。

  14. Agronomic potential of mineral concentrate from processed manure as fertiliser

    NARCIS (Netherlands)

    Velthof, G.L.; Hoeksma, P.; Schröder, J.J.; Middelkoop, van J.C.; Geel, van W.C.A.; Ehlert, P.A.I.; Holshof, G.; Klop, G.; Lesschen, J.P.

    2012-01-01

    Processing of manure intends to increase the use efficiency of nutrients. A concentrated solution of nitrogen (N) and potassium (K) (‘mineral concentrate’) is one of the possible products resulting from manure processing. A study is carried out in the Netherlands to determine the agronomic and envir

  15. Combined surface acoustic wave and surface plasmon resonance measurement of collagen and fibrinogen layer physical properties

    Directory of Open Access Journals (Sweden)

    J.-M. Friedt

    2016-12-01

    Full Text Available We use an instrument combining optical (surface plasmon resonance and acoustic (Love mode surface acoustic wave device real-time measurements on a same surface for the identification of water content in collagen and fibrinogen protein layers. After calibration of the surface acoustic wave device sensitivity by copper electrodeposition and surfactant adsorption, the bound mass and its physical properties – density and optical index – are extracted from the complementary measurement techniques and lead to thickness and water ratio values compatible with the observed signal shifts. Such results are especially usefully for protein layers with a high water content as shown here for collagen on an hydrophobic surface. We obtain the following results: collagen layers include 70±20% water and are 16±3 to 19±3 nm thick for bulk concentrations ranging from 30 to 300 μg/ml. Fibrinogen layers include 50±10% water for layer thicknesses in the 6±1.5 to 13±2 nm range when the bulk concentration is in the 46 to 460 μg/ml range.

  16. Spatially selective surface platforms for binding fibrinogen prepared by particle lithography with organosilanes

    OpenAIRE

    Englade-Franklin, Lauren E.; Saner, ChaMarra K.; Garno, Jayne C.

    2013-01-01

    We introduce an approach based on particle lithography to prepare spatially selective surface platforms of organosilanes that are suitable for nanoscale studies of protein binding. Particle lithography was applied for patterning fibrinogen, a plasma protein that has a major role in the clotting cascade for blood coagulation and wound healing. Surface nanopatterns of mercaptosilanes were designed as sites for the attachment of fibrinogen within a protein-resistant matrix of 2-[methoxy(polyethy...

  17. Exact solutions for chemical concentration waves of self-propelling camphor particles racing on a ring: A novel potential dynamics perspective

    CERN Document Server

    Frank, T D

    2015-01-01

    A potential dynamics approach is developed to determine the periodic standing and traveling wave patterns associated with self-propelling camphor objects floating on ring-shaped water channels. Exact solutions of the wave patterns are derived. The bifurcation diagram describing the transition between the immobile and self-propelling modes of camphor objects is derived semi-analytically. The bifurcation is of a pitchfork type which is consistent with earlier theoretical work in which natural boundary conditions have been considered.

  18. The Platelet Integrin αIIbβ3 Differentially Interacts with Fibrin Versus Fibrinogen.

    Science.gov (United States)

    Litvinov, Rustem I; Farrell, David H; Weisel, John W; Bennett, Joel S

    2016-04-08

    Fibrinogen binding to the integrin αIIbβ3 mediates platelet aggregation and spreading on fibrinogen-coated surfaces. However,in vivoαIIbβ3 activation and fibrinogen conversion to fibrin occur simultaneously, although the relative contributions of fibrinogenversusfibrin to αIIbβ3-mediated platelet functions are unknown. Here, we compared the interaction of αIIbβ3 with fibrin and fibrinogen to explore their differential effects. A microscopic bead coated with fibrinogen or monomeric fibrin produced by treating the immobilized fibrinogen with thrombin was captured by a laser beam and repeatedly brought into contact with surface-attached purified αIIbβ3. When αIIbβ3-ligand complexes were detected, the rupture forces were measured and displayed as force histograms. Monomeric fibrin displayed a higher probability of interacting with αIIbβ3 and a greater binding strength. αIIbβ3-fibrin interactions were also less sensitive to inhibition by abciximab and eptifibatide. Both fibrinogen- and fibrin-αIIbβ3 interactions were partially inhibited by RGD peptides, suggesting the existence of common RGD-containing binding motifs. This assumption was supported using the fibrin variants αD97E or αD574E with mutated RGD motifs. Fibrin made from a fibrinogen γ'/γ' variant lacking the γC αIIbβ3-binding motif was more reactive with αIIbβ3 than the parent fibrinogen. These results demonstrate that fibrin is more reactive with αIIbβ3 than fibrinogen. Fibrin is also less sensitive to αIIbβ3 inhibitors, suggesting that fibrin and fibrinogen have distinct binding requirements. In particular, the maintenance of αIIbβ3 binding activity in the absence of the γC-dodecapeptide and the α-chain RGD sequences suggests that the αIIbβ3-binding sites in fibrin are not confined to its known γ-chain and RGD motifs.

  19. Hematoxylin-stainability of keratohyalin granules is due to the novel component, fibrinogen γ-chain protein.

    Science.gov (United States)

    Takahashi, Masae; Horiuchi, Yoshitaka; Tezuka, Tadashi

    2010-11-01

    Hematoxylin-stainability of keratohyalin granules (KHG) using biochemical and immunohistochemical techniques is due to the presence of a fibrinogen γ-chain protein. A protein with a molecular weight of 100 kDa was stained with anti-Ted-H-1 monoclonal antibody and hematoxylin solution (hematoxylin-stainable protein). Since the amino acid sequence of the hematoxylin-stainable protein was to that of fibrinogen γ-chain protein, a peptide was synthesized and an antibody against the peptide was produced. This antibody reacted with the hematoxylin-stainable protein and fibrinogen γ-chain protein on immunoblot analysis and with KHG on immunohistochemical examination. Furthermore, a commercial anti-fibrinogen γ-chain protein antibody (Ab) also reacted with the hematoxylin-stainable protein as well as fibrinogen. In contrast, anti-fibrinogen β-chain protein Ab did not react with the hematoxylin-stainable protein. The fibrinogen γ-chain protein also stained with hematoxylin. These findings suggested that fibrinogen γ-chain protein may be a novel component protein of KHG and may induce the hematoxylin-stainability of KHG.

  20. Effect of Cordycepin-Enriched WIB801C from Cordyceps militaris Suppressing Fibrinogen Binding to Glycoprotein IIb/IIIa

    Science.gov (United States)

    Lee, Dong-Ha; Kim, Hyun-Hong; Lim, Deok Hwi; Kim, Jong-Lae; Park, Hwa-Jin

    2015-01-01

    In this study, we investigated the effects of cordycepin-enriched (CE)-WIB801C, a n-butanol extract of Cordyceps militaris-hypha on collagen-stimulated platelet aggregation. CE-WIB801C dose dependently inhibited collagen-induced platelet aggregation, and had a synergistic effect together with cordycepin (W-cordycepin) from CE-WIB801C on the inhibition of collagen-induced platelet aggregation. CE-WIB801C and cordycepin stimulated the phosphorylation of VASP (Ser157) and the dephosphorylation of PI3K and Akt, and inhibited the binding of fibrinogen to glycoprotein IIb/IIIa (αIIb/β3) and the release of ATP and serotonin in collagen-induced platelet aggregation. A-kinase inhibitor Rp-8-Br-cAMPS reduced CE-WIB801C-, and cordycepin-increased VASP (Ser157) phosphorylation, and increased CE-WIB801C-, and cordycepin-inhibited the fibrinogen binding to αIIb/β3. Therefore, we demonstrate that CE-WIB801C-, and cordycepin-inhibited fibrinogen binding to αIIb/β3 are due to stimulation of cAMP-dependent phosphorylation of VASP (Ser157), and inhibition of PI3K/Akt phosphorylation. These results strongly indicate that CE-WIB801C and cordycepin may have preventive or therapeutic potential for platelet aggregation-mediated diseases, such as thrombosis, myocardial infarction, atherosclerosis, and ischemic cerebrovascular disease. PMID:25593645

  1. Fibrinogen Aα Thr312Ala polymorphism specifically contributes to chronic thromboembolic pulmonary hypertension by increasing fibrin resistance.

    Directory of Open Access Journals (Sweden)

    Ji-Feng Li

    Full Text Available BACKGROUND: Polymorphisms are associated with chronic thromboembolic pulmonary hypertension (CTEPH and pulmonary thromboembolism (PTE, but no polymorphism specific to CTEPH but not PTE has yet been reported. Fibrin resistance is associated with CTEPH, but the mechanism has not been elucidated. METHODS: Polymorphisms were analyzed in 101 CTEPH subjects, 102 PTE subjects and 108 healthy controls by Massarray or restriction fragment length polymorphism (RFLP. Plasmin-mediated cleavage of fibrin was characterized in 69 subjects (29 with CTEPH, 21 with PTE and 19 controls. RESULTS: Genotype frequencies and allele frequencies of fibrinogen Aα Thr312Ala were significantly higher in CTEPH subjects than in controls and PTE subjects, while there was no difference between PTE subjects and controls. The odd ratio (OR 2.037 and 95% confidence interval (95% CI, 1.262-3.289 showed that Thr312Ala polymorphism was a risk factor for CTEPH but not PTE. Fibrin from CTEPH subjects was more resistant to lysis than that from PTE subjects and controls. Fibrin resistance was significantly different between Aα Thr312Ala (A/G genotypes within CTEPH subjects, and the fibrin with GG genotype was more resistant than that with AA and AG genotype. CONCLUSIONS: Fibrinogen Aα Thr312Ala (A/G polymorphism was associated with CTEPH, but not PTE, suggesting that the fibrinogen Aα Thr312Ala polymorphism may act as a potential biomarker in identifying CTEPH from PTE. GG genotype polymorphism contributes to CTEPH through increasing fibrin resistance, implying that PTE subjects with fibrinogen Aα GG genotype may need long-term anticoagulation therapy.

  2. Coexistence of High Fibrinogen and Low High-density Lipoprotein Cholesterol Levels Predicts Recurrent Cerebral Venous Thrombosis

    Directory of Open Access Journals (Sweden)

    Xin Ma

    2015-01-01

    Conclusions: Concomitant high fibrinogen and low HDL-C levels may be associated with recurrence of CVT. The effect of potential risk factors related to atherothrombosis on recurrent CVT should be closely monitored.

  3. The Effects of Hypothermia on Fibrinogen Metabolism and Coagulation Function in Swine

    Science.gov (United States)

    2007-01-01

    Continuous arteriovenous rewarming: experimental results and thermodynamic model simula- tion of treatment for hypothermia. J Trauma 1990;30:1436-49. [6...of fibrinogen in cirrhosis of the liver. J Clin Invest 1971;50:1690-701. [22] Rand MD, Lock JB, van’t Veer C, et al. Blood clotting in minimally...fibrinogen synthesis in hemodialysis patients with normal nutritional status. J Am Soc Nephrol 2001;12: 349 -54. [36] Olsen AK. The pig as a model in

  4. Correlation of fibrinogen level and absorbance change in both PT and APTT clotting curves on BCSXP

    Institute of Scientific and Technical Information of China (English)

    Xiaojie Zhang; Bing Bai

    2008-01-01

    Objective: To investigate the correlation of fibrinogen level and absorbance change in both PT and APTT clotting curves on BCSXP Analyzer. Methods:A serial of standard fibrinogen and 250 patient plasma samples with different qualities(normal, hemolysis,icterus, and lipemia) were run on BCSXP for assays PT, APTT and Fibrinogen. The absorbance change(DeltaA) from baseline to plateau in clotting curve was retrieved and analyzed on its correlation with the Fibrinogen result. Influence of plasma quality and PT/APTT result on this correlation was also studied respectively. Results:Both PT-DeltaA and APTT-DeltaA showed good linear regression with fibrinogen level in the sample, with Re close to 0.90 in both standard and patient samples. Hemolysis(H), itcterus(1) and lipemia(L) of the sample with valid clotting curves were found to have no significant difference in this correlation from normal(N) sample(R2: 0.83H, 0.92I 0.81L and 0.79N in PT; 0.89H, 0.95I, 0.91L and 0.89N in APTT) in either PT or APTT curve. PT or APTT result also has little impact on this correlation(0.71 in range 7 ~ 10 sec, 0.56 in10 ~ 20 sec, and 0.70 in 20 sec~; R2 in APTT: 0.88 in 20~30 sec,0.92 in 30~40 sec, and 0.95 in 40 sec~). Conclusion:The absorbance change in either PT or APTT clotting curve correlates well with the fibrinogen level in plasma, which is independent of plasma quality PT or APTT results. The absorbance change can be used as an alternative way to roughly estimate fibrinogen level in either PT or APTT clotting curve when the result of clauss-based fibrinogen measurement is not available.

  5. Study of the fibrinogen - fibrin transformation kinetics and modifications caused to this reaction by irradiation (X rays) of the fibrinogen solution; Etude de la cinetique de la transformation fibrinogene-fibrine et modifications apportees dans cette reaction par irradiation (rayons X) de solution de fibrinogene

    Energy Technology Data Exchange (ETDEWEB)

    Hollard, D.; Suscillon, M.; Marcille, G.; Rambaud, F.; Baloyan, M. [Commissariat a l' Energie Atomique, Grenoble (France). Centre d' Etudes Nucleaires

    1966-07-01

    The authors present a spectrophotometric method for studying the transformation fibrinogen - fibrin. This method has the advantage of drawing immediately in graph form the three, phases of this transformation: proteolysis or monomerization; polymerisation; clot stabilization. It is a simple, faithful and easily reproductive technic. Owing to this method, they studied modifications of this transformation due to irradiation of fibrinogen solution. Low doses (90 000 R/mn) prevent transverse polymerisation. To upper doses (180 000 R and more), the action of thrombin on fibrinogen does not give an organised clot but a lacteous and fragile gel. There is not here a coagulation in the physiological understanding. (author) [French] Les auteurs presentent une methode d'etude spectro-photometrique de la transformation fibrinogene - fibrine. Cette technique a l'avantage de visualiser instantanement-par le trace d'une courbe les 3 phases de cette transformation: proteolyse ou monomerisation; polymerisation; stabilisation du caillot. C'est une technique simple, fidele, reproductible; grace a cette methode les auteurs ont pu etudier les modifications apportees dans cette transformation par irradiation aux rayons X de la solution de fibrinogene. A faible dose (90 000 R) l'irradiation inhibe la polymerisation Transversale. A forte dose ( > 180 000 R) le fibrinogene n'est plus transforme par la thrombine en un caillot organise mais en un gel laiteux et fragile. Il ne s'agit plus alors de coagulation au sens physiologique du terme. (auteur)

  6. Mechanisms of fibrinogen adsorption at the silica substrate determined by QCM-D measurements.

    Science.gov (United States)

    Kubiak, Katarzyna; Adamczyk, Zbigniew; Wasilewska, Monika

    2015-11-01

    Adsorption kinetics of fibrinogen at a silica substrate was thoroughly studied in situ using the QCM-D method. Because of low dissipation, the Sauerbrey's equation was used for calculating the wet mass per unit area (wet coverage of the protein). Measurements were done for various bulk suspension concentrations, flow rates and pHs. These experimental data were compared with the theoretical dry coverage data derived from the solution of the mass transfer equation. In this way, the hydration functions and water factors of fibrinogen monolayers were quantitatively evaluated for various pHs. In the case of pH 7.4 and ionic strength of 0.15 M, the hydration function changed from 0.75 to 0.6 for the dry coverage Γ(d) equal to 0 and 4 mg m(-2), respectively. Interestingly, for pH 7.4 and 4.5 (ionic strength of 10(-2) M) a minimum of the hydration function appeared at Γ(d) ca. 2 mg m(-2). Analytical polynomial expressions were formulated for the interpolation of the experimental results. By using the hydration functions, the fibrinogen adsorption/desorption runs derived from QCM-D measurements were converted to the Γ(d) vs. the time relationships. This allowed to precisely determine the maximum coverage that varied between 1.2 mg m(-2) at pH 3.5 and 4.2 mg m(-2) at pH 7.4 for ionic strength of 0.15 M. These results agree with theoretical modeling and previous experimental data derived by using ellipsometry, OWLS and TIRF. Various fibrinogen adsorption mechanisms were revealed by exploiting the maximum coverage data whose validity was also confirmed by the dissipation vs. the dry mass relationships. Beside significance to basic science, these results enable to develop a robust technique, based on the QCM-D measurements, suitable for precisely determining the dry mass of protein monolayers adsorbed under various physicochemical conditions. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Venom Concentrations and Clotting Factor Levels in a Prospective Cohort of Russell's Viper Bites with Coagulopathy.

