Microangiopathic antiphospholipid antibody syndrome due to anti-phosphatidylserine/prothrombin complex IgM antibody.

PubMed

Senda, Yumi; Ohta, Kazuhide; Yokoyama, Tadafumi; Shimizu, Masaki; Furuichi, Kengo; Wada, Takashi; Yachie, Akihiro

2017-03-01

Herein we describe a case of microangiopathic antiphospholipid syndrome (MAPS) due to anti-phosphatidylserine/prothrombin complex (aPS/PT) IgM antibody successfully treated with rituximab. A significant correlation was observed between the clinical course and the aPS/PT IgM antibody titer, which can rise earlier before the appearance of clinical symptoms. Rituximab can be safely and effectively used for MAPS. Although detection of only aPS/PT IgM antibody is rare, aPS/PT IgM antibody might be associated with the pathogenesis of MAPS and might be a useful marker of disease activity. © 2017 Japan Pediatric Society.

Structural architecture of prothrombin in solution revealed by single molecule spectroscopy

DOE PAGES

Pozzi, Nicola; Bystranowska, Dominika; Zuo, Xiaobing; ...

2016-07-19

The coagulation factor prothrombin has a complex spatial organization of its modular assembly that comprises the N-terminal Gla domain, kringle-1, kringle-2, and the C-terminal protease domain connected by three intervening linkers. Here we use single molecule Förster resonance energy transfer to access the conformational landscape of prothrombin in solution and uncover structural features of functional significance that extend recent x-ray crystallographic analysis. Prothrombin exists in equilibrium between two alternative conformations, open and closed. The closed conformation predominates (70%) and features an unanticipated intramolecular collapse of Tyr 93 in kringle-1 onto Trp 547 in the protease domain that obliterates access tomore » the active site and protects the zymogen from autoproteolytic conversion to thrombin. The open conformation (30%) is more susceptible to chymotrypsin digestion and autoactivation, and features a shape consistent with recent x-ray crystal structures. Small angle x-ray scattering measurements of prothrombin wild type stabilized 70% in the closed conformation and of the mutant Y93A stabilized 80% in the open conformation directly document two envelopes that differ 50 Å in length. These findings reveal important new details on the conformational plasticity of prothrombin in solution and the drastic structural difference between its alternative conformations. Prothrombin uses the intramolecular collapse of kringle-1 onto the active site in the closed form to prevent autoactivation. As a result, the open-closed equilibrium also defines a new structural framework for the mechanism of activation of prothrombin by prothrombinase.« less

Structural Architecture of Prothrombin in Solution Revealed by Single Molecule Spectroscopy.

PubMed

Pozzi, Nicola; Bystranowska, Dominika; Zuo, Xiaobing; Di Cera, Enrico

2016-08-26

The coagulation factor prothrombin has a complex spatial organization of its modular assembly that comprises the N-terminal Gla domain, kringle-1, kringle-2, and the C-terminal protease domain connected by three intervening linkers. Here we use single molecule Förster resonance energy transfer to access the conformational landscape of prothrombin in solution and uncover structural features of functional significance that extend recent x-ray crystallographic analysis. Prothrombin exists in equilibrium between two alternative conformations, open and closed. The closed conformation predominates (70%) and features an unanticipated intramolecular collapse of Tyr(93) in kringle-1 onto Trp(547) in the protease domain that obliterates access to the active site and protects the zymogen from autoproteolytic conversion to thrombin. The open conformation (30%) is more susceptible to chymotrypsin digestion and autoactivation, and features a shape consistent with recent x-ray crystal structures. Small angle x-ray scattering measurements of prothrombin wild type stabilized 70% in the closed conformation and of the mutant Y93A stabilized 80% in the open conformation directly document two envelopes that differ 50 Å in length. These findings reveal important new details on the conformational plasticity of prothrombin in solution and the drastic structural difference between its alternative conformations. Prothrombin uses the intramolecular collapse of kringle-1 onto the active site in the closed form to prevent autoactivation. The open-closed equilibrium also defines a new structural framework for the mechanism of activation of prothrombin by prothrombinase. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Increased risk of volume overload with plasma compared with four‐factor prothrombin complex concentrate for urgent vitamin K antagonist reversal

PubMed Central

Refaai, Majed A.; Goldstein, Joshua N.; Lee, Martin L.; Durn, Billie L.; Milling, Truman J.; Sarode, Ravi

2015-01-01

BACKGROUND Plasma is commonly used for vitamin K antagonist (VKA) reversal, but observational studies suggest that it is associated with transfusion‐related adverse reactions (e.g., volume overload). However, this issue has not previously been addressed in a randomized controlled trial (RCT). STUDY DESIGN AND METHODS Factors associated with volume overload were examined using data from two Phase IIIb RCTs comparing plasma with four‐factor prothrombin complex concentrate (4F‐PCC, Beriplex/Kcentra, CSL Behring) for urgent VKA reversal. VKA‐treated patients with major bleeding (NCT00708435) or requiring an urgent surgical or invasive procedure (NCT00803101) were randomly assigned (1:1) to receive either plasma or 4F‐PCC, concomitant with vitamin K. Adverse events (AEs) and serious AEs were prospectively captured up to Day 10 and 45, respectively. Volume overload predictors were evaluated on a univariate and multivariate basis. RESULTS A total of 388 patients (4F‐PCC, n = 191; plasma, n = 197) were enrolled. Volume overload occurred in 34 (9%) patients (4F‐PCC, n = 9; plasma, n = 25). In univariate analyses, use of plasma (vs. 4F‐PCC), use of nonstudy plasma and/or platelets, race, history of congestive heart failure (CHF), and history of renal disease were associated with volume overload. In multivariate analyses, use of plasma (vs. 4F‐PCC), history of CHF, and history of renal disease were independent volume overload predictors. In an additional analysis restricted to volume overload events recorded up to Day 7, only use of plasma (vs. 4F‐PCC) was an independent volume overload predictor. CONCLUSIONS After adjusting for other potential risk factors, plasma use was independently associated with a greater risk of volume overload than 4F‐PCC in patients requiring urgent VKA reversal. PMID:26135740

Decarboxylation of bovine prothrombin fragment 1 and prothrombin.

PubMed

Tuhy, P M; Bloom, J W; Mann, K G

1979-12-25

Bovine prothrombin fragment 1 and prothrombin undergo decarboxylation of their gamma-carboxyglutamic acid residues when the lyophilized proteins are heated in vacuo at 110 degrees C for several hours. The fully decarboxylated fragment 1 product has lost its barium-binding ability as well as the calcium-binding function which causes fluorescence quenching in the presence of 2 mM Ca2+. There is no sign of secondary structure alteration in solution upon analysis by fluorescence emission and circular dichroic spectroscopy. A family of partially decarboxylated fragment 1 species generated by heating for shorter periods shows that the initial decrease in calcium-binding ability occurs almost twice as rapidly as the loss of gamma-carboxyglutamic acid. This is consistent with the idea that differential functions can be ascribed to the 10 gamma-carboxyglutamic acid residues in fragment 1, including both high- and low-affinity metal ion binding sites. Prothrombin itself also undergoes total decarboxylation without any apparent alteration in secondary structure. However, in this case the latent thrombin activity is progressively diminished during the heating process in terms of both clotting activity and hydrolysis of the amide substrate H-D-Phe-Pip-Arg-pNA. The present results indicate that in vitro decarboxylation of gamma-carboxyglutamic acid in dried proteins is useful for analyzing the detailed calcium-binding proteins of vitamin K dependent coagulation factors.

The Story of Serum Prothrombin Conversion Accelerator, Proconvertin, Stable Factor, Cothromboplastin, Prothrombin Accelerator or Autoprothrombin I, and Their Subsequent Merging into Factor VII.

PubMed

Girolami, Antonio; Cosi, Elisabetta; Santarossa, Claudia; Ferrari, Silvia; Luigia Randi, Maria

2015-06-01

Factor VII (FVII) deficiency is one of the two congenital coagulation disorders that was not discovered by the description of a new bleeding patient whose clotting pattern did not fit the blood coagulation knowledge of the time (the other is factor XIII deficiency). The existence of an additional factor capable of accelerating the conversion of prothrombin into thrombin was suspected before 1951, the year in which the first family with FVII deficiency was discovered. As several investigators were involved in the discovery of FVII deficiency from both sides of the Atlantic, several different names were tentatively suggested to define this entity, namely stable factor (in contrast with labile factor or FV), cothromboplastin, proconvertin, serum prothrombin conversion accelerator, prothrombin acceleration, and autoprothrombin I. The last term was proposed by those who denied the existence of this new entity, which was instead considered to be a derivate of prothrombin activation, namely autoprothrombin. The description of several families, from all over the world, of the same defect, however clearly demonstrated the singularity of the condition. Factor VII was then proposed to define this protein. In subsequent years, several variants were described with peculiar reactivity toward tissue thromboplastins of different origin. Molecular biology techniques demonstrated several gene mutations, usually missense mutations, often involving exon 8 of the FVII gene. Later studies dealt with the relation of FVII with tissue factor and activated FVII (FVIIa). The evaluation of circulating FVIIa was made possible by the use of a truncated form of tissue factor, which is only sensitive to FVIIa present in the circulation. The development of FVII concentrates, both plasma derived and recombinant, has facilitated therapeutic management of FVII-deficient patients. The use of FVIIa concentrates was noted to be associated with the occasional occurrence of thrombotic events, mainly

GROWTH INHIBITORY ACTIONS OF PROTHROMBIN ON NORMAL HEPATOCYTES

PubMed Central

Carr, Brian I.; Kar, Siddhartha; Wang, Meifang; Wang, Ziqiu

2007-01-01

Most hepatomas have a defect in prothrombin carboxylation, and can secrete under-carboxylated prothrombin or des-γ-carboxy-prothrombin (DCP), the function of which is unknown. We considered that prothrombin-DCP axis might also be involved in growth control. Hepatocytes and hepatoma cells were treated with prothrombin, and DNA synthesis and cytoskeleton were studied. Prothrombin inhibited DNA synthesis in hepatocytes on fibronectin, but not collagen matrix. Hepatoma cell lines were not inhibited. We found that hepatoma cell matrix conferred resistance to hepatocytes. Prothrombin decreased fibronectin but not collagen amounts, but only in the presence of hepatocytes and not hepatoma cells, indicating that it has a differential action on matrix proteins. It also caused changes in cell shape and actin depolymerization. In vivo, there was a decrease in plasma prothrombin activity after a partial hepatectomy (PH) concomitant with a peak of DNA synthesis by the hepatocyte at 24 h after PH. Injection of warfarin at the time of PH, further inhibited PT activity and enhanced this 24 h peak of DNA synthesis. Furthermore, repeated injection of prothrombin lowered the peak DNA synthesis after PH. The data support the hypothesis that prothrombin can act as a hepatocyte growth inhibitor, likely at the level of fibronectin loss and result in cytoskeletal changes. Hepatomas resist this action, possibly due to their different matrix proteins. This represents a novel mechanism for growth regulation and provides a possible biological significance for the tumor marker DCP. PMID:17490900

21 CFR 866.5735 - Prothrombin immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5735 Prothrombin immunological test system. (a) Identification. A prothrombin immunological test system is a device... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Prothrombin immunological test system. 866.5735...

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

PubMed

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

2018-01-01

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

Safety of 4-factor prothrombin complex concentrate (4F-PCC) for emergent reversal of factor Xa inhibitors.

PubMed

Tao, Jing; Bukanova, Elena N; Akhtar, Shamsuddin

2018-01-01

Although factor Xa inhibitors have become a popular choice for chronic oral anticoagulation, effective drug reversal remains difficult due to a lack of specific antidote. Currently, 4-factor prothrombin complex concentrate (4F-PCC) is considered the treatment of choice for factor Xa inhibitor-related major bleeding. However, safety of 4F-PCC and its risk of thrombosis when used for this off-label purpose remain unclear. The purpose of this retrospective study is to determine the rate of thromboembolism when 4F-PCC is used for the emergent reversal of factor Xa inhibitors. We conducted a single-center retrospective review of medical records between 2013 and 2017. Patients were included if they received 4F-PCC to reverse rivaroxaban, apixaban, or edoxaban for emergent invasive procedures or during episodes of major bleeding defined as bleeding with hemodynamic instability, fall in hemoglobin of 2 g/dL, or bleeding requiring blood transfusion. Thrombotic events including myocardial infarction, pulmonary embolism, deep vein thrombosis, cerebral vascular accident, and arterial thrombosis of the limb or mesentery were recorded if they occurred within 14 days of 4F-PCC administration. Data was analyzed using point and interval estimation to approximate the rate and confidence interval of thromboembolic events. Forty-three patients were identified in our review. Doses of 4F-PCC were determined by the treating physician and mainly ranged from 25 to 50 IU/kg. Twenty-two patients (51.2%) received both sequential compression devices (SCDs) and subcutaneous heparin for DVT prophylaxis. Twenty-one patients (48.8%) were placed on SCDs only. Three patients received concomitant FFP. Thrombotic events within 14 days of 4F-PCC administration occurred in 1 out of 43 patients (2.1%, 95% CI [0.1-12.3]). This thrombotic event was an upper extremity DVT which occurred 1 day after the patient received 1325 IU (25 IU/kg) of 4F-PCC to reverse rivaroxaban for traumatic intracranial

Simultaneous characterization of lateral lipid and prothrombin diffusion coefficients by z-scan fluorescence correlation spectroscopy.

PubMed

Stefl, Martin; Kułakowska, Anna; Hof, Martin

2009-08-05

A new (to our knowledge) robust approach for the determination of lateral diffusion coefficients of weakly bound proteins is applied for the phosphatidylserine specific membrane interaction of bovine prothrombin. It is shown that z-scan fluorescence correlation spectroscopy in combination with pulsed interleaved dual excitation allows simultaneous monitoring of the lateral diffusion of labeled protein and phospholipids. Moreover, from the dependencies of the particle numbers on the axial sample positions at different protein concentrations phosphatidylserine-dependent equilibrium dissociation constants are derived confirming literature values. Increasing the amount of membrane-bound prothrombin retards the lateral protein and lipid diffusion, indicating coupling of both processes. The lateral diffusion coefficients of labeled lipids are considerably larger than the simultaneously determined lateral diffusion coefficients of prothrombin, which contradicts findings reported for the isolated N-terminus of prothrombin.

Prothrombin activation on the activated platelet surface optimizes expression of procoagulant activity

PubMed Central

Wood, Jeremy P.; Silveira, Jay R.; Maille, Nicole M.; Haynes, Laura M.

2011-01-01

Effective hemostasis relies on the timely formation of α-thrombin via prothrombinase, a Ca2+-dependent complex of factors Va and Xa assembled on the activated platelet surface, which cleaves prothrombin at Arg271 and Arg320. Whereas initial cleavage at Arg271 generates the inactive intermediate prethrombin-2, initial cleavage at Arg320 generates the enzymatically active intermediate meizothrombin. To determine which of these intermediates is formed when prothrombin is processed on the activated platelet surface, the cleavage of prothrombin, and prothrombin mutants lacking either one of the cleavage sites, was monitored on the surface of either thrombin- or collagen-activated platelets. Regardless of the agonist used, prothrombin was initially cleaved at Arg271 generating prethrombin-2, with α-thrombin formation quickly after via cleavage at Arg320. The pathway used was independent of the source of factor Va (plasma- or platelet-derived) and was unaffected by soluble components of the platelet releasate. When both cleavage sites are presented within the same substrate molecule, Arg271 effectively competes against Arg320 (with an apparent IC50 = 0.3μM), such that more than 90% to 95% of the initial cleavage occurs at Arg271. We hypothesize that use of the prethrombin-2 pathway serves to optimize the procoagulant activity expressed by activated platelets, by limiting the anticoagulant functions of the alternate intermediate, meizothrombin. PMID:21131592

Prothrombin activation on the activated platelet surface optimizes expression of procoagulant activity.

PubMed

Wood, Jeremy P; Silveira, Jay R; Maille, Nicole M; Haynes, Laura M; Tracy, Paula B

2011-02-03

Effective hemostasis relies on the timely formation of α-thrombin via prothrombinase, a Ca(2+)-dependent complex of factors Va and Xa assembled on the activated platelet surface, which cleaves prothrombin at Arg271 and Arg320. Whereas initial cleavage at Arg271 generates the inactive intermediate prethrombin-2, initial cleavage at Arg320 generates the enzymatically active intermediate meizothrombin. To determine which of these intermediates is formed when prothrombin is processed on the activated platelet surface, the cleavage of prothrombin, and prothrombin mutants lacking either one of the cleavage sites, was monitored on the surface of either thrombin- or collagen-activated platelets. Regardless of the agonist used, prothrombin was initially cleaved at Arg271 generating prethrombin-2, with α-thrombin formation quickly after via cleavage at Arg320. The pathway used was independent of the source of factor Va (plasma- or platelet-derived) and was unaffected by soluble components of the platelet releasate. When both cleavage sites are presented within the same substrate molecule, Arg271 effectively competes against Arg320 (with an apparent IC(50) = 0.3μM), such that more than 90% to 95% of the initial cleavage occurs at Arg271. We hypothesize that use of the prethrombin-2 pathway serves to optimize the procoagulant activity expressed by activated platelets, by limiting the anticoagulant functions of the alternate intermediate, meizothrombin.

A Retrospective Propensity Score-Matched Early Thromboembolic Event Analysis of Prothrombin Complex Concentrate vs Fresh Frozen Plasma for Warfarin Reversal Prior to Emergency Neurosurgical Procedures.

PubMed

Agarwal, Prateek; Abdullah, Kalil G; Ramayya, Ashwin G; Nayak, Nikhil R; Lucas, Timothy H

2017-06-29

Reversal of therapeutic anticoagulation prior to emergency neurosurgical procedures is required in the setting of intracranial hemorrhage. Multifactor prothrombin complex concentrate (PCC) promises rapid efficacy but may increase the probability of thrombotic complications compared to fresh frozen plasma (FFP). To compare the rate of thrombotic complications in patients treated with PCC or FFP to reverse therapeutic anticoagulation prior to emergency neurosurgical procedures in the setting of intracranial hemorrhage at a level I trauma center. Sixty-three consecutive patients on warfarin therapy presenting with intracranial hemorrhage who received anticoagulation reversal prior to emergency neurosurgical procedures were retrospectively identified between 2007 and 2016. They were divided into 2 cohorts based on reversal agent, either PCC (n = 28) or FFP (n = 35). The thrombotic complications rates within 72 h of reversal were compared using the χ 2 test. A multivariate propensity score matching analysis was used to limit the threat to interval validity from selection bias arising from differences in demographics, laboratory values, history, and clinical status. Thrombotic complications were uncommon in this neurosurgical population, occurring in 1.59% (1/63) of treated patients. There was no significant difference in the thrombotic complication rate between groups, 3.57% (1/28; PCC group) vs 0% (0/35; FFP group). Propensity score matching analysis validated this finding after controlling for any selection bias. In this limited sample, thrombotic complication rates were similar between use of PCC and FFP for anticoagulation reversal in the management of intracranial hemorrhage prior to emergency neurosurgical procedures. Copyright © 2017 by the Congress of Neurological Surgeons

21 CFR 864.7720 - Prothrombin consumption test.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Prothrombin consumption test. 864.7720 Section 864.7720 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7720 Prothrombin...

21 CFR 864.7720 - Prothrombin consumption test.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Prothrombin consumption test. 864.7720 Section 864.7720 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7720 Prothrombin...

21 CFR 864.7750 - Prothrombin time test.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Prothrombin time test. 864.7750 Section 864.7750 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7750 Prothrombin time...

21 CFR 864.7750 - Prothrombin time test.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Prothrombin time test. 864.7750 Section 864.7750 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7750 Prothrombin time...

21 CFR 864.7750 - Prothrombin time test.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Prothrombin time test. 864.7750 Section 864.7750 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7750 Prothrombin time...

21 CFR 864.7720 - Prothrombin consumption test.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Prothrombin consumption test. 864.7720 Section 864.7720 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7720 Prothrombin...

21 CFR 864.7720 - Prothrombin consumption test.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Prothrombin consumption test. 864.7720 Section 864.7720 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7720 Prothrombin...

21 CFR 864.7720 - Prothrombin consumption test.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Prothrombin consumption test. 864.7720 Section 864.7720 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7720 Prothrombin...

21 CFR 864.7750 - Prothrombin time test.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Prothrombin time test. 864.7750 Section 864.7750 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7750 Prothrombin time...

Comparison of the behavior of normal factor IX and the factor IX Bm variant Hilo in the prothrombin time test using tissue factors from bovine, human, and rabbit sources.

PubMed

Lefkowitz, J B; Monroe, D M; Kasper, C K; Roberts, H R

1993-07-01

A subset of hemophilia B patients have a prolonged bovine-brain prothrombin time. These CRM+ patients are classified as having hemophilia Bm. The prolongation of the prothrombin time has been reported only with bovine brain (referred to as ox brain in some literature) as the source of thromboplastin; prothrombin times determined with thromboplastin from rabbit brain or human brain are not reported to be prolonged. Factor IX from a hemophilia Bm patient (factor IX Hilo) was isolated. The activity of factor IX Hilo was compared to that of normal factor IX in prothrombin time assays when the thromboplastin source was of bovine, rabbit, or human origin. Factor IX, either normal or Hilo, prolonged a prothrombin time regardless of the tissue factor source. However, unless thromboplastin was from a bovine source, this prolongation required high concentrations of factor IX. Further, factor IX normal was as effective as factor IX Hilo in prolonging the prothrombin time when rabbit or human thromboplastin was used. With bovine thromboplastin, factor IX Hilo was significantly better than factor IX normal at prolonging the prothrombin time. The amount of prolongation was dependent on the amount of factor IX Hilo added. In addition, the prolongation was dependent on the concentration of factor X present in the sample. The prothrombin time changed as much as 20 seconds when the factor X concentration was varied from 50% to 150% to normal (fixed concentration of factor IX Hilo). These results demonstrate the difficulty of classifying the severity of a hemophilia Bm patient based on the bovine brain prothrombin time unless both the factor IX and factor X concentrations are known.

Cost-Effectiveness Analysis of Biogeneric Recombinant Activated Factor VII (AryoSeven™) and Activated Prothrombin Complex Concentrates (FEIBA™) to Treat Hemophilia A Patients with Inhibitors in Iran.

PubMed

Golestani, Mina; Eshghi, Peyman; Rasekh, Hamid Reza; Cheraghali, Abdoll Majid; Salamzadeh, Jamshid; Naderi, Majid; Managhchi, Mohammad Reza; Hoorfar, Hamid; Toogeh, Gholam Reza; Imani, Ali; Khodayari, Mohammad Taghi; Habibpanah, Behnaz; Hantooshzadeh, Razieh

2016-01-01

Nowadays, bypassing agents such as recombinant activated factor VII (rFVIIa) and activated prothrombin complex concentrates (aPCC) are used to treat bleeding episodes in the Hemophilia patients with inhibitors. AryoSeven® is an Iranian biogeneric rFVIIa with homogeneity of efficacy and the nature to NovoSeven in a comparative trial. The current clinical trial aimed to evaluate the cost-effectiveness of FEIBA and AryoSeven® by Decision Analytic Model according to the Iranian healthcare system. An open label, multi-center, cross-over clinical trial was designed. Patients were categorized into 3 groups based on their prior tendency to one or none of the products. To determine the premium therapeutic strategy, the Incremental cost-effectiveness ratio (ICER) was calculated. Protocol F led to more treatment success in group F than the other groups (P= 0.03). Also, there was a significant statistical difference between the mean of effectiveness scores in the groups using protocol F (P = 0.01). The effectiveness of protocol F and A were 89% and 72%, respectively. ICER cost US$ to manage an episode of bleeding to get one more unit of effectiveness using FEIBA VS. AryoSeven. Although the results showed that AryoSeven was more cost-effective compared to FEIBA, the two strategies were undominated. In other words, both medicines can be applied in the first line of the treatment if the cost of FEIBA was reduced. The present clinical trial was registered at IRCT website, under ID No.2013020612380N1.

Antibodies to Phosphatidylserine/Prothrombin Complex in Antiphospholipid Syndrome: Analytical and Clinical Perspectives.

PubMed

Peterson, Lisa K; Willis, Rohan; Harris, E Nigel; Branch, Ware D; Tebo, Anne E

2016-01-01

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombosis and/or pregnancy-related morbidity accompanied by persistently positive antiphospholipid antibodies (aPL). Current laboratory criteria for APS classification recommend testing for lupus anticoagulant as well as IgG and IgM anticardiolipin, and beta-2 glycoprotein I (anti-β2GPI) antibodies. However, there appears to be a subset of patients with classical APS manifestations who test negative for the recommended criteria aPL tests. While acknowledging that such patients may have clinical features that are not of an autoimmune etiology, experts also speculate that these "seronegative" patients may test negative for relevant autoantibodies as a result of a lack of harmonization and/or standardization. Alternatively, they may have aPL that target other antigens involved in the pathogenesis of APS. In the latter, autoantibodies that recognize a phosphatidylserine/prothrombin (PS/PT) complex have been reported to be associated with APS and may have diagnostic relevance. This review highlights analytical and clinical attributes associated with PS/PT antibodies, taking into consideration the performance characteristics of criteria aPL tests in APS with specific recommendations for harmonization and standardization efforts. © 2016 Elsevier Inc. All rights reserved.

Thromboembolic Events After Vitamin K Antagonist Reversal With 4-Factor Prothrombin Complex Concentrate: Exploratory Analyses of Two Randomized, Plasma-Controlled Studies.

PubMed

Milling, Truman J; Refaai, Majed A; Goldstein, Joshua N; Schneider, Astrid; Omert, Laurel; Harman, Amy; Lee, Martin L; Sarode, Ravi

2016-01-01

We evaluated thromboembolic events after vitamin K antagonist reversal in post hoc analyses of pooled data from 2 randomized trials comparing 4-factor prothrombin complex concentrate (4F-PCC) (Beriplex/Kcentra) with plasma. Unblinded investigators identified thromboembolic events, using standardized terms (such as "myocardial infarction," "deep vein thrombosis," "pulmonary embolism," and "ischemic stroke"). A blinded safety adjudication board reviewed serious thromboembolic events, as well as those referred by an independent unblinded data and safety monitoring board. We descriptively compared thromboembolic event and patient characteristics between treatment groups and included detailed patient-level outcome descriptions. We did not power the trials to assess safety. We enrolled 388 patients (4F-PCC: n=191; plasma: n=197) in the trials. Thromboembolic events occurred in 14 of 191 patients (7.3%) in the 4F-PCC group and 14 of 197 (7.1%) in the plasma group (risk difference 0.2%; 95% confidence interval -5.5% to 6.0%). Investigators reported serious thromboembolic events in 16 patients (4F-PCC: n=8; plasma: n=8); the data and safety monitoring board referred 2 additional myocardial ischemia events (plasma group) to the safety adjudication board for review. The safety adjudication board judged serious thromboembolic events in 10 patients (4F-PCC: n=4; plasma: n=6) as possibly treatment related. There were 8 vascular thromboembolic events in the 4F-PCC group versus 4 in the plasma group, and 1 versus 6 cardiac events, respectively. Among patients with thromboembolic events, 3 deaths occurred in each treatment group. All-cause mortality for the pooled population was 13 per group. We observed no relationship between thromboembolic event occurrence and factor levels transiently above the upper limit of normal; there were no notable differences in median factor or proteins C and S levels up to 24 hours postinfusion start in patients with and without thromboembolic events

Elevated levels of antibodies against phosphatidylserine/prothrombin complex and/or cardiolipin associated with infection and recurrent purpura in a child: a forme fruste of antiphospholipid syndrome?

PubMed

Kinoshita, Yuri; Mayumi, Nobuko; Inaba, Motoyuki; Igarashi, Touru; Katagiri, Ichigen; Kawana, Seiji

2015-07-15

Antiphospholipid syndrome is an autoimmune disorder characterized by the occurrence of venous and arterial thrombosis, as well as morbidity in pregnancy, in the presence of anti-phospholipid antibodies. The diagnosis of antiphospholipid syndrome is usually established based on clinical and laboratory findings by strictly following the 2006 Sapporo classification. However, the diagnosis remains challenging owing to the ongoing debates on the serological criteria. We report a case we describe as forme fruste antiphospholipid syndrome in which these criteria were not fulfilled. Purpura appeared repeatedly in a female infant starting from the age of 6 months and following episodes of upper respiratory infections and vaccinations. The levels of anti-cardiolipin IgG antibodies and anti-phosphatidylserine/prothrombin complex antibodies were elevated in accordance with these events. Histopathological evaluation revealed multiple small vessel thrombi in the dermis and adipose tissue. After 2 weeks of treatment with aspirin and heparin, the cutaneous symptoms subsided. Infection has long been associated with antiphospholipid syndrome, and anti-phosphatidylserine/prothrombin antibodies are considered a new marker for the diagnosis of antiphospholipid syndrome. Forme fruste antiphospholipid syndrome should be considered even if the antiphospholipid syndrome diagnostic criteria are not completely fulfilled, especially in the presence of elevated levels of anti-phosphatidylserine/prothrombin antibodies and known preceding infections.

Economic analysis of recombinant activated factor VII versus plasma-derived activated prothrombin complex concentrate in mild to moderate bleeds: haemophilia registry data from the Czech Republic.

PubMed

Salaj, Peter; Penka, Miroslav; Smejkal, Petr; Geierova, Vera; Ovesná, Petra; Brabec, Petr; Cetkovsky, Petr; Kubes, Radovan; Mesterton, Johan; Lindgren, Peter

2012-05-01

Several studies suggest that recombinant activated factor VII (rFVIIa) is more cost-effective than plasma-derived activated prothrombin complex concentrate (pd-aPCC) in haemophilia with inhibitors. However, most do not consider differences between treated patients. This study compared the pharmacoeconomics of rFVIIa versus pd-aPCC treatment of mild to moderate bleeds in inhibitor patients, taking co-variables into account. The HemoRec and HemIS registries capture exhaustive bleeding data in inhibitor patients in the Czech Republic. For each bleed, patient and bleed characteristics, treatment outcomes and bypassing agent use were retrospectively analysed, and direct costs of care per bleed calculated. Generalised Linear Model regression methods with cluster effect were employed to account for the possibility of several bleedings from the same patient. There were 108 and 53 mild to moderate bleeds in the rFVIIa and pd-aPCC groups, respectively. Although re-bleeding rates were similar in both groups, deeper analyses revealed significant differences in time to bleed resolution: 93.8% of bleeds treated with rFVIIa were resolved within ≤ 12 h, versus 60.4% with pd-aPCC (P < 0.001). Mean total cost/bleed was lower with rFVIIa (336,852 [median, 290,696] CZK; €12,760 [11,011]) than pd-aPCC (522,768 [341,310] CZK; €19,802 [12,928]) (P = 0.002). Results were maintained after controlling for potential co-variables (bleed nature, time to treatment, target joints). The lower total treatment costs per bleed with rFVIIa than pd-aPCC suggest that first-line rFVIIa is more cost-effective than pd-aPCC in mild to moderate bleeds. Time to bleed resolution was also significantly shorter with rFVIIa. These results were maintained when controlled for potential confounders. Copyright © 2012 Elsevier Ltd. All rights reserved.

Prothrombin Activation by Platelet-associated Prothrombinase Proceeds through the Prethrombin-2 Pathway via a Concerted Mechanism*

PubMed Central

Haynes, Laura M.; Bouchard, Beth A.; Tracy, Paula B.; Mann, Kenneth G.

2012-01-01

The protease α-thrombin is a key enzyme of the coagulation process as it is at the cross-roads of both the pro- and anti-coagulant pathways. The main source of α-thrombin in vivo is the activation of prothrombin by the prothrombinase complex assembled on either an activated cell membrane or cell fragment, the most relevant of which is the activated platelet surface. When prothrombinase is assembled on synthetic phospholipid vesicles, prothrombin activation proceeds with an initial cleavage at Arg-320 yielding the catalytically active, yet effectively anticoagulant intermediate meizothrombin, which is released from the enzyme complex ∼30–40% of the time. Prothrombinase assembled on the surface of activated platelets has been shown to proceed through the inactive intermediate prethrombin-2 via an initial cleavage at Arg-271 followed by cleavage at Arg-320. The current work tests whether or not platelet-associated prothrombinase proceeds via a concerted mechanism through a study of prothrombinase assembly and function on collagen-adhered, thrombin-activated, washed human platelets in a flow chamber. Prothrombinase assembly was demonstrated through visualization of bound factor Xa by confocal microscopy using a fluorophore-labeled anti-factor Xa antibody, which demonstrated the presence of distinct platelet subpopulations capable of binding factor Xa. When prothrombin activation was monitored at a typical venous shear rate over preassembled platelet-associated prothrombinase neither potential intermediate, meizothrombin or prethrombin-2, was observed in the effluent. Collectively, these findings suggest that platelet-associated prothrombinase activates prothrombin via an efficient concerted mechanism in which neither intermediate is released. PMID:22989889

[Continuously perfused cultivation of genetically-engineered CHO cells producing prothrombin in a modified Super-Spinner].

PubMed

Chen, Z L; Iding, K; Lütkemeyer, D; Lehmann, J

2001-01-01

A Super-Spinner was Modified by mounting a stainless steel filter(pore size 75 microns) to the impeller shaft to retain cells while fresh nutrient is perfused. Using Macroporous microcarrier Cytopore 1, continuously perfused cultivation of a recombinant CHO cell line, CHO2DS producing prothrombin was performed with the perfusion of a protein-free medium DF6S. The cell retention rate was more than 90% during the 24 days continuously perfused cultivation. The viable cell density of CHO2DS and prothrombin concentration reached 4.62 x 10(6)(cells.m/L) and 11.3(mg/L) respectively after 9 days culture.

Genetics Home Reference: prothrombin thrombophilia

MedlinePlus

... risk for a type of clot called a deep venous thrombosis , which typically occurs in the deep veins of the legs. Affected people also have ... 3 links) GeneReview: Prothrombin-Related Thrombophilia MedlinePlus Encyclopedia: Deep venous ... Encyclopedia: Pulmonary embolus General Information ...

Plasma fibrin clot properties in the G20210A prothrombin mutation carriers following venous thromboembolism: the effect of rivaroxaban.

PubMed

Janion-Sadowska, Agnieszka; Natorska, Joanna; Siudut, Jakub; Ząbczyk, Michal; Stanisz, Andrzej; Undas, Anetta

2017-08-30

We sought to investigate whether the G20210A prothrombin mutation modifies plasma fibrin clot properties in patients after venous thromboembolism (VTE) and how rivaroxaban treatment affects these alterations. We studied 34 prothrombin mutation heterozygous carriers and sex- and age-matched 34 non-carriers, all at least three months since the first VTE episode, before and during treatment with rivaroxaban. Clot permeability (K s ) and clot lysis time (CLT) with or without elimination of thrombin activatable fibrinolysis inhibitor (TAFI) were assessed at baseline, 2-6 hours (h) after and 20-25 h after intake of rivaroxaban (20 mg/day). At baseline, the prothrombin mutation group formed denser clots (K s -12 %, p=0.0006) and had impaired fibrinolysis (CLT +14 %, p=0.004, and CLT-TAFI +13 %, p=0.03) compared with the no mutation group and were similar to those observed in 15 healthy unrelated prothrombin mutation carriers. The G20210A prothrombin mutation was the independent predictor for K s and CLT before rivaroxaban intake. At 2-6 h after rivaroxaban intake, clot properties improved in both G20210A carriers and non-carriers (K s +38 %, and +37 %, CLT -25 % and -25 %, CLT-TAFI -20 % and -24 %, respectively, all p<0.001), but those parameters were worse in the prothrombin mutation group (K s -12.8 %, CLT +17 %, CLT-TAFI +13 %, all p<0.001). Rivaroxaban concentration correlated with fibrin clot properties. After 20-25 h since rivaroxaban intake most clot properties returned to baseline. Rivaroxaban-related differences in clot structure were confirmed by scanning electron microscopy images. In conclusion, rivaroxaban treatment, though improves fibrin clot properties, cannot abolish more prothrombotic fibrin clot phenotype observed in prothrombin mutation carriers following VTE.

Plasma Prothrombin Time and Esophageal Varices in Patients with Cirrhosis of Liver.

PubMed

Islam, Md Nasirul; Khan, Mobin; Ahmad, Nooruddin; Mamun-Al-Mahtab; Karim, Md Fazal

2016-01-01

Cirrhosis of the liver is a common complication of chronic liver disease and is associated with portal hypertension and esophageal varices. In this study, we checked the implication of prothrombin time, if any, in the genesis of esophageal varices. Sixty patients with cirrhosis of the liver were randomly assigned into two groups: Group I - 30 cirrhotic patients with esophageal varices, and group II - 30 cirrhotic patients without esophageal varices. The prothrombin time was checked for both groups. A positive correlation was found between the prolonged plasma prothrombin time (> 4 seconds) and esophageal varices with a sensitivity of 56.67% and specificity of 73.33%. The Child-Pugh score showed a correlation; however, the size of varices did not exhibit any such relation. Prothrombin time may be cautiously used to assess portal hypertension in a field level and rural setting where endoscopy is not available or feasible. Islam MN, Khan M, Ahmad N, Al-Mahtab M, Karim MF. Plasma Prothrombin Time and Esophageal Varices in Patients with Cirrhosis of Liver. Euroasian J Hepato-Gastroenterol 2016;6(1):10-12.

Cost analysis of prophylaxis with activated prothrombin complex concentrate vs. on-demand therapy with activated factor VII in severe haemophilia A patients with inhibitors, in Spain.

PubMed

Villarrubia, R; Oyagüez, I; Álvarez-Román, M T; Mingot-Castellano, M E; Parra, R; Casado, M A

2015-05-01

A cost analysis model was developed to compare annual cost of prophylaxis with activated prothrombin complex concentrate (aPCC) vs. on-demand therapy with activated recombinant factor VII (rFVIIa) in severe haemophilia A patients with inhibitors for the Spanish National Health System (NHS). Model inputs were drug cost for prophylaxis (aPCC) and for on-demand treatment (rFVIIa or aPCC); bleeding episodes management (excluding bypassing agent cost); surgical costs and disease management (excluding bleeding episodes). Annual bleeding episodes treated on-demand was assumed to be 25, whereas breakthrough bleeds on prophylaxis was 8. Dose for prophylaxis was 75.72 U kg(-1) , three times per week. The total on-demand dose/bleeding episode was 679.66 μg kg(-1) (rFVIIa) and 235.28 U kg(-1) (aPCC). The average bleeding cost (€2998) considered different bleeding sites (62.5% joints, 28.6% muscles and soft tissues, 3.6% mucocutaneous tissues and 5.4% other areas). A 7.5% deduction was applied to ex-factory drug prices. Unitary costs (€2013) derived from local databases. Sensitivity analyses (SA) were performed. Annual cost of aPCC prophylaxis (€524,358) was 16% lower than on-demand treatment with rFVIIa (€627,876). Yearly drug costs were €497,017 for aPCC (€73,166 for on-demand treatment and €423,850 for prophylaxis), and €548,870 for rFVIIa. Disease management cost (€2645 per year) and surgical procedures (€708 per year) were common for both strategies. In the SA prophylactic treatment led to savings between €26,225 and €-1,008,960. Prophylaxis with aPCC reduces number of bleeding episodes in severe haemophilia A patients with inhibitors. aPCC prophylaxis resulted in savings in excess of €100,000 per-patient per year, being 16% less costly than on-demand treatment with rFVIIa, for the Spanish NHS. © 2015 John Wiley & Sons Ltd.

Stability of prothrombin and factor VII in freeze-dried plasma

PubMed Central

Brozović, M.; Gurd, L. J.; Robertson, I.; Bangham, D. R.

1971-01-01

The stability of prothrombin and factor VII was studied using accelerated degradation tests in three preparations of freeze-dried pooled normal plasmas. In a previous report (Brozović, Gurd, Robertson, and Bangham, 1971) factor X was shown to be relatively unstable in these preparations of freeze-dried plasma: it was calculated that up to 8% of the original factor X activity would be lost after 10 years at −20°C, up to 54% at 4°C, and up to 90% at room temperature. The losses of factor VII activity were estimated to be negligible at −20°C, between 2 and 18% at 4°C, and between 20 and 70% of the original activity at 20°C, after 10 years of storage. Prothrombin was found to be less stable than factor VII: the expected loss in 10 years at −20°C may be up to 4%, at 4°C up to 30%, and at 20°C up to 83% of the initial activity. These findings indicate that in freeze-dried plasma prothrombin as well as factor X may be insufficiently stable for plasma to serve as long-term reference material for the standardization of the one-stage prothrombin time. Moreover, the loss of prothrombin and factor X in freeze-dried plasma stored at 4°C may be so high that when it is required to preserve these factors it may be necessary to store freeze-dried plasma at lower temperatures. PMID:5130534

The linker connecting the two kringles plays a key role in prothrombin activation

PubMed Central

Pozzi, Nicola; Chen, Zhiwei; Pelc, Leslie A.; Shropshire, Daniel B.; Di Cera, Enrico

2014-01-01

The zymogen prothrombin is proteolytically converted by factor Xa to the active protease thrombin in a reaction that is accelerated >3,000-fold by cofactor Va. This physiologically important effect is paradigmatic of analogous cofactor-dependent reactions in the coagulation and complement cascades, but its structural determinants remain poorly understood. Prothrombin has three linkers connecting the N-terminal Gla domain to kringle-1 (Lnk1), the two kringles (Lnk2), and kringle-2 to the C-terminal protease domain (Lnk3). Recent developments indicate that the linkers, and particularly Lnk2, confer on the zymogen significant flexibility in solution and enable prothrombin to sample alternative conformations. The role of this flexibility in the context of prothrombin activation was tested with several deletions. Removal of Lnk2 in almost its entirety (ProTΔ146–167) drastically reduces the enhancement of thrombin generation by cofactor Va from >3,000-fold to 60-fold because of a significant increase in the rate of activation in the absence of cofactor. Deletion of Lnk2 mimics the action of cofactor Va and offers insights into how prothrombin is activated at the molecular level. The crystal structure of ProTΔ146–167 reveals a contorted architecture where the domains are not vertically stacked, kringle-1 comes within 9 Å of the protease domain, and the Gla-domain primed for membrane binding comes in contact with kringle-2. These findings broaden our molecular understanding of a key reaction of the blood coagulation cascade where cofactor Va enhances activation of prothrombin by factor Xa by compressing Lnk2 and morphing prothrombin into a conformation similar to the structure of ProTΔ146–167. PMID:24821807

G20210A prothrombin gene mutation identified in patients with venous leg ulcers.

PubMed

Jebeleanu, G; Procopciuc, L

2001-01-01

The G20210A mutation variant of prothrombin gene is the second most frequent mutation identified in patients with deep venous thrombosis, after factor V Leiden. The risk for developing deep venous thrombosis is high in patients identified as heterozygous for G20210A mutation. In order to identify this polymorphism in the gene coding prothrombin, the 345bp fragment in the 3'- untranslated region of the prothrombin gene was amplified using amplification by polymerase chain reaction and enzymatic digestion by HindIII (restriction endonuclease enzyme). The products of amplification and enzymatic's digestion were analized using agarose gel electrophoresis. We investigated 20 patients with venous leg ulcers and we found 2 heterozygous (10%) for G20210A mutation. None of the patients in the control group had G20210A mutation. Our study confirms the presence of G20210A mutation in the Romanian population. Our study also shows the link between venous leg ulcers and this polymorphism in the prothrombin gene.

Preparation of factor VII concentrate using CNBr-activated Sepharose 4B immunoaffinity chromatography

PubMed Central

Mousavi Hosseini, Kamran; Nasiri, Saleh

2015-01-01

Background: Factor VII concentrates are used in patients with congenital or acquired factor VII deficiency or treatment of hemophilia patients with inhibitors. In this research, immunoaffinity chromatography was used to purify factor VII from prothrombin complex (Prothrombin- Proconvertin-Stuart Factor-Antihemophilic Factor B or PPSB) which contains coagulation factors II, VII, IX and X. The aim of this study was to improve purity, safety and tolerability as a highly purified factor VII concentrate. Methods: PPSB was prepared using DEAE-Sephadex and was used as the starting material for purification of coagulation factor VII. Prothrombin complex was treated by solvent/detergent at 24°C for 6 h with constant stirring. The mixture of PPSB in the PBS buffer was filtered and then chromatographed using CNBr-activated Sepharose 4B coupled with specific antibody. Factors II, IX, VII, X and VIIa were assayed on the fractions. Fractions of 48-50 were pooled and lyophilized as a factor VII concentrate. Agarose gel electrophoresis was performed and Tween 80 was measured in the factor VII concentrate. Results: Specific activity of factor VII concentrate increased from 0.16 to 55.6 with a purificationfold of 347.5 and the amount of activated factor VII (FVIIa) was found higher than PPSB (4.4-fold). Results of electrophoresis on agarose gel indicated higher purity of Factor VII compared to PPSB; these finding revealed that factor VII migrated as alpha-2 proteins. In order to improve viral safety, solvent-detergent treatment was applied prior to further purification and nearly complete elimination of tween 80 (2 μg/ml). Conclusion: It was concluded that immuonoaffinity chromatography using CNBr-activated Sepharose 4B can be a suitable choice for large-scale production of factor VII concentrate with higher purity, safety and activated factor VII. PMID:26034723

Preparation of factor VII concentrate using CNBr-activated Sepharose 4B immunoaffinity chromatography.

PubMed

Mousavi Hosseini, Kamran; Nasiri, Saleh

2015-01-01

Factor VII concentrates are used in patients with congenital or acquired factor VII deficiency or treatment of hemophilia patients with inhibitors. In this research, immunoaffinity chromatography was used to purify factor VII from prothrombin complex (Prothrombin- Proconvertin-Stuart Factor-Antihemophilic Factor B or PPSB) which contains coagulation factors II, VII, IX and X. The aim of this study was to improve purity, safety and tolerability as a highly purified factor VII concentrate. PPSB was prepared using DEAE-Sephadex and was used as the starting material for purification of coagulation factor VII. Prothrombin complex was treated by solvent/detergent at 24°C for 6 h with constant stirring. The mixture of PPSB in the PBS buffer was filtered and then chromatographed using CNBr-activated Sepharose 4B coupled with specific antibody. Factors II, IX, VII, X and VIIa were assayed on the fractions. Fractions of 48-50 were pooled and lyophilized as a factor VII concentrate. Agarose gel electrophoresis was performed and Tween 80 was measured in the factor VII concentrate. Specific activity of factor VII concentrate increased from 0.16 to 55.6 with a purificationfold of 347.5 and the amount of activated factor VII (FVIIa) was found higher than PPSB (4.4-fold). RESULTS of electrophoresis on agarose gel indicated higher purity of Factor VII compared to PPSB; these finding revealed that factor VII migrated as alpha-2 proteins. In order to improve viral safety, solvent-detergent treatment was applied prior to further purification and nearly complete elimination of tween 80 (2 μg/ml). It was concluded that immuonoaffinity chromatography using CNBr-activated Sepharose 4B can be a suitable choice for large-scale production of factor VII concentrate with higher purity, safety and activated factor VII.

Prothrombin fragments in cardiovascular disease.

PubMed

Páramo, J A

2010-01-01

Prothrombin fragment 1+2 (F1+2), which comes from in vivo cleavage of prothrombin by factor Xa, is considered to be useful for diagnosis of thrombosis. Recognition of the central role of thrombosis in the pathogenesis ofcardiovascular disease has prompted growing interest in the association o F1+2 with cardiovascular clinical syndromes. Increased F1+2 levels have reported in venous thromboembolism, inflammation, cancer, sepsis, acute coronary syndromes, stroke, peripheral arterial disease, atrial fibrillation and during the postoperative period. However, a clear relationship with the appearance of thrombosis has not always been consistently demonstrated. Besides its potential prognostic and diagnostic value, it could also be usefu in assessing the impact of various therapies. However, it should be kept in mind that measurement of hemostasis activation markers has several important biological and methodological disadvantages. Activation markers reflect the presence of thrombosis in any vascular bed, so they are not specific. Furthermore, elevations occur not only in the presence of overt thrombosis but also during the hypercoagulable state. The cutoff level to be used for the definition of elevations is still largely unknown due to the use of different analytical methods, none of which have been standardized until know. Finally, the prognostic value of F1+2 and other markers of coagulation activation remains to be fully defined in future studies.

Prothrombin fragment 1+2 in urine as a marker on coagulation activity in patients with suspected pulmonary embolism.

PubMed

Wexels, Fredrik; Dahl, Ola E; Pripp, Are H; Seljeflot, Ingebjørg; Borris, Lars C; Haslund, Anniken; Gudmundsen, Tor E; Lauritzen, Trine; Lassen, Michael R

2014-07-01

We have recently reported that increased levels of urine prothrombin fragment 1+2 reflected radiologically verified deep vein thrombosis. In this study we evaluated whether urine prothrombin fragment 1+2 was associated with pulmonary embolism in non-selected patients. Patients with clinical suspected pulmonary embolism were interviewed on comorbidities and medications. Urine was collected from each patient before radiological examination and snap frozen until analysed on urine prothrombin fragment 1+2 with an ELISA kit. Imaging of the pulmonary arteries were conducted with contrast enhanced computer tomography. Pulmonary embolism was diagnosed in 44/197 patients. Non-significantly higher urine prothrombin fragment 1+2 levels were found in non-selected patients with pulmonary embolism vs. those without (p=0.324). Significantly higher urine prothrombin fragment 1+2 levels were found in the pulmonary embolism positive patients without comorbidities (n=13) compared to the control group (n=28) (p=0.009). The calculated sensitivity, specificity and negative predictive value using the lowest detectable urine prothrombin fragment 1+2 level was 82%, 34% and 87%, respectively. There was no significant urine prothrombin fragment 1+2 level difference in patients with and without pulmonary embolism. In non-comorbide pulmonary embolism positive patients the urine prothrombin fragment 1+2 levels were significantly higher compared to the control group. The negative predictive value found in this study indicates that uF1+2 has the potential to identify patients with a low risk of PE. Copyright © 2014 Elsevier Ltd. All rights reserved.

21 CFR 866.5735 - Prothrombin immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... factor II) in serum. Measurements of the amount of antigenically competent (ability to react with protein antibodies) prothrombin aid in the diagnosis of blood-clotting disorders. (b) Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part...

Cost-effectiveness of recombinant activated factor VII vs. plasma-derived activated prothrombin complex concentrate in the treatment of mild-to-moderate bleeding episodes in patients with severe haemophilia A and inhibitors in Spain.

PubMed

Jimenez-Yuste, V; Núñez, R; Romero, J A; Montoro, B; Espinós, B

2013-11-01

Several analyses have shown that recombinant activated factor VII (rFVIIa) is a cost-effective intervention compared with plasma-derived activated prothrombin complex concentrate (pd-aPCC) for the on-demand treatment of mild-to-moderate bleeds in haemophilia patients with inhibitors. The aim of the study was to assess the cost-effectiveness of rFVIIa vs. pd-aPCC in the treatment of bleeding episodes in severe haemophilia A patients with inhibitors in Spain. A decision analytic model was designed to evaluate the costs and clinical outcomes of using rFVIIa or pd-aPCC to treat mild-to-moderate joint bleeds in children (≤14 years old) and adults with inhibitors. Data were obtained from a published meta-analysis and a panel of haemophilia experts. The analysis was conducted from the perspective of the Spanish National Healthcare System. One-way sensitivity analyses were performed to assess the impact of model assumptions on study results. In the Treur meta-analysis, rFVIIa resulted in cumulative joint bleed resolution of 88% and 95% after 24 and 36 h, respectively, compared with 62% and 76%, respectively, with pd-aPCC (Treur et al. Haemophilia 2009; 15: 420-36). Here, the mean cost per bleed was estimated at €8473 and €15 579 in children and adults treated with rFVIIa, vs. €8627 and €15 677 in children and adults treated with pd-aPCC. rFVIIa treatment was found to be the dominating option (cheaper and more effective). The one-way sensitivity analysis also confirmed that rFVIIa was less costly than pd-aPCC. The model suggests that rFVIIa is a cost-effective option compared with pd-aPCC for the treatment of mild-to-moderate bleeding episodes in a Spanish setting. © 2013 John Wiley & Sons Ltd.