    Directory of Open Access Journals (Sweden)

    Geoffrey K Isbister

    Full Text Available Russell's viper envenoming is a major problem in South Asia and causes venom induced consumption coagulopathy. This study aimed to investigate the kinetics and dynamics of venom and clotting function in Russell's viper envenoming.In a prospective cohort of 146 patients with Russell's viper envenoming, we measured venom concentrations, international normalised ratio [INR], prothrombin time (PT, activated partial thromboplastin time (aPTT, coagulation factors I, II, V, VII, VIII, IX and X, and von Willebrand factor antigen. The median age was 39 y (16-82 y and 111 were male. The median peak INR was 6.8 (interquartile range [IQR]: 3.7 to >13, associated with low fibrinogen [median,3 at 6 h post-antivenom but had reduced to <2, by 24 h. The aPTT had also returned to close to normal (<50 sec at 24 h. Factor VII, VIII and IX levels were unusually high pre-antivenom, median peak concentrations of 393%, 307% and 468% respectively. Pre-antivenom venom concentrations and the INR (r = 0.20, p = 0.02 and aPTT (r = 0.19, p = 0.03 were correlated (non-parametric Spearman analysis.Russell's viper coagulopathy results in prolonged aPTT, INR, low fibrinogen, factors V, VIII and X which recover over 48 h. Severity of clotting abnormalities was associated with venom concentrations.

  8. The Internal Dynamics of Fibrinogen and Its Implications for Coagulation and Adsorption.

    Directory of Open Access Journals (Sweden)

    Stephan Köhler

    2015-09-01

    Full Text Available Fibrinogen is a serum multi-chain protein which, when activated, aggregates to form fibrin, one of the main components of a blood clot. Fibrinolysis controls blood clot dissolution through the action of the enzyme plasmin, which cleaves fibrin at specific locations. Although the main biochemical factors involved in fibrin formation and lysis have been identified, a clear mechanistic picture of how these processes take place is not available yet. This picture would be instrumental, for example, for the design of improved thrombolytic or anti-haemorrhagic strategies, as well as, materials with improved biocompatibility. Here, we present extensive molecular dynamics simulations of fibrinogen which reveal large bending motions centered at a hinge point in the coiled-coil regions of the molecule. This feature, likely conserved across vertebrates according to our analysis, suggests an explanation for the mechanism of exposure to lysis of the plasmin cleavage sites on fibrinogen coiled-coil region. It also explains the conformational variability of fibrinogen observed during its adsorption on inorganic surfaces and it is supposed to play a major role in the determination of the hydrodynamic properties of fibrinogen. In addition the simulations suggest how the dynamics of the D region of fibrinogen may contribute to the allosteric regulation of the blood coagulation cascade through a dynamic coupling between the a- and b-holes, important for fibrin polymerization, and the integrin binding site P1.

  9. The fibrinogen cleavage product Aα-Val360, a specific marker of neutrophil elastase activity in vivo

    DEFF Research Database (Denmark)

    Carter, Richard I; Mumford, Richard A; Treonze, Kelly M

    2011-01-01

    Alpha-1-antitrypsin (A1AT) deficiency is the only recognised genetic risk factor for chronic obstructive pulmonary disease (COPD), a leading cause of morbidity and mortality worldwide. Since A1AT is the major inhibitor of neutrophil elastase (NE), this enzyme has become widely implicated in the p...

  10. Existence and mass concentration of 2D attractive Bose-Einstein condensates with periodic potentials

    Science.gov (United States)

    Wang, Qingxuan; Zhao, Dun

    2017-02-01

    In this paper we consider a two-dimensional attractive Bose-Einstein condensate with periodic potential, described by Gross-Pitaevskii (GP) functional. By concentration-compactness lemma we show that minimizers of this functional exist when the interaction strength a satisfies a* 0, and there is no minimizer for aa*. When a approaches a*, using concentration-compactness arguments again we obtain an optimal energy estimate depending on the shape of periodic potential. Moreover, we analyze the mass concentration.

  11. Prediction of stroke in the general population in Europe. EUROSTROKE: Is there a role for fibrinogen and electrocardiography?

    NARCIS (Netherlands)

    K.G.M. Moons (Karel); M.L. Bots (Michiel); J.T. Salonen; P.C. Elwood; A. Freire de Concalves; Y. Nikitin; J. Sivenius; D. Inzitari; V. Benetou (Vassiliki); J. Tuomilehto; P.J. Koudstaal (Peter Jan); D.E. Grobbee (Diederick)

    2002-01-01

    textabstractBACKGROUND: To decide whether a person with certain characteristics should be given any kind of intervention to prevent a cardiovascular event, it would be helpful to classify subjects in low, medium and high risk categories. The study evaluated which well known cerebrovascular and cardi

  12. Plasma fibrinogen levels are correlated with postoperative distant metastasis and prognosis in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Zhang, Danhong; Zhou, Xia; Bao, Wuan; Chen, Ying; Cheng, Lei; Qiu, Guoqin; Sheng, Liming; Ji, Yongling; Du, Xianghui

    2015-11-10

    This study investigated the correlation of preoperative plasma fibrinogen level with distant metastasis and prognosis in esophageal squamous cell carcinoma (ESCC). A total of 255 patients with ESCC who underwent surgery in Zhejiang cancer hospital (Hangzhou, China), between October 2006 and December 2009, were evaluated in this retrospective study. Population controls were selected from a pool of cancer-free subjects in the same region. Each patient and cancer-free people provided 3-mL pretreatment blood. Plasma fibrinogen level was measured by the Clauss method. The effects of hyperfibrinogenemia on locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS), relapse-free survival (RFS), and overall survival (OS) were assessed using Kaplan-Meier analysis. Independent prognostic factors were identified in the multivariate Cox analysis. The proportion of hyperfibrinogenemia was higher in ESCC patients than those in controls (40.4% vs 13.6%). Subjects with hyperfibrinogenemia had a significantly higher risk of ESCC than those with normal plasma fibrinogen level (adjust OR = 4.61; 95% CI = 3.02-7.01, P fibrinogen level were independent prognostic factors of ESCC (P fibrinogen level was significantly associated with elevated risk of ESCC. Preoperative plasma fibrinogen level was a predictor of distant metastasis and independently associated with prognosis of patients with ESCC.

  13. LIPID PROFILE, PLASMA FIBRINOGEN, AND PLATELET COUNT AS MARKERS OF CARDIO VASCULAR DISEASE IN SMOKERS DUE TO FREE RADICAL GENERATION

    Directory of Open Access Journals (Sweden)

    N Kannan

    2013-06-01

    Full Text Available Cigarette smoking & tobacco chewing are risk factors not only for oral and lung tumours but also for the development of systemic disorders like atherosclerosis, coronary artery disease and peripheral vascular disease. This study was undertaken to evaluate the lipid profile, plasma fibrinogen and platelet count in male smokers, compared with healthy non smokers in rural area of south India, Out of 100 male healthy volunteers, 50 members were healthy smokers and 50 healthy non smokers, subjects were divided in both groups in age around 30 to 45yrs, with no past history of diabetes mellitus, hypertension, hepatic disorders and were neither on anti hypertensive, lipid lowering drugs were included in the study. Lipid profile, plasma fibrinogen and platelet count were analyzed by standard methods. Our results showed mean platelet count for smokers is 2, 86,345per mm3 and for non-smokers 2, 04,484.6per mm3. The mean plasma fibrinogen concentration for smokers is 3.48gm/dl and for non smokers is 3.12gm/dl. The platelet count and plasma fibrinogen concentration shows a higher value for smokers when compared to non- smokers. This is statistically significant. The mean total cholesterol level for smokers (186±30.10 mg/dl and non smokers (166.3±24.26 mg/dl and the mean triglyceride level for smokers (175±59.43 mg/dl and non smokers (132.09±+33.80 mg/dl are also statistically significant. The mean HDL level for smokers (40.4±4.13 mg/dl and for non smokers (44.68±4.13 mg/dl, the mean LDL level for smokers (105.8±28.16 mg/dl and non smokers (89.68±16.50 mg/dl and the mean VLDL level for smokers (28.4± 8.16 mg/dl and non smokers (14.3.±3.2 mg/dl indicate that the Lipid profile also is statistically significant between the two groups. We concluded that there is an elevated lipid profile; plasma fibrinogen and platelet count in smokers when compared to non smokers, which shows that smokers have high risk of prevalence of cardiovascular and vessel wall

  14. Fibrinogen is not elevated in the cerebrospinal fluid of patients with multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Ehling Rainer

    2011-10-01

    Full Text Available Abstract Background Elevated plasma fibrinogen levels are a well known finding in acute infectious diseases, acute stroke and myocardial infarction. However its role in the cerebrospinal fluid (CSF of acute and chronic central (CNS and peripheral nervous system (PNS diseases is unclear. Findings We analyzed CSF and plasma fibrinogen levels together with routine parameters in patients with multiple sclerosis (MS, acute inflammatory diseases of the CNS (bacterial and viral meningoencephalitis, BM and VM and PNS (Guillain-Barré syndrome; GBS, as well as in non-inflammatory neurological controls (OND in a total of 103 patients. Additionally, MS patients underwent cerebral MRI scans at time of lumbar puncture. CSF and plasma fibrinogen levels were significantly lower in patients with MS and OND patients as compared to patients with BM, VM and GBS. There was a close correlation between fibrinogen levels and albumin quotient (rho = 0.769, p Conclusions Although previous work has shown clear evidence of the involvement of fibrinogen in MS pathogenesis, this is not accompanied by increased fibrinogen in the CSF compartment.

  15. [The role of post-translational modification of fibrinogen in the pathogenesis of thrombosis].

    Science.gov (United States)

    Tadeusiewicz, Justyna; Nowak, Paweł

    2015-02-01

    Fibrinogen is a precursor of fibrin, which is the main component of the blood clot. The opposite of coagulation is fibrinolysis. The proper functioning of both systems allow to maintain a hemostasis. Increasing level of fibrinogen is an important risk factor for myocardial infarction or ischemic stroke. Reactive oxygen, nitrogen and chlorine species are created in inflammatory conditions, ischemia and tissues reperfusion. They can modify the fibrinogen molecule. The most important changes are associated with nitration and chlorination of tyrosine residues, oxidation of methionine, histidine and tryptophan residues, as well as formation dityrosine and carbonyl groups. Moreover, structure of fibrinogen is modified by glycation and homocysteinylation in hyperglycemia and hyperhomocysteinemia conditions. Non-enzymatic posttranslational modifications of fibrinogen contribute to formation of thrombogenic fibrin structure. The degree of fibrinogen modification is responsible for fiber structure, packing and susceptibility of fibrin clots to fibrinolysis. Additionally, the viscoelastic properties are changed. Resistance to fibrinolysis is largely associated with the modification of lysine residues in the protein molecule. Each of these alternations may contribute to increased risk of arterial and venous thrombosis.

  16. Staphylococcus intermedius binding to immobilized fibrinogen, fibronectin and cytokeratin in vitro.

    Science.gov (United States)

    Schmidt, Vanessa; Nuttall, Tim; Fazakerley, Jennie; McEwan, Neil

    2009-10-01

    Bacterial adhesion is a key step in colonization of the skin. Staphylococcus intermedius adheres strongly to canine and feline corneocytes, and adhesion is greater to corneocytes from dogs affected with atopic dermatitis, but comparatively little is known about adhesion-receptor interaction compared to S. aureus. The aim of this study was to compare the binding of S. intermedius isolates from healthy (n = 21) and atopic dogs (n = 33) to immobilized human fibronectin and epidermal cytokeratin and canine fibrinogen in vitro. Staphylococcus intermedius and the positive control S. aureus P1 exhibited concentration-dependent binding to all three protein layers. The negative control S. aureus Newman strain and S. hominis did not bind. The majority of S. intermedius isolates adhered strongly, and there was no significant difference between isolates from atopic and healthy dogs or from lesional or nonlesional skin of atopic dogs (fibronectin P = 0.971 and 0.837; fibrinogen P = 0.811 and 0.564; cytokeratin P = 0.409 and 0.564). These results suggest that S. intermedius may possess specific microbial components recognizing adhesive matrix molecules, like S. aureus, that bind to the substrates used in this study. Adherence and therefore colonization and infection in canine atopic dermatitis, however, are more likely to be related to host factors rather than the possession of specific virulence factors.

  17. Cross-linking methods of electrospun fibrinogen scaffolds for tissue engineering applications

    Energy Technology Data Exchange (ETDEWEB)

    Sell, Scott A; Garg, Koyal; McClure, Michael J; Bowlin, Gary L [Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23284-3067 (United States); Francis, Michael P [Department of Pathology, Virginia Commonwealth University, Richmond, VA 23298-0709 (United States); Simpson, David G [Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA 23298-0709 (United States)], E-mail: glbowlin@vcu.edu

    2008-12-15

    The purpose of this study was to enhance the mechanical properties and slow the degradation of an electrospun fibrinogen scaffold, while maintaining the scaffold's high level of bioactivity. Three different cross-linkers were used to achieve this goal: glutaraldehyde vapour, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) in ethanol and genipin in ethanol. Scaffolds with a fibrinogen concentration of 120 mg ml{sup -1} were electrospun and cross-linked with one of the aforementioned cross-linkers. Mechanical properties were determined through uniaxial tensile testing performed on scaffolds incubated under standard culture conditions for 1 day, 7 days and 14 days. Cross-linked scaffolds were seeded with human foreskin fibroblasts (BJ-GFP-hTERT) and cultured for 7, 14 and 21 days, with histology and scanning electron microscopy performed upon completion of the time course. Mechanical testing revealed significantly increased peak stress and modulus values for the EDC and genipin cross-linked scaffolds, with significantly slowed degradation. However, cross-linking with EDC and genipin was shown to have some negative effect on the bioactivity of the scaffolds as cell migration throughout the thickness of the scaffold was slowed.

  18. Coexistence of High Fibrinogen and Low High-density Lipoprotein Cholesterol Levels Predicts Recurrent Cerebral Venous Thrombosis

    Institute of Scientific and Technical Information of China (English)

    Xin Ma; Xun-Ming Ji; Paul Fu; Yu-Chuan Ding; Qiang Xue; Yue Huang

    2015-01-01

    Background:Cerebral venous thrombosis (CVT) may lead to serious neurological disorders;however,little is known about the risk factors for recurrent CVT.Our aim was to determine the association between elevated fibrinogen and decreased high-density lipoprotein cholesterol (HDL-C) levels with recurrent CVT.Methods:This retrospective cohort study included participants if they had a first episode of objectively defined CVT and were admitted to Xuan Wu Hospital,Capital Medical University from August 2005 to September 2009.Demographic and clinical variables were collected,as well as laboratory parameters,including plasma fibrinogen and HDL-C.Patients with CVT were followed for recurrent symptomatic CVT.Follow-up was through the end of September 2010.Potential predictors of recurrence were analyzed using Cox survival analysis.Results:At the end of the follow-up,95 patients were eligible for the study.Twelve of 95 patients (12.6%) had recurred CVT.The median time of recurrence was 7 months (range:1-39 months).Eight of these 12 (66.7%) experienced recurrence within the first 12 months after their initial CVT.The recurrence rate of CVT was 2.76 per 100 patient-years.Multivariate Cox regression analysis demonstrated that the coexistence of high fibrinogen (>4.00 g/L) and low HDL-C (<1.08 mmol/L) levels at baseline was the only independent predictor for recurrent CVT (hazard ratio:4.69;95% confidence interval:1.10-20.11;P < 0.05).Of the twelve patients with recurrent CVT in our study,7 (58.3%) had high fibrinogen plus low HDL-C levels.All 7 of these patients took warfarin for 3-12 months,and 6 of 7 had recurrent CVT after the discontinuation of anticoagulant treatment.Conclusions:Concomitant high fibrinogen and low HDL-C levels may be associated with recurrence of CVT.The effect of potential risk factors related to atherothrombosis on recurrent CVT should be closely monitored.