Disruption of Prostate Microvasculature by Combining Microbubble-Enhanced Ultrasound and Prothrombin

PubMed Central

Liu, Yongliang; Qiao, Lu; Gao, Wenhong; Zhang, Weiguo; Liu, Zheng

2016-01-01

Previous studies have shown a unique method to disrupt tumor vasculature using pulsed, high-pressure amplitude therapeutic ultrasound combined with microbubbles. In this study, we attempted to destroy the prostate vasculature of canine prostates using microbubble-enhanced ultrasound (MEUS) and prothrombin. The prostates of 43 male mongrel canines were surgically exposed. Twenty-two prostates were treated using MEUS (n = 11) or MEUS and prothrombin (PMEUS, n = 11). The other 21 prostates, which were treated using microbubbles (n = 7), ultrasound (n = 7) or prothrombin (n = 7) only, served as the controls. Prothrombin was intravenously infused at 20 IU/kg. MEUS was induced using a therapeutic ultrasound device at a peak negative pressure of 4.47 MPa and a microbubble injection. Contrast-enhanced ultrasound was performed to assess the blood perfusion of the prostates. Then, the prostate tissue was harvested immediately after treatment and at 48 hours later for pathological examination. The contrast-enhanced ultrasound peak value of the prostate decreased significantly from 36.2 ± 5.6 to 27.1 ± 6.3 after treatment in the PMEUS group, but it remained unchanged in the other groups. Histological examination found severe microvascular rupture, hemorrhage and thrombosis in both MEUS- and PMEUS-treated prostates immediately after treatment, while disruption in the PMEUS group was more severe than in the MEUS group. Forty-eight hours after treatment, massive necrosis and infiltration of white blood cells occurred in the PMEUS group. This study demonstrated that PMEUS disrupted the normal microvasculature of canine prostates and induced massive necrosis. PMEUS could potentially become a new noninvasive method used for the treatment of benign prostatic hyperplasia. PMID:27643992

21 CFR 864.7735 - Prothrombin-proconvertin test and thrombotest.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Prothrombin-proconvertin test and thrombotest. 864.7735 Section 864.7735 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864...

21 CFR 864.7735 - Prothrombin-proconvertin test and thrombotest.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Prothrombin-proconvertin test and thrombotest. 864.7735 Section 864.7735 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864...

21 CFR 864.7735 - Prothrombin-proconvertin test and thrombotest.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Prothrombin-proconvertin test and thrombotest. 864.7735 Section 864.7735 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864...

21 CFR 864.7735 - Prothrombin-proconvertin test and thrombotest.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Prothrombin-proconvertin test and thrombotest. 864.7735 Section 864.7735 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864...

21 CFR 864.7735 - Prothrombin-proconvertin test and thrombotest.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Prothrombin-proconvertin test and thrombotest. 864.7735 Section 864.7735 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864...

Presence of anti-phosphatidylserine-prothrombin complex antibodies and anti-moesin antibodies in patients with polyarteritis nodosa.

PubMed

Okano, Tatsuro; Takeuchi, Sora; Soma, Yoshinao; Suzuki, Koya; Tsukita, Sachiko; Ishizu, Akihiro; Suzuki, Kazuo; Kawakami, Tamihiro

2017-01-01

We measured both serum anti-phosphatidylserine-prothrombin complex (anti-PSPT) antibodies and anti-moesin antibodies, as well as various cytokines (interleukin [IL]-2, IL-4, IL-5, IL-10, IL-13, IL-17, granulocyte macrophage colony-stimulating factor, γ-interferon, tumor necrosis factor-α) levels in polyarteritis nodosa (PAN) patients with cutaneous manifestations. All patients showed the presence of a histological necrotizing vasculitis in the skin specimen. They were treated with i.v. cyclophosphamide pulse therapy (IV-CY) and prednisolone therapy or steroid pulse therapy. The immunological assessments were performed on sera collected prior to and after treatment with IV-CY or steroid pulse therapy. We found a significant positive correlation between serum anti-moesin antibodies and both clinical Birmingham Vasculitis Activity Scores and Vasculitis Damage Index. Anti-PSPT antibody and IL-2 levels after treatment in PAN patients were significantly lower than before treatment. In contrast, anti-moesin antibody levels were higher following IV-CY or steroid pulse therapy compared with the pretreatment levels. In the treatment-resistant PAN patients (n = 8), anti-PSPT antibody levels after treatment were significantly lower than before treatment. In contrast, anti-moesin antibody levels after treatment in the patients were significantly higher compared with the pretreatment levels. Immunohistochemical staining revealed moesin overexpression in mainly fibrinoid necrosis of the affected arteries in the PAN patients. We suggest that measurement of serum anti-PSPT antibody levels could serve as a marker for PAN and aid in earlier diagnosis of PAN. We also propose that elevated serum anti-moesin antibodies could play some role of the exacerbation in patients with PAN. © 2016 Japanese Dermatological Association.

D-Dimer and prothrombin fragment 1 + 2 in urine and plasma in patients with clinically suspected venous thromboembolism.

PubMed

Wexels, Fredrik; Seljeflot, Ingebjørg; Pripp, Are H; Dahl, Ola E

2016-06-01

Increased levels of urine prothrombin fragment 1 + 2 was recently reported to be associated with imaging-verified venous thromboembolism. In this study we evaluated the relationship between plasma D-dimer and plasma and urine prothrombin fragment 1 + 2 in patients with suspected venous thromboembolism. Urine and blood samples were collected from patients with suspected pulmonary embolism or deep vein thrombosis. The samples were analysed with commercially available ELISA kits. The diagnosis of venous thromboembolism was verified with contrast-enhanced computer tomography of the pulmonary arteries or lower extremity deep vein compression ultrasound and venography as appropriate. Venous thromboembolism was diagnosed in 150 of 720 patients. Significantly higher levels of plasma D-dimer and prothrombin fragment 1 + 2 in plasma and urine were found in those with imaging-confirmed venous thromboembolism versus those without (P < 0.001). The correlation between the three biomarkers was statistically significant (range of rs values 0.45-0.65, P < 0.001). Plasma D-dimer had the highest diagnostic accuracy followed by prothrombin fragment 1 + 2 in plasma. Further development of ELISA analyses for urine testing of prothrombin fragment 1 + 2 may improve its diagnostic accuracy.

Factor V Leiden 1691G/A and prothrombin gene 20210G/A polymorphisms as prothrombotic markers in adult Egyptian acute leukemia patients.

PubMed

El Sissy, Azza Hamdy; El Sissy, Maha H; Elmoamly, Shereef

2014-11-01

Factor V Leiden 1691G/A and prothrombin gene 20210G/A mutations are the most common genetic defects leading to thrombosis. This work aimed to study the FV Leiden and the prothrombin gene polymorphism in adult Egyptian patients with acute leukemia and their importance in thrombophilia screening. The study included 76 patients with acute leukemia and 100 healthy controls. Genotyping was done by real-time polymerase chain reaction technique. For factor V Leiden, the frequency of G/A mutation conferred more than 2.5-fold of increased risk of (OR 2.639 95 % CI 1.045-6.669). The frequency of factor V Leiden combined (G/A + A/A) genotypes conferred 2.83-fold of increased risk (OR 2.828, CI 1.13-7.075), The A allele conferred almost threefold increased risk (OR 2.824, 95 % CI 1.175-6.785). Despite higher frequency in patients compared to controls, there was no risk of association between prothrombin gene mutation and acute leukemia in adult Egyptians nor was there between combined genotypes of prothrombin gene mutation and factor V Leiden.

Certification of reference materials for detection of the human prothrombin gene G20210A sequence variant.

PubMed

Gancberg, David; Corbisier, Philippe; Meeus, Nele; Marki-Zay, Janos; Mannhalter, Christine; Schimmel, Heinz

2008-01-01

There is a need for reference materials (RMs) in the field of genetic testing for verification of test results obtained in patients and probands. For the frequent genetic variation G20210A in the prothrombin gene, it has been shown that purified plasmids containing the gene fragment harbouring the mutation constitute good candidate RMs. Plasmid-type RMs were characterised for homogeneity, stability, sequence identity and fitness for purpose. Their certification required the use of different real-time PCR methods for genotyping and quantification of the plasmid copy number. Homogeneity, stability and fitness for the purpose of the plasmids could be demonstrated. The long-term stability (up to 24 months) of the materials was confirmed by highly sensitive and specific quantitative real-time PCR methods. New types of certified RMs (CRMs) for genetic testing of the human prothrombin gene G20210A sequence variant are available. Their fitness for purpose was demonstrated and no evidence was found that they would not work with other methods as long as these are targeting the whole or parts of the prothrombin gene fragment inserted into the plasmids. The described CRMs support the efforts of the international community in development, validation and harmonisation of tests for molecular genetic testing.

Genetic diminution of circulating prothrombin ameliorates multiorgan pathologies in sickle cell disease mice.

PubMed

Arumugam, Paritha I; Mullins, Eric S; Shanmukhappa, Shiva Kumar; Monia, Brett P; Loberg, Anastacia; Shaw, Maureen A; Rizvi, Tilat; Wansapura, Janaka; Degen, Jay L; Malik, Punam

2015-10-08

Sickle cell disease (SCD) results in vascular occlusions, chronic hemolytic anemia, and cumulative organ damage. A conspicuous feature of SCD is chronic inflammation and coagulation system activation. Thrombin (factor IIa [FIIa]) is both a central protease in hemostasis and a key modifier of inflammatory processes. To explore the hypothesis that reduced prothrombin (factor II [FII]) levels in SCD will limit vaso-occlusion, vasculopathy, and inflammation, we used 2 strategies to suppress FII in SCD mice. Weekly administration of FII antisense oligonucleotide "gapmer" to Berkeley SCD mice to selectively reduce circulating FII levels to ∼10% of normal for 15 weeks significantly diminished early mortality. More comprehensive, long-term comparative studies were done using mice with genetic diminution of circulating FII. Here, cohorts of FII(lox/-) mice (constitutively carrying ∼10% normal FII) and FII(WT) mice were tracked in parallel for a year following the imposition of SCD via hematopoietic stem cell transplantation. This genetically imposed suppression of FII levels resulted in an impressive reduction in inflammation (reduction in leukocytosis, thrombocytosis, and circulating interleukin-6 levels), reduced endothelial cell dysfunction (reduced endothelial activation and circulating soluble vascular cell adhesion molecule), and a significant improvement in SCD-associated end-organ damage (nephropathy, pulmonary hypertension, pulmonary inflammation, liver function, inflammatory infiltration, and microinfarctions). Notably, all of these benefits were achieved with a relatively modest 1.25-fold increase in prothrombin times, and in the absence of hemorrhagic complications. Taken together, these data establish that prothrombin is a powerful modifier of SCD-induced end-organ damage, and present a novel therapeutic target to ameliorate SCD pathologies. © 2015 by The American Society of Hematology.

Quality control in the development of coagulation factor concentrates.

PubMed

Snape, T J

1987-01-01

Limitation of process change is a major factor contributing to assurance of quality in pharmaceutical manufacturing. This is particularly true in the manufacture of coagulation factor concentrates, for which presumptive testing for poorly defined product characteristics is an integral feature of finished product quality control. The development of new or modified preparations requires that this comfortable position be abandoned, and that the effect on finished product characteristics of changes to individual process steps (and components) be assessed. The degree of confidence in the safety and efficacy of the new product will be determined by, amongst other things, the complexity of the process alteration and the extent to which the results of finished product tests can be considered predictive. The introduction of a heat-treatment step for inactivation of potential viral contaminants in coagulation factor concentrates presents a significant challenge in both respects, quite independent of any consideration of assessment of the effectiveness of the viral inactivation step. These interactions are illustrated by some of the problems encountered with terminal dry heat-treatment (72 h. at 80 degrees C) of factor VIII and prothrombin complex concentrates manufactured by the Blood Products Laboratory.

Functional characterization of transcription factor binding sites for HNF1-alpha, HNF3-beta (FOXA2), HNF4-alpha, Sp1 and Sp3 in the human prothrombin gene enhancer.

PubMed

Ceelie, H; Spaargaren-Van Riel, C C; De Jong, M; Bertina, R M; Vos, H L

2003-08-01

Prothrombin is a key component in blood coagulation. Overexpression of prothrombin leads to an increased risk of venous thrombosis. Therefore, the study of the transcriptional regulation of the prothrombin gene may help to identify mechanisms of overexpression. The aim of our study was to localize the regions within the prothrombin enhancer responsible for its activity, to identify the proteins binding to these regions, and to establish their functional importance. We constructed a set of prothrombin promoter 5' deletion constructs containing the firefly luciferase reporter gene, which were transiently transfected in HepG2, HuH7 and HeLa cells. Putative transcription factor (TF) binding sites were evaluated by electrophoretic mobility shift assays. The functional importance of each TF binding site was evaluated by site directed mutagenesis and transient transfection of the mutant constructs. We confirmed the major contribution of the enhancer region to the transcriptional activity of the prothrombin promoter. Analysis of this region revealed putative binding sites for hepatocyte nuclear factor HNF4, HNF3-beta and specificity protein(Sp)1. We identified six different TFs binding to three evolutionary conserved sites in the enhancer: HNF4-alpha (site 1), HNF1-alpha, HNF3-beta and an as yet unidentified TF (site 2) and the ubiquitously expressed TFs Sp1 and Sp3 (site 3). Mutagenesis studies showed that loss of binding of HNF3-beta resulted in a considerable decrease of enhancer activity, whereas loss of HNF4-alpha or Sp1/Sp3 resulted in milder reductions. The prothrombin enhancer plays a major role in regulation of prothrombin expression. Six different TFs are able to bind to this region. At least three of these TFs, HNF4-alpha, HNF3-beta and Sp1/Sp3, are important in regulation of prothrombin expression.

Utility of a point-of-care device for rapid determination of prothrombin time in trauma patients: a preliminary study.

PubMed

David, Jean-Stéphane; Levrat, Albrice; Inaba, Kenji; Macabeo, Caroline; Rugeri, Lucia; Fontaine, Oriane; Cheron, Aurélie; Piriou, Vincent

2012-03-01

Rapid and accurate determination of prothrombin time in trauma patients may help to faster control of bleeding induced coagulopathy. The goal of this prospective observational study was to investigate the accuracy of bedside measurements of prothrombin time by the mean of a point-of-care device (INRatio) in trauma patients. Fifty blood samples were drawn at admission and during the acute care phase for standard coagulation assays (prothrombin time, International Normalized Ratio [INR], and fibrinogen) and INRatio testing (INR(A)) from 48 trauma patients. Standard coagulation assays were available after a mean of 66 minutes. Median Injury Severity Score was 18, and 16 patients (33%) had a coagulopathy. Significant correlation was found between INR and INR(A) (r: 0.93, 95% confidence interval: 0.87-0.96). The mean difference (bias) for INR was 0.00, and standard deviation (precision) of the difference was 0.78. However, in cases where there was decreased hemoglobin (<10 gr · L(-1)) and fibrinogen (<1.5 gr · L(-1)), bias and precision were increased. To predict the need for fresh frozen plasma transfusion (INR > 1.5), INR(A) cutoff value of 1.3 resulted in a sensitivity of 92% and a specificity of 79%. The area under the receiver operating characteristic curve was 0.946 (95% confidence interval: 0,845-0,982). INRatio may be a useful device in the management of trauma patients with ongoing or suspected coagulopathy that may help to save at least 60 minutes in the process of obtaining a prothrombin time result. It may allow earlier detection of coagulopathy and, together with vital sign and hemoglobin, may help to guide fresh frozen plasma transfusion.

Reversal of Apixaban Induced Alterations in Hemostasis by Different Coagulation Factor Concentrates: Significance of Studies In Vitro with Circulating Human Blood

PubMed Central

Arellano-Rodrigo, Eduardo; Roquer, Jaume; Reverter, Joan Carles; Sanz, Victoria Veronica; Molina, Patricia; Lopez-Vilchez, Irene; Diaz-Ricart, Maribel; Galan, Ana Maria

2013-01-01

Apixaban is a new oral anticoagulant with a specific inhibitory action on FXa. No information is available on the reversal of the antihemostatic action of apixaban in experimental or clinical settings. We have evaluated the effectiveness of different factor concentrates at reversing modifications of hemostatic mechanisms induced by moderately elevated concentrations of apixaban (200 ng/ml) added in vitro to blood from healthy donors (n = 10). Effects on thrombin generation (TG) and thromboelastometry (TEM) parameters were assessed. Modifications in platelet adhesive, aggregating and procoagulant activities were evaluated in studies with blood circulating through damaged vascular surfaces, at a shear rate of 600 s−1. The potential of prothrombin complex concentrates (PCCs; 50 IU/kg), activated prothrombin complex concentrates (aPCCs; 75 IU/kg), or activated recombinant factor VII (rFVIIa; 270 μg/kg), at reversing the antihemostatic actions of apixaban, were investigated. Apixaban interfered with TG kinetics. Delayed lag phase, prolonged time to peak and reduced peak values, were improved by the different concentrates, though modifications in TG patterns were diversely affected depending on the activating reagents. Apixaban significantly prolonged clotting times (CTs) in TEM studies. Prolongations in CTs were corrected by the different concentrates with variable efficacies (rFVIIa≥aPCC>PCC). Apixaban significantly reduced fibrin and platelet interactions with damaged vascular surfaces in perfusion studies (p<0.05 and p<0.01, respectively). Impairments in fibrin formation were normalized by the different concentrates. Only rFVIIa significantly restored levels of platelet deposition. Alterations in hemostasis induced by apixaban were variably compensated by the different factor concentrates investigated. However, effects of these concentrates were not homogeneous in all the tests, with PCCs showing more efficacy in TG, and rFVIIa being more effective on TEM

Current use of factor concentrates in pediatric cardiac anesthesia.

PubMed

Guzzetta, Nina A; Williams, Glyn D

2017-07-01

Excessive bleeding following pediatric cardiopulmonary bypass is associated with increased morbidity and mortality, both from the effects of hemorrhage and the therapies employed to achieve hemostasis. Neonates and infants are especially at risk because their coagulation systems are immature, surgeries are often complex, and cardiopulmonary bypass technologies are inappropriately matched to patient size and physiology. Consequently, these young children receive substantial amounts of adult-derived blood products to restore adequate hemostasis. Adult and pediatric data demonstrate associations between blood product transfusions and adverse patient outcomes. Thus, efforts to limit bleeding after pediatric cardiopulmonary bypass and minimize allogeneic blood product exposure are warranted. The off-label use of factor concentrates, such as fibrinogen concentrate, recombinant activated factor VII, and prothrombin complex concentrates, is increasing as these hemostatic agents appear to offer several advantages over conventional blood products. However, recognizing that these agents have the potential for both benefit and harm, well-designed studies are needed to enhance our knowledge and to determine the optimal use of these agents. In this review, our primary objective was to examine the evidence regarding the use of factor concentrates to treat bleeding after pediatric CPB and identify where further research is required. PubMed, MEDLINE/OVID, The Cochrane Library and the Cochrane Central Register of Controlled Trials (CENTRAL) were systematically searched to identify existing studies. © 2017 John Wiley & Sons Ltd.

[Recurrent vascular access trombosis associated with the prothrombin mutation G20210A in a adult patient in haemodialysis].

PubMed

Quintana, L F; Coll, E; Monteagudo, I; Collado, S; López-Pedret, J; Cases, A

2005-01-01

Vascular access-related complications are a frequent cause of morbidity in haemodialysis patients and generate high costs. We present the case of an adult patient with end-stage renal disease and recurrent vascular access thrombosis associated with the prothrombin mutation G20210A and renal graft intolerance. The clinical expression of this heterozygous gene mutation may have been favoured by inflammatory state, frequent in dialysis patients. In this patient, the inflammatory response associated with the renal graft intolerance would have favored the development of recurrent vascular access thrombosis in a adult heterozygous for prothrombin mutation G20210A. In the case of early dysfunction of haemodialysis vascular access and after ruling out technical problems, it is convenient to carry out a screening for thrombophilia.

High prevalence of factor V Leiden and prothrombin G20101A mutations in Kashmiri patients with venous thromboembolism.

PubMed

Shafia, Syed; Zargar, Mahrukh H; Khan, Nabeela; Ahmad, Rehana; Shah, Zafar Amin; Asimi, Ravouf

2018-05-15

The genetic variants of the factor V (G1691A), prothrombin (G20210A) and MTHFR (C677T) genes have been widely implicated as inherited risk factors for developing venous thrombosis. This study was undertaken to reveal the frequency of these mutations in Kashmiri patients with venous thromboembolism. A case-control study was designed with 250 VTE patients and 250 healthy controls. The mutations were analysed using ARMS-PCR and PCR-RFLP approach. The factor V Leiden G1691A mutation was found in 17/250 (6.8%) VTE patients and prothrombin G20210A mutation was found in 7/250 (2.8%) VTE patients while no mutation was found in any of the healthy controls. Both the mutations were found to be significantly associated with the increased risk of VTE (p = 0.0001 and 0.0150 respectively) while no association of VTE risk with MTHFR C677T polymorphism was found (p = 0.53). The increased frequency of factor V Leiden G1691A and prothrombin G20210A mutation in VTE patients indicates a significant role of these mutations in the development of VTE in our population. We therefore suggest the routine screening of these two mutations as thrombophilic markers in Kashmiri patients with venous thromboembolism. Copyright © 2018 Elsevier B.V. All rights reserved.

The risk of early mortality of polytrauma patients associated to ISS, NISS, APACHE II values and prothrombin time.

PubMed

Mica, Ladislav; Rufibach, Kaspar; Keel, Marius; Trentz, Otmar

2013-01-01

The early hemodynamic normalization of polytrauma patients may lead to better survival outcomes. The aim of this study was to assess the diagnostic quality of trauma and physiological scores from widely used scoring systems in polytrauma patients. In total, 770 patients with ISS > 16 who were admitted to a trauma center within the first 24 hours after injury were included in this retrospective study. The patients were subdivided into three groups: those who died on the day of admission, those who died within the first three days, and those who survived for longer than three days. ISS, NISS, APACHE II score, and prothrombin time were recorded at admission. The descriptive statistics for early death in polytrauma patients who died on the day of admission, 1-3 days after admission, and > 3 days after admission were: ISS of 41.0, 34.0, and 29.0, respectively; NISS of 50.0, 50.0, and 41.0, respectively; APACHE II score of 30.0, 25.0, and 15.0, respectively; and prothrombin time of 37.0%, 56.0%, and 84%, respectively. These data indicate that prothrombin time (AUC: 0.89) and APACHE II (AUC: 0.88) have the greatest prognostic utility for early death. The estimated densities of the scores may suggest a direction for resuscitative procedures in polytrauma patients. "Retrospektive Analysen in der Chirurgischen Intensivmedizin"StV01-2008.

Different outcome of six homozygotes for prothrombin A20210A gene variant

PubMed Central

Di Micco, Pierpaolo; Di Fiore, Rosanna; Niglio, Alferio; Quaranta, Sandro; Angiolillo, Antonella; Cardillo, Giuseppe; Castaldo, Giuseppe

2008-01-01

Prothrombin G20210A gene variant (FII G20210A) is a risk factor for venous thrombotic disease while conflicting results have been reported for the risk of arterial thrombotic events. However, vascular episodes were absent in up to 40% of the 67 homozygotes for the G20210A described so far, which indicates that the clinical expression depends on additional risk/trigger factors. We describe six homozygotes for the G20210A variant, among which the first pair of siblings (cases n. 3 and 4) reported so far that displayed a strongly heterogeneous clinical outcome. Case 1, a female of 27 years, developed a full thrombosis of common femoral, superficial and popliteal veins. She assumed oral contraceptives in the last two years. Case n. 2, 34 years old, suffered of recurrent pregnancy loss in absence of any causative alteration. Cases n. 3 and n. 5 experienced arterial thrombotic disease, i.e., juvenile myocardial infarction (40 years old) and stroke (48 years old), respectively, in absence of other risk factors. Finally, cases n. 4 and 6 identified as homozygotes for the FII G20210A variant being consanguineous of symptomatic subjects bearing the variant, did not experience any episode of venous nor arterial disease. Both of them have chronic liver disease with an impairement of the prothrombin time INR. Thus, homozygotes for the G20210A are at risk for arterial (in addition to venous) thromobotic events; chronic liver disease might modulate this risk. PMID:18627609

[False positive serum des-gamma-carboxy prothrombin after resection of hepatocellular carcinoma].

PubMed

Hiramatsu, Kumiko; Tanaka, Yasuhito; Takagi, Kazumi; Iida, Takayasu; Takasaka, Yoshimitsu; Mizokami, Masashi

2007-04-01

Measurements of serum concentrations of des-gamma-carboxy-prothrombin (PIVKA-II) are widely used for diagnosing hepatocellular carcinoma (HCC). Recently, when we evaluated the correlation of PIVKA-II between two commercially available PIVKA-II immunoassay kits (Lumipulse f vs. Picolumi) to introduce it in our hospital, false high values of PIVKA-II were observed in Lumipulse assay. Four(4%) of 100 serum samples showed false high values, and all of them were obtained from patients less than 2 month after curative resection of HCC. Examining additional 7 patients with HCC resection, serum samples from the 5 patients had the same trend. To elucidate the non-specific reaction by Lumipulse assay which utilized alkaline phosphatase (ALP) enzymatic reaction, inhibition assays by various absorbents such as inactive ALP and IgM antibodies were performed. Excess of inactive ALP reduced the high values of PIVKA-II. Note that anti-bleeding sheets (fibrinogen combined drug), which included bovine thrombin, were directly attached on liver of all patients with HCC resection in this study. As the sheets also contaminate ALP and probably produce IgM antibodies to ALP, the IgM may cross-react with anti-PIVKA-II antibodies directly. Taken together, it was suggested that produced antibodies against ALP derived from anti-bleeding sheets led false high values of PIVKA-II in the patients with HCC resection.