  19. Function of fibrinogen gamma-chain dodecapeptide-conjugated latex beads under flow.

    Science.gov (United States)

    Takeoka, Shinji; Okamura, Yosuke; Teramura, Yuji; Watanabe, Naohide; Suzuki, Hidenori; Tsuchida, Eishun; Handa, Makoto; Ikeda, Yasuo

    2003-12-19

    In order to perform a fundamental study of platelet substitutes, novel particles that bound to activated platelets were prepared using two oligopeptides conjugated to latex beads. The oligopeptides were CHHLGGAKQAGDV (H12), which is a fibrinogen gamma-chain carboxy-terminal sequence (gamma 400-411), and CGGRGDF (RGD), which contains a fibrinogen alpha-chain sequence (alpha 95-98 RGDF). Both peptides contained an additional amino-terminal cysteine to enable conjugation. Human serum albumin was adsorbed onto the surface of latex beads (average diameter 1microm) and pyridyldisulfide groups were chemically introduced into the adsorbed protein. H12 or RGD peptides were then chemically linked to the modified surface protein via disulfide linkages. H12- or RGD-conjugated latex beads prepared in this way enhanced the in vitro thrombus formation of activated platelets on collagen-immobilized plates under flowing thrombocytopenic-imitation blood. Based on the result of flow cytometric analyses of agglutination, PAC-1 binding, antiP-selectin antibody binding, and annexin V binding, the H12-conjugated latex beads showed minimal interaction with non-activated platelets. These results indicate the excellent potential of H12-conjugated particles as a candidate for a platelet substitute.

  20. The plasma protein fibrinogen stabilizes clusters of red blood cells in microcapillary flows

    CERN Document Server

    Brust, M; Thiebaud, M; Flormann, D; Verdier, C; Kaestner, L; Laschke, M W; Selmi, H; Benyoussef, A; Podgorski, T; Coupier, G; Misbah, C; Wagner, C

    2014-01-01

    The supply of oxygen and nutrients and the disposal of metabolic waste in the organs depend strongly on how blood, especially red blood cells, flow through the microvascular network. Macromolecular plasma proteins such as fibrinogen cause red blood cells to form large aggregates, called rouleaux, which are usually assumed to be disaggregated in the circulation due to the shear forces present in bulk flow. This leads to the assumption that rouleaux formation is only relevant in the venule network and in arterioles at low shear rates or stasis. Thanks to an excellent agreement between combined experimental and numerical approaches, we show that despite the large shear rates present in microcapillaries, the presence of either fibrinogen or the synthetic polymer dextran leads to an enhanced formation of robust clusters of red blood cells, even at haematocrits as low as 1%. Robust aggregates are shown to exist in microcapillaries even for fibrinogen concentrations within the healthy physiological range. These pers...

  1. Directional growth of Ag nanorod from polymeric silver cyanide: A potential substrate for concentration dependent SERS signal enhancement leading to melamine detection

    Science.gov (United States)

    Roy, Anindita; Sahoo, Ramkrishna; Chowdhury, Joydeep; Bhattacharya, Tara Shankar; Agarwal, Ratnesh; Pal, Tarasankar

    2017-08-01

    Attention has been directed to prepare exclusive one-dimensional silver nanostructure from the linear inorganic polymer AgCN. Successive color change from yellow to orange, to red and finally to green reflects the evolution of high yielding Ag nanorods (NRs) from well-known -[Ag-CN]- chains of polymeric AgCN at room temperature. The parental 1D morphology of AgCN is retained within the as-synthesized Ag NRs. So we could successfully exploit the Ag NR for surface-enhanced Raman scattering (SERS) studies for sensing a popular milk adulterant melamine down to picomolar level. We observed interesting concentration dependent selective SERS band enhancement of melamine. The enhanced 1327 cm- 1 SERS signal intensity at lower concentration (10- 9 and 10- 12 M) of melamine speaks for the preferential participation of -C-N of melamine molecule with Ag surface. On the other hand, '-NH2' group together with ring 'N' participation of melamine molecule onto Ag surface suggested an adsorptive stance at higher (10- 3-10- 7 M) concentration range. Thus the binding modes of the molecule at the Ag surface justify its fluxional behavior.

  2. ICAM1 and fibrinogen-γ are increased in uterine epithelial cells at the time of implantation in rats.

    Science.gov (United States)

    Lecce, Laura; Kaneko, Yui; Madawala, Romanthi J; Murphy, Christopher R

    2011-05-01

    Uterine epithelial cells transform into a receptive state to adhere to an implanting blastocyst. Part of this transformation includes the apical concentration of cell adhesion molecules at the time of implantation. This study, for the first time, investigates the expression of ICAM1 and fibrinogen-γ (FGG) in uterine epithelial cells during normal pregnancy, pseudopregnancy and in hormone-treated rats. An increase (P FGG dimerization increased (P FGG in the uterine epithelium at the time of implantation in the rat is similar to that seen in lymphocyte-endothelium adhesion, and we suggest a similar mechanism in embryo-uterine epithelium adhesion is utilized.

  3. Long-term performance potential of concentrated photovoltaic (CPV) systems

    KAUST Repository

    Burhan, Muhammad

    2017-07-17

    Owing to the diverse photovoltaic (PV) systems’ design and technology, as well as the dynamic nature of insolation data received on the aperture surfaces, the instantaneous output from a PV system fluctuates greatly. For accurate performance estimation of a large PV field, the long term performance as electrical output is a more rational approach over the conventional testing methods, such as at Standard Testing Conditions (STC) and at the Nominal Operating Cell Temperature (NOCT) available hitherto. In this paper, the long-term performances of concentrated PVs (Cassegrain reflectors and Fresnel lens) with 2-axes tracking and a variety of PV systems, namely the stationary flat-plate PV (mono-crystalline, poly-crystalline and thin-films CIS types), is presented over a period of one year for the merit comparison of system design, under the tropical weather conditions of Singapore. From the measured field performances, the total energy output of 240.2 kW h/m/year is recorded for CPV operation in Singapore, which is nearly two folds higher than the stationary PV panels.

  4. Environmental cadmium and lead concentrations in the Bahía Blanca Estuary (Argentina. Potential toxic effects of Cd and Pb on crab larvae

    Directory of Open Access Journals (Sweden)

    Laura Ferrer

    2000-12-01

    Full Text Available The Bahía Blanca Estuary includes a large tidal plain with an area close to 1150 km2. Mud is predominant in its sediments, where a significant population of the crab Chasmagnathus granulata lives during the whole year. Moreover, there are important urban and industrial discharges into this environment. Cd and Pb concentrations were determined in samples of water (for both dissolved and suspended particulate matter and surface sediments (total and 63 µm fractions. Organic matter was analysed in the sediments, while temperature, salinity, pH and dissolved oxygen were measured in the estuarine water. The metal concentrations determined in this study were: 1.47 ± 1.08 µg Cd g–1 and 14.68 ± 4.31 µg Pb g–1 in surface sediments; 2.21 ± 1.33 µg Cd g–1 and 25.70 ± 7.09 µg Pb g–1 in the –1 and below the analytical detection limit of Pb in suspended particulate matter. Furthermore, dissolved Cd and Pb were lower than the norms for marine and estuarine waters (2 µg dm–3 for Cd and 5 µg dm–3 for Pb, E.P.A.. Simultaneously, the effects of Cd and Pb were studied on recently hatched larvae of Ch. granulata, through 96-hour semi-static acute assays. Viability was the criterion assessed in the assays. LC50 (96 h for Cd was 46.43 µg dm–3 (36.92 - 56.34 µg dm–3, whilst that for Pb was 1.00 mg m–3 (0.79 - 1.23 mg dm–3, which demonstrates that Cd is more toxic towards larvae. Finally, both LC50 values determined for Cd and Pb were higher than the corresponding metal concentrations measured in the Bahía Blanca environment.

  5. 脓毒症患者纤维蛋白原/C反应蛋白对弥漫性血管内凝血的预测价值%Fibrinogen/C reactive protein ratio as a parameter for diagnosis of disseminated intravascular coagulation in patients with sepsis.

    Institute of Scientific and Technical Information of China (English)

    王武超; 曹宝平

    2014-01-01

    目的 探讨脓毒症患者纤维蛋白原/C反应蛋白(fibrinogen/CRP)比值水平与弥漫性血管内凝血(DIC)发生的相关性.方法 选择北京大学人民医院急诊重症监护病房脓毒症患者共61例,收入急诊重症监护病房24 h内进行血常规、CRP、血浆凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原、D-二聚体(D-dimer)水平的检测.收集纳入研究患者的临床资料,进行APACHEⅡ评分、ISTH的DIC评分及JAAM的DIC评分.根据DIC评分结果将患者分为DIC组和非DIC组,对比组间血小板、CRP、血浆凝血酶原时间(PT)、活化部分凝血活酶时间(ApTT)、纤维蛋白原水平(FIB)、Fibrinogen/CRP比值,并建立ROC曲线明确CRP,Fibrinogen/CRP比值对于诊断DIC的敏感性及特异性.计算CRP,Fibrinogen/CRP与JAAM评分诊断DIC的OR值.所有数据采用SPSS 17.0版统计软件进行分析.结果 ①DIC组Fibrinogen/CRP比值明显低于非DIC组.②ISTH的DIC评分:Fibrinogen/CRP比值ROC曲线下为0.691,高于C反应蛋白ROC曲线下0.561,纤维蛋白原ROC曲线下0.608.③JAAM的DIC评分:Fibrinogen/CRP比值ROC曲线下为0.814,高于C反应蛋白ROC曲线下0.788,纤维蛋白原ROC曲线下为0.429.④JAAM评分诊断DIC:Fibrinogen/CRP比值(<45) OR值为11.14,CRP(>70 mg/l) OR值为8.05.结论 Fibrinogen/CRP比值可以作为脓毒症患者DIC诊断的早期判读指标.%Objective To determine if the fibrinogen/C reactive protein (CRP) ratio could be used in sepsis patients as a predictor for disseminated intravascular coagulation.Methods A total of 61 patients with sepsis admitted to emergency intensive care unit (EICU) were enrolled.C reactive protein (CRP) and variables of coagulation such as Platelet (PLT),prothrombin time (PT),activated partial thrombopastin time (APTT),fibrinogen and D-dimer were analyzed during 24 hours after admission to EICU.APACHE Ⅱ score,ISTH score and JAAM score were evaluated.According to DIC score (JAAM score and

  6. High-concentration zeta potential measurements using light-scattering techniques.

    Science.gov (United States)

    Kaszuba, Michael; Corbett, Jason; Watson, Fraser Mcneil; Jones, Andrew

    2010-09-28

    Zeta potential is the key parameter that controls electrostatic interactions in particle dispersions. Laser Doppler electrophoresis is an accepted method for the measurement of particle electrophoretic mobility and hence zeta potential of dispersions of colloidal size materials. Traditionally, samples measured by this technique have to be optically transparent. Therefore, depending upon the size and optical properties of the particles, many samples will be too concentrated and will require dilution. The ability to measure samples at or close to their neat concentration would be desirable as it would minimize any changes in the zeta potential of the sample owing to dilution. However, the ability to measure turbid samples using light-scattering techniques presents a number of challenges. This paper discusses electrophoretic mobility measurements made on turbid samples at high concentration using a novel cell with reduced path length. Results are presented on two different sample types, titanium dioxide and a polyurethane dispersion, as a function of sample concentration. For both of the sample types studied, the electrophoretic mobility results show a gradual decrease as the sample concentration increases and the possible reasons for these observations are discussed. Further, a comparison of the data against theoretical models is presented and discussed. Conclusions and recommendations are made from the zeta potential values obtained at high concentrations.

  7. A novel regulatory element between the human FGA and FGG genes.

    Science.gov (United States)

    Fish, Richard J; Neerman-Arbez, Marguerite

    2012-09-01

    High circulating fibrinogen levels correlate with cardiovascular disease (CVD) risk. Fibrinogen levels vary between people and also change in response to physiological and environmental stimuli. A modest proportion of the variation in fibrinogen levels can be explained by genotype, inferring that variation in genomic sequences that regulate the fibrinogen genes ( FGA , FGB and FGG ) may affect hepatic fibrinogen production and perhaps CVD risk. We previously identified a conserved liver enhancer in the fibrinogen gene cluster (CNC12), between FGB and FGA . Genome-wide Chromatin immunoprecipitation-sequencing (ChIP-seq) demonstrated that transcription factors which bind fibrinogen gene promoters also interact with CNC12, as well as two potential fibrinogen enhancers (PFE), between FGA and FGG . Here we show that one of the PFE sequences has potent hepatocyte enhancer activity. Using a luciferase reporter gene system, we found that PFE2 enhances minimal promoter- and FGA promoter-driven gene expression in hepatoma cells, regardless of its orientation with respect to the promoters. A region within PFE2 bears a short series of conserved nucleotides which maintain enhancer activity without flanking sequence. We also demonstrate that PFE2 is a liver enhancer in vivo, driving enhanced green fluorescent protein expression in transgenic zebrafish larval livers. Our study shows that combining public domain ChIP-seq data with in vitro and in vivo functional tests can identify novel fibrinogen gene cluster regulatory sequences. Variation in such elements could affect fibrinogen production and influence CVD risk.

  8. A Small Oxygen Concentrator

    Science.gov (United States)

    1985-12-01

    150- S40- 20- 10 0 0 10 i0 30 40 NUIT PRESS=R (psig Figure 7. Percentage of oxygen. versus inlet pressure when using Soc with 131 molecular s ieve. 70...chick valve ano *move the plunger and spring. Disca the plunger; the spring will W• reused. Mill a SS sleeve to 0.535" 0.0. and 0.50" I.D. and press tit...the fjur 1" caps. The i n- side of two of the caps is milled flat to a diameteýr of 7/8". P-Kace one ena of a 10’, length of 1/2" SS tube in each Of

  9. Association of Fibrinogen with Severity of Stable Coronary Artery Disease in Patients with Type 2 Diabetic Mellitus

    Directory of Open Access Journals (Sweden)

    Li-Feng Hong

    2014-01-01

    Full Text Available Background. Some studies have suggested a relation of plasma fibrinogen to the severity of coronary artery disease (CAD. However, whether plasma fibrinogen can predict the presence and severity of CAD in patients with diabetes mellitus has not been determined. Methods. A total of consecutive 373 diabetic patients with typical angina pectoris who received coronary angiography were enrolled and classified into three groups by tertiles of Gensini score (GS, low group 28. The relationship between fibrinogen and GS was evaluated. Results. There were correlations of fibrinogen with hemoglobin A1c, C-reactive protein, and GS (r=0.17, r=0.52, and r=0.21, resp.; all P<0.001. Area under the receivers operating characteristic curve of fibrinogen was 0.62 (95% CI 0.56–0.68, P<0.001 for predicting a high GS. Multivariate analysis suggested that plasma fibrinogen was an independent predictor of a high GS for diabetic patients (OR=1.40, 95% CI 1.04–1.88, and P=0.026 after adjusting for traditional risk factors of CAD. Conclusions. The present data indicated that plasma fibrinogen, a readily measurable systematic inflammatory marker, appeared to be an independent predictor for the severity of CAD in diabetic patients.

  10. Dynamics of leaf gas exchange, xylem and phloem transport, water potential and carbohydrate concentration in a realistic 3-D model tree crown.

    Science.gov (United States)

    Nikinmaa, Eero; Sievänen, Risto; Hölttä, Teemu

    2014-09-01

    Tree models simulate productivity using general gas exchange responses and structural relationships, but they rarely check whether leaf gas exchange and resulting water and assimilate transport and driving pressure gradients remain within acceptable physical boundaries. This study presents an implementation of the cohesion-tension theory of xylem transport and the Münch hypothesis of phloem transport in a realistic 3-D tree structure and assesses the gas exchange and transport dynamics. A mechanistic model of xylem and phloem transport was used, together with a tested leaf assimilation and transpiration model in a realistic tree architecture to simulate leaf gas exchange and water and carbohydrate transport within an 8-year-old Scots pine tree. The model solved the dynamics of the amounts of water and sucrose solute in the xylem, cambium and phloem using a fine-grained mesh with a system of coupled ordinary differential equations. The simulations predicted the observed patterns of pressure gradients and sugar concentration. Diurnal variation of environmental conditions influenced tree-level gradients in turgor pressure and sugar concentration, which are important drivers of carbon allocation. The results and between-shoot variation were sensitive to structural and functional parameters such as tree-level scaling of conduit size and phloem unloading. Linking whole-tree-level water and assimilate transport, gas exchange and sink activity opens a new avenue for plant studies, as features that are difficult to measure can be studied dynamically with the model. Tree-level responses to local and external conditions can be tested, thus making the approach described here a good test-bench for studies of whole-tree physiology.

  11. Interaction between Fibrinogen and Insulin-Like Growth Factor-Binding Protein-1 in Human Plasma under Physiological Conditions.

    Science.gov (United States)

    Gligorijević, N; Nedić, O

    2016-02-01

    Fibrinogen is a plasma glycoprotein and one of the principle participants in blood coagulation. It interacts with many proteins during formation of a blood clot, including insulin-like growth factors (IGFs) and their binding proteins (IGFBP). Fibrinogen complexes were found as minor fractions in fibrinogen preparations independently of the coagulation process, and their presence influences the kinetics of polymerization. The idea of this work was to investigate whether fibrinogen in human plasma interacts with IGFBPs independently of the tissue injury or coagulation process. The results have shown that fibrinogen forms complexes with IGFBP-1 under physiological conditions. Several experimental approaches have confirmed that complexes are co-isolated with fibrinogen from plasma, they are relatively stable, and they appear as a general feature of human plasma. Several other experiments excluded the possibility that alpha-2 macroglobulin/IGFBP-1 complexes or IGFBP-1 oligomers contributed to IGFBP-1 immunoreactivity. The role of fibrinogen/IGFBP-1 complexes is still unknown. Further investigation in individuals expressing both impaired glucose control and coagulopathy could contribute to identification and understanding of their possible physiological role.

  12. Polymethyl methacrylate-co-methacrylic acid coatings with controllable concentration of surface carboxyl groups: A novel approach in fabrication of polymeric platforms for potential bio-diagnostic devices

    Energy Technology Data Exchange (ETDEWEB)

    Hosseini, Samira; Ibrahim, Fatimah [Center for Innovation in Medical Engineering, Department of Biomedical Engineering, Faculty of Engineering, University of Malaya, Kuala Lumpur 50603 (Malaysia); Djordjevic, Ivan, E-mail: ivan.djordjevic@um.edu.my [Center for Innovation in Medical Engineering, Department of Biomedical Engineering, Faculty of Engineering, University of Malaya, Kuala Lumpur 50603 (Malaysia); Koole, Leo H. [Center for Innovation in Medical Engineering, Department of Biomedical Engineering, Faculty of Engineering, University of Malaya, Kuala Lumpur 50603 (Malaysia); Department of Biomedical Engineering, Faculty of Health. Medicine and Life Science, Maastricht University, PO Box 616, NL 6200 MD Maastricht (Netherlands)

    2014-05-01

    Highlights: • Synthesis and processing of PMMA-co-MAA spin-coatings on silicon wafers. • Surface chemistry and morphology as a function of tailored co-polymer structure. • Polymer coatings with controlled number of surface carboxyl groups. - Abstract: The generally accepted strategy in development of bio-diagnostic devices is to immobilize proteins on polymeric surfaces as a part of detection process for diseases and viruses through antibody/antigen coupling. In that perspective, polymer surface properties such as concentration of functional groups must be closely controlled in order to preserve the protein activity. In order to improve the surface characteristics of transparent polymethacrylate plastics that are used for diagnostic devices, we have developed an effective fabrication procedure of polymethylmetacrylate-co-metacrylic acid (PMMA-co-MAA) coatings with controlled number of surface carboxyl groups. The polymers were processed effectively with the spin-coating technique and the detailed control over surface properties is here by demonstrated through the variation of a single synthesis reaction parameter. The chemical structure of synthesized and processed co-polymers has been investigated with nuclear magnetic resonance spectroscopy (NMR) and matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-ToF-MS). The surface morphology of polymer coatings have been analyzed with atomic force microscopy (AFM) and scanning electron microscopy (SEM). We demonstrate that the surface morphology and the concentration of surface –COOH groups (determined with UV–vis surface titration) on the processed PMMA-co-MAA coatings can be precisely controlled by variation of initial molar ratio of reactants in the free-radical polymerization reaction. The wettability of developed polymer surfaces also varies with macromolecular structure.

  13. Research Progress on the Relationship of Coronary Heart Disease and D-dimer,Lipoprotein(a),Fibrinogen%D-二聚体、脂蛋白(a)、纤维蛋白原和冠心病关系研究进展

    Institute of Scientific and Technical Information of China (English)

    龚小鹏

    2012-01-01

    冠心病(CHD)与D-二聚体、脂蛋白(a)、纤维蛋白原(FG)有着密切的关联,CHD患者中D-二聚体、脂蛋白(a)、FG较高,但它们之间相互作用的机制仍不明确.近年来的研究显示,D-二聚体、脂蛋白(a)和FG可能参与CHD的发病过程,因此通过测定D-二聚体、脂蛋白(a)和FG在不同危险程度的CHD患者中的含量,评估它们对于CHD的发生、发展具有重要意义.%Coronary heart disease( CHD)is closely associated with D-dimer,lipoprotein( a)and fibrino-gen( FG),CHD patients have higher levels of D-dimer,lipoprotein( a),fibrinogen while the mechanism of the interaction between them remains unclear. In recent years, studies have shown that D-dimer,lipoprotein ( a )and fibrinogen may be involved in the pathogenesis of coronary heart disease, so by measuring D-dimer, lipoprotein( a )and fibrinogen level in patients with coronary heart disease is of great significance for assessing the genesis and development of CHD.

  14. Albumin modulates lateral assembly of fibrin polymers: evidence of enhanced fine fibril formation and of unique synergism with fibrinogen

    Energy Technology Data Exchange (ETDEWEB)

    Galanakis, D.K.; Lane, B.P.; Simon, S.R.

    1987-04-21

    The authors identified a new property of human albumin. It enhances formation of fine fibril (or leptofibril) structure during fibrin gelation, and by nephelometric and electron microscopic measurements, this property is independent of and synergistic with that of fibrinogen. They examined fibrin aggregation using physiologic temperatures and pH and albumin:fibrin concentration ratios below those at which the known accelerating effect on fibrin aggregation occurs. An albumin concentration dependent decrease in gel turbidity maxima was consistently demonstrable in buffers containing or lacking (2-5 mM) CaCl/sub 2/. Electron microscopic measurements of cross-sectional fibril widths, performed on sections of glutaraldehyde-fixed gels, disclosed differences between albumin-containing and control gels which were significant. Spin-labeled albumin displayed no change in electron (para) magnetic spin resonance spectral measurements during its inhibition of fibrin, indicating no perturbation on albumin conformation in the vicinities of Cys-34 and of fatty acid binding sites. Certain fibrinogen:albumin ratios designed to induce maximal inhibition yet permit gelation in the presence of either alone prevented gelation of buffer-diluted fibrin monomers. Aliquots from these which were dried and negatively stained on formvar-coated grids disclosed strands of 5-17 nm width, most displaying a 60-250-nm approximate length. The amounts of /sup 131/I-labeled coagulable fibrin which remained soluble in fibrinogen solutions were increased by albumin. They conclude that albumin enhances formation of leptofibril-rich gel domains when other plasma factors favor formation of such structures. Available evidence indicating decreased permeability implies that such gel domains limit efflux rates from the intrathrombus environment and from intra- to extravascular space.

  15. Mapping of residues of fibrinogen cleaved by protease II of Bacillus thuringiensis var. israelensis IMV B-7465

    Directory of Open Access Journals (Sweden)

    E. M. Stohniy

    2016-04-01

    Full Text Available The limited proteolysis of macromolecules allows obtaining the fragments that preserve the structure and functional properties of the whole molecule and could be used in the study of proteins structure and function. Proteases targeted to fibrinogen and fibrin are of interest as the tool for obtaining of functionally active fragments of fibrin(ogen and for the direct defibrination in vivo. That is why the aim of the present work was to study the proteolytic action of Protease II (PII purified from Bacillus thuringiensis var. israelensis IMV B-7465 on fibrinogen. Hydrolysis products of fibrinogen by PII were analysed by SDS-PAGE under reducing conditions with further immunoprobing using the mouse monoclonal 1-5A (anti-Aα509-610 and ІІ-5С (anti-Aα20-78 antibodies. It was shown that PII cleaved preferentially the Aα-chain of fibrinogen splitting off the peptide with apparent molecular weight of 10 kDa that corresponded the C-terminal part of Aα-chain of fibrinogen molecule. MALDI-TOF analysis of hydrolysis of fibrinogen was performed using a Voyager-DE. Results analyzed by Data Explorer 4.0.0.0 allowed to detect the main peak occurring at mass/charge (M/Z ratio of 11 441 Da. According to “Peptide Mass Calculator” this peptide corresponded to fragment Аα505-610 of fibrinogen molecule. The result showed that PII cleaves the peptide bond AαAsp-Thr-Ala504-Ser505. Thus, PII can be used for the obtaining of unique fragments of fibrinogen molecule. As far as αC-domain contains numerous sites of fibrin intermolecular interactions we can consider PII as a prospective agent for their study and for the defibrination.

  16. ACUTE NEUROTOXIC EFFECTS OF INHALED PERCHLOROETHYLENE ON PATTERN VISUAL EVOKED POTENTIALS AS A FUNCTION OF EXPOSURE AND ESTIMATED BLOOD AND BRAIN CONCENTRATION.

    Science.gov (United States)

    Previous experiments have shown the effects of acute inhalation exposure to trichloroethylene (TCE) and toluene are related to the target tissue concentration at the time of testing. The current studies examined exposure to another volatile organic compound, perchloroethylene (P...

  17. ACUTE NEUROTOXIC EFFECTS OF INHALED PERCHLOROETHYLENE ON PATTERN VISUAL EVOKED POTENTIALS AS A FUNCTION OF EXPOSURE AND ESTIMATED BLOOD AND BRAIN CONCENTRATION.

    Science.gov (United States)

    Previous experiments have shown the effects of acute inhalation exposure to trichloroethylene (TCE) and toluene are related to the target tissue concentration at the time of testing. The current studies examined exposure to another volatile organic compound, perchloroethylene (P...

  18. ATR-FTIR measurements of albumin and fibrinogen adsorption: Inert versus calcium phosphate ceramics.

    Science.gov (United States)

    Boix, Marcel; Eslava, Salvador; Costa Machado, Gil; Gosselin, Emmanuel; Ni, Na; Saiz, Eduardo; De Coninck, Joël

    2015-11-01

    Arthritis, bone fracture, bone tumors and other musculoskeletal diseases affect millions of people across the world. Nowadays, inert and bioactive ceramics are used as bone substitutes or for bone regeneration. Their bioactivity is very much dictated by the way proteins adsorb on their surface. In this work, we compared the adsorption of albumin and fibrinogen on inert and calcium phosphates ceramics (CaPs) using attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) to follow in situ protein adsorption on these materials. To this effect, we developed a sol-gel technique to control the surface chemistry of an ATR-FTIR detector. Hydroxyapatite adsorbed more albumin and β-tricalcium phosphate adsorbed more fibrinogen. Biphasic calcium phosphate presented the lowest adsorption among CaP for both proteins, illustrating the effect of surface heterogeneities. Inert ceramics adsorbed a lower amount of both proteins compared with bioactive ceramics. A significant change was observed in the conformation of the adsorbed protein versus the surface chemistry. Hydroxyapatite produced a larger loss of α-helix structure on albumin and biphasic calcium phosphate reduced β-sheet percentage on fibrinogen. Inert ceramics produced large α-helix loss on albumin and presented weak interaction with fibrinogen. Zirconia did not adsorb albumin and titanium dioxide promoted huge denaturalization of fibrinogen.

  19. Spatially selective surface platforms for binding fibrinogen prepared by particle lithography with organosilanes.

    Science.gov (United States)

    Englade-Franklin, Lauren E; Saner, Chamarra K; Garno, Jayne C

    2013-06-06

    We introduce an approach based on particle lithography to prepare spatially selective surface platforms of organosilanes that are suitable for nanoscale studies of protein binding. Particle lithography was applied for patterning fibrinogen, a plasma protein that has a major role in the clotting cascade for blood coagulation and wound healing. Surface nanopatterns of mercaptosilanes were designed as sites for the attachment of fibrinogen within a protein-resistant matrix of 2-[methoxy(polyethyleneoxy)propyl] trichlorosilane (PEG-silane). Preparing site-selective surfaces was problematic in our studies, because of the self-reactive properties of PEG-organosilanes. Certain organosilanes presenting hydroxyl head groups will cross react to form mixed surface multi-layers. We developed a clever strategy with particle lithography using masks of silica mesospheres to protect small, discrete regions of the surface from cross reactions. Images acquired with atomic force microscopy (AFM) disclose that fibrinogen attached primarily to the surface areas presenting thiol head groups, which were surrounded by PEG-silane. The activity for binding anti-fibrinogen was further evaluated using ex situ AFM studies, confirming that after immobilization the fibrinogen nanopatterns retained capacity for binding immunoglobulin G. Studies with AFM provide advantages of achieving nanoscale resolution for detecting surface changes during steps of biochemical surface reactions, without requiring chemical modification of proteins or fluorescent labels.

  20. Concentration of Mercury in Cockles (Anadara granosa and A. antiquata) Harvested from Estuaries of Western Lombok, Indonesia, and Potential Risks to Human Health.

    Science.gov (United States)

    Rahayu, Rachmawati Noviana; Irawan, Bambang; Soegianto, Agoes

    2016-01-01

    This study measured the levels of total mercury (tHg) in the whole tissues of cockles (Anadara granosa and A. antiquata) harvested from three estuaries of Western Lombok Island (WLI), Indonesia. This paper also evaluated the hazard level posed by the mercury in relation to the maximum residual limit for human consumption and to estimate the weekly intake and compare it with the provisional tolerable weekly intake (PTWI). The tHg concentrations in A. granosa ranged from 0.020 to 0.070 mg kg(-1), and those in A. antiquata were between 0.032 and 0.077 mg kg(-1) at all locations. All samples of cockles harvested from WLI contain tHg below the permissible limit for human consumption. The maximum weekly intakes for total mercury by coastal people range from 0.28 to 1.08 µg kg(-1) b.w., and they are below the recommended values of PTWI (5.6 µg kg(-1) b.w.). If it is assumed that 100% of the Hg in cockles is methyl mercury (MeHg), consumption of the indicated amounts at the measured values wouldn't exceed the MeHg PTWI (1.6 µg kg(-1) b.w.).

  1. Albumin and fibrinogen levels’ relation with orthopedics traumatic patients’ outcome after massive transfusion

    Science.gov (United States)

    Bazavar, Mohammadreza; Tabrizi, Ali; Abedini, Naghi; Elmi, Asghar

    2014-01-01

    Background: Severe bleeding is common during limb trauma. It can lead to hemorrhagic shock required to massive blood transfusion. Coagulopathy is the major complication of massive transfusion-induced increased mortality rate. Aim of this study was evaluation of fibrinogen and albumin levels association with orthopedics traumatic patients’ outcome who received massive transfusion. Methods: In a cross sectional study, 23 patients with severe limb injury admitted to orthopedic emergency department were studied. All the patients received massive transfusion, that is, >10 unit blood. Albumin and fibrinogen levels are measured at admission and 24 h later, and compared according to final outcome. Results: Twenty-three traumatic patients with severe limb injuries were studied, out of which ten (43.2%) died and 13 (56.8%) were alive. There was significant difference between patients outcome in fibrinogen level after 24 h, but no difference was observed in albumin levels. Based on regression model, fibrinogen after 24 h had a significant role in determining the final outcome in traumatic patients who received massive transfusion (odds ratio 0.48, 95% confidence interval 0.15–0.92, P = 0.02). Conclusions: According to our results, fibrinogen level is the most important factor in determination of orthopedics traumatic patients when received massive transfusion. However, serum albumin does not play any role in patients’ outcome. PMID:24665235

  2. Comparison of plasma with whole blood prothrombin time and fibrinogen on the same instrument.

    Science.gov (United States)

    Amukele, Timothy K; Ferrell, Chris; Chandler, Wayne L

    2010-04-01

    We compared plasma with whole blood (WB) international normalized ratio (INR) and fibrinogen using the same instrument and reagents. WBINRs were 50% higher than plasma INRs. After increasing the WB sample volume 40% and adjusting the International Sensitivity Index, WBINRs were similar to plasma INRs [adjusted WBINR = 0.99(plasma INR) - 0.02; r(2) = 0.98; n = 155], but the average difference in WB vs plasma INR was 4-fold higher than duplicate plasma INRs. Variation in hematocrit was a major determinant of the accuracy of the WBINR, with increased error at high INRs. The WB fibrinogen assay was highly dependent on the sample hematocrit (r(2) = 0.83), even after the sample volume was adjusted. Accurate WB fibrinogen measurements required a mathematical hematocrit correction. We conclude that WBINR and fibrinogen assays can be performed on point-of-care or automated analyzers, but sample volume must be adjusted to account for hematocrit. Accuracy is limited by variations in hematocrit with worsening accuracy for samples with high INRs or low fibrinogen levels.