Fiber optic immunosensor for cross-linked fibrin concentration

NASA Astrophysics Data System (ADS)

Moskowitz, Samuel E.

2000-08-01

Working with calcium ions in the blood, platelets produce thromboplastin which transforms prothrombin into thrombin. Removing peptides, thrombin changes fibrinogen into fibrin. Cross-linked insoluble fibrin polymers are solubilized by enzyme plasmin found in blood plasma. Resulting D-dimers are elevated in patients with intravascular coagulation, deep venous thrombosis, pulmonary embolism, myocardial infarction, multiple trauma, cancer, impaired renal and liver functions, and sepsis. Consisting principally of a NIR 780 nm GaAlAs laser diode and a 800 nm avalanche photodiode (APD), the fiber-optic immunosensor can determined D-dimer concentration to levels <0.1 ng/ml. A capture monoclonal antibody to the antigen soluble cross-linked fibrin is employed. Immobilized at the tip of an optical fiber by avidin-biotin, the captured antigen is detected by a second antibody which is labeled with NN 382 fluorescent dye. An evanescent wave traveling on an excitation optical fiber excites the antibody-antigen fluorophore complex. Concentration of cross-linked fibrin is directly proportional to the APD measured intensity of fluorescence. NIR fluorescence has advantages of low background interference, short fluorescence lifetime, and large difference between excitation and emission peaks. Competitive ELISA test for D-dimer concentration requires trained personnel performing a time consuming operation.

Quantification of trace metals in water using complexation and filter concentration.

PubMed

Dolgin, Bella; Bulatov, Valery; Japarov, Julia; Elish, Eyal; Edri, Elad; Schechter, Israel

2010-06-15

Various metals undergo complexation with organic reagents, resulting in colored products. In practice, their molar absorptivities allow for quantification in the ppm range. However, a proper pre-concentration of the colored complex on paper filter lowers the quantification limit to the low ppb range. In this study, several pre-concentration techniques have been examined and compared: filtering the already complexed mixture, complexation on filter, and dipping of dye-covered filter in solution. The best quantification has been based on the ratio of filter reflectance at a certain wavelength to that at zero metal concentration. The studied complex formations (Ni ions with TAN and Cd ions with PAN) involve production of nanoparticle suspensions, which are associated with complicated kinetics. The kinetics of the complexation of Ni ions with TAN has been investigated and optimum timing could be found. Kinetic optimization in regard to some interferences has also been suggested.

The Prothrombin G20210A Mutation is Associated with Young-Onset Stroke: The Genetics of Early Onset Stroke Study and Meta-Analysis

PubMed Central

Jiang, Baijia; Ryan, Kathleen A.; Hamedani, Ali; Cheng, Yuching; Sparks, Mary J.; Koontz, Deborah; Bean, Christopher J.; Gallagher, Margaret; Hooper, W. Craig; McArdle, Patrick F.; O'Connell, Jeffrey R.; Stine, O. Colin; Wozniak, Marcella A.; Stern, Barney J.; Mitchell, Braxton D.; Kittner, Steven J.; Cole, John W.

2014-01-01

Background and Purpose Although the prothrombin G20210A mutation has been implicated as a risk factor for venous thrombosis, its role in arterial ischemic stroke is unclear, particularly among young-adults. To address this issue, we examined the association between prothrombin G20210A and ischemic stroke in a Caucasian case-control population and additionally performed a meta-analysis Methods From the population-based Genetics of Early Onset Stroke (GEOS) study we identified 397 individuals of European ancestry aged 15-49 years with first-ever ischemic stroke and 426 matched-controls. Logistic regression was used to calculate odds ratios in the entire population and for subgroups stratified by gender, age, oral contraceptive use, migraine and smoking status. A meta-analysis of 17 case-control studies (n=2305 cases <55 years) was also performed with and without GEOS data. Results Within GEOS, the association of the prothrombin G20210A mutation with ischemic stroke did not achieve statistical significance (OR=2.5,95%CI=0.9-6.5,p=0.07). However, among adults aged 15-42 (younger than median age), cases were significantly more likely than controls to have the mutation (OR=5.9,95%CI=1.2-28.1,p=0.03), whereas adults ages 42-49 were not (OR=1.4,95%CI=0.4-5.1,p=0.94). In our meta-analysis, the mutation was associated with significantly increased stroke risk in adults <=55 years (OR=1.4;95%CI=1.1-1.9;p=0.02) with significance increasing with addition of the GEOS results (OR=1.5;95%CI=1.1-2.0;p=0.005). Conclusions The prothrombin G20210A mutation is associated with ischemic stroke in young-adults and may have an even stronger association among those with earlier onset strokes. Our finding of a stronger association in the younger-young adult population requires replication. PMID:24619398

Clinical impact of factor V Leiden, prothrombin G20210A, and MTHFR C677T mutations among sickle cell disease patients of Central India.

PubMed

Nishank, Sudhansu Sekhar; Singh, Mendi Prema Shyam Sunder; Yadav, Rajiv

2013-11-01

It is known that patients with sickle cell disease (SCD) present activation of the blood coagulation and fibrinolytic systems, especially during vaso-occlusive crises and also during the steady state of the disease. We determined whether the presence of the factor prothrombin gene G20210A variant, factor V gene G1691A mutation (factor V Leiden), and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms may be risk factors for vascular complications in individuals with SCD. The study involved 150 patients with sickle cell anemia and 150 healthy controls of Central India. Genotyping of three thrombophilic mutations was carried out by PCR-RFLP methods using MnlI, Hind III, and Hinf I, respectively, for factor V Leiden, prothrombin, and MTHFR mutations. Patients with SCD had significantly higher prevalence of mutant variants of MTHFR gene (28.0% heterozygotes and 14.6% homozygotes) and FVL gene (14.6% heterozygotes) as compared to normal/control individuals, but complete absence of mutant variants of prothrombin gene. The patients with SCD having mutant variants of MTHFR and FVL genes showed higher incidence of pain in chest, abdomen, and bone joints along with early age of onset of clinical manifestations as well as frequent dependence on blood transfusion than those patients with SCD having wild variants of these thrombotic genes. As compared to control subjects, SCD individuals having mutant variants of FVL and MTHFR genes had significant association with higher levels of prothrombin fragment (F1+2), D-dimer, thrombin-antithrombin (TAT), and lower level of protein C. MTHFR C677T and FVL G1691A polymorphisms may be risk factors for increased vascular complications in patient with SCD. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Factor V Leiden G1691A and prothrombin G20210A mutations among Palestinian patients with sickle cell disease.

PubMed

Samarah, Fekri; Srour, Mahmoud A

2018-01-01

Vascular thrombosis is an important pathophysiological aspect of sickle cell disease (SCD). This study aimed to investigate the prevalence and clinical impact of factor V Leiden G1691A (FVL) and prothrombin G20210A mutations among Palestinian sickle cell disease (SCD) patients. A total of 117 SCD patients, including 59 patients with sickle cell anemia (SS), 33 patients with sickle β-thalassemia and 25 individuals with sickle cell trait (AS) were studied. The control group consisted of 118 healthy individuals. FVL and prothrombin G20210A mutations were determined by RFLP PCR. Analysis of the clinical history of SCD patients revealed that seven patients have had vascular complications such as ischemic stroke or deep vein thrombosis. In SCD patients, the inheritance of the FVL mutation showed a significantly higher incidence of pain in joints, chest and abdomen as well as regular dependence on blood transfusion compared to SCD with the wild type. Age- and sex-adjusted logistic regression analysis revealed a significant association between FVL and sickle cell anemia with an odds ratio (OR) of 5.6 (95% confidence intervals [CI] of 1.91-39.4, P  = 0.039) in SS patients. However, increased prevalence of the FVL in AS subjects and sickle β-thalassemia patients was not statistically significant compared to controls (OR 3.97, 95% CI 0.51-28.6, P  = 0.17 and OR 3.59, 95% CI 0.35-41.6, P  = 0.26, respectively). The distribution of prothrombin G20210A mutation among SCD patients compared to controls was not significantly different, thus our findings do not support an association of this mutation with SCD. FVL was more prevalent among SS patients compared to controls and it was associated with higher incidence of disease complications among SCD patients.

Fixed Versus Variable Dosing of 4-factor Prothrombin Complex Concentrate for Emergent Warfarin Reversal

ClinicalTrials.gov

2018-04-06

Acute Bleeding on Long-Term Anticoagulation Therapy; Hemorrhage; Significant Bleeding in Patients With a Coagulopathy (Prolonged Thrombin Time); Urgent Reversal of Vitamin K Antagonist (VKA) Anticoagulation

Coagulation Management in Jersey Calves: An ex vivo Study.

PubMed

Gröning, Sabine; Maas, Judith; van Geul, Svenja; Rossaint, Rolf; Steinseifer, Ulrich; Grottke, Oliver

2017-01-01

Jersey calves are frequently used as an experimental animal model for in vivo testing of cardiac assist devices or orthopedic implants. In this ex vivo study, we analyzed the coagulation system of the Jersey calves and the potential of human-based coagulation management to circumvent perioperative bleeding complications during surgery. Experimental Procedure: Blood from 7 Jersey calves was subjected to standard laboratory tests and thromboelastometry analysis. An ex vivo model of dilutional coagulopathy was used to study the effects of fibrinogen or prothrombin complex concentrate supplementation. Fibrinolysis was induced with tissue plasminogen activator to identify potential therapeutic strategies involving tranexamic acid or aprotinin. Furthermore, anticoagulation strategies were evaluated by incubating the blood samples with dabigatran or rivaroxaban. Baseline values for thromboelastometry and standard laboratory parameters, including prothrombin time, activated partial thromboplastin time, fibrinogen, antithrombin III, and D-dimers, were established. Fifty percent diluted blood showed a statistically significant impairment of hemostasis. The parameters significantly improved after the administration of fibrinogen or prothrombin complex concentrate. Tranexamic acid and aprotinin ameliorated tissue plasminogen activator-induced fibrinolysis. Both dabigatran and rivaroxaban significantly prolonged the coagulation parameters. In this ex vivo study, coagulation factors, factor concentrate, antifibrinolytic reagents, and anticoagulants regularly used in the clinic positively impacted coagulation parameters in Jersey calf blood. © 2017 S. Karger AG, Basel.

Characteristics of scrub typhus, murine typhus, and Q fever among elderly patients: Prolonged prothrombin time as a predictor for severity.

PubMed

Chang, Ko; Lee, Nan-Yao; Ko, Wen-Chien; Lin, Wei-Ru; Chen, Yen-Hsu; Tsai, Jih-Jin; Chen, Tun-Chieh; Lin, Chun-Yu; Chang, Ya-Ting; Lu, Po-Liang

2017-06-22

The clinical manifestations of scrub typhus, murine typhus and acute Q fever in the elderly are not clear. We conducted a retrospective study to identify the characteristics of the elderly aged ≥65 years with a comparison group aged 18-64 years among patients with scrub typhus, murine typhus, or acute Q fever who were serologically confirmed at three hospitals in Taiwan during 2002-2011. Among 441 cases, including 187 cases of scrub typhus, 166 acute Q fever, and 88 murine typhus, 68 (15.4%) cases were elderly patients. The elderly had a higher severe complication rate (10.3% vs. 3.5%, p = 0.022), but did not have a significantly higher mortality rate (1.47% vs. 0.54%, p = 0.396). Compared with those without severe complications, we found the elderly (p = 0.022), dyspnea (p = 0.006), less relative bradycardia (p = 0.004), less febrile illness (p = 0.004), prolonged prothrombin time (PT) (p = 0.002), higher levels of initial C-reactive protein (p = 0.039), blood leukocyte counts (p = 0.01), and lower platelet counts (p = 0.012) are significantly associated with severe complications. Only prolonged prothrombin time was associated with severe complications in multivariate analysis (p = 0.018, CI 95% 0.01-0.66). Among clinical symptoms and laboratory data, multivariate analysis revealed chills was less frequently occurred in the elderly (p = 0.012, 95% confidence interval [CI]: 1.33-9.99). The elderly cases with scrub typhus, murine typhus, or acute Q fever would be more likely to have severe complications, for which prothrombin time prolongation is an important predictor for severe complications. Copyright © 2017. Published by Elsevier B.V.

Anti-prothrombin antibodies are associated with adverse pregnancy outcome.

PubMed

Marozio, Luca; Curti, Antonella; Botta, Giovanni; Canuto, Emilie M; Salton, Loredana; Tavella, Anna Maria; Benedetto, Chiara

2011-11-01

Women with antiphospholipid antibodies (aPL) such as lupus anticoagulant, anticardiolipin antibodies, and anti-β(2) glycoprotein-1 antibodies are at high risk of late pregnancy complications, such as severe pre-eclampsia, placental insufficiency, and fetal loss. It has been observed that aPL consists of a heterogeneous group of antibodies targeting several phospholipid-binding plasma proteins, including also anti-prothrombin (anti-PT), anti-protein S (anti-PS), and anti-protein C (anti-PC) antibodies. Their potential role in late pregnancy complications is not known. The aim of this work was to investigate the association between those autoantibodies and histories for adverse pregnancy outcome. Anti-PT, anti-PS, and anti-PC antibodies were evaluated in 163 patients with previous severe pre-eclampsia, fetal death, and/or placental abruption and in as many women with previous uneventful pregnancies, negative for aPL. The prevalence of anti-PT antibodies was higher in cases than in controls (OR, 95% CI: 10.92, 4.52-26.38). The highest prevalence was observed in subjects with fetal death. Anti-PT antibodies appear to be associated with adverse pregnancy outcome, irrespectively of aPL. © 2011 John Wiley & Sons A/S.

Prolonged Prothrombin Time After Recombinant Activated Factor VII Therapy in Critically Bleeding Trauma Patients Is Associated With Adverse Outcomes

DTIC Science & Technology

2010-07-01

using the FVII coagulant activity (FVII:C) assay, a one- stage assay using thromboplastin tissue factor , which quantifies FVII clotting activity in...and the resultant production of dysfunctional factors II, VII, and X. This study focused on PT specifically because this measure examines the TF...ORIGINAL ARTICLE Prolonged Prothrombin Time After Recombinant Activated Factor VII Therapy in Critically Bleeding Trauma Patients Is Associated With

Cerebral Venous Thrombosis and Pulmonary Embolism with Prothrombin G20210A Gene Mutation.

PubMed

Dagli, Canan Eren; Koksal, Nurhan; Guler, Selma; Gelen, Mehmet Emin; Atilla, Nurhan; Tuncel, Deniz

2010-04-01

A 25-year-old man presented with symptoms of syncope, cough, headache and hemoptysis. Cranial MR and venography showed thrombus formation in the right transverse sinus and superior sagittal sinus. Computed tomographic pulmonary angiography (CTPA) showed an embolic thrombus in the right pulmonary truncus and lung abscess. The patient was young, and there were no signs of lower extremity deep venous thrombosis or other major risk factors for pulmonary embolism (PE) including cardiac anomaly. The only risk factor we were able to identify was the presence of the prothrombin G20210A gene mutation. Anticoagulant treatment with oral warfarin (10 mg daily) and imipenem (4X500 mg) was started. The patient was hospitalized for antibiotic and anticoagulation therapies for three weeks and was discharged on lifelong treatment with warfarin (5 mg daily).

On the value of routine prothrombin time screening in elective neurosurgical procedures.

PubMed

Dützmann, Stephan; Gessler, Florian; Marquardt, Gerhard; Seifert, Volker; Senft, Christian

2012-11-01

The authors performed a study to evaluate whether preoperative assessment of prothrombin time (PT) is mandatory in patients undergoing routinely planned neurosurgical procedures. The charts of all patients admitted to general wards of the authors' department for routinely planned surgery (excluding trauma and ICU patients) between 2006 and 2010 were retrospectively reviewed. The authors assessed preoperative PT and the clinical courses of all patients, with special consideration for patients receiving coagulation factor substitution. All cases involving hemorrhagic complications were analyzed in detail with regard to pre- and postoperative PT abnormalities. Prothrombin time was expressed as the international normalized ratio, and values greater than 1.28 were regarded as elevated. Clinical courses and PT values of 4310 patients were reviewed. Of these, 33 patients (0.7%) suffered hemorrhagic complications requiring repeat surgery. Thirty-one patients (94%) had a normal PT before the initial operation, while 2 patients had slightly elevated PT values of 1.33 and 1.65, which were anticipated based on the patient's history. In the latter 2 cases, surgery was performed without prior correction of PT. Preoperatively, PT was elevated in 78 patients (1.8%). In 73 (93.6%) of the 78 patients, the PT elevation was expected and explained by each patient's medical history. In only 5 (0.1%) of 4310 patients did we find an unexpected PT elevation (mean 1.53, range 1.37-1.74). All 5 patients underwent surgery without complications, while 2 had received coagulation factor substitution preoperatively, as requested by the surgeon, because of an estimated risk of bleeding complications. None of the 5 patients received coagulation factor substitution postoperatively, and later detailed laboratory studies ruled out single coagulation factor deficiencies. There was no statistically significant association between preoperatively elevated PT levels and the occurrence of hemorrhagic

Influence of Structure, Charge, and Concentration on the Pectin-Calcium-Surfactant Complexes.

PubMed

Joshi, Nidhi; Rawat, Kamla; Bohidar, H B

2016-05-12

Polymer-surfactant complex formation of pectin with different types of surfactants, cationic (cetyltrimethylammonium bromide, CTAB and dodecyl trimethylammonium bromide, DTAB), anionic (sodium dodecyl sulfate, SDS), and neutral (Triton X-100, TX-100), was investigated at room temperature in the presence and absence of cross-linker calcium chloride using light scattering, zeta potential, rheology, and UV-vis spectroscopic measurements where the surfactant concentration was maintained below their critical micellar concentration (CMC). Results indicated that the interaction of cationic surfactant with pectin in the presence and absence of calcium chloride was much stronger compared to anionic and neutral surfactants. The neutral surfactant showed identifiable interaction despite the absence of any charged headgroup, while anionic surfactant showed feeble or very weak interaction with the polymer. The pectin-CTAB or DTAB complex formation was attributed to associative electrostatic and hydrophobic interactions. On comparison between the cationic surfactants, it was found that CTAB interacts strongly with pectin because of its long hydrocarbon chain. The morphology of complexes formed exhibited random coil structures while at higher concentration of surfactant, rod-like or extended random coil structures were noticed. Thus, functional characteristics of the complex could be tuned by varying the type of surfactant (charge and structure) and its concentration. The differential network rigidity (pectin-CTAB versus pectin-DTAB gels) obtained from rheology measurements showed that addition of a very small amount of surfactant (concentration ≪ CMC) was required for enhancing network strength, while the presence of a large amount of surfactant resulted in the formation of fragile gels. No gel formation occurred when the surfactant concentration was close to their CMC values. Considering the importance of pectin in food and pharmaceutical industry, this study is relevant.

A retrospective discussion of the prognostic value of combining prothrombin time(PT) and fibrinogen(Fbg) in patients with Hepatocellular carcinoma.

PubMed

Wang, Xue-Ping; Mao, Min-Jie; He, Zhong-Lian; Zhang, Lin; Chi, Pei-Dong; Su, Jia-Rui; Dai, Shu-Qin; Liu, Wan-Li

2017-01-01

Aims: The levels of coagulation system tests have been studied in various cancers. In this study, our aim is to evaluate the prognostic value of pretreatment plasma coagulation tests in hepatocellular carcinoma (HCC) patients. Patient and methods: A retrospective study was performed in 539 patients with HCC, and follow-up period was at least 60 months until recurrence or death. The prognostic significance of coagulation system tests (prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen) were determined by univariate and multivariate Cox hazard models. Then, according to the results of the multivariate analyses, we proposed the coagulation-Based Stage, which combined the independent risk factors (prothrombin time and fibrinogen). Results: Coagulation system tests including prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fbg) were analyzed. Patients with prolonged PT (≥12.1 sec) levels had significantly poor overall survival (OS) and disease-free survival (DFS), not only in the entire cohort (HR: 1.661, 95%CI: 1.125-2.451, p= 0.011 vs. HR: 1.660, 95%CI: 1.125-2.451, p= 0.011), but also in the subgroups stratified by pathological stage (stage I-II and stage III-IV). Additionally, high Fbg (≥2.83 g/L) levels experienced significantly decreased OS and DFS (HR: 2.158, 95%CI: 1.427-3.263, p< 0.001 vs. HR: 2.161, 95%CI: 1.429-3.267, p< 0.001), not only in the entire cohort but also in the subgroups stratified by pathological stage (stage I-II and stage III-IV). All the patients were then stratified (based on combined PT and Fbg) into three groups, The OS for HCC patients were (41.37±17.76), (31.83±19.84) and (18.68±18.41) months, and the DFS for HCC patients were (41.15±17.88), (31.65±19.81) and (18.66±18.39) months. Conclusions: Our findings suggest that the combination of plasma PT and Fbg levels should be evaluated as the valuable predictor of survival in patients with HCC.

The interval between prothrombin time tests and the quality of oral anticoagulants treatment in patients with chronic atrial fibrillation.

PubMed

Shalev, Varda; Rogowski, Ori; Shimron, Orit; Sheinberg, Bracha; Shapira, Itzhak; Seligsohn, Uri; Berliner, Shlomo; Misgav, Mudi

2007-01-01

The incidence of stroke in patients with atrial fibrillation (AF) can be significantly reduced with warfarin therapy especially if optimally controlled. To evaluate the effect of the interval between consecutive prothrombin time measurements on the time in therapeutic range (INR 2-3) in a cohort of patients with AF on chronic warfarin treatment in the community. All INR measurements available from a relatively large cohort of patients with chronic AF were reviewed and the mean interval between consecutive INR tests of each patient was correlated with the time in therapeutic range (TTR). Altogether 251,916 INR measurements performed in 4408 patients over a period of seven years were reviewed. Sixty percent of patients had their INR measured on average every 2 to 3 weeks and most others were followed at intervals of 4 weeks or longer. A small proportion (3.6%) had their INR measured on average every week. A significant decline in the time in therapeutic range was observed as the intervals between tests increased. At one to three weeks interval the TTR was 48%, at 4 weeks interval 45% and at 5 weeks 41% (P<0.0005). A five percent increment in TTR was observed if more tests were performed at multiplications of exactly 7 days (43% vs 48% P<0.0001). A better control with an increase in the TTR was observed in patients with atrial fibrillation if prothrombin time tests are performed at regular intervals of no longer than 3 weeks.

[Biohydrometallurgical technology of a complex copper concentrate process].

PubMed

Murav'ev, M I; Fomchenko, N V; Kondrat'eva, T F

2011-01-01

Leaching of sulfide-oxidized copper concentrate of the Udokan deposit ore with a copper content of 37.4% was studied. In the course of treatment in a sulfuric acid solution with pH 1.2, a copper leaching rate was 6.9 g/kg h for 22 h, which allowed extraction of 40.6% of copper. As a result of subsequent chemical leaching at 80 degrees C during 7 h with a solution of sulphate ferric iron obtained after bio-oxidation by an association of microorganisms, the rate of copper recovery was 52.7 g/kg h. The total copper recovery was 94.5% (over 29 h). Regeneration of the Fe3+ ions was carried out by an association of moderately thermophilic microorganisms, including bacteria of genus Sulfobacillus and archaea of genus Ferroplasma acidiphilum, at 1.0 g/l h at 40 degrees C in the presence of 3% solids obtained by chemical leaching of copper concentrate. A technological scheme of a complex copper concentrate process with the use of bacterial-chemical leaching is proposed.

Environmental and Body Concentrations of Heavy Metals at Sites Near and Distant from Industrial Complexes in Ulsan, Korea.

PubMed

Sung, Joo Hyun; Oh, Inbo; Kim, Ahra; Lee, Jiho; Sim, Chang Sun; Yoo, Cheolin; Park, Sang Jin; Kim, Geun Bae; Kim, Yangho

2018-01-29

Industrial pollution may affect the heavy metal body burden of people living near industrial complexes. We determined the average concentrations of atmospheric heavy metals in areas close to and distant from industrial complexes in Korea, and the body concentrations of these heavy metals in residents living near and distant from these facilities. The atmospheric data of heavy metals (lead and cadmium) were from the Regional Air Monitoring Network in Ulsan. We recruited 1,148 participants, 872 who lived near an industrial complex ("exposed" group) and 276 who lived distant from industrial complexes ("non-exposed" group), and measured their concentrations of blood lead, urinary cadmium, and urinary total mercury. The results showed that atmospheric and human concentrations of heavy metals were higher in areas near industrial complexes. In addition, residents living near industrial complexes had higher individual and combined concentrations (cadmium + lead + mercury) of heavy metals. We conclude that residents living near industrial complexes are exposed to high concentrations of heavy metals, and should be carefully monitored. © 2018 The Korean Academy of Medical Sciences.