  3. The fibrinogen gamma 10034C>T polymorphism is not associated with Peripheral Arterial Disease.

    Science.gov (United States)

    Bahadori, Babak; Uitz, Elisabeth; Dehchamani, Dadbeh; Pilger, Ernst; Renner, Wilfried

    2010-10-01

    Conversion of fibrinogen to fibrin plays an essential role in hemostasis and results in stabilization of the fibrin clot. Fibrinogen consists of three pairs of non-identical polypeptide chains, encoded by different genes (fibrinogen alpha [FGA], fibrinogen beta [FGB] and fibrinogen gamma [FGG]). A functional single nucleotide polymorphism (SNP) in the 3' untranslated region of the FGG gene (FGG 10034C>T, rs2066865) has been associated with deep venous thrombosis and myocardial infarction. Aim of the present study was to analyze the role of this polymorphism in peripheral arterial disease (PAD). The study was designed as case-control study including 891 patients with documented PAD and 777 control subjects. FGG genotypes were determined by exonuclease (TaqMan) assays. FGG genotype frequencies were not significantly different between PAD patients (CC: 57.3%, CT: 36.7%, TT: 5.8%) and control subjects (CC: 60.9%, CT: 33.5%, TT 5.6%; p=0.35). In a multivariate logistic regression analysis including age, sex, smoking, diabetes, arterial hypertension and hypercholesterolemia, the FGG 10034 T variant was not significantly associated with the presence of PAD (Odds ratio 1.07, 95% confidence interval 0.84 - 1.37; p = 0.60). The FGG 10034C>T polymorphism was furthermore not associated with age at onset of PAD. We conclude that the thrombophilic FGG 10034 T gene variant does not contribute to the genetic susceptibility to PAD.

  4. Thin films growth parameters in MAPLE; application to fibrinogen

    Energy Technology Data Exchange (ETDEWEB)

    Jelinek, M [Institute of Physics ASCR, Na Slovance 2, 182 21Prague 8 (Czech Republic); Cristescu, R [Institute of Physics ASCR, Na Slovance 2, 182 21Prague 8 (Czech Republic); Kocourek, T [Institute of Physics ASCR, Na Slovance 2, 182 21Prague 8 (Czech Republic); Vorlicek, V [Institute of Physics ASCR, Na Slovance 2, 182 21Prague 8 (Czech Republic); Remsa, J [Institute of Physics ASCR, Na Slovance 2, 182 21Prague 8 (Czech Republic); Stamatin, L [Longhin Scarlat Dermato-Venerologic Hospital, Bucharest (Romania); Mihaiescu, D [University of Agriculture Sciences and Veterinary Medicine, 59 Marasti, Bucharest (Romania); Stamatin, I [University of Bucharest, Faculty of Physics, PO Box MG-11, 3Nano-SAE, Bucharest-Magurele (Romania); Mihailescu, I N [National Institute for Laser, Plasma and Radiation Physics, MG-36, RO-77125, Bucharest (Romania); Chrisey, D B [Naval Research Laboratory, Code 6851 Washington, DC 20375 (United States)

    2007-04-15

    Increasingly requirements on the thin film quality of functionalized materials are efficiently met by a novel laser processing technique - Matrix Assisted Pulsed Laser Evaporation (MAPLE). Examples of deposition conditions and main features characteristic to film growth rate of MAPLE-fabricated organic materials are summarized. MAPLE experimental results are compared with ones corresponding to the classical Pulsed Laser Deposition (PLD). In particular, the results of investigation of MAPLE-deposited fibrinogen blood protein thin films using a KrF* excimer laser and characterized by FTIR and Raman spectrometry are reported.

  5. Effect of postharvest handling practices on phytochemical concentrations and bioactive potential in wild blueberry fruit

    Science.gov (United States)

    In this study, we quantified anthocyanin (ANC), proanthocyanidin (PAC), and chlorogenic acid (CA) concentrations in wild blueberry fruit (WBB) exposed to a variety of postharvest handling practices relevant to consumers and to industry. Additionally, we analyzed the bioactive potential of WBB subjec...

  6. Inverse correlation between fibrinogen and bone mineral density in women: Preliminary findings.

    Science.gov (United States)

    Chen, Jui-Tung; Kotani, Kazuhiko

    2016-01-01

    Hemostatic factors may be involved in bone health. The present preliminary study investigated the association between plasma fibrinogen and bone mineral density (BMD) in perimenopausal women. A significant inverse correlation between fibrinogen and BMD was observed (correlation coefficient = -0.42, p high level of high-sensitivity C-reactive protein than in that with a low level of high-sensitivity C-reactive protein, and in the subgroup with a high level of diacron reactive oxygen metabolites (an oxidative stress marker) than in that with a low level of diacron reactive oxygen metabolites. Thus, fibrinogen may be a possible marker of BMD in this population. More studies on the associations among hemostasis, inflammation, oxidative stress, and bone metabolism are warranted in the clinical setting.

  7. Interaction of platelets, fibrinogen and endothelial cells with plasma deposited PEO-like films

    Science.gov (United States)

    Yang, Zhilu; Wang, Jin; Li, Xin; Tu, Qiufen; Sun, Hong; Huang, Nan

    2012-02-01

    For blood-contacting biomedical implants like retrievable vena cava filters, surface-based diagnostic devices or in vivo sensors, limiting thrombosis and cell adhesion is paramount, due to a decrease even failure in performance. Plasma deposited PEO-like films were investigated as surface modifications. In this work, mixed gas composed of tetraethylene glycol dimethyl ether (tetraglyme) vapor and oxygen was used as precursor. It was revealed that plasma polymerization under high ratio of oxygen/tetraglyme led to deposition of the films that had high content of ether groups. This kind of PEO-like films had good stability in phosphate buffer solution. In vitro hemocompatibility and endothelial cell (EC) adhesion revealed low platelet adhesion, platelet activation, fibrinogen adhesion, EC adhesion and proliferation on such plasma deposited PEO-like films. This made it a potential candidate for the applications in anti-fouling surfaces of blood-contacting biomedical devices.

  8. Concentrations of thiocyanate and goitrin in human plasma, their precursor concentrations in brassica vegetables, and associated potential risk for hypothyroidism.

    Science.gov (United States)

    Felker, Peter; Bunch, Ronald; Leung, Angela M

    2016-04-01

    Brassica vegetables are common components of the diet and have beneficial as well as potentially adverse health effects. Following enzymatic breakdown, some glucosinolates in brassica vegetables produce sulforaphane, phenethyl, and indolylic isothiocyanates that possess anticarcinogenic activity. In contrast, progoitrin and indolylic glucosinolates degrade to goitrin and thiocyanate, respectively, and may decrease thyroid hormone production. Radioiodine uptake to the thyroid is inhibited by 194 μmol of goitrin, but not by 77 μmol of goitrin. Collards, Brussels sprouts, and some Russian kale (Brassica napus) contain sufficient goitrin to potentially decrease iodine uptake by the thyroid. However, turnip tops, commercial broccoli, broccoli rabe, and kale belonging to Brassica oleracae contain less than 10 μmol of goitrin per 100-g serving and can be considered of minimal risk. Using sulforaphane plasma levels following glucoraphanin ingestion as a surrogate for thiocyanate plasma concentrations after indole glucosinolate ingestion, the maximum thiocyanate contribution from indole glucosinolate degradation is estimated to be 10 μM, which is significantly lower than background plasma thiocyanate concentrations (40-69 μM). Thiocyanate generated from consumption of indole glucosinolate can be assumed to have minimal adverse risks for thyroid health.

  9. Crevice Repassivation Potentials for Alloy 22 in Simulated Concentrated Ground Waters

    Energy Technology Data Exchange (ETDEWEB)

    Rebak, R B; Evans, K J; Ilevbare, G O

    2006-11-08

    The resistance of Alloy 22 (N06022) to localized corrosion, mainly crevice corrosion, has been extensively investigated in the last few years. However, the behavior of Alloy 22 in concentrated aqueous solutions that may simulate concentrated ground waters was not fully understood. Systematic electrochemical tests using cyclic potentiodynamic polarization as well as the Tsujikawa-Hisamatsu electrochemical method were performed to determine the crevice corrosion susceptibility of Alloy 22 in simulated concentrated water (SCW), simulated acidified water (SAW) and basic saturated water (BSW). Results show that Alloy 22 is immune to crevice corrosion in SCW and SAW but may suffer crevice corrosion initiation in BSW. Results also show that in a naturally aerated environment, the corrosion potential would never reach the critical potential for crevice corrosion initiation.

  10. Albumin removal from human fibrinogen preparations for manufacturing human fibrin-based biomaterials

    Directory of Open Access Journals (Sweden)

    Vaibhav Sharma

    2015-01-01

    Full Text Available Commercially available two component human fibrin sealants are commonly used to manufacture human fibrin-based biomaterials. However, this method is costly and allows little room for further tuning of the biomaterial. Human fibrinogen solutions offer a more cost-effective and versatile alternative to manufacture human fibrin-based biomaterials. Yet, human fibrinogen is highly unstable and contains certain impurities like human albumin. Within the context of biomaterials and tissue engineering we offer a simple yet novel solution based on classical biochemical techniques to significantly reduce albumin in human fibrinogen solutions. This method can be used for various tissue engineering and biomedical applications as an initial step in the manufacturing of human fibrin-based biomaterials to optimise their regenerative application.

  11. Are fibrinogen and complete blood count parameters predictive in incarcerated abdominal hernia repair?

    Science.gov (United States)

    Kahramanca, Sahin; Kaya, Oskay; Ozgehan, Gulay; Guzel, Hakan; Azili, Cem; Gokce, Emre; Kucukpinar, Tevfik; Kulacoglu, Hakan

    2014-01-01

    Therapeutic delays in cases of external incarcerated hernias typically result in increasing morbidity, mortality, and health expenditures. We investigated the diagnostic role of blood fibrinogen level, white blood count (WBC), mean platelet volume (MPV), and platelet distribution width (PDW) in patients with incarcerated hernia. Two groups, each containing 100 patients, were studied. Group A underwent elective, and group B underwent incarcerated and urgent external hernia repair. We observed high fibrinogen and WBC levels but low MPV and PDW values for patients in group B. Contrary to our expectations, we found lower MPV and PDW values in the complicated group than in the elective group. The morbidity rate and cost burden were higher in group B, and the results were statistically significant. Early operation should be recommended for patients with incarcerated external hernias if their fibrinogen and WBC levels are high.

  12. cyp2c19基因多态性、高水平FIB对氯吡格雷抗凝效应的相关性研究%Study on correlation between cyp2c19 gene polymorphisms and high concentration of fibrinogen with clopidogrel resistance

    Institute of Scientific and Technical Information of China (English)

    李勤琴

    2016-01-01

    Objective To investigate the relationship between cyp2c19 gene polymorphisms and high concentration of fibrinogen with clopidogrel anticoagulation effect in the patients with coronary atherosclerotic heart disease (CAHD) .Methods A total of 611 CAHD patients taking oral clopidogrel in our hospital from May 2015 to November 2015 were selected and their cyp2c19 gene char‐acteristics and the fibrinogen(FIB)levels were analyzed .The patients were divided into the cyp2c19 gene homozygote strong metab‐olism group(n=261) ,heterozygote strong metabolim group(n=272)and weak metabolism group(n=78) .In all the cases ,408 cases were detected the coagulation indicators and divided into the high FIB level group (n=116) ,normal FIB level group (n=224)and low FIB level group(n=68);then re‐divided into the cyp2c19 gene weak metabolism and high FIB level group(n=24) ,the cyp2c19 gene homozygote strong metabolism and high FIB level group (n=48)and cyp2c19 gene heterozygote strong metabolism and high FIB level group(n=48) .The thrombin time(TT)was compared among 3 groups .Results cyp2c19 genotypes were *1/*1 ,*1/*2 ,*1/*3 ,*2/*2 ,*2/*3 and *3/*3 .The gene chip detection found that the above genotypes had 261 cases(42 .7% )of cyp2c19* 1/* 1 ,235 cases (38 .4% ) of cyp2c19 * 1/* 2 ,6% 37 cases (6 .0% ) of cyp2c19 * 1/* 3 ,60 cases (9 .8% ) of cyp2c19*2/*2 ,17 cases(2 .9% )of cyp2c19*2/*3 and 1 case(0 .2% )of cyp2c19*3/*3 .The cyp2c19 *1 ,*2 and *3 allele frequencies were 65 .0% (794/1 222) ,30 .5% (373/1 222)and 4 .5% (55/1 222)respectively ;The homozygote strong metabolism group accounted for 42 .7% (n=261) ,the heterozygote strong metabolism group accounted for 44 .4% (n=272)and the weak me‐tabolism group accounted for 12 .9% (n=78) .The TT level had no statistical difference between the high FIB level group and the normal FIB level group(P=0 .400 8);no matter homozygote or heterozygote ,the cyp2c19 gene strong metabolism type had more sensitivity to the clopidogrel

  13. Localization and distribution of fibrinogen C domain containing 1 (FIBCD1) in human tissues

    DEFF Research Database (Denmark)

    von Huth, Sebastian; Møller, Jesper Bonnet; Schlosser, Anders

    in an immunohistochemistry-based analysis and demonstrate that FIBCD1 protein is highly expressed at the apical surfaces of the epithelium throughout the gastrointestinal tract, in the uterus, testis, bladder, gallbladder and the salivary glands. To a lesser extent, FIBCD1 is expressed in the pancreas, the spleen......Introduction: We have previously identified and characterized fibrinogen C domain-containing 1 (FIBCD1) as a homotetrameric type II transmembrane protein. FIBCD1 is a member of the fibrinogen- related protein (FReP) family, and is thought to play a crucial role in the innate immune system...

  14. Challenges of the management of severe hemophilia A with inhibitors: two case reports emphasizing the potential interest of a high-purity human Factor VIII/von Willebrand factor concentrate and individually tailored prophylaxis guided by thrombin-generation test.

    Science.gov (United States)

    Mathieu, Sophie; Crampe, Carine; Dargaud, Yesim; Lavigne-Lissalde, Géraldine; Escuriola-Ettingshausen, Carmen; Tardy, Brigitte; Meley, Roland; Thouvenin, Sandrine; Stephan, Jean L; Berger, Claire

    2015-12-01

    Severe hemophilia A is an X-linked bleeding disorder. Immune tolerance induction (ITI) is the best strategy of treatment when patients develop inhibitors. The objective is to illustrate the benefit of a high-purity human factor VIII/von Willebrand factor (VWF) concentrate (Octanate) in the management of ITI. We also wanted to raise the potential interest of laboratory assays such as thrombin-generation test (TGT) and epitope mapping. Two patients were treated during ITI, first with a recombinant FVIII and then with plasma-derived factor VIII without success, and, finally, with Octanate. Bypassing agents were used based on the results of TGT. Epitope mapping was performed during ITI therapy. These observations suggest the potential contribution of Octanate in the management of ITI in difficult cases. The use of bypassing agents can be necessary in prophylaxis or to treat bleedings, and may be guided by TGT results. Epitope mapping is used to describe the inhibitor. This article shows a decrease of the inhibitor directed against the C2 domain after initiation of Octanate. A high-purity human factor VIII/von Willebrand factor concentrate (Octanate) may be a valuable therapeutical option for ITI therapy. TGT and epitope mapping could be of help in the management of ITI.

  15. Bone marrow concentrate for autologous transplantation in minipigs. Characterization and osteogenic potential of mesenchymal stem cells.

    Science.gov (United States)

    Herten, M; Grassmann, J P; Sager, M; Benga, L; Fischer, J C; Jäger, M; Betsch, M; Wild, M; Hakimi, M; Jungbluth, P

    2013-01-01

    Autologous bone marrow plays an increasing role in the treatment of bone, cartilage and tendon healing disorders. Cell-based therapies display promising results in the support of local regeneration, especially therapies using intra-operative one-step treatments with autologous progenitor cells. In the present study, bone marrow-derived cells were concentrated in a point-of-care device and investigated for their mesenchymal stem cell (MSC) characteristics and their osteogenic potential. Bone marrow was harvested from the iliac crest of 16 minipigs. The mononucleated cells (MNC) were concentrated by gradient density centrifugation, cultivated, characterized by flow cytometry and stimulated into osteoblasts, adipocytes, and chondrocytes. Cell differentiation was investigated by histological and immunohistological staining of relevant lineage markers. The proliferation capacity was determined via colony forming units of fibroblast and of osteogenic alkaline-phosphatase-positive-cells. The MNC could be enriched 3.5-fold in nucleated cell concentrate in comparison to bone marrow. Flow cytometry analysis revealed a positive signal for the MSC markers. Cells could be differentiated into the three lines confirming the MSC character. The cellular osteogenic potential correlated significantly with the percentage of newly formed bone in vivo in a porcine metaphyseal long-bone defect model. This study demonstrates that bone marrow concentrate from minipigs display cells with MSC character and their osteogenic differentiation potential can be used for osseous defect repair in autologous transplantations.

  16. Fibrinogen adsorption onto 316L stainless steel under polarized conditions.

    Science.gov (United States)

    Gettens, Robert T T; Gilbert, Jeremy L

    2008-04-01

    Adsorption of the plasma protein fibrinogen onto electrically polarized 316L stainless steel was observed and quantified using both in situ and ex situ atomic force microscopy (AFM) techniques. Significant differences in fibrinogen adsorption were observed across voltages. Ex situ studies showed significantly lower area coverage (theta) and height of adsorbed Fb on cathodically polarized surfaces when compared to anodically polarized surfaces. Conformational differences in the protein may explain the distinctions in Fb surface area coverage (theta) and height between the anodic and cathodic cases. In situ studies showed significantly slower kinetics of Fb adsorption onto surfaces below -100 mV (vs. Ag/AgCl) compared to surfaces polarized above -100 mV. Electrochemical current density data showed large charge transfer processes (approximately 1 x 10(-5) to 1 x 10(-4) A/cm(2)) taking place on the 316L SS surfaces at voltages below -100 mV (vs. Ag/AgCl). These relatively large current densities point to flux of ionic species away from the surface as a major source of the reduction in adsorption kinetics rather than just hydrophilic or electrostatic effects.

  17. Pre-treatment and ethanol fermentation potential of olive pulp at different dry matter concentrations

    DEFF Research Database (Denmark)

    Haagensen, Frank Drøscher; Skiadas, Ioannis V.; Gavala, Hariklia N.

    2009-01-01

    potential of the olive pulp, which is the semi solid residue generated from the two-phase processing of the olives for olive oil production. Wet oxidation and enzymatic hydrolysis have been applied aiming at the enhancement of carbohydrates' bioavailability. Different concentrations of enzymes and enzymatic......, implying that wet oxidation is not a recommended pre-treatment process for olive pulp at the conditions tested. It was also showed that increased dry matter concentration did not have a negative effect on the release of sugars, indicating that the cellulose and xylan content of the olive pulp is relatively...

  18. Hemostatic, milk clotting and blood stain removal potential of cysteine proteases from Calotropis gigantea (L. R. Br. Latex

    Directory of Open Access Journals (Sweden)

    Omana Sukumaran Bindhu

    2014-01-01

    Full Text Available Introduction: Plant latex is a natural source of biologically active compounds and several hydrolytic enzymes responsible for their diverse health benefits. Recent past has witnessed substantial progress in understanding their supplementary industrial and pharmaceutical utility. Calotropis gigantea is one of the important latex producing plants belonging to asclepediaceae family with wide ethnopharmacological applications and is rich in proteolytic enzymes. Present study investigates hemostatic, milk clotting and blood stain removal potential of C. gigantea latex proteases. Materials and Methods: The protease activity of crude enzyme (CE, obtained by centrifugation followed by ammonium sulphate precipitation and dialysis, was assayed using casein as the substrate. Effect of pH, temperature and specific inhibitors on protease activity was determined. Native PAGE and in gel protease activity of CE was performed. Hemostatic (Fibrinogen polymerization, fibrinogen agarose plate and blood clot lysis assays, milk clotting and blood stain removal efficacies of CE were determined. Results: CE exhibited high caseinolytic activity. Enzyme activity was optimum at 37-50ºC and pH 8.0. Fibrinogen polymerization assay showed concentration dependent increase in turbidity indicating thrombin like activity which was further confirmed by fibrinogen agarose plate assays. Clot lysis assay indicated 92.41% thrombolysis by CE in 90 min. CE also revealed significantly high ratio of milk clotting to protease activity (Milk Clotting Index, MCI = 827.59 ± 1.52. Complete destaining of blood stained fabric was observed when incubated with 1% detergent incorporated with 0.1mg/ml CE. The study highlights and validates the compound application potential of latex cysteine proteases from C. gigantea.

  19. Tethering of Ficolin-1 to cell surfaces through recognition of sialic acid by the fibrinogen-like domain

    DEFF Research Database (Denmark)

    Honore, C.; Rorvig, S.; Hummelshoj, T.;

    2010-01-01

    surface is restricted to monocytes and granulocytes. Ficolin-1 is tethered to the cell surface of these cells through its fibrinogen-like domain, and the ligand involved in the binding of Ficolin-1 is shown to be sialic acid. Moreover, rFicolin-1 bound activated but not resting T lymphocytes. Together......, these results demonstrate a novel self-recognition mechanism of leukocytes mediated by the fibrinogen-like domain of Ficolin-1....

  20. Plasma levels of thrombomodulin, plasminogen activator inhibitor-1 and fibrinogen in elderly, diabetic patients with depressive symptoms

    OpenAIRE

    2015-01-01

    Background Diabetes, depression and aging have been associated with pro-inflammatory and prothrombotic state. Aim The aim of the study was to determine the plasma levels of thrombomodulin, plasminogen activator inhibitor-1 (PAI-1) and fibrinogen in elderly diabetic patients with and without depressive symptoms and to examine factors (including thrombomodulin, PAI-1, fibrinogen levels) associated with depressive symptoms in elderly patients with type 2 diabetes (T2DM). Methods A total of 276 T...

  1. Tumor necrosis factor (TNF) is induced in mice by Candida albicans: role of TNF in fibrinogen increase.

    Science.gov (United States)

    Riipi, L; Carlson, E

    1990-09-01

    One intraperitoneal dose of Candida albicans (10(8) CFU) caused a chronic (longer than 2 months), significant elevation of plasma fibrinogen levels (Clauss method) in mice of strain C3H/HeN. Even a small dose (10(6) CFU) resulted in a significant increase in fibrinogen level for 5 days following injection, whereas other blood parameters (leukocytes, erythrocytes, platelets, hematocrit, hemoglobin, blood urea nitrogen, aspartate aminotransferase, albumin, alkaline phosphatase, antithrombin III, glucose, calcium, and total protein) measured by standard methods were normal. Blood taken during this period was negative for C. albicans. The role of tumor necrosis factor (TNF) in C. albicans infections was investigated by measuring the fibrinogen response after the administration of C. albicans or recombinant mouse TNF-alpha. Both challenges resulted in an elevated fibrinogen level. When polyclonal antibodies to mouse TNF-alpha were given prior to challenge with C. albicans or mouse TNF-alpha, the fibrinogen increase was significantly inhibited. C. albicans injections were found to significantly elevate endogenous TNF levels in mice (enzyme-linked immunosorbent assay). It was concluded that C. albicans induces TNF in the mouse. Furthermore, these data give evidence which supports a relationship between TNF and the fibrinogen increase induced by C. albicans.

  2. Fibrinogen gene haplotypes in relation to risk of coronary events and coronary and extracoronary atherosclerosis: the Rotterdam Study.

    Science.gov (United States)

    Kardys, Isabella; Uitterlinden, André G; Hofman, Albert; Witteman, Jacqueline C M; de Maat, Moniek P M

    2007-02-01

    Fibrin network structure has been correlated with coronary disease. Fibrinogen gamma and alpha (FGG and FGA) gene haplotypes (chromosome 4q28) may be associated with fibrin network structure, and thereby with rigidity of the fibrin clot and sensitivity of the fibrin clot to the fibrinolytic system. Through these mechanisms they may influence risk of cardiovascular disease. We set out to investigate the relation between combined fibrinogen FGG and FGA gene haplotypes, representing the common variation of the fibrinogen FGG and FGA genes, coronary events and measures of coronary and extracoronary atherosclerosis. The study was embedded in the Rotterdam Study, a prospective population-based study among men and women aged >or=55 years. Common haplotypes were studied using seven tagging SNPs across a 30-kb region with the FGG and FGA genes. Incident coronary events were registered, and carotid intima-media thickness, carotid plaques, ankle-arm index, aortic calcification and coronary calcification were assessed. Seven haplotypes with frequencies >1% covered 97.5% of the genetic variation. In 5,667 participants without history of coronary heart disease (CHD), 733 CHD cases occurred during a median follow-up time of 11.9 years. Fibrinogen gene haplotypes were not associated with coronary events. Fibrinogen gene haplotypes did not show a consistent association with measures of coronary and extracoronary atherosclerosis. In conclusion, fibrinogen FGG and FGA gene haplotypes are not associated with coronary events, coronary atherosclerosis or extracoronary atherosclerosis. Confirmation of these findings by future population-based studies is warranted.

  3. Concentration of field and skim latex by microfiltration - membrane fouling and biochemical methane potential of serum.

    Science.gov (United States)

    Thongmak, Narumol; Sridang, Porntip; Puetpaiboon, Udomphon; Grasmick, Alain

    2015-01-01

    Cross-flow microfiltration was used to concentrate field and skim latex suspensions and recover the smallest compounds (proteins, sugars, etc.) in permeate (serum solutions). The experiments were performed in a lab-scale microfiltration unit equipped with ceramic membranes. In continuous mode, the operations were performed at constant trans-membrane pressure (0.5 bars), constant cross-flow velocity (3 m/s) and constant temperature (28 ± 2°C). In retentate, the volumetric concentration factor was only close to 2 (about 54% of total solid content, TSC) when concentrating the field latex suspensions, and it reached 10 (close to 40% TSC) when concentrating skim latex suspensions. The quality of retentate suspensions let envisage a significant potential of industrial valorization. The membrane fouling rates appeared as an increasing function of dry rubber content suspension, and the main fouling origin (94%) was linked to a reversible accumulation of suspended compounds on the membrane surface. Permeate appeared as a clear yellow solution containing the smallest soluble organic fractions that show a high degree of biodegradability when using biochemical methane potential tests. The chemical oxygen demand (COD) removal was then higher than 92% and the methane production yield was close to 0.29 NLCH4/gCODremoved. The association of a membrane separation step and anaerobic digestion appeared, then, as a relevant solution to recover rubber content from skim latex suspensions and energy from the anaerobic digestion of serum.

  4. Radioiodine concentrated in a wetland.

    Science.gov (United States)

    Kaplan, Daniel I; Zhang, Saijin; Roberts, Kimberly A; Schwehr, Kathy; Xu, Chen; Creeley, Danielle; Ho, Yi-Fang; Li, Hsiu-Ping; Yeager, Chris M; Santschi, Peter H

    2014-05-01

    Most subsurface environmental radioactivity contamination is expected to eventually resurface in riparian zones, or wetlands. There are a number of extremely sharp biogeochemical interfaces in wetlands that could alter radionuclide speciation and promote accumulation. The objective of this study was to determine if a wetland concentrated (129)I emanating from a former waste disposal basin located on the Savannah River Site (SRS) in South Carolina, USA. Additionally, studies were conducted to evaluate the role of sediment organic matter in immobilizing the radioiodine. Groundwater samples were collected along a 0.7-km transect away from the seepage basin and in the downstream wetlands. The samples were analyzed for (129)I speciation (iodide (I(-)), iodate (IO3(-)), and organo-I). Groundwater (129)I concentrations in many locations in the wetlands (as high as 59.9 Bq L(-1)(129)I) were greatly elevated with respect to the source term (5.9 Bq L(-1)(129)I). (129)I concentration profiles in sediment cores were closely correlated to organic matter concentrations (r(2) = 0.992; n = 5). While the sediment organic matter promoted the uptake of (129)I to the wetland sediment, it also promoted the formation of a soluble organic fraction: 74% of the wetland groundwater (129)I could pass through a 1 kDa (wetlands may be highly effective at immobilizing aqueous (129)I, they may also promote the formation of a low-molecular-weight organic species that does not partition to sediments. This study provides a rare example of radioactivity concentrations increasing rather than decreasing as it migrates from a point source and brings into question assumptions in risk models regarding continuous dilution of released contaminants.

  5. Osmotic potential calculations of inorganic and organic aqueous solutions over wide solute concentration levels and temperatures

    Energy Technology Data Exchange (ETDEWEB)

    Cochrane, T. T., E-mail: agteca@hotmail.com [AGTECA S.A., 230 Oceanbeach Road, Mount Maunganui, Tauranga 3116 (New Zealand); Cochrane, T. A., E-mail: tom.cochrane@canterbury.ac.nz [Department of Civil and Natural Resources Engineering, University of Canterbury, Private Bag 4800, Christchurch 8140 (New Zealand)

    2016-01-15

    Purpose: To demonstrate that the authors’ new “aqueous solution vs pure water” equation to calculate osmotic potential may be used to calculate the osmotic potentials of inorganic and organic aqueous solutions over wide ranges of solute concentrations and temperatures. Currently, the osmotic potentials of solutions used for medical purposes are calculated from equations based on the thermodynamics of the gas laws which are only accurate at low temperature and solute concentration levels. Some solutions used in medicine may need their osmotic potentials calculated more accurately to take into account solute concentrations and temperatures. Methods: The authors experimented with their new equation for calculating the osmotic potentials of inorganic and organic aqueous solutions up to and beyond body temperatures by adjusting three of its factors; (a) the volume property of pure water, (b) the number of “free” water molecules per unit volume of solution, “N{sub f},” and (c) the “t” factor expressing the cooperative structural relaxation time of pure water at given temperatures. Adequate information on the volume property of pure water at different temperatures is available in the literature. However, as little information on the relative densities of inorganic and organic solutions, respectively, at varying temperatures needed to calculate N{sub f} was available, provisional equations were formulated to approximate values. Those values together with tentative t values for different temperatures chosen from values calculated by different workers were substituted into the authors’ equation to demonstrate how osmotic potentials could be estimated over temperatures up to and beyond bodily temperatures. Results: The provisional equations formulated to calculate N{sub f}, the number of free water molecules per unit volume of inorganic and organic solute solutions, respectively, over wide concentration ranges compared well with the calculations of N{sub f

  6. [Study on the selective removal of plasma low-density lipoprotein and fibrinogen by degraded guar sulfate].

    Science.gov (United States)

    Zhu, Ye; Fang, Bo; Huang, Li; Guan, Chen; Yang, Guang

    2008-10-01

    Degraded guar was prepared by acid with guar as the main material, which was then brought into reaction with chlorosulfonic acid under proper conditions, the sulfonated degraded guar was obtained successfully. The effects of sulfonation conditions on the SO4(2-) content were investigated, and the proper reaction conditions were determined. The results of infrared spectrometry showed that this sulfated derivative is a novel heparin-like polysaccharide. At the same time, the selective removal of low density lipoprotein (LDL) and fibrinogen (Fib) by degraded guar gum sulfate was studied. The experimental results showed that degraded guar gum sulfate is a novel LDL/ Fib purifying agent. When pH= 5.15 and the initial concentration of the degraded guar gum sulfate is 2500 mg/L, the reduction percentages were about 60%-66% for total cholesterol, about 76%-89% for LDL and very low-density lipoproteins (VLDL), and almost 100% for fibrinogen. There were no significant changes regarding the level of high-density lipoproteins and total proteins.