Environmental and Body Concentrations of Heavy Metals at Sites Near and Distant from Industrial Complexes in Ulsan, Korea

PubMed Central

2017-01-01

Background Industrial pollution may affect the heavy metal body burden of people living near industrial complexes. We determined the average concentrations of atmospheric heavy metals in areas close to and distant from industrial complexes in Korea, and the body concentrations of these heavy metals in residents living near and distant from these facilities. Methods The atmospheric data of heavy metals (lead and cadmium) were from the Regional Air Monitoring Network in Ulsan. We recruited 1,148 participants, 872 who lived near an industrial complex (“exposed” group) and 276 who lived distant from industrial complexes (“non-exposed” group), and measured their concentrations of blood lead, urinary cadmium, and urinary total mercury. Results The results showed that atmospheric and human concentrations of heavy metals were higher in areas near industrial complexes. In addition, residents living near industrial complexes had higher individual and combined concentrations (cadmium + lead + mercury) of heavy metals. Conclusion We conclude that residents living near industrial complexes are exposed to high concentrations of heavy metals, and should be carefully monitored. PMID:29349943

Evaluation of Factor V Leiden, Prothrombin G20210A, MTHFR C677T and MTHFR A1298C gene polymorphisms in retinopathy of prematurity in a Turkish cohort.

PubMed

Aydin, Hatip; Gunay, Murat; Celik, Gokhan; Gunay, Betul Onal; Aydin, Umeyye Taka; Karaman, Ali

2016-12-01

To assess Factor V Leiden (FVL) (rs6025), Prothrombin G20210A (rs1799963), MTHFR C677T (rs1801133), and MTHFR A1298C (rs1801131) gene mutations as risk factors in the development of retinopathy of prematurity (ROP). A total of 105 children were included in this cross-sectional study. Patients were divided into two groups. The study group consisted of 55 infants with a history of ROP and the control group comprised 50 healthy infants with term birth. All subjects were screened for the presence of certain mutations (FVL, Prothrombin G20210A, MTHFR C677T and MTHFR A1298C) by Real-Time PCR at 1 year of age. The mean gestational age (GA) and birth weight (BW) of the study group were, 28.65 ± 2.85 weeks and 1171 ± 385.74 g, respectively. There were no significant differences of genotype and allele frequency of Prothrombin G20210A, MTHFR A1298C and MTHFR C677T between the study and control groups (p > 0.05). Eight children (14.5 %) had heterozygous and one child (1.8%) had homozygous FVL mutation in the study group. One child (2%) in the control group had heterozygous FVL mutation. There was statistically significant differences of FVL allele and genotype frequencies between the groups (p < 0.05). The prevalence of FVL polymorphism (16.3 %) was higher in ROP patients than control subjects in this Turkish cohort. We suggest a possible association of FVL mutation with ROP at the end of the study.

The association of factor V G1961A (factor V Leiden), prothrombin G20210A, MTHFR C677T and PAI-1 4G/5G polymorphisms with recurrent pregnancy loss in Bosnian women.

PubMed

Jusić, Amela; Balić, Devleta; Avdić, Aldijana; Pođanin, Maja; Balić, Adem

2018-08-01

Aim To investigate association of factor V Leiden, prothrombin G20210A, MTHFR C677T and PAI-1 4G/5G polymorphisms with recurrent pregnancy loss in Bosnian women. Methods A total of 60 women with two or more consecutive miscarriages before 20 weeks of gestation with the same partners and without history of known causes or recurrent pregnancy loss were included. A control group included 80 healthy women who had one or more successful pregnancies without history of any complication which could be associated with miscarriages. Genotyping of factor V Leiden, prothrombin G20210A, MTHFR C677T and PAI-1 4G/5G polymorphisms were performed by polymerase chain reaction/restriction fragments length polymorphism method (PCR/RFLP). Results Both factor V Leiden and MTHFR C677T polymorphisms were significantly associated with recurrent pregnancy loss (RPL) in Bosnian women while prothrombin G20210A and PAI-1 4G/5G polymorphisms did not show strongly significant association. Conclusion The presence of thrombophilic polymorphisms may predispose women to recurrent pregnancy loss. Future investigation should be addressed in order to find when carriers of those mutations, polymorphisms should be treated with anticoagulant therapy. Copyright© by the Medical Assotiation of Zenica-Doboj Canton.

Analysis of Metals Concentration in the Soils of SIPCOT Industrial Complex, Cuddalore, Tamil Nadu

PubMed Central

Mathivanan, V.; Prabavathi, R.; Prithabai, C.; Selvisabhanayakam

2010-01-01

Phytoremediation is a promising area of new research, both for its low cost and great benefit to society in the clean retrieval of contaminated sites. Phytoremediation is the use of living green plants for in situ risk reduction and/or removal of contaminants from contaminated soil, water, sediments, and air. Specially selected or engineered plants are used in the process. The soil samples were taken from Cuddalore Old Town (OT) and the samples from SIPCOT industrial complex, which was the study area and analyzed for various metals concentrations. Fifteen metals have been analyzed by adopting standard procedure. The detection limits of metal concentration are drawn as control. The various (15) metal concentrations in the soil samples were found higher in soil taken from SIPCOT industrial complex, compared with samples taken from Cuddalore OT. In all the observations, it was found that most of the metals like calcium, cadmium, chromium, cobalt, nickel, and zinc showed maximum concentrations, whereas arsenic, antimony, lead, magnesium, sodium have shown minimum concentrations, both when compared with control. From the present study, it was found that the soil collected from SIPCOT complex area were more polluted due to the presence of various industrial effluents, municipal wastes, and sewages when compared with the soil collected from Cuddalore OT. PMID:21170256

Anti-Phosphatidylserine/Prothrombin Antibodies Are Associated with Adverse Pregnancy Outcomes.

PubMed

Žigon, Polona; Perdan Pirkmajer, Katja; Tomšič, Matija; Kveder, Tanja; Božič, Borut; Sodin Šemrl, Snežna; Čučnik, Saša; Ambrožič, Aleš

2015-01-01

Objective. To determine the prevalence and clinical association of anti-phosphatidylserine/prothrombin antibodies (aPS/PT) in patients with a history of pregnancy complications relevant to antiphospholipid syndrome (APS). Materials and Methods. Two hundred and eleven patients with a history of (a) three or more consecutive miscarriages before 10th week of gestation (WG) (n = 64), (b) death of a morphologically normal fetus beyond 10th WG (n = 72), (c) premature birth of a morphologically normal neonate before 34th WG due to eclampsia, preeclamsia and placental insufficiency (n = 33), and (d) less than three unexplained consecutive miscarriages before 10th WG (n = 42). Subjects sera were analyzed for lupus anticoagulant (LA), anti-cardiolipin (aCL), anti-β 2-glycoprotein I (anti-β 2GPI), and aPS/PT antibodies. Results. 41/169 (24.3%) of patients were positive for at least one measured aPL. The highest prevalence was found for aPS/PT and aCL (13.0% and 12.4%, resp.) followed by LA (7.7%) and anti-β 2GPI (7.1%). 11/169 with APS-related obstetric manifestations had only aPS/PT. 17.8% of patients were positive for LA or aCL and/or anti-β 2GPI; however when adding the aPS/PT results, an additional 7% of patients could be evaluated for APS. Conclusion. aPS/PT are associated with recurrent early or late abortions and with premature delivery irrespective of other aPL.

Anti-Phosphatidylserine/Prothrombin Antibodies Are Associated with Adverse Pregnancy Outcomes

PubMed Central

Žigon, Polona; Tomšič, Matija; Kveder, Tanja; Božič, Borut; Sodin Šemrl, Snežna; Čučnik, Saša; Ambrožič, Aleš

2015-01-01

Objective. To determine the prevalence and clinical association of anti-phosphatidylserine/prothrombin antibodies (aPS/PT) in patients with a history of pregnancy complications relevant to antiphospholipid syndrome (APS). Materials and Methods. Two hundred and eleven patients with a history of (a) three or more consecutive miscarriages before 10th week of gestation (WG) (n = 64), (b) death of a morphologically normal fetus beyond 10th WG (n = 72), (c) premature birth of a morphologically normal neonate before 34th WG due to eclampsia, preeclamsia and placental insufficiency (n = 33), and (d) less than three unexplained consecutive miscarriages before 10th WG (n = 42). Subjects sera were analyzed for lupus anticoagulant (LA), anti-cardiolipin (aCL), anti-β 2-glycoprotein I (anti-β 2GPI), and aPS/PT antibodies. Results. 41/169 (24.3%) of patients were positive for at least one measured aPL. The highest prevalence was found for aPS/PT and aCL (13.0% and 12.4%, resp.) followed by LA (7.7%) and anti-β 2GPI (7.1%). 11/169 with APS-related obstetric manifestations had only aPS/PT. 17.8% of patients were positive for LA or aCL and/or anti-β 2GPI; however when adding the aPS/PT results, an additional 7% of patients could be evaluated for APS. Conclusion. aPS/PT are associated with recurrent early or late abortions and with premature delivery irrespective of other aPL. PMID:26078985

Limiting prothrombin activation to meizothrombin is compatible with survival but significantly alters hemostasis in mice

PubMed Central

Shaw, Maureen A.; Kombrinck, Keith W.; McElhinney, Kathryn E.; Sweet, David R.; Flick, Matthew J.; Palumbo, Joseph S.; Cheng, Mei; Esmon, Naomi L.; Esmon, Charles T.; Brill, Alexander; Wagner, Denisa D.; Degen, Jay L.

2016-01-01

Thrombin-mediated proteolysis is central to hemostatic function but also plays a prominent role in multiple disease processes. The proteolytic conversion of fII to α-thrombin (fIIa) by the prothrombinase complex occurs through 2 parallel pathways: (1) the inactive intermediate, prethrombin; or (2) the proteolytically active intermediate, meizothrombin (fIIaMZ). FIIaMZ has distinct catalytic properties relative to fIIa, including diminished fibrinogen cleavage and increased protein C activation. Thus, fII activation may differentially influence hemostasis and disease depending on the pathway of activation. To determine the in vivo physiologic and pathologic consequences of restricting thrombin generation to fIIaMZ, mutations were introduced into the endogenous fII gene, resulting in expression of prothrombin carrying 3 amino acid substitutions (R157A, R268A, and K281A) to limit activation events to yield only fIIaMZ. Homozygous fIIMZ mice are viable, express fII levels comparable with fIIWT mice, and have reproductive success. Although in vitro studies revealed delayed generation of fIIaMZ enzyme activity, platelet aggregation by fIIMZ is similar to fIIWT. Consistent with prior analyses of human fIIaMZ, significant prolongation of clotting times was observed for fIIMZ plasma. Adult fIIMZ animals displayed significantly compromised hemostasis in tail bleeding assays, but did not demonstrate overt bleeding. More notably, fIIMZ mice had 2 significant phenotypic advantages over fIIWT animals: protection from occlusive thrombosis after arterial injury and markedly diminished metastatic potential in a setting of experimental tumor metastasis to the lung. Thus, these novel animals will provide a valuable tool to assess the role of both fIIa and fIIaMZ in vivo. PMID:27252233

Complex Adaptive System Models and the Genetic Analysis of Plasma HDL-Cholesterol Concentration

PubMed Central

Rea, Thomas J.; Brown, Christine M.; Sing, Charles F.

2006-01-01

Despite remarkable advances in diagnosis and therapy, ischemic heart disease (IHD) remains a leading cause of morbidity and mortality in industrialized countries. Recent efforts to estimate the influence of genetic variation on IHD risk have focused on predicting individual plasma high-density lipoprotein cholesterol (HDL-C) concentration. Plasma HDL-C concentration (mg/dl), a quantitative risk factor for IHD, has a complex multifactorial etiology that involves the actions of many genes. Single gene variations may be necessary but are not individually sufficient to predict a statistically significant increase in risk of disease. The complexity of phenotype-genotype-environment relationships involved in determining plasma HDL-C concentration has challenged commonly held assumptions about genetic causation and has led to the question of which combination of variations, in which subset of genes, in which environmental strata of a particular population significantly improves our ability to predict high or low risk phenotypes. We document the limitations of inferences from genetic research based on commonly accepted biological models, consider how evidence for real-world dynamical interactions between HDL-C determinants challenges the simplifying assumptions implicit in traditional linear statistical genetic models, and conclude by considering research options for evaluating the utility of genetic information in predicting traits with complex etiologies. PMID:17146134

Kinetic Model Facilitates Analysis of Fibrin Generation and Its Modulation by Clotting Factors: Implications for Hemostasis-Enhancing Therapies

DTIC Science & Technology

2014-01-01

facilitates analysis of fibrin generation and its modulation by clotting factors : implications for hemostasis-enhancing therapies† Alexander Y...investigate the ability of fibrinogen and a recently proposed prothrombin complex concentrate composition, PCC-AT (a combination of the clotting factors II...kinetics. Moreover, the model qualitatively predicted the impact of tissue factor and tPA/tenecteplase level variations on the fibrin output. In the

Effect of salt and surfactant concentration on the structure of polyacrylate gel/surfactant complexes.

PubMed

Nilsson, Peter; Unga, Johan; Hansson, Per

2007-09-20

Small-angle X-ray scattering was used to elucidate the structure of crosslinked polyacrylate gel/dodecyltrimethylammonium bromide complexes equilibrated in solutions of varying concentrations of surfactant and sodium bromide (NaBr). Samples were swollen with no ordering (micelle free), or they were collapsed with either several distinct peaks (cubic Pm3n) or one broad correlation peak (disordered micellar). The main factor determining the structure of the collapsed complexes was found to be the NaBr concentration, with the cubic structure existing up to approximately 150 mM NaBr and above which only the disordered micellar structure was found. Increasing the salt concentration decreases the polyion mediated attractive forces holding the micelles together causing swelling of the gel. At sufficiently high salt concentration the micelle-micelle distance in the gel becomes too large for the cubic structure to be retained, and it melts into a disordered micellar structure. As most samples were above the critical micelle concentration, the bulk of the surfactant was in the form of micelles in the solution and the surfactant concentration thereby had only a minor influence on the structure. However, in the region around 150 mM NaBr, increasing the surfactant concentration, at constant NaBr concentration, was found to change the structure from disordered micellar to ordered cubic and back to disordered again.

Rational and timely haemostatic interventions following cardiac surgery - coagulation factor concentrates or blood bank products.

PubMed

Tang, Mariann; Fenger-Eriksen, Christian; Wierup, Per; Greisen, Jacob; Ingerslev, Jørgen; Hjortdal, Vibeke; Sørensen, Benny

2017-06-01

Cardiac surgery may cause a serious coagulopathy leading to increased risk of bleeding and transfusion demands. Blood bank products are commonly first line haemostatic intervention, but has been associated with hazardous side effect. Coagulation factor concentrates may be a more efficient, predictable, and potentially a safer treatment, although prospective clinical trials are needed to further explore these hypotheses. This study investigated the haemostatic potential of ex vivo supplementation of coagulation factor concentrates versus blood bank products on blood samples drawn from patients undergoing cardiac surgery. 30 adults were prospectively enrolled (mean age=63.9, females=27%). Ex vivo haemostatic interventions (monotherapy or combinations) were performed in whole blood taken immediately after surgery and two hours postoperatively. Fresh-frozen plasma, platelets, cryoprecipitate, fibrinogen concentrate, prothrombin complex concentrate (PCC), and recombinant FVIIa (rFVIIa) were investigated. The haemostatic effect was evaluated using whole blood thromboelastometry parameters, as well as by thrombin generation. Immediately after surgery the compromised maximum clot firmness was corrected by monotherapy with fibrinogen or platelets or combination therapy with fibrinogen. At two hours postoperatively the coagulation profile was further deranged as illustrated by a prolonged clotting time, a reduced maximum velocity and further diminished maximum clot firmness. The thrombin lagtime was progressively prolonged and both peak thrombin and endogenous thrombin potential were compromised. No monotherapy effectively corrected all haemostatic abnormalities. The most effective combinations were: fibrinogen+rFVIIa or fibrinogen+PCC. Blood bank products were not as effective in the correction of the coagulopathy. Coagulation factor concentrates appear to provide a more optimal haemostasis profile following cardiac surgery compared to blood bank products. Copyright © 2017

Structural complexes in the squid giant axon membrane sensitive to ionic concentrations and cardiac glycosides

PubMed Central

Villegas, GM; Villegas, J

1976-01-01

Giant nerve fibers of squid Sepioteuthis sepiodea were incubated for 10 min in artificial sea water (ASW) under control conditions, in the absence of various ions, and in the presence of cardiac glycosides. The nerve fibers were fixed in OsO(4) and embedded in Epon, and structural complexes along the axolemma were studied. These complexes consist of a portion of axolemma exhibiting a three-layered substructure, an undercoating of a dense material (approximately 0.1μm in length and approximately 70-170 A in thickness), and a narrowing to disappearance of the axon-Schwann cell interspace. In the controls, the incidence of complexes per 1,000μm of axon perimeter was about 137. This number decreased to 10-25 percent when magnesium was not present in the incubating media, whatever the calcium concentration (88, 44, or 0 mM). In the presence of magnesium, the number and structural features of the complexes were preserved, though the number decreased to 65 percent when high calcium was simultaneously present. The complexes were also modified and decreased to 26-32 percent by incubating the nerves in solutions having low concentrations of sodium and potassium. The adding of 10(-5) M ouabain or strophanthoside to normal ASW incubating solution decreased them to 20-40 percent. Due to their sensitivity to changes in external ionic concentrations and to the presence of cardiac glycosides, the complexes are proposed to represent the structural correlate of specialized sites for active ion transport, although other factors may be involved. PMID:1254642

Management of Coagulopathy in the Patients With Multiple Injuries: Results From an International Survey of Clinical Practice

DTIC Science & Technology

2008-10-01

Fresh whole blood D Not available D Trigger: D Treatment protocol: Comment: Adjuvant therapy D Aprotinin D Tranexamic acid D Desmopressin D Ca...that were mentioned included prothrombin complex concentrate (PCC), activated recombinant factor VII (rFVIIa), aprotinin, and tranexamic acid (Fig. 2...of respondents, followed by Ca (53%) and vitamin K (38%), and to a lesser extent tranexamic acid (28%), aprotinin (26%), desmopressin (24%), and

Action of multi-enzyme complex on protein extraction to obtain a protein concentrate from okara.

PubMed

de Figueiredo, Vitória Ribeiro Garcia; Yamashita, Fábio; Vanzela, André Luis Laforga; Ida, Elza Iouko; Kurozawa, Louise Emy

2018-04-01

The objective of this study was to optimize the extraction of protein by applying a multi-enzymatic pretreatment to okara, a byproduct from soymilk processing. The multi-enzyme complex Viscozyme, containing a variety of carbohydrases, was used to hydrolyze the okara cell walls and facilitate extraction of proteins. Enzyme-assisted extraction was carried out under different temperatures (37-53 °C), enzyme concentrations (1.5-4%) and pH values (5.5-6.5) according to a central composite rotatable design. After extraction, the protein was concentrated by isoelectric precipitation. The optimal conditions for maximum protein content and recovery in protein concentrate were 53 °C, pH 6.2 and 4% of enzyme concentration. Under these conditions, protein content of 56% (dry weight basis) and a recovery of 28% were obtained, representing an increase of 17 and 86%, respectively, compared to the sample with no enzymatic pretreatment. The multi-enzyme complex Viscozyme hydrolyzed the structural cell wall polysaccharides, improving extraction and obtaining protein concentrate from the okara. An electrophoretic profile of the protein concentrate showed two distinct bands, corresponding to the acidic and basic subunits of the protein glycinin. There were no limiting amino acids in the protein concentrate, which had a greater content of arginine.

Influence of detergent concentration on aggregation and spectroscopic properties of light-harvesting complex II.

PubMed

Voigt, Bernd; Krikunova, Maria; Lokstein, Heiko

2008-01-01

Aggregation of photosynthetic light-harvesting complexes strongly influences their spectroscopic properties. Fluorescence yield and excited state lifetimes of the main light-harvesting complex (LHC II) of higher plants strongly depend on its aggregation state. Detergents are commonly used to solubilize membrane proteins and/or to circumvent their aggregation in aqueous environments. Nonlinear polarization spectroscopy in the frequency domain (NLPF) was performed with LHC II over a wide concentration range of the mild detergent n-dodecyl beta-D: -maltoside (beta-DM). Additionally, conventional absorption-, fluorescence- and circular dichroism-spectra were measured.The results indicate that: (i) conventional spectroscopic techniques are not well suited to investigate aggregation effects. NLPF provides a novel approach to overcome this problem: NLPF spectra display dramatic alterations upon even minor beta-DM concentration changes. (ii) Commonly used detergent concentrations (around or slightly above the critical micellar concentration) apparently do not lead to complete trimerization of LHC II. A long-wavelength species in the NLPF spectra (peaking at about 685 nm), indicative of residual aggregation, persists up to DM-concentrations of 0.06%. (iii) High-resolution NLPF spectra indicate the existence of a species with a considerably shortened excited state lifetime. (iv) No indication of denaturation was found even at the highest beta-DM concentrations used. (v) A specific change in interaction between certain chlorophyll(s) b and a xanthophyll molecule, probably neoxanthin, was detected upon aggregation as well as at higher beta-DM concentrations. The results are discussed with respect to the still elusive mechanism of nonradiative dissipation of excess excitation energy in the antenna system.

Structural perturbation of proteins in low denaturant concentrations.

PubMed

Basak, S; Debnath, D; Haque, E; Ray, S; Chakrabarti, A

2001-01-01

The presence of very low concentrations of the widely used chemical denaturants, guanidinium chloride and urea, induce changes in the tertiary structure of proteins. We have presented results on such changes in four structurally unrelated proteins to show that such structural perturbations are common irrespective of their origin. Data representative of such structural changes are shown for the monomeric globular proteins such as horseradish peroxidase (HRP) from a plant, human serum albumin (HSA) and prothrombin from ovine blood serum, and for the membrane-associated, worm-like elongated protein, spectrin, from ovine erythrocytes. Structural alterations in these proteins were reflected in quenching studies of tryptophan fluorescence using the widely used quencher acrylamide. Stern-Volmer quenching constants measured in presence of the denaturants, even at concentrations below 100 mM, were higher than those measured in absence of the denaturants. Both steady-state and time-resolved fluorescence emission properties of tryptophan and of the extrinsic probe PRODAN were used for monitoring conformational changes in the proteins in presence of different low concentrations of the denaturants. These results are consistent with earlier studies from our laboratory indicating structural perturbations in proteins at the tertiary level, keeping their native-like secondary structure and their biological activity more or less intact.

Concentration, Complexation and Chemical Speciation of Zinc and Cadmium in the Western North Pacific Ocean : Exploring Sources and Transport of Trace Metals and Complexing Ligands.

NASA Astrophysics Data System (ADS)

Carrasco, G. G.; Morton, P. L.; Donat, J. R.

2008-12-01

We determined Zn and Cd total dissolved (0.45 µm-filtered) concentrations, organic complexation and chemical speciation in surface water samples collected along the transect of the 2002 IOC Baseline Contaminant Survey expedition in the Western North Pacific and in vertical profile water samples at nine stations. The goals of this work were (1) to compare and contrast various trace metal sources, including both natural and anthropogenic atmospheric deposition, upwelling, marginal seas and others; (2) to study the organic ligand sources, generally thought to be phytoplankton; and (3) to investigate metal and ligand transport mechanisms, residence times and eventual upwelling in the Eastern North Pacific. Total dissolved (TD) Zn and Cd values were obtained using a combination of differential pulse stripping anodic voltammetry (DPASV), preconcentration with 8-HQ or APDC/DDC and quantification at ICPMS or AA. Organic complexation and chemical speciation of Zn and Cd were determined simultaneously using DPASV at a thin-mercury-film, glassy-carbon-disk-electrode. Surface transect TDZn and TDCd concentrations were low in the Subtropical Gyre (STG), in contrast with high values in the Western Subarctic Gyre (WSG). Zn and Cd were organically complexed in most surface samples: at least one ligand class was detected for Zn and Cd, whose conditional stability constants (log K') averaged 10.2 and 10.5, respectively. These ligands were found in excess of the total dissolved metal throughout the region of study except in the WSG for Cd. Vertical distributions of TDZn and TDCd exhibited nutrient-type profiles for all the STG stations. While constant Zn/Si and Cd/P values were observed throughout the water column in the WSG, some deviations were observed within the STG. In addition, the mode and intermediate water masses of the STG displayed very high concentrations of a Zn-complexing ligand (log K' 10.0) in excess of TDZn. As these water masses moved eastward, we observed that the

Effect of EDTA and Fe-EDTA complex concentration on TCF Kraft mill effluent degradability. Batch and continuous treatments.

PubMed

Diez, M C; Pouleurs, D; Navia, R; Vidal, G

2005-09-01

The effect of ethylenediaminetetracetic acid (EDTA) and Fe-EDTA complex on synthetic totally chlorine-free (TCF) effluent degradability in batch and continuously operating reactors was evaluated. Under batch treatment, the addition of EDTA and Fe-EDTA complex was studied in the range of 80 to 320 mg l(-1). Under continuously operated reactors, the Fe-EDTA complex concentration varied from 20 to 80 mg l(-1), and the hydraulic retention time (HRT) varied from 48 to 24 h. Sludge oxygen uptake rate (OUR) and chemical oxygen demand (COD) removal decreased when EDTA concentration increased in the influent under batch treatment; however, this inhibitory effect was reduced by the addition of Fe-EDTA complex. Without the addition of EDTA, COD removal decreased from 71% to 8%. The most efficient EDTA removal treatment (almost 10%) was the treatment of 80 mg l(-1) Fe-EDTA. Under continuously operated reactors, COD removal was greater than 57% in the synthetic TCF effluent with a Fe-EDTA concentration that varied from 20 to 80 mg l(-1); however, EDTA removal was lower than 25% in all cases. Synthetic TCF effluent with a Fe -EDTA concentration higher than 80 mg l(-1) could not be treated by the activated sludge treatment due to EDTA's inhibitory effect on the sludge.

Modification of liposomal concentration in liposome/adenoviral complexes allows significant protection of adenoviral vectors from neutralising antibody, in vitro.

PubMed

Steel, Jason C; Cavanagh, Heather M A; Burton, Mark A; Dingwall, Daniel J; Kalle, Wouter H J

2005-06-01

Adenoviral vectors have been commonly used in gene therapy protocols, however the success of their use is often limited by the induction of host immunity to the vector. Following exposure to the adenoviral vector, adenoviral-specific neutralising antibodies are produced which limits further administration. This study examines the efficacy of complexing liposomes to adenovirus for the protection of the adenovirus from neutralising antibodies in an in vitro setting. Dimethyldioctadecylammonium bromide (DDAB)-dioleoyl-l-phosphatidylethanolamine (DOPE) liposomes were bound at varying concentrations to adenovirus to form AL complexes and tested these complexes' ability to prevent adenoviral neutralisation. It is shown that by increasing the concentration of liposomes in the adenoviral-liposome (AL) complexes we can increase the level of immuno-shielding afforded the adenovirus. It is also shown that the increase in liposomal concentration may lead to drawbacks such as increased cytotoxicity and reductions in expression levels.

Augmentation of thrombin generation in neonates undergoing cardiopulmonary bypass.

PubMed

Guzzetta, N A; Szlam, F; Kiser, A S; Fernandez, J D; Szlam, A D; Leong, T; Tanaka, K A

2014-02-01

Factor concentrates are currently available and becoming increasingly used off-label for treatment of bleeding. We compared recombinant activated factor VII (rFVIIa) with three-factor prothrombin complex concentrate (3F-PCC) for the ability to augment thrombin generation (TG) in neonatal plasma after cardiopulmonary bypass (CPB). First, we used a computer-simulated coagulation model to assess the impact of rFVIIa and 3F-PCC, and then performed similar measurements ex vivo using plasma from neonates undergoing CPB. Simulated TG was computed according to the coagulation factor levels from umbilical cord plasma and the therapeutic levels of rFVIIa, 3F-PCC, or both. Subsequently, 11 neonates undergoing cardiac surgery were enrolled. Two blood samples were obtained from each neonate: pre-CPB and post-CPB after platelet and cryoprecipitate transfusion. The post-CPB products sample was divided into control (no treatment), control plus rFVIIa (60 nM), and control plus 3F-PCC (0.3 IU ml(-1)) aliquots. Three parameters of TG were measured ex vivo. The computer-simulated post-CPB model demonstrated that rFVIIa failed to substantially improve lag time, TG rate and peak thrombin without supplementing prothrombin. Ex vivo data showed that addition of rFVIIa post-CPB significantly shortened lag time; however, rate and peak were not statistically significantly improved. Conversely, 3F-PCC improved all TG parameters in parallel with increased prothrombin levels in both simulated and ex vivo post-CPB samples. Our data highlight the importance of prothrombin replacement in restoring TG. Despite a low content of FVII, 3F-PCC exerts potent procoagulant activity compared with rFVIIa ex vivo. Further clinical evaluation regarding the efficacy and safety of 3F-PCC is warranted.

Effect of Concentration on the Electrochemistry and Speciation of the Magnesium Aluminum Chloride Complex Electrolyte Solution.

PubMed

See, Kimberly A; Liu, Yao-Min; Ha, Yeyoung; Barile, Christopher J; Gewirth, Andrew A

2017-10-18

Magnesium batteries offer an opportunity to use naturally abundant Mg and achieve large volumetric capacities reaching over four times that of conventional Li-based intercalation anodes. High volumetric capacity is enabled by the use of a Mg metal anode in which charge is stored via electrodeposition and stripping processes, however, electrolytes that support efficient Mg electrodeposition and stripping are few and are often prepared from highly reactive compounds. One interesting electrolyte solution that supports Mg deposition and stripping without the use of highly reactive reagents is the magnesium aluminum chloride complex (MACC) electrolyte. The MACC exhibits high Coulombic efficiencies and low deposition overpotentials following an electrolytic conditioning protocol that stabilizes species necessary for such behavior. Here, we discuss the effect of the MgCl 2 and AlCl 3 concentrations on the deposition overpotential, current density, and the conditioning process. Higher concentrations of MACC exhibit enhanced Mg electrodeposition current density and much faster conditioning. An increase in the salt concentrations causes a shift in the complex equilibria involving both cations. The conditioning process is strongly dependent on the concentration suggesting that the electrolyte is activated through a change in speciation of electrolyte complexes and is not simply due to the annihilation of electrolyte impurities. Additionally, the presence of the [Mg 2 (μ-Cl) 3 ·6THF] + in the electrolyte solution is again confirmed through careful analysis of experimental Raman spectra coupled with simulation and direct observation of the complex in sonic spray ionization mass spectrometry. Importantly, we suggest that the ∼210 cm -1 mode commonly observed in the Raman spectra of many Mg electrolytes is indicative of the C 3v symmetric [Mg 2 (μ-Cl) 3 ·6THF] + . The 210 cm -1 mode is present in many electrolytes containing MgCl 2 , so its assignment is of broad interest

Glucose, fructose and sucrose increase the solubility of protein-tannin complexes and at high concentration, glucose and sucrose interfere with bisulphite bleaching of wine pigments.

PubMed

Harbertson, James F; Yuan, Chunlong; Mireles, Maria S; Hanlin, Rachel L; Downey, Mark O

2013-05-01

Wines were modified with increasing sugar concentrations and decreasing tannin concentrations and analysed by a combination of protein precipitation and bisulphite bleaching. Increasing sugar concentration decreased the precipitation of tannin and protein-precipitable polymeric pigments (PPP). The use of a hydrogen bond disruptor (urea) to reduce protein-tannin and protein-pigment complex formation showed that the effect of sugar concentration occurred by increasing the solubility of the tannin-protein complex, not by interfering with protein-tannin complex formation. By increasing the solubility of pigment-protein complexes, non-protein-precipitable polymeric pigments (nPPP) appeared to increase. There was also an increase in total polymeric pigments at each tannin concentration with increasing glucose and sucrose concentration, indicating that sugar concentration might also affect bisulphite bleaching of wine pigments. While a significant effect of sugar concentration on tannin-protein complex solubility was observed, these effects were greatest at sugar concentrations far in excess of normal wine making conditions. Under normal wine making conditions, sugar concentration will have a negligible effect on protein-precipitable tannin, PPP and nPPP concentrations. Copyright © 2012 Elsevier Ltd. All rights reserved.

Phosphorothioate oligonucleotides inhibit the intrinsic tenase complex.

PubMed

Sheehan, J P; Lan, H C

1998-09-01

Systemic administration of ISIS 2302, a 20-mer antisense phosphorothioate oligonucleotide targeting human intercellular adhesion molecule-1 mRNA, causes prolongation of plasma clotting times in both monkey and human studies. The anticoagulant effects of ISIS 2302 were investigated with both in vitro coagulation assays in human plasma and purified enzyme systems. At high oligonucleotide plasma concentrations (>100 microgram/mL), prolongation of the prothrombin and thrombin times was observed. In a thrombin time assay using purified components, high concentrations of ISIS 2302 inhibited thrombin clotting activity both by stimulating inhibition by heparin cofactor II and directly competing with fibrinogen for binding to anion binding exosite I. In contrast, low concentrations of ISIS 2302 (<100 microgram/mL) showed a selective, linear prolongation of the activated partial thromboplastin time (PTT). The rate limiting effect of 50 microgram/mL ISIS 2302, which prolonged the PTT to 1.5 times control, was identified by sequential modification of the clotting assay. Delaying addition of oligonucleotide until after contact activation failed to correct prolongation of the PTT. The calcium-dependent steps of the intrinsic pathway were individually assessed by adding sufficient activated coagulation factor to correct the PTT in plasma deficient in that specific factor. Addition of factor XIa, IXa, VIIIa, or Va failed to correct the PTT in the presence of ISIS 2302. In contrast, 0.2 nmol/L factor Xa corrected prolongation of the PTT in factor X-deficient plasma with or without oligonucleotide present. ISIS 2302 (50 microgram/mL) did not prolong a modified Russel viper venom time, suggesting no significant inhibition of prothrombinase. Thus, 50 microgram/mL ISIS 2302 prolonged the PTT by selectively inhibiting intrinsic tenase activity. ISIS 2302 showed partial inhibition of intrinsic tenase activity (to approximately 35% of control) at clinically relevant oligonucleotide

Selective concentration for ciprofloxacin resistance in Escherichia coli grown in complex aquatic bacterial biofilms.

PubMed

Kraupner, Nadine; Ebmeyer, Stefan; Bengtsson-Palme, Johan; Fick, Jerker; Kristiansson, Erik; Flach, Carl-Fredrik; Larsson, D G Joakim

2018-04-25

There is concern that antibiotics in the environment can select for and enrich bacteria carrying acquired antibiotic resistance genes, thus increasing the potential of those genes to emerge in a clinical context. A critical question for understanding and managing such risks is what levels of antibiotics are needed to select for resistance in complex bacterial communities. Here, we address this question by examining the phenotypic and genotypic profiles of aquatic communities exposed to ciprofloxacin, also evaluating the within-species selection of resistant E. coli in complex communities. The taxonomic composition was significantly altered at ciprofloxacin exposure concentrations down to 1 μg/L. Shotgun metagenomic analysis indicated that mobile quinolone resistance determinants (qnrD, qnrS and qnrB) were enriched as a direct consequence of ciprofloxacin exposure from 1 μg/L or higher. Only at 5-10 μg/L resistant E.coli increased relative to their sensitive counterparts. These resistant E. coli predominantly harbored non-transferrable, chromosomal triple mutations (gyrA S83 L, D87N and parC S80I), which confer high-level resistance. In a controlled experimental setup such as this, we interpret effects on taxonomic composition and enrichment of mobile quinolone resistance genes as relevant indicators of risk. Hence, the lowest observed effect concentration for resistance selection in complex communities by ciprofloxacin was 1 μg/L and the corresponding no observed effect concentration 0.1 μg/L. These findings can be used to define and implement discharge or surface water limits to reduce risks for selection of antibiotic resistance in the environment. Copyright © 2018 Elsevier Ltd. All rights reserved.

A complexity measure based method for studying the dependance of 222Rn concentration time series on indoor air temperature and humidity.

PubMed

Mihailovic, D T; Udovičić, V; Krmar, M; Arsenić, I

2014-02-01

We have suggested a complexity measure based method for studying the dependence of measured (222)Rn concentration time series on indoor air temperature and humidity. This method is based on the Kolmogorov complexity (KL). We have introduced (i) the sequence of the KL, (ii) the Kolmogorov complexity highest value in the sequence (KLM) and (iii) the KL of the product of time series. The noticed loss of the KLM complexity of (222)Rn concentration time series can be attributed to the indoor air humidity that keeps the radon daughters in air. © 2013 Published by Elsevier Ltd.

PAI-1 4G-4G, MTHFR 677TT, V Leiden 506Q, and Prothrombin 20210A in Splanchnic Vein Thrombosis: Analysis of Individual Patient Data From Three Prospective Studies

PubMed Central

Pasta, Linda; Pasta, Francesca; D’Amico, Mario

2016-01-01

Background There are no univocal opinions on the role of genetic thrombophilia on splanchnic vein thrombosis (SVT). We defined genetic thrombophilia the presence of one of these thrombophilic genetic factors (THRGFs): PAI-1 4G-4G, MTHFR 677TT, V Leiden 506Q, and prothrombin 20210A. Objectives To evaluate the frequencies of these THRGFs in SVT patients, we analyzed individual data of 482 Caucasian patients, recruited from 2000 to 2014 in three prospective studies. SVT was defined as the presence of thrombosis of portal (PVT), mesenteric (MVT), splenic (SPVT), cava (CT), and hepatic vein (Budd Chiari syndrome, BCS). Pre-hepatic SVT (pre-HSVT) was defined as PVT with or without MVT/SPVT, without BCS. Post-hepatic SVT (post-HSVT) was BCS with or without PVT/MVT/SPVT. Methods We compared 350 patients with liver cirrhosis (LC), 47 hepatocellular carcinoma (HCC), 37 myeloproliferative neoplasm (MPN), 38 associated disease (AD), 10 without any associated disease (WAD), vs 150 healthy controls (HC); 437 patients showed pre-HSVT and 45 post-HSVT. Results Thrombophilia was present in 294/482 (60.9%) patients: 189/350 LC (54.0%), 31/47 (66.0%) HCC, 29/39 (74.4%) MPN, 35/38 AD (92.1%), and 10/10 (100%) WAD, and 54/150 (36.0%) in HC. In the total group, we found 175 PAI-1 4G-4G, 130 MTHFR 677TT, 42V Leiden 506Q, and 27 prothrombin 20210A; 75 patients showed presence of >1 TRHGF; the more frequent association was PAI-1 4G-4G/MTHFR 677TT, in 36 patients. PAI-1 4G-4G and MTHFR 677TT were significantly more frequent in patients with SVT (P values <0.005), whereas V Leiden Q506 and prothrombin G20210A were not. PAI-1 4G-4G and MTHFR 677TT distributions deviated significantly from that expected from a population in Hardy–Weinberg equilibrium. Thrombophilia was significantly less frequent in patients with pre-HSVT (250/437, 57.2%) than in patients with post-HSVT (44/45, 97.8%). Conclusions Our study shows the significant prevalence of PAI-1 4G-4G and MTHFR 677TT in SVT, mainly in

Eu(III)-Fulvic Acid Complexation: Evidence of Fulvic Acid Concentration Dependent Interactions by Time-Resolved Luminescence Spectroscopy.

PubMed

Kouhail, Yasmine Z; Benedetti, Marc F; Reiller, Pascal E

2016-04-05

Europium speciation is investigated by time-resolved luminescence spectroscopy (TRLS) in the presence of Suwannee River fulvic acid (SRFA). From complexation isotherms built at different total Eu(III) concentrations, pH values, ionic strength, and SRFA concentrations, it appears that two luminescence behaviors of Eu(III) are occurring. The first part, at the lowest CSRFA values, is showing the typical luminescence evolution of Eu(III) complexed by humic substances--that is, the increase of the asymmetry ratio between the (5)D0 → (7)F2 and (5)D0 → (7)F1 transitions up to a plateau--, and the occurrence of a biexponential decay--the first decay being faster than free Eu(3+). At higher CSRFA, a second luminescence mode is detected as the asymmetry ratio is increasing again after the previous plateau, and could correspond to the formation of another type of complex, and/or it can reflect a different spatial organization of complexed europium within the SRFA structure. The luminescence decay keeps on evolving but link to hydration number is not straightforward due to quenching mechanisms. The Eu(III) chemical environment evolution with CSRFA is also ionic strength dependent. These observations suggest that in addition to short-range interactions--intraparticulate complexation--, there might be interactions at longer range--interparticulate repulsion--between particles that are complexing Eu(III) at high CSRFA. These interactions are not yet accounted by the different complexation models.

Changes in amniotic fluid concentration of thrombin-antithrombin III complexes in patients with preterm labor: evidence of an increased thrombin generation

PubMed Central

Erez, Offer; Romero, Roberto; Vaisbuch, Edi; Chaiworapongsa, Tinnakorn; Kusanovic, Juan Pedro; Mazaki-Tovi, Shali; Gotsch, Francesca; Gomez, Ricardo; Maymon, Eli; Pacora, Percy; Edwin, Samuel S.; Kim, Chong Jai; Than, Nandor Gabor; Mittal, Pooja; Yeo, Lami; Dong, Zhong; Yoon, Bo Hyun; Hassan, Sonia S; Mazor, Moshe

2012-01-01

Objective Preterm labor is associated with excessive maternal thrombin generation as evidenced by increased circulating thrombin–antithrombin (TAT) III complexes concentration. In addition to its hemostatic functions, thrombin has uterotonic properties that may participate in the mechanism leading to preterm birth in cases of intrauterine bleeding. Thrombin also has a proinflammatory role, and inflammation is associated with increased thrombin generation. The aim of this study was to determine whether intra-amniotic infection/inflammation (IAI) is associated with increased amniotic fluid (AF) thrombin generation in women with preterm and term deliveries. Study design This cross-sectional study included the following groups: 1) mid-trimester (n=74); 2) term not in labor (n=39); 3) term in labor (n=25); 4) term in labor with IAI (n=22); 5) spontaneous preterm labor (PTL) who delivered at term (n=62); 6) PTL without IAI who delivered preterm (n=59); 7) PTL with IAI (n=71). The AF TAT III complexes concentration was measured by ELISA. Non-parametric statistics were used for analysis. Results 1) TAT III complexes were identified in all AF samples; 2) patients with PTL who delivered preterm, with and without IAI, had a significantly higher median AF TAT III complexes concentration than those with an episode of PTL who delivered at term (p<0.001, p=0.03, respectively); 3) among patients with preterm labor without IAI, elevated AF TAT III complexes concentration were independently associated with a shorter amniocentesis-to-delivery interval (hazard ratio- 1.5, 95%CI, 1.07–2.1); 4) among patients at term, those with IAI had a higher median AF TAT III complexes concentration than those without IAI, whether in labor or not in labor (p=0.02); 5) there was no significant difference between the median AF TAT III complexes concentration of patients at term with and without labor; and 6) patients who had a mid-trimester amniocentesis had a lower median AF TAT III complexes

Divacancy-hydrogen complexes in dislocation-free high-purity germanium. [Annealing, Hall effect, steady-state concentration energy dependence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haller, E.E.; Hubbard, G.S.; Hansen, W.L.

1976-09-01

A defect center with a single acceptor level at E/sub v/ + 0.08 eV appears in H/sub 2/-grown dislocation-free high-purity germanium. Its concentration changes reversibly upon annealing up to 650 K. By means of Hall-effect and conductivity measurements over a large temperature range the temperature dependence of the steady-state concentration between 450 and 720 K as well as the transients following changes in temperature were determined. The observed acceptor level is attributed to the divacancy-hydrogen complex V/sub 2/H. The complex reacts with hydrogen, dissolved in the Ge lattice or stored in traps, according to V/sub 2/H + H reversible V/submore » 2/H/sub 2/. An energy level associated with the divacancy-dihydrogen complex was not observed. These results are in good agreement with the idea that hydrogen in germanium forms a ''very deep donor'' (i.e., the energy level lies inside the valence band).« less

Prevalence of nucleic acid sequences specific for human parvoviruses, hepatitis A and hepatitis E viruses in coagulation factor concentrates.

PubMed

Modrow, S; Wenzel, J J; Schimanski, S; Schwarzbeck, J; Rothe, U; Oldenburg, J; Jilg, W; Eis-Hübinger, A M

2011-05-01

Due to their high resistance to inactivation procedures, nonenveloped viruses such as parvovirus B19, human bocavirus (HBoV), human parvovirus 4 (PARV4), hepatitis A (HAV) and hepatitis E virus (HEV) pose a particular threat to blood products. Virus transmission to patients treated with blood products presents an additional burden to disease. We determined the frequency and the amount of nucleic acid specific for nonenveloped viruses in recently manufactured preparations of commercial coagulation factor concentrates. At least three different batches of each of 13 different plasma-derived and recombinant coagulation factor products were tested for the presence and the amount of nucleic acid for parvovirus B19, HBoV, human parvovirus 4, hepatitis A virus and HEV by using quantitative polymerase chain reaction. Whereas none of the recombinant products tested positive for any of these viruses, parvovirus B19 DNA with amounts ranging between 2×10(1) and 1.3×10(3) genome equivalents/ml was detected in five plasma-derived products. In addition to parvovirus B19 genotype 1, genotypes 2 and 3 were observed in two batches of a factor VIII/von-Willebrand factor product. In two products (one factor VIII concentrate and one activated prothrombin complex concentrate), a combination of both genotypes 1 and 2 of parvovirus B19 was detected. The data show that nucleic acids from several relevant nonenveloped viruses are not found at detectable levels in coagulation factor concentrates. In some cases, parvovirus B19 DNA was detectable at low levels. Testing of the plasma pools for the full range of parvovirus genotypes is advocated for ensuring product safety. © 2010 The Author(s). Vox Sanguinis © 2010 International Society of Blood Transfusion.

The effect of concentration of guanidine hydrochloride on the sulfasalazine serum albumin complex

NASA Astrophysics Data System (ADS)

Sułkowska, A.; Równicka, J.; Pożycka, J.; Bojko, B.; Sułkowski, W. W.

2005-06-01

A detailed study of the effect of Gu·HCl concentration is presented in this work. Destabilization of the tertiary structure of BSA was observed by using fluorescence measurements of excitation wavelength of 280 and 295 nm. We ascertained that in terms of the effect on the fluorescence emission spectrum of BSA, Gu·HCl concentration falls into three regions: I, 0.1-1.6 M; II, 1.6-3 M and III, 3-6 M. The intermediate state of BSA denaturation for 1.6-1.7 M Gu·HCl was noticed. Quenching of the native BSA fluorescence by sulfasalazine (SSZ), a drug used in inflammatory bowel disease, was shown. In the presence of Gu·HCl, BSA fluorescence rises or decreases depending on the concentration region I or II, respectively. A similar effect of Gu·HCl on the fluorescence spectrum of BSA, quenched by sulfasalazine, can be found. However, Gu·HCl concentration-dependent reduction of the quenching effect of the SSZ points to the gradual loss of the binding properties. Binding and quenching constants for the SSZ-BSA complexes were calculated in the absence and presence of the denaturant. Since Gu·HCl at concentration 0.1-1.6 M increases and at concentration 1.6-3 M decreases the BSA fluorescence, the mechanism of the destabilization of the native structure of serum albumin differs for these two ranges of Gu·HCl concentration. The small concentration of the denaturant causes a disorder in the hydration layer of the albumin and the higher one causes the binding of the denaturant molecule close to the Trp 135 in the IB subdomain.

Thrombin generation, ProC(®)Global, prothrombin time and activated partial thromboplastin time in thawed plasma stored for seven days and after methylene blue/light pathogen inactivation.

PubMed

Thiele, Thomas; Hron, Gregor; Kellner, Sarah; Wasner, Christina; Westphal, Antje; Warkentin, Theodore E; Greinacher, Andreas; Selleng, Kathleen

2016-01-01

Methylene blue pathogen inactivation and storage of thawed plasma both lead to changes in the activity of several clotting factors. We investigated how this translates into a global loss of thrombin generation potential and alterations in the protein C pathway. Fifty apheresis plasma samples were thawed and each divided into three subunits. One subunit was stored for 7 days at 4 °C, one was stored for 7 days at 22 °C and one was stored at 4 °C after methylene blue/light treatment. Thrombin generation parameters, ProC(®)Global-NR, prothrombin time and activated partial thromboplastin time were assessed on days 0 and 7. The velocity of thrombin generation increased significantly after methylene blue treatment (increased thrombin generation rate; time to peak decreased) and decreased after storage (decreased thrombin generation rate and peak thrombin; increased lag time and time to peak). The endogenous thrombin generation potential remained stable after methylene blue treatment and storage at 4 °C. Methylene blue treatment and 7 days of storage at 4 °C activated the protein C pathway, whereas storage at room temperature and storage after methylene blue treatment decreased the functional capacity of the protein C pathway. Prothrombin time and activated partial thromboplastin time showed only modest alterations. The global clotting capacity of thawed plasma is maintained at 4 °C for 7 days and directly after methylene blue treatment of thawed plasma. Thrombin generation and ProC(®)Global are useful tools for investigating the impact of pathogen inactivation and storage on the clotting capacity of therapeutic plasma preparations.

A Blown Pupil and Intracranial Hemorrhage in a 4-Week-Old: A Case of Delayed Onset Vitamin K Deficiency Bleeding, a Rare "Can't Miss" Diagnosis.

PubMed

Enz, Ryley; Anderson, Robert S

2016-08-01

Infants are at risk for vitamin K deficiency bleeding (VKDB) because of limited stores of vitamin K (VK) at birth and a low concentration of VK in human breast milk. Therefore, the administration of intramuscular (IM) VK at birth has been recommended since 1961 in the United States. Infants who do not receive IM VK and who are exclusively breast-fed are at increased risk for VKDB. While VKDB is rare, a common presentation of late onset VKDB is intracranial hemorrhage. We report the case of a 4-week-old infant who presented to the emergency department with lethargy and a grossly dilated right pupil. The parents denied trauma. A computed tomography scan revealed a right-sided subdural hematoma with midline shift. The infant's international normalized ratio was >10.9 and his prothrombin time PT was >120 seconds. VK was administered and the child was transferred to a tertiary care center for emergent neurosurgery. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The difficult part of making this critical diagnosis is considering it. Any bleeding in a newborn without trauma should prompt inquiry regarding neonatal VK administration and a serum prothrombin time level. Fortunately, once the diagnosis is made, therapy in the emergency department can be lifesaving and is familiar to emergency physicians. Treatment parallels usual care for the adult with excess anticoagulation caused by warfarin. Prompt intravenous VK is universally accepted. Studies to support fresh frozen plasma or prothrombin complex concentrate are lacking but make good clinical sense for life-threatening bleeding. Copyright © 2016 Elsevier Inc. All rights reserved.

New procyanidin B3-human salivary protein complexes by mass spectrometry. Effect of salivary protein profile, tannin concentration, and time stability.

PubMed

Perez-Gregorio, Maria Rosa; Mateus, Nuno; De Freitas, Victor

2014-10-15

Several factors could influence the tannin-protein interaction such as the human salivary protein profile, the tannin tested, and the tannin/protein ratio. The goal of this study aims to study the effect of different salivas (A, B, and C) and different tannin concentrations (0.5 and 1 mg/mL) on the interaction process as well as the complex's stability over time. This study is focused on the identification of new procyanidin B3-human salivary protein complexes. Thus, 48 major B3-human salivary protein aggregates were identified regardless of the saliva and tannin concentration tested. A higher number of aggregates was found at lower tannin concentration. Moreover, the number of protein moieties involved in the aggregation process was higher when the tannin concentration was also higher. The selectivity of the different groups of proteins to bind tannin was also confirmed. It was also verified that the B3-human salivary protein complexes formed evolved over time.