  7. Effect of Pyramidal Training on Plasma Lipid Profile and Fibrinogen, and Blood Viscosity of Untrained Young Men

    Directory of Open Access Journals (Sweden)

    Abbass Ghanbari-Niaki

    2013-09-01

    Full Text Available The present study examined the effects of progressive exercise (pyramidal short-term program on plasma fibrinogen, lipid profile and blood viscosity in untrained young men. Changes and imbalances in homeostasis lead to cause of heart attacks. There is conflicting information about the effect of exercise on these factors. 19 young healthy untrained men were randomly assigned to the exercise group (n = 10 and controls (n = 9 groups. Exercise training group with increasing severity of heart maximum 25 to 100 percent began to run the practice (pyramid in 42-minute sessions, 3 times a week, for 4 weeks. There was no significant difference between the parameters of body composition, control, and training groups. Levels of total cholesterol and low density lipoprotein density and viscosity of the blood significantly decreased in the training group compared with the control group (p value, respectively is 0.001, 0.001 and 0.035. The changes in the concentration of fibrinogen, high-density lipoprotein and triglycerides in both groups are not significant in both groups (p value, respectively is 0.645, 0.993 and 0.421. The present results show that it is possible that progressive training (pyramidal short-term program changed the levels of cardiovascular risk factors by reducing blood viscosity.

  8. Urinary bisphenol A concentrations in pregnant women.

    Science.gov (United States)

    Callan, Anna Carita; Hinwood, Andrea Lee; Heffernan, Amy; Eaglesham, Geoff; Mueller, Jochen; Odland, Jon Øyvind

    2013-11-01

    Bisphenol A is a chemical that is present in a number of products and types of food packaging. Prenatal exposure to bisphenol A may cause behavioural changes in young children. The aim of this study was to investigate exposure to bisphenol A in pregnant Australian women as a surrogate of neonatal exposure. First morning void urine samples were collected from 26 pregnant women at around week 38 of gestation. Bisphenol A was detectable in 85% of the samples analysed. The median concentration in this group of women was 2.41μg/L with a range of bisphenol A concentrations, as did women with a pre-pregnancy BMI of bisphenol A exposure in Australia and reveals that pregnant women have measured biological concentrations of urinary bisphenol A similar to those reported for pregnant women in other developed countries. Given the potential impacts of prenatal bisphenol A exposure, further research in this area is warranted.

  9. Crystal structure of the fibrinogen-like recognition domain of FIBCD1

    DEFF Research Database (Denmark)

    Møller, Jesper Bonnet; Schlosser, Anders; Sørensen, Grith Lykke;

    The high resolution crystal structures of a recombinant fragment of the C-terminal fibrinogen-related domain of FIBCD1, a vertebrate chitin receptor, have been determined. The overall structure shows similarity in structure and aggregation to the homologous innate immune protein tachylectin 5A...

  10. Potentially toxic concentrations of synthetic pyrethroids associated with low density residential land use

    Directory of Open Access Journals (Sweden)

    Stephen Marshall

    2016-11-01

    Full Text Available Trace organic compounds associated with human activity are now ubiquitous in the environment. As the population becomes more urbanised and the use of pesticides and person care products continues to increase, urban waterways are likely to receive higher loads of trace organic contaminants with unknown ecological consequences. To establish the extent of trace organic contamination in urban runoff, concentrations of emerging chemicals of concern were determined in sediments from 99 urban wetlands in and around Melbourne, Australia between February and April, 2015. As a preliminary estimation of potential risks to aquatic biota, we compared measured concentrations with thresholds for acute and chronic toxicity, and modelled toxic units as a function of demographic and land use trends. The synthetic pyrethroid insecticide bifenthrin was common and widespread, and frequently occurred at concentrations likely to cause toxicity to aquatic life. Personal care products DEET and triclosan were common and widely distributed, while the herbicides diuron and prometryn, and the fungicides pyrimethanil and trifloxystrobin occurred less frequently. Toxic unit modelling using random forests found complex and unexpected associations between urban land uses and trace organic concentrations. Synthetic pyrethroid insecticides were identified as emerging compounds of concern, particularly bifenthrin. In contrast with previous surveys, the highest bifenthrin concentrations were associated with lower housing and population density, implicating low-density residential land use in bifenthrin contamination. We discuss the implications for pesticide regulation and urban wetland management in a global context.

  11. Effects of Fungicide Treatment on Free Amino Acid Concentration and Acrylamide-Forming Potential in Wheat.

    Science.gov (United States)

    Curtis, Tanya Y; Powers, Stephen J; Halford, Nigel G

    2016-12-28

    Acrylamide forms from free asparagine and reducing sugars during frying, baking, roasting, or high-temperature processing, and cereal products are major contributors to dietary acrylamide intake. Free asparagine concentration is the determining factor for acrylamide-forming potential in cereals, and this study investigated the effect of fungicide application on free asparagine accumulation in wheat grain. Free amino acid concentrations were measured in flour from 47 varieties of wheat grown in a field trial in 2011-2012. The wheat had been supplied with nitrogen and sulfur and treated with growth regulators and fungicides. Acrylamide formation was measured after the flour had been heated at 180 °C for 20 min. Flour was also analyzed from 24 (of the 47) varieties grown in adjacent plots that were treated in identical fashion except that no fungicide was applied, resulting in visible infection by Septoria tritici, yellow rust, and brown rust. Free asparagine concentration in the fungicide-treated wheat ranged from 1.596 to 3.987 mmol kg(-1), with a significant (p acrylamide formation, which ranged from 134 to 992 μg kg(-1). There was a significant (p acrylamide formation. Both free asparagine concentration and acrylamide formation increased in response to a lack of fungicide treatment, the increases in acrylamide ranging from 2.7 to 370%. Free aspartic acid concentration also increased, whereas free glutamic acid concentration increased in some varieties but decreased in others, and free proline concentration decreased. The study showed disease control by fungicide application to be an important crop management measure for mitigating the problem of acrylamide formation in wheat products.

  12. Study of albumin and fibrinogen membranes formed by interfacial crosslinking using microfluidic flow

    Energy Technology Data Exchange (ETDEWEB)

    Chang Hong; Khan, Rachel; Rong, Zimei; Vadgama, Pankaj [IRC in Biomedical Materials, Queen Mary University of London, Mile End Road, London E1 4NS (United Kingdom); Sapelkin, Andrei, E-mail: p.vadgama@qmul.ac.u [Department of Physics, Queen Mary University of London, Mile End Road, London E1 4NS (United Kingdom)

    2010-09-15

    Microfluidics enables scale reduction in sample volume with obvious benefits for reagent conservation. In contrast to conventional macro-scale flow, microfluidics also offers unprecedented control over flow dynamics. In particular, laminar flow is readily achieved, allowing for new analytical and synthetic strategies. Here, two parallel flows of buffer and xylene were used to create a stable liquid-liquid interface within linear micro-channels. These, respectively, carried protein (albumin or fibrinogen) and an acyl chloride to effect protein crosslinking. This created robust, micro-membranes at the interface that bisected the fluid channel. Membrane formation was self-limiting, with fibrinogen membranes showing greater solute permeability than albumin, based on dye transport (Ponceau S, Meldola Blue). The crosslinker isophthaloyl dichloride led to thinner, less permeable membranes than terephthaloyl chloride. Larger surface area membranes formed at a static liquid-liquid interface served as a more physically accessible model and allowed precise electrochemical determination of acetaminophen, catechol and peroxide diffusion coefficients, which confirmed the greater fibrinogen permeability. Scanning electron microscopy (SEM) of the membranes also indicated a higher population of discrete nanopores at the fibrinogen surface. A crosslinking pH had a strong effect on overall permeability. Adhesion of B50 neuronal cells was demonstrated, and it is proposed that the membranes could facilitate cell growth through bidirectional nutrient supply in a micrbioreactor format.

  13. Multivariate analysis of potential biomarkers of oxidative stress in Notopterus notopterus tissues from Mahanadi River as a function of concentration of heavy metals.

    Science.gov (United States)

    Mohanty, Deepali; Samanta, Luna

    2016-07-01

    In this study, investigation were done on the Mahanadi River water and health of dwelling Indian Knife fish Notopterus notopterus from three sites along the course of the river in an around Cuttack city (Odisha). Oxidative stress biomarker assays such as thiobarbituric acid reactive substances, protein carbonyls, protein and non-protein thionyls, reduced glutathione, metallothionein, superoxide dismutase, catalase, glutathione peroxidase/reductase couple, glutathione-S-transferase, and tissue metal (Fe, Cu, Ni, Cd, Pb and Zn) levels along with water quality assessments were assayed to measure the impacts on fish health. Results indicate that except Fe all other metals studied were within approved limits for fish liver and gill as approved by FAO/WHO. However, the muscle tissue do not have any metal beyond the permissible limit. A site and tissue specific response of the above mentioned oxidative biomarkers as well as metal accumulation in the fish tissues were noticed. Lipid peroxidation and protein carbonylation were increased gradually in the fish tissues collected from experimental sites along the course of the River in comparison to upstream reference site. Glutathione-S-transferase, glutathione peroxidase/reductase couple, reduced glutathione and non-protein thiol content were significantly decreased in fish tissues from experimental sites. An increase in metallothionein content was observed while superoxide dismutase and catalase showed tissue specific responses. Multivariate (Discriminant Function) analysis revealed that lipid peroxidation, protein carbonylation and superoxide dismutase have highest association as predictors of impact in the muscle and liver while that for gill is protein carbonylation, superoxide dismutase and glutathione reductase. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Beyond genetic factors in familial amyloidotic polyneuropathy: protein glycation and the loss of fibrinogen's chaperone activity.

    Directory of Open Access Journals (Sweden)

    Gonçalo da Costa

    Full Text Available Familial amyloidotic polyneuropathy (FAP is a systemic conformational disease characterized by extracellular amyloid fibril formation from plasma transthyretin (TTR. This is a crippling, fatal disease for which liver transplantation is the only effective therapy. More than 80 TTR point mutations are associated with amyloidotic diseases and the most widely accepted disease model relates TTR tetramer instability with TTR point mutations. However, this model fails to explain two observations. First, native TTR also forms amyloid in systemic senile amyloidosis, a geriatric disease. Second, age at disease onset varies by decades for patients bearing the same mutation and some mutation carrier individuals are asymptomatic throughout their lives. Hence, mutations only accelerate the process and non-genetic factors must play a key role in the molecular mechanisms of disease. One of these factors is protein glycation, previously associated with conformational diseases like Alzheimer's and Parkinson's. The glycation hypothesis in FAP is supported by our previous discovery of methylglyoxal-derived glycation of amyloid fibrils in FAP patients. Here we show that plasma proteins are differentially glycated by methylglyoxal in FAP patients and that fibrinogen is the main glycation target. Moreover, we also found that fibrinogen interacts with TTR in plasma. Fibrinogen has chaperone activity which is compromised upon glycation by methylglyoxal. Hence, we propose that methylglyoxal glycation hampers the chaperone activity of fibrinogen, rendering TTR more prone to aggregation, amyloid formation and ultimately, disease.

  15. Increased thrombin generation and fibrinogen level after therapeutic plasma transfusion: relation to bleeding.

    NARCIS (Netherlands)

    Schols, S.E.; Meijden, PE van der; Oerle, R. van; Curvers, J.; Heemskerk, J.W.M.; Pampus, EC van

    2008-01-01

    In a clinical setting, fresh frozen plasma (FFP) is transfused to diluted patients with complicated surgery or trauma, as guided by prolonged conventional coagulation times or low fibrinogen levels. However, the limited sensitivity of these coagulation tests may restrict their use in measuring the e

  16. Effects of nitrogen ion implantation on Ca2+ concentration and membrane potential of pollen cell

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The effects of low energy nitrogen ion implantation on Ca2+ concentration and membrane potential of lily (lilium davidii Duch) pollen cell have been studied. The results showed that the Ca2+ concentration was increased when pollen grain was implanted by nitrogen ion with energy 100keV and dose 1013 ions/cra2. However, the increase of Ca2+ concentration was partly inhibited by the addition of Ca2+channel inhibitor depending on dose. And nitrogen ion implantation caused depolarization of pollen cell membrane potential. In other words, membrane potential was increased,but the effect decreased by adding Ca2+ channel inhibitor.However, it was still significantly higher than the membrane potential of control cells. It was indicated that the depolarization of cell membrane potential opened the calcium channel on the membrane that caused the increasing of intraceilular calcium concentration. This might be an earlier step of the effect of low energy nitrogen ion implantation on pollen germination.

  17. Rapid evaluation of fibrinogen levels using the CG02N whole blood coagulation analyzer.

    Science.gov (United States)

    Hayakawa, Mineji; Gando, Satoshi; Ono, Yuichi; Mizugaki, Asumi; Katabami, Kenichi; Maekawa, Kunihiko; Miyamoto, Daisuke; Wada, Takeshi; Yanagida, Yuichiro; Sawamura, Atsushi

    2015-04-01

    Rapid evaluation of fibrinogen (Fbg) levels is essential for maintaining homeostasis in patients with massive bleeding during severe trauma and major surgery. This study evaluated the accuracy of fibrinogen levels measured by the CG02N whole blood coagulation analyzer (A&T Corporation, Kanagawa, Japan) using heparinized blood drawn for blood gas analysis (whole blood-Fbg). A total of 100 matched pairs of heparinized blood samples and citrated blood samples were simultaneously collected from patients in the intensive care unit. Whole blood-Fbg results were compared with those of citrated plasma (standard-Fbg). The whole blood coagulation analyzer measured fibrinogen levels within 2 minutes. Strong correlations between standard-Fbg and whole blood-Fbg were observed (ρ = 0.91, p blood-Fbg was 0.980 (95% confidence interval 0.951-1.000, p blood coagulation analyzer can rapidly measure fibrinogen levels in heparinized blood and could be useful in critical care settings where excessive bleeding is a concern.

  18. Assessing breeding potential of peregrine falcons based on chlorinated hydrocarbon concentrations in prey

    Energy Technology Data Exchange (ETDEWEB)

    Elliott, J.E. [Canadian Wildlife Service, Pacific Wildlife Research Centre, 5421 Robertson Rd., RR no. 1, Delta, British Columbia, V4K 3N2 (Canada)]. E-mail: john.elliott@ec.gc.ca; Miller, M.J. [Iolaire Ecological Consulting, 7899 Thrasher St., Mission, British Columbia, V2V 5H3 (Canada); Wilson, L.K. [Canadian Wildlife Service, Pacific Wildlife Research Centre, 5421 Robertson Rd., RR no. 1, Delta, British Columbia, V4K 3N2 (Canada)

    2005-03-01

    Peregrine falcons (Falco peregrinus) now breed successfully in most areas of North America from which they were previously extirpated. The loss during the mid-part of the last century of many of the world's peregrine populations was largely a consequence of impaired reproduction caused by the effects of DDE on eggshell quality and embryo hatchability. Population recovery has been attributed to re-introduction efforts, coupled with regulatory restrictions on the use of organochlorine pesticides. Peregrines have not returned to breed in some areas, such as the Okanagan Valley of British Columbia. That region has been extensively planted in fruit orchards which were treated annually with DDT during the early 1950s to the 1970s. Ongoing contamination of avian species, including potential peregrine prey, inhabiting orchards has been documented. In response to an initiative to release peregrines around the city of Kelowna in the Okanagan Valley, we collected potential peregrine prey species and analyzed whole bodies for chlorinated hydrocarbon residues. We used a simple bioaccumulation model to predict concentrations of DDE in peregrine eggs using concentrations in prey and estimates of dietary makeup as input. Peregrines would be expected to breed successfully only if they fed on a diet primarily of doves. Feeding on as little as 10% of other species such as starlings, robins, gulls and magpies would produce DDE concentrations in peregrine eggs greater than the threshold of 15 mg/kg. We also estimated the critical concentration of DDE in total prey to be about 0.5 mg/kg, one half of the previous most conservative criterion for peregrine prey. Concentrations of dieldrin and PCBs in peregrine prey are less than suggested critical levels. - Based on the level of DDE contamination of prey items, it seems unlikely that peregrine falcons could breed successfully throughout most of the Okanagan Valley of British Columbia.