Anti-inflammatory effect of a human prothrombin fragment-2-derived peptide, NSA9, in EOC2 microglia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Ji Yeon; Kim, Tae Hyong; Kim, Soung Soo

2008-04-11

Pro-inflammatory mediators, such as nitric oxide (NO), prostaglandin E{sub 2} (PGE{sub 2}), and several cytokines (tumor necrosis factor (TNF)-{alpha}, interleukin (IL)-1{beta}, and IL-6) are responsible for central nervous system (CNS) injuries that include ischemia, Alzheimer's disease, and neural death. Inhibition of these pro-inflammatory mediators would be an effective therapy to reduce the progression of neurodegenerative diseases. In this study, we examined the anti-inflammatory effects of a human prothrombin fragment-2-derived peptide, NSA9 (NSAVQLVEN), on the production of pro-inflammatory mediators in lipopolysaccharide (LPS)-activated brain microglia. NSA9 significantly inhibited the release of NO, PGE{sub 2}, and pro-inflammatory cytokines in a dose-dependent manner. Furthermore,more » NSA9 reduced the expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 mRNA and protein, which control the production of NO and PGE{sub 2}, respectively. Moreover, NSA9 suppressed the LPS-induced nuclear translocation and activation of nuclear factor-{kappa}B (NF-{kappa}B). These results suggest that NSA9 strongly inhibits the pro-inflammatory responses of microglia through the modulation of NF-{kappa}B activity.« less

The effects of proton radiation on the prothrombin and partial thromboplastin times of irradiated ferrets

PubMed Central

Krigsfeld, Gabriel S.; Sanzari, Jenine K.; Kennedy, Ann R.

2013-01-01

Purpose To determine whether proton radiation affects coagulation. Material and methods Ferrets were exposed to solar particle event-like proton radiation at doses of 0, 25, 100, or 200 centigray (cGy), and dose rates of 50 cGy/minute (high dose rate or HDR) or 50 cGy/hour (low dose rate or LDR). Plasma was isolated from blood collected prior to radiation exposure and at 3–7 h post-radiation. Prothrombin time (PT) assays and activated partial thromboplastin time (aPTT) assays were performed as were mixing studies to determine the coagulation factors involved. Results HDR and LDR exposure led to statistically significant increases in PT values. It was determined that the HDR-induced increase in PT was due to Factor VII, while Factors II, V, and VII contributed to the LDR-induced increase in PT values. Only acute LDR exposure caused an increase in aPTT values, which remained elevated for 48 h post-irradiation (which was the latest time assayed in these studies). Mixing studies revealed that Factor IX contributed to the increased aPTT values. A majority of the animals exposed at the LDR had an International Normalized Ratio approaching or surpassing 2.0. Conclusions PT/aPTT assays resulted in increased clotting times due to different coagulation factors, indicating potential radiation-induced coagulopathy. PMID:22221163

In vitro efficacy of pro- and anticoagulant strategies in compensated and acutely ill patients with cirrhosis.

PubMed

Lisman, Ton; Kleiss, Simone; Patel, Vishal C; Fisher, Caleb; Adelmeijer, Jelle; Bos, Sarah; Singanayagam, Arjuna; Stoy, Sidsel Hyldgaard; Shawcross, Debbie L; Bernal, William

2018-05-16

A simultaneous decline in pro- and anticoagulant drivers in patients with liver diseases results in a 'rebalanced' hemostatic system, even in acutely ill patients. Nevertheless, both bleeding and thrombotic events are common. Here, we explored efficacy of pro- and antihemostatic strategies in compensated and acutely ill cirrhotics which may be unpredictable given the profound hemostatic changes. We tested the effects in vitro of the addition of clinically relevant doses of commonly used pro- and antihemostatic strategies in plasma from healthy individuals (n=30) and patients with compensated (n=18) and acutely decompensated cirrhosis (n=18), and acute-on-chronic liver failure (n=10). We used thrombin generation tests and fibrin clot permeability assays to assess potency of various approaches. Fresh frozen plasma and recombinant factor VIIa modestly increased thrombin generation (10-20%). Prothrombin complex concentrate increased thrombin generation 2-fold in controls and 2-4-fold in patients. Clot permeability decreased after addition of fibrinogen concentrate by 51% in controls and by 50-60% in patients. Low molecular weight heparin decreased thrombin generation by 18% in controls and by 23-54% in patients. Similarly, dabigatran decreased thrombin generation by 33% in controls and by 47-100% in patients. In contrast, rivaroxaban decreased thrombin generation by 55% in controls, but only by 11-38% in patients. These in vitro data suggest little prohemostatic effect of fresh frozen plasma and recombinant factor VIIa in acutely ill cirrhotics, whereas prothrombin complex concentrate and fibrinogen concentrate clearly improved hemostasis. Furthermore, our data suggest the requirement for dose-adjustments of commonly used anticoagulants in these patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Evaluation of the marker of hypercoagulability prothrombin fragment F 1+2 in patients with mechanical or biological heart valve prostheses.

PubMed

Ferreira, Claudia Natália; Vieira, Lauro Mello; Dusse, Luci Maria Sant'Ana; Amaral, Carlos Faria Santos; de Magalhães Esteves, William Antônio; Fenelon, Lúcia Maria Amorim; das Graças Carvalho, Maria

2002-11-01

To investigate whether patients with heart valve prostheses and similar International Normalized Ratios (INR) have the same level of protection against thromboembolic events, that is, whether the anticoagulation intensity is related to the intensity of hypercoagulability suppression. INR and plasma levels of prothrombin fragment 1+2 (F1+2) were assessed in blood samples of 27 patients (7 with mechanical heart valves and 20 with biological heart valves) and 27 blood samples from healthy donors that were not taking any medication. Increased levels of F1+2 were observed in blood samples of 5 patients with heart valve prostheses taking warfarin. These findings reinforce the idea that even though patients may have INRs, within the therapeutic spectrum, they are not free from new thromboembolic events. Determination of the hypercoagulability marker F1+2 might result in greater efficacy and safety for the use of oral anticoagulants, resulting in improved quality of life for patients.

Association of Hospital Market Concentration With Costs of Complex Hepatopancreaticobiliary Surgery.

PubMed

Cerullo, Marcelo; Chen, Sophia Y; Dillhoff, Mary; Schmidt, Carl; Canner, Joseph K; Pawlik, Timothy M

2017-09-20

��< .001) compared with moderately concentrated markets and 10.5% lower (95% CI, -16.2% to -4.4%; P = .001) compared with unconcentrated markets. Higher market concentration was associated with lower overall charges and lower costs of pancreatic and hepatic surgery. For complex, highly specialized procedures, hospital market consolidation may represent the best value proposition: better quality of care with lower costs.

Influence of the organic complex concentration on adsorption of herbicide in organic modified montmorillonite

NASA Astrophysics Data System (ADS)

Kaludjerovic, Lazar; Tomic, Zorica; Djurovic, Rada; Milosevic, Maja

2016-04-01

Pesticides are recognized as an important source of potential pollution to soil and water due to their mobility and degradation in soils. Results presented in this paper show impact of the organic complex concentration on the adsorption of herbicides (acetochlor) at the surface of the organic modified montmorillonite. In this work, natural montmorillonite from Bogovina, located near Boljevac municipality, was used for organic modification. Cation-exchange capacity of this montmorillonite was determined by extraction with ammonium acetate (86 mmol/100g of clay). Montmorillonite have been modified first with NaCl and than with two organic complexes, hexadecyltrimethylammonium bromide (HDTMA) and phenyltrimethylammonium chloride (PTMA). For both organic complexes, three saturation concentrations were selected for monitoring of the herbicide adsorption (43 mmol/100g of clay (0.5 CEC), 86 mmol/100g of clay (1 CEC) and 129 mmol/100g of clay (1.5 CEC)). Changes in the properties of the inorganic and organic bentonite have been examined using the X-ray powder diffraction (XRPD) and batch equilibrium method. Increase in basal spacing (d) of montmorillonites saturated with 1.5 CEC of organic cation indicate that sorption of PTMA and HDTMA can exceed the saturation of 1 CEC. Both organic montmorillonites have shown higher uptake of the herbicide, compared to the inorganic montmorillonite. Comparing the values Freundlich coefficients in batch equilibrium method, (presented in the form of log Kf and 1/n), it can be seen that the sorption decreases in the series: 0.5CEC> 1CEC> 1.5CEC> NaM, for both organic montmorillonites.

THREE-STAGE ANALYSIS OF BLOOD COAGULATION

PubMed Central

Milstone, J. H.

1948-01-01

1. Blood-clotting mechanism has been analyzed by a procedure which devotes a separate experimental step to each of the three primary reactions: 1. Prothrombokinase → thrombokinase 2. Prothrombin → thrombin 3. Fibrinogen → fibrin 2. Activation of prothrombin by thrombokinase followed the course of a unimolecular reaction, and the concentration of thrombokinase determined the initial rate. By this relation thrombokinase was measured, and the activation of its precursor was charted. 3. When the activation of prothrombokinase was plotted against time, the experimental points fell close to the theoretical curve for a simple autocatalytic reaction. Moreover, the process was accelerated by seeding with a small amount of crude thrombokinase. It was concluded that the activation of prothrombokinase involves an autocatalytic or chain reaction. 4. The three-stage procedure made possible the separate estimation of the power to activate prothrombin, on one hand, and the capacity to accelerate the transformation of prothrombokinase on the other. Drastic losses of both activities occurred when crude thrombokinase solutions were heated at 60°C., or adsorbed with barium sulfate. 5. The concentration of calcium was important for the normal progress of prothrombin activation, and also for the transformation of prothrombokinase. PMID:18904755

Discovery of Novel Nonactive Site Inhibitors of the Prothrombinase Enzyme Complex.

PubMed

Kapoor, Karan; McGill, Nicole; Peterson, Cynthia B; Meyers, Harold V; Blackburn, Michael N; Baudry, Jerome

2016-03-28

The risk of serious bleeding is a major liability of anticoagulant drugs that are active-site competitive inhibitors targeting the Factor Xa (FXa) prothrombin (PT) binding site. The present work identifies several new classes of small molecule anticoagulants that can act as nonactive site inhibitors of the prothrombinase (PTase) complex composed of FXa and Factor Va (FVa). These new classes of anticoagulants were identified, using a novel agnostic computational approach to identify previously unrecognized binding pockets at the FXa-FVa interface. From about three million docking calculations of 281,128 compounds in a conformational ensemble of FXa heavy chains identified by molecular dynamics (MD) simulations, 97 compounds and their structural analogues were selected for experimental validation, through a series of inhibition assays. The compound selection was based on their predicted binding affinities to FXa and their ability to successfully bind to multiple protein conformations while showing selectivity for particular binding sites at the FXa/FVa interface. From these, thirty-one (31) compounds were experimentally identified as nonactive site inhibitors. Concentration-based assays further identified 10 compounds represented by four small-molecule families of inhibitors that achieve dose-independent partial inhibition of PTase activity in a nonactive site-dependent and self-limiting mechanism. Several compounds were identified for their ability to bind to protein conformations only seen during MD, highlighting the importance of accounting for protein flexibility in structure-based drug discovery approaches.

Effects of Tramadol Coadministration on Prothrombin Time-International Normalized Ratio in Patients Receiving Warfarin.

PubMed

Hosono, Tomomi; Kondo, Aiko; Kambayashi, Yasuyuki; Homma, Masato

2017-01-01

Several case studies have reported a possible drug interaction between warfarin and tramadol where tramadol coadministration enhanced the antithrombotic effects of warfarin. To assess this drug interaction, changes in prothrombin time-international normalized ratio (PT-INR) before and after tramadol coadministration were investigated in patients receiving warfarin. For this study, we examined 54 patients (male/female: 22/32, 68.4±12.7 years) who were being treated with warfarin for deep vein thrombosis, atrial fibrillation, arteriosclerosis obliterans, congestive heart failure, and other vascular diseases. Significant increases in PT-INR were observed 9.5 (1-118) d after coadministration of tramadol (1.81±0.56 vs. 2.47±1.10, p<0.01). Twenty-eight patients (PT-INR increased group) with PT-INR elevation of greater than 0.5 or dose reduction of warfarin after coadministration of tramadol were compared with other groups of patients to find drug interaction risk factors. Logistic regression analysis revealed that lower levels of albumin (3.5 g/dL or less) [odds ratio (OR) 22.1; 95%CI 2.9-169.9]; lower eGFR (50 mL/min or less) (OR 7.7; 95%CI 1.4-42.0); and PT-INR before tramadol coadministration (OR 38.2; 95%CI 3.7-397.6) were characteristic of the PT-INR increased group. These results suggest that tramadol coadministration enhanced the antithrombotic effects of warfarin in patients with higher PT-INR, lower albumin levels and decreased renal function as the risk factors for this drug interaction.

Meta-analysis of factor V Leiden and prothrombin G20210A polymorphism in migraine.

PubMed

Lippi, Giuseppe; Mattiuzzi, Camilla; Cervellin, Gianfranco

2015-01-01

Migraine is a frequent and disabling condition, which exhibits a substantial genetic background and is frequently associated with abnormalities of primary and secondary hemostasis. We performed a systematic literature search and a meta-analysis of available data about the potential associations between migraine and factor V (FV) Leiden or prothrombin (FII) G20210A gene polymorphism. The final number of studies included was 15 (all cross-sectional) about migraine and FV Leiden, and 12 (all cross-sectional) about migraine and FII G20210A polymorphism, with broad inter-study heterogeneity (I², 82 and 85%). The cumulative prevalence of the FV 1691A allele was found to be similar between cases (n = 1450; 4.9%) and controls (n = 3468; 4.7%; P = 0.74). The cumulative prevalence of the FII 20210A allele was also found to be similar between cases (n = 1226; 4.2%) and controls (n = 3144; 4.5%; P = 0.59). Nevertheless, sub-analysis of studies in adults and children revealed that both polymorphisms were not associated with migraine in adults, but FV Leiden and the FII 20210A allele were approximately two-fold more prevalent in children with migraine than in those without. In conclusion, despite migraine exhibits a clear neurovascular origin and is frequently associated with thrombotic disorders, isolate thrombophilic mutations seem to play a negligible pathogenetic role in this condition in adults, whereas the increased prevalence of FV Leiden and the FII 20210A allele in children with migraine deserves further scrutiny.

Management Strategies for Vitamin K Antagonists Reversal in Patients With Major Bleeding: A Survey of Italian Emergency Departments.

PubMed

Bernardi, Enrico; Imberti, Davide; Ferrari, Annamaria

2017-01-01

Emergency physicians frequently deal with patients on vitamin K antagonists (VKAs) suffering major bleeding events, and rapid reversal of anticoagulation in this setting is of paramount importance. In Italy, given the absence of specific national guidelines, local policies are likely to differ, possibly impacting on clinical outcomes. We decided to perform a telephone survey among Italian emergency physicians to evaluate management strategies for VKAs reversal in patients with major bleeding. We conducted a computer-assisted, 10-minute telephone survey of 15 questions, focusing on the local prevalence, assessment, and management strategies of major and intracranial hemorrhage (ICH) occurring in patients on VKAs. We planned to interview a sample of 320 Italian emergency physicians. Institutions from all geographic areas of Italy were to participate in the survey. Of the 320 physicians contacted, 150 (47%) completed the survey, 95% being employed in public hospitals. Focusing on ICH, only 29% of the responders stated they would reverse anticoagulation irrespective of the international normalized ratio value, and only 27% would use prothrombin-complex concentrate as first-line agent. In patients needing urgent neurosurgical operation, less than 50% would administer prothrombin-complex concentrate before surgery. The average knowledge of management strategies for reversal of anticoagulation displayed by Italian emergency physicians appears to be unsatisfactory. The need for an extensive educational program and for the implementation of specific guidelines, possibly endorsed by Scientific Societies, cannot be underemphasized. © The Author(s) 2015.

Thrombophilic Genetic Factors PAI-1, MTHFRC677T, V Leiden 506Q, and Prothrombin 20210A in Noncirrhotic Portal Vein Thrombosis and Budd-Chiari Syndrome in a Caucasian Population

PubMed Central

D'Amico, Mario; Sammarco, Pietro; Pasta, Linda

2013-01-01

Thrombophilic genetic factors PAI-1, MTHFRC677T, V Leiden 506Q, and Prothrombin 20210A were studied as risk factors in 235 Caucasian subjects: 85 patients with abdominal thrombosis (54 with portal vein thrombosis (PVT) and 31 with Budd-Chiari syndrome (BCS) without liver cirrhosis or hepatocellular carcinoma) and 150 blood bank donors. Seventy-five patients with PVT/BCS showed associated disease or particular clinical status (46 PVT/29 BCS): 37 myeloproliferative neoplasm (20 PVT/17 BCS), 12 abdominal surgery (10 PVT/2 BCS), 10 contraception or pregnancy (6 PVT/4 BCS), 7 abdominal acute disease (6 PVT/1 BCS), and 9 chronic disease (4 PVT/5 BCS); ten patients did not present any association (8 PVT/2 BCS). PAI-14G-4G, MTHFR677TT, and V Leiden 506Q were significantly frequent (OR 95% CI and χ 2 test with P value) in abdominal thrombosis; in these patients PAI-14G-4G and MTHFR677TT distributions deviated from that expected from a population in the Hardy-Weinberg equilibrium (PAI-1: χ 2 = 13.8, P < 0.001; MTHFR677: χ 2 = 7.1, P < 0.01), whereas the equilibrium was respected in healthy controls. V Leiden Q506 and Prothrombin 20210A were in the Hardy-Weinberg equilibrium both in patients with abdominal thrombosis and healthy controls. Our study shows an important role of PAI-14G-4G and MTHFR677TT in abdominal thrombosis without liver cirrhosis or hepatocellular carcinoma. PMID:24455271

The localization of a vitamin K-induced modification in an N-terminal fragment of human prothrombin

PubMed Central

Skotland, Tore; Holm, Turid; Østerud, Bjarne; Flengsrud, Ragnar; Prydz, Hans

1974-01-01

1. The N-terminal fragment (PF-I) split off from prothrombin during coagulation was purified to homogeneity from human serum. 2. The apparent molecular weight is 27000±2000 in sodium dodecyl sulphate–polyacrylamide-gel electrophoresis, whereas a value of about 19600 is obtained by calculation based on amino acid and carbohydrate analyses. The N-terminal sequence is an Ala-Asx bond. The fragment contains about 16% carbohydrate, binds phospholipids in the presence of Ca2+ and is adsorbed to BaSO4. The pKa of its BaSO4-binding group(s) is 3.1–3.5. 3. By CNBr cleavage of fragment PF-I two peptides (C-1 and C-2) were obtained with molecular weights of about 5900 (C-2) and 12400 (C-1) on the basis of amino acid and carbohydrate analyses. Only the smaller (N-terminal) peptide is adsorbed to BaSO4 and, since the ability of the whole protein to bind to BaSO4 is known to be absent in samples obtained from patients treated with vitamin K antagonists, this peptide probably contains the site of a modification to the structure of the protein which occurs during biosynthesis and depends on vitamin K. This peptide does not contain hexosamine or sialic acid. ImagesFig. 2. PMID:4219283

Coexistence of anti-β2-glycoprotein I domain I and anti-phosphatidylserine/prothrombin antibodies suggests strong thrombotic risk.

PubMed

Lee, Jee-Soo; Gu, JaYoon; Park, Hee Sue; Yoo, Hyun Ju; Kim, Hyun Kyung

2017-05-01

Highly specific assays for measuring antiphospholipid antibodies (aPLs) are required for accurate assessment of thrombotic risk. aPLs against β2-glycoprotein I domain I (anti-β2GPIdI) and against prothrombin complexed with phosphatidylserine (anti-PS/PT) have been recently identified as being associated with a hypercoagulable state. This study evaluated the synergism between anti-β2GPIdI and anti-PS/PT for predicting thrombotic events. A total of 180 patients with clinical suspicion of hypercoagulability were evaluated. The plasma levels of lupus anticoagulant (LA) and antibodies against anticardiolipin (anti-CL) (IgG and IgM), β2GPI (IgG and IgM), PS/PT (IgG and IgM), and β2GPI dI (IgG) were measured. IgG anti-β2GPIdI and LA were highly associated with thrombosis. Mean values and positivity rates of IgG anti-β2GPI dI and IgG anti-PS/PT were significantly higher in the triple-positive group (LA+, IgG anti-CL+, IgG anti-β2GPI+) than in the other groups. Interestingly, the thrombotic risk [odds ratio (OR) 24.400, 95% confidence interval (CI) 1.976-63.273, p<0.001] of the newly defined triple positive group (LA+, IgG anti-CL+, IgG anti-β2GPIdI+; OR 11.182, 95% CI 1.976-63.273, p=0.006) was more than twice that of the triple-positive group (LA+, IgG anti-CL+, IgG anti-β2GPI+). Double positivity for IgG anti-PS/PT and IgG anti-β2GPI also indicated significant thrombotic risk (OR 7.467, 95% CI 2.350-23.729, p=0.001). Furthermore, the thrombotic risk associated with double positivity for IgG anti-PS/PT and IgG anti-β2GPIdI was markedly elevated (OR 33.654, 95% CI 6.322-179.141, p<0.001). Our data suggest that simultaneous measurement of IgG anti-β2GPIdI and IgG anti-PS/PT may improve clinical decision-making for aPL-positive patients.

Relationship between residual feed intake and lymphocyte mitochondrial complex protein concentration and ratio in crossbred steers.

PubMed

Davis, M P; Brooks, M A; Kerley, M S

2016-04-01

Rate of oxygen uptake by muscle mitochondria and respiratory chain protein concentrations differed between high- and low-residual feed intake (RFI) animals. The hypothesis of this research was that complex I (CI), II (CII), and III (CIII) mitochondria protein concentrations in lymphocyte (blood) mitochondria were related to the RFI phenotype of beef steers. Daily feed intake (ADFI) was individually recorded for 92 Hereford-crossbreed steers over 63 d using GrowSafe individual feed intake system. Predicted ADFI was calculated as the regression of ADFI on ADG and midtest BW. Difference between ADFI and predicted ADFI was RFI. Lymphocytes were isolated from low-RFI (-1.32 ± 0.11 kg/d; = 10) and high-RFI (1.34 ± 0.18 kg/d; = 8) steers. Immunocapture of CI, CII, and CIII proteins from the lymphocyte was done using MitoProfile CI, CII, and CIII immunocapture kits (MitoSciences Inc., Eugene, OR). Protein concentrations of CI, CII, and CIII and total protein were quantified using bicinchoninic acid colorimetric procedures. Low-RFI steers consumed 30% less ( = 0.0004) feed and had a 40% improvement ( < 0.0001) in feed efficiency compared with high-RFI steers with similar growth ( = 0.78) and weight measurements ( > 0.65). High- and low-RFI steers did not differ in CI ( = 0.22), CII ( = 0.69), and CIII ( = 0.59) protein concentrations. The protein concentration ratios for CI to CII ( = 0.03) were 20% higher and the ratios of CI to CIII ( = 0.01) were 30% higher, but the ratios of CII to CIII ( = 0.89) did not differ when comparing low-RFI steers with high-RFI steers. The similar magnitude difference in feed intake, feed efficiency measurements, and CI-to-CIII ratio between RFI phenotypes provides a plausible explanation for differences between the phenotypes. We also concluded that mitochondria isolated from lymphocytes could be used to study respiratory chain differences among differing RFI phenotypes. Further research is needed to determine if lymphocyte mitochondrial

A generic standard additions based method to determine endogenous analyte concentrations by immunoassays to overcome complex biological matrix interference.

PubMed

Pang, Susan; Cowen, Simon

2017-12-13

We describe a novel generic method to derive the unknown endogenous concentrations of analyte within complex biological matrices (e.g. serum or plasma) based upon the relationship between the immunoassay signal response of a biological test sample spiked with known analyte concentrations and the log transformed estimated total concentration. If the estimated total analyte concentration is correct, a portion of the sigmoid on a log-log plot is very close to linear, allowing the unknown endogenous concentration to be estimated using a numerical method. This approach obviates conventional relative quantification using an internal standard curve and need for calibrant diluent, and takes into account the individual matrix interference on the immunoassay by spiking the test sample itself. This technique is based on standard additions for chemical analytes. Unknown endogenous analyte concentrations within even 2-fold diluted human plasma may be determined reliably using as few as four reaction wells.

Influence of compositional complexity on interdiffusion in Ni-containing concentrated solid-solution alloys

DOE PAGES

Jin, Ke; Zhang, Chuan; Zhang, Fan; ...

2018-03-07

To investigate the compositional effects on thermal-diffusion kinetics in concentrated solid-solution alloys, interdiffusion in seven diffusion couples with alloys from binary to quinary is systematically studied. The alloys with higher compositional complexity exhibit in general lower diffusion coefficients against homologous temperature, however, an exception is found that diffusion in NiCoFeCrPd is faster than in NiCoFeCr and NiCoCr. While the derived diffusion parameters suggest that diffusion in medium and high entropy alloys is overall more retarded than in pure metals and binary alloys, they strongly depend on specific constituents. The comparative features are captured by computational thermodynamics approaches using a self-consistentmore » database.« less

Exosites in the substrate specificity of blood coagulation reactions.

PubMed

Bock, P E; Panizzi, P; Verhamme, I M A

2007-07-01

The specificity of blood coagulation proteinases for substrate, inhibitor, and effector recognition is mediated by exosites on the surfaces of the catalytic domains, physically separated from the catalytic site. Some thrombin ligands bind specifically to either exosite I or II, while others engage both exosites. The involvement of different, overlapping constellations of exosite residues enables binding of structurally diverse ligands. The flexibility of the thrombin structure is central to the mechanism of complex formation and the specificity of exosite interactions. Encounter complex formation is driven by electrostatic ligand-exosite interactions, followed by conformational rearrangement to a stable complex. Exosites on some zymogens are in low affinity proexosite states and are expressed concomitant with catalytic site activation. The requirement for exosite expression controls the specificity of assembly of catalytic complexes on the coagulation pathway, such as the membrane-bound factor Xa*factor Va (prothrombinase) complex, and prevents premature assembly. Substrate recognition by prothrombinase involves a two-step mechanism with initial docking of prothrombin to exosites, followed by a conformational change to engage the FXa catalytic site. Prothrombin and its activation intermediates bind prothrombinase in two alternative conformations determined by the zymogen to proteinase transition that are hypothesized to involve prothrombin (pro)exosite I interactions with FVa, which underpin the sequential activation pathway. The role of exosites as the major source of substrate specificity has stimulated development of exosite-targeted anticoagulants for treatment of thrombosis.