  19. Oleic acid-induced lung injury in rabbits: effect of fibrinogen depletion with Arvin

    Energy Technology Data Exchange (ETDEWEB)

    Allard, M.F.; Doerschuk, C.M.; Brumwell, M.L.; Belzberg, A.; Hogg, J.C.

    1988-03-01

    The role of fibrinogen in the evolution of the increased permeability after oleic acid-induced lung injury was studied in New Zealand White rabbits. Animals depleted of fibrinogen by treatment with Malayan pit viper venom were compared with untreated rabbits immediately and at 1 and 24 h after injury. The increased permeability to albumin and elevated extravascular lung water (EVLW) associated with lung injury returned to control values by 24 h in untreated animals. Fibrinogen-depleted animals had a higher mortality (10/25 vs. 2/17, P less than 0.02) and showed a greater immediate increase in permeability to albumin that returned to control values at 1 and 24 h after injury, as well as trends toward elevated blood-free dry lung weight and larger increases in EVLW that persisted for 24 h. These findings indicate that fibrinogen-related proteins play an important role in controlling the microvascular injury that is produced by oleic acid. However, when these proteins are depleted, other mechanisms partially control the leak at later stages of the repair process.

  20. Elevated plasma fibrinogen, psychological distress, antidepressant use, and hospitalization with depression

    DEFF Research Database (Denmark)

    Wium-Andersen, Marie Kim; Ørsted, David Dynnes; Nordestgaard, Børge Grønne

    2013-01-01

    OBJECTIVES: Low-grade systemic inflammation may contribute to the development of depression. We tested the hypothesis that elevated plasma levels of the inflammatory marker fibrinogen are associated with psychological distress, use of antidepressant medication, and with hospitalization with depre......OBJECTIVES: Low-grade systemic inflammation may contribute to the development of depression. We tested the hypothesis that elevated plasma levels of the inflammatory marker fibrinogen are associated with psychological distress, use of antidepressant medication, and with hospitalization...... with depression in the general population. METHODS: We examined 73,367 20-100 year old men and women from two large population-based studies, the Copenhagen General Population Study and the Copenhagen City Heart Study. We measured plasma fibrinogen and recorded symptoms of psychological distress, use...... of antidepressant medication, and hospitalization with depression in both cross-sectional and prospective studies. RESULTS: In cross-sectional analyses, a stepwise increase in fibrinogen percentile categories was associated with a stepwise increase in risk of psychological distress, use of antidepressant medication...

  1. Effect of genetic background and diet on plasma fibrinogen in mice. Possible relation with susceptibility to atherosclerosis

    NARCIS (Netherlands)

    Rezaee, F.; Maas, A.; Maat, M.P.M.de; Verheijen, J.H.; Koopman, J.

    2002-01-01

    Many epidemiological studies suggest that elevated plasma fibrinogen concentrations form one of the most important independent risk factors in blood for cardiovascular disease and particularly atherosclerosis in humans. To clarify the effect of genetic factors, diets and their interactions on plasma

  2. Studies of electrochemical properties of compacted clays by concentration potential method.

    Science.gov (United States)

    Yaroshchuk, Andriy; Glaus, Martin A; Van Loon, Luc R

    2007-05-15

    The development of concentration (membrane) potential upon step-wise change in salt concentration has been studied for diaphragms made of various strongly compacted clays (montmorillonite, illite, kaolinite) equilibrated with 0.1 M NaCl solution. Porous ceramic filters were used to confine the clays mechanically to be able to achieve high extent of compaction (dry density approximately 2000 kg/m3). A theoretical analysis has revealed that the relaxation pattern is primarily controlled by the properties of porous filters and only slightly depends on the clay properties. At the same time, quasi-stationary values of concentration potential are directly related to the electrochemical perm-selectivity of clay. This property has revealed considerable differences in the electrochemical behaviour of various clays used in this study. This has been attributed to the differences in the micro-structure of clays, in particular to the existence or nonexistence of the so-called interlayer water where cations may retain some mobility. It has also been shown that in clays with high electrochemical perm-selectivity, one can expect a strong increase in the diffusivity of cationic radio-tracers with decreasing ionic strength of equilibrium electrolyte solution. At the same time, low electrochemical perm-selectivity means no noticeable dependence of this kind. The correctness of this observation has been corroborated by the comparison of our findings with the literature data on the diffusion of cationic radio-tracers through compacted montmorillonite (high perm-selectivity) and kaolinite (low perm-selectivity). To check the self-consistency of our approach, we have also carried out sample measurements of diffusion of cationic and anionic radio-tracers through compacted illite. It has been found that the measured effective diffusion coefficients were in excellent agreement with the electrochemical perm-selectivity estimated for this clay from the measurements of concentration potential.

  3. A time-varying magnetic flux concentrator

    Science.gov (United States)

    Kibret, B.; Premaratne, M.; Lewis, P. M.; Thomson, R.; Fitzgerald, P. B.

    2016-08-01

    It is known that diverse technological applications require the use of focused magnetic fields. This has driven the quest for controlling the magnetic field. Recently, the principles in transformation optics and metamaterials have allowed the realization of practical static magnetic flux concentrators. Extending such progress, here, we propose a time-varying magnetic flux concentrator cylindrical shell that uses electric conductors and ferromagnetic materials to guide magnetic flux to its center. Its performance is discussed based on finite-element simulation results. Our proposed design has potential applications in magnetic sensors, medical devices, wireless power transfer, and near-field wireless communications.

  4. Design and development of a high-concentration photovoltaic concentrator

    Energy Technology Data Exchange (ETDEWEB)

    Hodge, R C

    1982-04-01

    The design and development of a high concentration photovoltaic concentrator module is discussed. The design concept described herein incorporates a curved groove domed Fresnel lens, a high concentration etched multiple vertical junction (EMVJ) solar cell and a passively cooled direct-bonded copper cell mount all packaged in a plastic module. Two seven inch diameter 1200x domed Fresnel lenses were fabricated using single point diamond turning technology. Testing at both GE and Sandia confirmed optical transmission efficiencies of over 83%. Samples of the latest available EMVJ cells were mounted and installed, with a domed Fresnel lens, into a prototype module. Subsequent testing demonstrated net lens-cell efficiencies of 10 to 13%. As a result of this program, salient conclusions have been formulated as to this technology.

  5. Real Time Monitoring of Dissolved Organic Carbon Concentration and Disinfection By-Product Formation Potential in a Surface Water Treatment Plant with Simulaneous UV-VIS Absorbance and Fluorescence Excitation-Emission Mapping

    Science.gov (United States)

    Gilmore, A. M.

    2015-12-01

    This study describes a method based on simultaneous absorbance and fluorescence excitation-emission mapping for rapidly and accurately monitoring dissolved organic carbon concentration and disinfection by-product formation potential for surface water sourced drinking water treatment. The method enables real-time monitoring of the Dissolved Organic Carbon (DOC), absorbance at 254 nm (UVA), the Specific UV Absorbance (SUVA) as well as the Simulated Distribution System Trihalomethane (THM) Formation Potential (SDS-THMFP) for the source and treated water among other component parameters. The method primarily involves Parallel Factor Analysis (PARAFAC) decomposition of the high and lower molecular weight humic and fulvic organic component concentrations. The DOC calibration method involves calculating a single slope factor (with the intercept fixed at 0 mg/l) by linear regression for the UVA divided by the ratio of the high and low molecular weight component concentrations. This method thus corrects for the changes in the molecular weight component composition as a function of the source water composition and coagulation treatment effects. The SDS-THMFP calibration involves a multiple linear regression of the DOC, organic component ratio, chlorine residual, pH and alkalinity. Both the DOC and SDS-THMFP correlations over a period of 18 months exhibited adjusted correlation coefficients with r2 > 0.969. The parameters can be reported as a function of compliance rules associated with required % removals of DOC (as a function of alkalinity) and predicted maximum contaminant levels (MCL) of THMs. The single instrument method, which is compatible with continuous flow monitoring or grab sampling, provides a rapid (2-3 minute) and precise indicator of drinking water disinfectant treatability without the need for separate UV photometric and DOC meter measurements or independent THM determinations.

  6. In vitro properties and in vivo behavior of technetium-99m labeled fibrinogens

    Energy Technology Data Exchange (ETDEWEB)

    Karube, Yoshiharu; Ito, Sanae; Katsuno, Kentaro; Takata, Jiro [Fukuoka Univ. (Japan). Faculty of Pharmaceutical Sciences

    1996-02-01

    Fibrinogen was labeled with Tc-99m by two methods and the in vitro stability and in vivo behavior in mice were studied. The Tc-99m labeling was performed by mixing an unreduced fibrinogen (UnFib) or a reduced fibrinogen (ReFib) with Tc-99m pertechnetate in the presence of stannous chloride. In both of them, chelation with Tc-99m resulted in a single radiochemical product. For the in vitro stability studies, Tc-99m labeled fibrinogen (Tc-99m UnFib) was prepared with UnFib, and transchelation with cysteine solution was easy to produce compared to Tc-99m labeled fibrinogen (Tc-99m ReFib) prepared with ReFib. The radioactivity bound to clottable protein for Tc-99m UnFib and Tc-99m ReFib was about 70% and about 69%, respectively. The in vivo behavior of these labeled fibrinogens was studied, and their efficiencies for imaging an abscess and Ehrlich tumor in mice were determined with a gamma camera. Technetium-99m UnFib underwent a rapid partial exchange of the Tc-99m with compounds of the blood buffer system in vivo, resulting in early urinary excretion. On the other hand, the fraction of Tc-99m ReFib that remained intact in vivo was biologically active and would be incorporated into the abscess and tumor. The uptake in the abscess increased slightly over time with Tc-99m ReFib, but the abscess to blood and abscess to muscle ratios were 0.09 and 2.6 at 5 hr, respectively. Clearly delineated images of the abscess were obtained beginning at about 5 hr after injection. The tumor to blood and tumor to muscle ratios were 0.05 and 1.4 at 5 hr, respectively. The Ehrlich tumor image in mice was slightly visible at 10 hr. The short half-life of Tc-99m was inappropriate for fibrinogen with a low pharmacokinetic value, because it was necessary for imaging of the abscess and tumor to take a long time. (author).

  7. Fast Measurement of Methanol Concentration in Ionic Liquids by Potential Step Method

    Directory of Open Access Journals (Sweden)

    Michael L. Hainstock

    2015-01-01

    Full Text Available The development of direct methanol fuel cells required the attention to the electrolyte. A good electrolyte should not only be ionic conductive but also be crossover resistant. Ionic liquids could be a promising electrolyte for fuel cells. Monitoring methanol was critical in several locations in a direct methanol fuel cell. Conductivity could be used to monitor the methanol content in ionic liquids. The conductivity of 1-butyl-3-methylimidazolium tetrafluoroborate had a linear relationship with the methanol concentration. However, the conductivity was significantly affected by the moisture or water content in the ionic liquid. On the contrary, potential step could be used in sensing methanol in ionic liquids. This method was not affected by the water content. The sampling current at a properly selected sampling time was proportional to the concentration of methanol in 1-butyl-3-methylimidazolium tetrafluoroborate. The linearity still stood even when there was 2.4 M water present in the ionic liquid.

  8. Surface modification with poly(sulfobetaine methacrylate-co-acrylic acid) to reduce fibrinogen adsorption, platelet adhesion, and plasma coagulation.

    Science.gov (United States)

    Kuo, Wei-Hsuan; Wang, Meng-Jiy; Chien, Hsiu-Wen; Wei, Ta-Chin; Lee, Chiapyng; Tsai, Wei-Bor

    2011-12-12

    Zwitterionic sulfobetaine methacrylate (SBMA) polymers were known to possess excellent antifouling properties due to high hydration capacity and neutral charge surface. In this study, copolymers of SBMA and acrylic acid (AA) with a variety of compositions were synthesized and were immobilized onto polymeric substrates with layer-by-layer polyelectrolyte films via electrostatic interaction. The amounts of platelet adhesion and fibrinogen adsorption were determined to evaluate hemocompatibility of poly(SBMA-co-AA)-modified substrates. Among various deposition conditions by modulating SBMA ratio in the copolymers and pH of the deposition solution, poly(SBMA(56)-co-AA(44)) deposited at pH 3.0 possessed the best hemocompatibility. This work demonstrated that poly(SBMA-co-AA) copolymers adsorbed on polyelectrolyte-base films via electrostatic interaction improve hemocompatibility effectively and are applicable for various substrates including TCPS, PU, and PDMS. Furthermore, poly(SBMA-co-AA)-coated substrate possesses great durability under rigorous conditions. The preliminary hemocompatibility tests regarding platelet adhesion, fibrinogen adsorption, and plasma coagulation suggest the potential of this technique for the application to blood-contacting biomedical devices.

  9. Fibrinogen and ceruloplasmin in plasma and milk from dairy cows with subclinical and clinical mastitis.

    Science.gov (United States)

    Tabrizi, A Davasaz; Batavani, R A; Rezaei, S Asri; Ahmadi, M

    2008-02-15

    The potential using of Acute Phase Proteins (APPs) in the assessment of mammary gland health was studied by examining the levels of Fibrinogen (Fb) and Ceruloplasmin (Cp) in plasma and milk from dairy cows with different grades of mastitis. Plasma samples were taken from jugular vein and milk samples were collected from quarters of cows with subclinical and clinical mastitis, as well as healthy controls. California Mastitis Test (CMT) were performed on each udder quarter of cows for detection of CMT2+ and CMT3+ quarters. CMT (0) and culture negative cases were considered healthy cows. Clinical mastitis, was graded as mild (clots in milk) or moderate (clots in milk and visible signs of inflammation in the mammary gland/s). The concentrations of Fb in the plasma of the cows with subclinical and clinical mastitis were higher than in the plasma of the healthy cows (p0.05), but differences between clinical and healthy groups were significant (pmastitis were higher than in the milk of the healthy cows (pmastitis in dairy cows.

  10. Relevance of plasma fibrinogen estimation in obstetric complications.

    Directory of Open Access Journals (Sweden)

    Parasnis H

    1992-10-01

    Full Text Available We present a study of fibrinogen levels in 133 patients who were prone to develop disseminated intravascular coagulation as a result of an underlying complication of pregnancy such as abruptio placentae, pregnancy-induced hypertension, missed abortion, septic abortion, intrauterine fetal death, vesicular mole and amniotic fluid embolism. A high incidence of hypofibrinogenemia was found in cases of abruptio placentae (43.9% and pregnancy-induced hypertension (25%. Hypofibrinogenemia occurred in 10% cases of intrauterine fetal death within 4 weeks of fetal demise. The use of this simple investigation makes possible the diagnosis of hemostatic failure and also helps to guide replacement therapy during the fibrinopenic state. There were 4 maternal deaths and 12 perinatal losses in this study.

  11. Clinical and Prognostic Significance of Preoperative Plasma Fibrinogen Levels in Patients with Operable Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Yu Mei

    Full Text Available Elevated plasma fibrinogen levels are associated with tumor progression and poor outcomes in different cancer patients. The objective of this study was to investigate the clinical and prognostic value of preoperative plasma fibrinogen levels in patients with operable breast cancer.Two hundred and twenty-three patients diagnosed with breast cancer were retrospectively evaluated in this study. Plasma fibrinogen levels were examined before treatment and analyzed along with patient clinicopathological parameters, disease-free survival (DFS and overall survival (OS. Both univariate and multivariate analyses were performed to identify the clinicopathological parameters associated with DFS and OS.Elevated preoperative plasma fibrinogen levels were directly associated with age of diagnose (≤47 vs. >47, p<0.001, menopause (yes vs. no, p<0.001, tumor size (T1&T2 vs. T3&T4, p = 0.033, tumor stage (I vs. II vs. III, p = 0.034 and lymph node involvement (N = 0 vs. 1≤N≤3 vs. N≥4, p<0.001, but not with histological grade, molecular type and other Immunohistochemical parameters (ER, PR, HER2 and Ki-67. In a univariate survival analysis, tumor stage, tumor size, lymph node involvement (p<0.001/p<0.001 and plasma fibrinogen (p<0.001/p<0.0