The human prothrombin kringle-2 derived peptide, NSA9, is internalized into bovine capillary endothelial cells through endocytosis and energy-dependent pathways

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hwang, Hyun Sook; Kim, Soung Soo

Human prothrombin kringle-2 and its partial peptide, NSA9 (NSAVQLVEN), have been reported to have potent anti-angiogenic activities. Here, the internalization mechanism of NSA9 into bovine capillary endothelial (BCE) cells was examined using lactate dehydrogenase (LDH) release assay, fluorescence microscopy, and flow cytometry. LDH release assay results suggested that the integrity of the BCE cell membrane was unaffected by NSA9. Fluorescence microscopy indicated that internalized NSA9 was localized in the cytoplasm around the nucleus, and showed a punctuated fluorescence pattern, which is indicative of endocytic vesicles. Also, the cellular internalization of NSA9 is significantly inhibited by depletion of the cellular ATPmore » pool, endocytosis inhibitors such as chloroquine and nocodazole, and incubation at low temperature (4 deg C). In addition, the anti-proliferative activity of NSA9 against BCE cells was diminished in the presence of endocytosis or metabolic inhibitors. In conclusion, these results strongly suggest that NSA9 might exert its anti-proliferative activity through internalization into BCE cells by endocytosis and energy-dependent pathways.« less

Prothrombin polymorphism A19911G, factor V HR2 haplotype A4070G, and plasminogen activator-inhibitor-1 polymorphism 4G/5G and the risk of retinal vein occlusion.

PubMed

Kuhli-Hattenbach, Claudia; Hellstern, Peter; Nägler, Dorit Karin; Kohnen, Thomas; Hattenbach, Lars-Olof

2017-01-01

Thus far, no data has become available to evaluate systematically the prevalences of prothrombin polymorphism A19911G (PT A19911G), factor V HR2 haplotype A4070G (FV A4070G), or plasminogen activator-inhibitor-1 polymorphism 4G/5G (PAI-1 4G/5G) in patients who develop retinal vein occlusion (RVO) without cardiovascular risk factors. We retrospectively evaluated comprehensive thrombophilia data from 42 preselected RVO patients without cardiovascular risk factors. The prevalences of different gene mutations and polymorphisms including factor V Leiden mutation G1691A (FVL), FV A4070G, prothrombin mutation G20210A, PT A19911G, and PAI-1 4G/5G were compared with 241 healthy controls matched for age and sex. A total of 20 patients (47.7%) were found to carry thrombophilic gene polymorphisms including FVL, FV A4070G, and homozygous PT A19911G compared with 72 of 241 controls (29.9%; p = 0.03). Subgroup analysis of patients with a significant personal or family history of thromboembolism revealed a high prevalence of FVL, FV A4070G, and homozygous PT A19911G (p = 0.005). FV A4070G was found to be significantly associated with at least two other heterozygous or one homozygous gene polymorphisms (p = 0.02). Multivariate analysis revealed the presence of FVL (p = 0.0017) and homozygous PT A19911G (p = 0.03) polymorphism as independent risk factors for the development of RVO. Our results indicate that in selected RVO patients screening for thrombophilic gene polymorphisms including FVL, FV A4070G and homozygous PT G19911A may be helpful in a high percentage of cases. Our findings suggest that hereditary thrombophilia associated with RVO is more likely to be multigenic than caused by any single risk factor.

Combined analysis of modeled and monitored SO2 concentrations at a complex smelting facility.

PubMed

Rehbein, Peter J G; Kennedy, Michael G; Cotsman, David J; Campeau, Madonna A; Greenfield, Monika M; Annett, Melissa A; Lepage, Mike F

2014-03-01

Vale Canada Limited owns and operates a large nickel smelting facility located in Sudbury, Ontario. This is a complex facility with many sources of SO2 emissions, including a mix of source types ranging from passive building roof vents to North America's tallest stack. In addition, as this facility performs batch operations, there is significant variability in the emission rates depending on the operations that are occurring. Although SO2 emission rates for many of the sources have been measured by source testing, the reliability of these emission rates has not been tested from a dispersion modeling perspective. This facility is a significant source of SO2 in the local region, making it critical that when modeling the emissions from this facility for regulatory or other purposes, that the resulting concentrations are representative of what would actually be measured or otherwise observed. To assess the accuracy of the modeling, a detailed analysis of modeled and monitored data for SO2 at the facility was performed. A mobile SO2 monitor sampled at five locations downwind of different source groups for different wind directions resulting in a total of 168 hr of valid data that could be used for the modeled to monitored results comparison. The facility was modeled in AERMOD (American Meteorological Society/U.S. Environmental Protection Agency Regulatory Model) using site-specific meteorological data such that the modeled periods coincided with the same times as the monitored events. In addition, great effort was invested into estimating the actual SO2 emission rates that would likely be occurring during each of the monitoring events. SO2 concentrations were modeled for receptors around each monitoring location so that the modeled data could be directly compared with the monitored data. The modeled and monitored concentrations were compared and showed that there were no systematic biases in the modeled concentrations. This paper is a case study of a Combined Analysis

Modeling Interactions among Individual P2 Receptors to Explain Complex Response Patterns over a Wide Range of ATP Concentrations

PubMed Central

Xing, Shu; Grol, Matthew W.; Grutter, Peter H.; Dixon, S. Jeffrey; Komarova, Svetlana V.

2016-01-01

Extracellular ATP acts on the P2X family of ligand-gated ion channels and several members of the P2Y family of G protein-coupled receptors to mediate intercellular communication among many cell types including bone-forming osteoblasts. It is known that multiple P2 receptors are expressed on osteoblasts (P2X2,5,6,7 and P2Y1,2,4,6). In the current study, we investigated complex interactions within the P2 receptor network using mathematical modeling. To characterize individual P2 receptors, we extracted data from published studies of overexpressed human and rodent (rat and mouse) receptors and fit their dependencies on ATP concentration using the Hill equation. Next, we examined responses induced by an ensemble of endogenously expressed P2 receptors. Murine osteoblastic cells (MC3T3-E1 cells) were loaded with fluo-4 and stimulated with varying concentrations of extracellular ATP. Elevations in the concentration of cytosolic free calcium ([Ca2+]i) were monitored by confocal microscopy. Dependence of the calcium response on ATP concentration exhibited a complex pattern that was not explained by the simple addition of individual receptor responses. Fitting the experimental data with a combination of Hill equations from individual receptors revealed that P2Y1 and P2X7 mediated the rise in [Ca2+]i at very low and high ATP concentrations, respectively. Interestingly, to describe responses at intermediate ATP concentrations, we had to assume that a receptor with a K1∕2 in that range (e.g. P2Y4 or P2X5) exerts an inhibitory effect. This study provides new insights into the interactions among individual P2 receptors in producing an ensemble response to extracellular ATP. PMID:27468270

Modeling uranium(VI) adsorption onto montmorillonite under varying carbonate concentrations: A surface complexation model accounting for the spillover effect on surface potential

NASA Astrophysics Data System (ADS)

Tournassat, C.; Tinnacher, R. M.; Grangeon, S.; Davis, J. A.

2018-01-01

The prediction of U(VI) adsorption onto montmorillonite clay is confounded by the complexities of: (1) the montmorillonite structure in terms of adsorption sites on basal and edge surfaces, and the complex interactions between the electrical double layers at these surfaces, and (2) U(VI) solution speciation, which can include cationic, anionic and neutral species. Previous U(VI)-montmorillonite adsorption and modeling studies have typically expanded classical surface complexation modeling approaches, initially developed for simple oxides, to include both cation exchange and surface complexation reactions. However, previous models have not taken into account the unique characteristics of electrostatic surface potentials that occur at montmorillonite edge sites, where the electrostatic surface potential of basal plane cation exchange sites influences the surface potential of neighboring edge sites ('spillover' effect). A series of U(VI) - Na-montmorillonite batch adsorption experiments was conducted as a function of pH, with variable U(VI), Ca, and dissolved carbonate concentrations. Based on the experimental data, a new type of surface complexation model (SCM) was developed for montmorillonite, that specifically accounts for the spillover effect using the edge surface speciation model by Tournassat et al. (2016a). The SCM allows for a prediction of U(VI) adsorption under varying chemical conditions with a minimum number of fitting parameters, not only for our own experimental results, but also for a number of published data sets. The model agreed well with many of these datasets without introducing a second site type or including the formation of ternary U(VI)-carbonato surface complexes. The model predictions were greatly impacted by utilizing analytical measurements of dissolved inorganic carbon (DIC) concentrations in individual sample solutions rather than assuming solution equilibration with a specific partial pressure of CO2, even when the gas phase was

Hemostatic variables, plasma lactate concentration, and inflammatory biomarkers in dogs with gastric dilatation-volvulus.

PubMed

Verschoof, J; Moritz, A; Kramer, M; Bauer, N

2015-01-01

Prospective characterization of hemostastatic variables, plasma lactate concentration, and inflammatory biomarkers in dogs with gastric dilatation-volvulus (GDV). Coagulation variables (platelets, prothrombin time [PT], activated partial thromboplastin time [aPTT], fibrinogen, antithrombin [AT], protein C [PC], protein S [PS], D-dimers), plasma lactate concentration and inflammatory biomarkers (C-reactive protein, white blood cell [WBC] count, lymphocyte and neutrophil numbers) were assessed in 20 dogs with GDV presented between 2011 and 2012. Blood was taken preoperatively and at days 1 and 3 postoperatively. The prognostic value of these variables before and after surgery was evaluated as well as the behavior of variables during the study. Overall, 7/20 (35%) dogs did not survive; two dogs (29%) were euthanized during surgery due to severe gastric necrosis and 5 (71%) dogs after surgery due to sepsis and disseminated intravascular coagulopathy. Prior to surgery, median plasma lactate concentration was significantly (p = 0.01) lower in survivors (6.2 mmol/l, range 1.9-9.7 mmol/l) when compared to non-survivors (11.8 mmol/l, range 7.5-16.2 mmol/l). In dogs dying after surgery, significantly higher plasma lactate concentration, coagulation times and D-dimer concentration were present as well as lower fibrinogen concentration and activity of PC and AT compared to survivors. At discharge, activity of AT, PC and PS were markedly below the reference interval in 6/13 (46%), 11/13 (85%), and 8/13 (62%) dogs, respectively. Only lactate plasma concentration was of preoperative prognostic value. After surgery, severe abnormalities of coagulation variables, especially the endogenous anticoagulants were present in most of the dogs. The severity of the abnormalities was associated with survival.

Reduction of arsenic content in a complex galena concentrate by Acidithiobacillus ferrooxidans

PubMed Central

Makita, Mario; Esperón, Margarita; Pereyra, Benito; López, Alejandro; Orrantia, Erasmo

2004-01-01

Background Bioleaching is a process that has been used in the past in mineral pretreatment of refractory sulfides, mainly in the gold, copper and uranium benefit. This technology has been proved to be cheaper, more efficient and environmentally friendly than roasting and high pressure moisture heating processes. So far the most studied microorganism in bioleaching is Acidithiobacillus ferrooxidans. There are a few studies about the benefit of metals of low value through bioleaching. From all of these, there are almost no studies dealing with complex minerals containing arsenopyrite (FeAsS). Reduction and/or elimination of arsenic in these ores increase their value and allows the exploitation of a vast variety of minerals that today are being underexploited. Results Arsenopyrite was totally oxidized. The sum of arsenic remaining in solution and removed by sampling represents from 22 to 33% in weight (yield) of the original content in the mineral. The rest of the biooxidized arsenic form amorphous compounds that precipitate. Galena (PbS) was totally oxidized too, anglesite (PbSO4) formed is virtually insoluble and remains in the solids. The influence of seven factors in a batch process was studied. The maximum rate of arsenic dissolution in the concentrate was found using the following levels of factors: small surface area of particle exposure, low pulp density, injecting air and adding 9 K medium to the system. It was also found that ferric chloride and carbon dioxide decreased the arsenic dissolution rate. Bioleaching kinetic data of arsenic solubilization were used to estimate the dilution rate for a continuous culture. Calculated dilution rates were relatively small (0.088–0.103 day-1). Conclusion Proper conditions of solubilization of arsenic during bioleaching are key features to improve the percentage (22 to 33% in weight) of arsenic removal. Further studies are needed to determine other factors that influence specifically the solubilization of arsenic in

The Dual Regulatory Role of Amino Acids Leu480 and Gln481 of Prothrombin*

PubMed Central

Wiencek, Joesph R.; Hirbawi, Jamila; Yee, Vivien C.; Kalafatis, Michael

2016-01-01

Prothrombin (FII) is activated to α-thrombin (IIa) by prothrombinase. Prothrombinase is composed of a catalytic subunit, factor Xa (fXa), and a regulatory subunit, factor Va (fVa), assembled on a membrane surface in the presence of divalent metal ions. We constructed, expressed, and purified several mutated recombinant FII (rFII) molecules within the previously determined fVa-dependent binding site for fXa (amino acid region 473–487 of FII). rFII molecules bearing overlapping deletions within this significant region first established the minimal stretch of amino acids required for the fVa-dependent recognition exosite for fXa in prothrombinase within the amino acid sequence Ser478–Val479–Leu480–Gln481–Val482. Single, double, and triple point mutations within this stretch of rFII allowed for the identification of Leu480 and Gln481 as the two essential amino acids responsible for the enhanced activation of FII by prothrombinase. Unanticipated results demonstrated that although recombinant wild type α-thrombin and rIIaS478A were able to induce clotting and activate factor V and factor VIII with rates similar to the plasma-derived molecule, rIIaSLQ→AAA with mutations S478A/L480A/Q481A was deficient in clotting activity and unable to efficiently activate the pro-cofactors. This molecule was also impaired in protein C activation. Similar results were obtained with rIIaΔSLQ (where rIIaΔSLQ is recombinant human α-thrombin with amino acids Ser478/Leu480/Gln481 deleted). These data provide new evidence demonstrating that amino acid sequence Leu480–Gln481: 1) is crucial for proper recognition of the fVa-dependent site(s) for fXa within prothrombinase on FII, required for efficient initial cleavage of FII at Arg320; and 2) is compulsory for appropriate tethering of fV, fVIII, and protein C required for their timely activation by IIa. PMID:26601957

Evidence for the complex relationship between free amino acid and sugar concentrations and acrylamide-forming potential in potato

PubMed Central

Muttucumaru, N; Powers, SJ; Elmore, JS; Briddon, A; Mottram, DS; Halford, NG

2014-01-01

Free amino acids and reducing sugars participate in the Maillard reaction during high-temperature cooking and processing. This results not only in the formation of colour, aroma and flavour compounds, but also undesirable contaminants, including acrylamide, which forms when the amino acid that participates in the reaction is asparagine. In this study, tubers of 13 varieties of potato (Solanum tuberosum), which had been produced in a field trial in 2010 and sampled immediately after harvest or after storage for 6 months, were analysed to show the relationship between the concentrations of free asparagine, other free amino acids, sugars and acrylamide-forming potential. The varieties comprised five that are normally used for crisping, seven that are used for French fry production and one that is used for boiling. Acrylamide formation was measured in heated flour, and correlated with glucose and fructose concentration. In French fry varieties, which contain higher concentrations of sugars, acrylamide formation also correlated with free asparagine concentration, demonstrating the complex relationship between precursor concentration and acrylamide-forming potential in potato. Storage of the potatoes for 6 months at 9°C had a significant, variety-dependent impact on sugar and amino acid concentrations and acrylamide-forming potential. PMID:25540460

An update on the use of massive transfusion protocols in obstetrics.

PubMed

Pacheco, Luis D; Saade, George R; Costantine, Maged M; Clark, Steven L; Hankins, Gary D V

2016-03-01

Obstetrical hemorrhage remains a leading cause of maternal mortality worldwide. New concepts involving the pathophysiology of hemorrhage have been described and include early activation of both the protein C and fibrinolytic pathways. New strategies in hemorrhage treatment include the use of hemostatic resuscitation, although the optimal ratio to administer the various blood products is still unknown. Massive transfusion protocols involve the early utilization of blood products and limit the traditional approach of early massive crystalloid-based resuscitation. The evidence behind hemostatic resuscitation has changed in the last few years, and debate is ongoing regarding optimal transfusion strategies. The use of tranexamic acid, fibrinogen concentrates, and prothrombin complex concentrates has emerged as new potential alternative treatment strategies with improved safety profiles. Copyright © 2016 Elsevier Inc. All rights reserved.

A new machine-learning method to prognosticate paraquat poisoned patients by combining coagulation, liver, and kidney indices.

PubMed

Hu, Lufeng; Li, Huaizhong; Cai, Zhennao; Lin, Feiyan; Hong, Guangliang; Chen, Huiling; Lu, Zhongqiu

2017-01-01

The prognosis of paraquat (PQ) poisoning is highly correlated to plasma PQ concentration, which has been identified as the most important index in PQ poisoning. This study investigated the predictive value of coagulation, liver, and kidney indices in prognosticating PQ-poisoning patients, when aligned with plasma PQ concentrations. Coagulation, liver, and kidney indices were first analyzed by variance analysis, receiver operating characteristic curves, and Fisher discriminant analysis. Then, a new, intelligent, machine learning-based system was established to effectively provide prognostic analysis of PQ-poisoning patients based on a combination of the aforementioned indices. In the proposed system, an enhanced extreme learning machine wrapped with a grey wolf-optimization strategy was developed to predict the risk status from a pool of 103 patients (56 males and 47 females); of these, 52 subjects were deceased and 51 alive. The proposed method was rigorously evaluated against this real-life dataset, in terms of accuracy, Matthews correlation coefficients, sensitivity, and specificity. Additionally, the feature selection was investigated to identify correlating factors for risk status. The results demonstrated that there were significant differences in the coagulation, liver, and kidney indices between deceased and surviving subjects (p<0.05). Aspartate aminotransferase, prothrombin time, prothrombin activity, total bilirubin, direct bilirubin, indirect bilirubin, alanine aminotransferase, urea nitrogen, and creatinine were the most highly correlated indices in PQ poisoning and showed statistical significance (p<0.05) in predicting PQ-poisoning prognoses. According to the feature selection, the most important correlated indices were found to be associated with aspartate aminotransferase, the aspartate aminotransferase to alanine ratio, creatinine, prothrombin time, and prothrombin activity. The method proposed here showed excellent results that were better than

A noninvasive method of examination of the hemostasis system.

PubMed

Kuznik, B I; Fine, I W; Kaminsky, A V

2011-09-01

We propose a noninvasive method of in vivo examination the hemostasis system based on speckle pattern analysis of coherent light scattering from the skin. We compared the results of measuring basic blood coagulation parameters by conventional invasive and noninvasive methods. A strict correlation was found between the results of measurement of soluble fibrin monomer complexes, international normalized ratio (INR), prothrombin index, and protein C content. The noninvasive method of examination of the hemostatic system enable rough evaluation of the intensity of the intravascular coagulation and correction of the dose of indirect anticoagulants maintaining desired values of INR or prothrombin index.

Immune complex-induced human monocyte procoagulant activity. I. a rapid unidirectional lymphocyte-instructed pathway.

PubMed

Schwartz, B S; Edgington, T S

1981-09-01

It has previously been described that soluble antigen:antibody complexes in antigen excess can induce an increase in the procoagulant activity of human peripheral blood mononuclear cells. It has been proposed that this response may explain the presence of fibrin in immune complex-mediated tissue lesions. In the present study we define cellular participants and their roles in the procoagulant response to soluble immune complexes. Monocytes were shown by cell fractionation and by a direct cytologic assay to be the cell of origin of the procoagulant activity; and virtually all monocytes were able to participate in the response. Monocytes, however, required the presence of lymphocytes to respond. The procoagulant response required cell cooperation, and this collaborative interaction between lymphocytes and monocytes appeared to be unidirectional. Lymphocytes once triggered by immune complexes induced monocytes to synthesize the procoagulant product. Intact viable lymphocytes were required to present instructions to monocytes; no soluble mediator could be found to subserve this function. Indeed, all that appeared necessary to induce monocytes to produce procoagulant activity was an encounter with lymphocytes that had previously been in contact with soluble immune complexes. The optimum cellular ratio for this interaction was four lymphocytes per monocyte, about half the ratio in peripheral blood. The procoagulant response was rapid, reaching a maximum within 6 h after exposure to antigen:antibody complexes. The procoagulant activity was consistent with tissue factor because Factors VII and X and prothrombin were required for clotting of fibrinogen. WE propose that this pathway differs from a number of others involving cells of the immune system. Elucidation of the pathway may clarify the role of this lymphocyte-instructed monocyte response in the Shwartzman phenomenon and other thrombohemorrhagic events associated with immune cell function and the formation of immune

Effects of aspirin, carprofen, deracoxib, and meloxicam on platelet function and systemic prostaglandin concentrations in healthy dogs.

PubMed

Blois, Shauna L; Allen, Dana G; Wood, R Darren; Conlon, Peter D

2010-03-01

To determine effects of therapeutic dosages of aspirin, carprofen, deracoxib, and meloxicam on platelet function and systemic prostaglandin concentrations in healthy dogs. 10 hound-crossbred dogs. Aspirin (10 mg/kg, PO, q 12 h), carprofen (4.4 mg/kg, PO, q 24 h), deracoxib (2 mg/kg, PO, q 24 h), meloxicam (0.1 mg/kg, PO, q 24 h), and a placebo were administered for 7 days in a random order to each of 10 healthy dogs; there was a 21-day washout period between subsequent treatments. One-stage prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen concentration, and plasma concentrations of thromboxane (TX)B(2) and 6-keto prostaglandin (PG)F(1alpha) were measured before and after treatment administration. Platelet function was assessed by use of a platelet-function analyzer and aggregation. Aspirin, carprofen, and meloxicam did not significantly affect platelet function. Deracoxib caused a mild decrease in platelet aggregation induced by 50microM ADP. Platelet number, Hct, PT, aPTT, and plasma TXB(2) and 6-keto PGF(1alpha) concentrations were unchanged after NSAID administration. Meloxicam administration resulted in a significant decrease in fibrinogen concentration, but results remained within the laboratory reference interval. Oral administration of commonly used NSAIDs at therapeutic dosages in healthy dogs did not alter plasma TXB(2) and 6-keto PGF(1alpha) concentrations. Deracoxib administration resulted in a minor abnormality in platelet aggregation. Anti-inflammatory doses of aspirin did not affect platelet function as measured by use of optical aggregometry and a platelet-function analyzer. Further evaluation of the effects of aspirin and cyclooxygenase-2-selective inhibitors on hemostasis should be performed.

Determination of refractive index, size, and concentration of nonabsorbing colloidal nanoparticles from measurements of the complex effective refractive index.

PubMed

Márquez-Islas, Roberto; Sánchez-Pérez, Celia; García-Valenzuela, Augusto

2014-02-01

We describe a method for obtaining the refractive index (RI), size, and concentration of nonabsorbing nanoparticles in suspension from relatively simple optical measurements. The method requires measuring the complex effective RI of two dilute suspensions of the particles in liquids of different refractive indices. We describe the theoretical basis of the proposed method and provide experimental results validating the procedure.

Factor V Leiden, Prothrombin and MTHFR Mutation in Patients with Preeclamsia, Intrauterine Growth Restriction and Placental Abruption.

PubMed

Livrinova, Vesna; Lega, Marija Hadzi; Dimcheva, Anita Hristova; Samardziski, Igor; Isjanovska, Rozalinda

2015-12-15

Factor V Leiden, Prothrombin and MTHFR gene mutation, could have an influence in pregnancy with adverse outcome Preeclamsia, IUGR and Placental abruption. The aim of this study is to investigate the presence of above mentioned inherited thrombophilias and its statistical significance, distribution among the complicated and normal pregnancy, and relative risk for carrier of mutation to develop preeclampsia, IUGR and placental abruption. Prospective cohort study is implemented at University Clinic for Obstetric and Gynecology in Skopje, Republic of Macedonia. The study included 109 delivered patients: 40 with preeclapmsia, 22 with IUGR, 17 with placental abruption and 30 as control group with normal pregnancy. The amount of 3 ml venous blood has been used for detection of these point mutations using ThromboStrip -Opegen, QIAGEN kit manufactured for thrombotic risk. The highest frequency was found: in the group with preeclampsia 35% were MTHFR homozygous, IUGR -MTHFR heterozygous 45%, Placental abruption- 52.9% MTHFR heterozygous, and in the control group without thrombophilia 56.7%. There were combined thrombophilia in 3 patients. There aren`t statistical significance in presence of thrombophilia among groups (p > 0.05). Statistical significance (p < 0.05) was found between carriers of MTHFR homozygous in preeclampsia and group with placental abruption and control group. Relative risk in IUGR group for MTHFR homozygous was 5.54 (1.37

Factor V Leiden, Prothrombin and MTHFR Mutation in Patients with Preeclamsia, Intrauterine Growth Restriction and Placental Abruption

PubMed Central

Livrinova, Vesna; Lega, Marija Hadzi; Dimcheva, Anita Hristova; Samardziski, Igor; Isjanovska, Rozalinda

2015-01-01

BACKGROUND: Factor V Leiden, Prothrombin and MTHFR gene mutation, could have an influence in pregnancy with adverse outcome Preeclamsia, IUGR and Placental abruption. AIM: The aim of this study is to investigate the presence of above mentioned inherited thrombophilias and its statistical significance, distribution among the complicated and normal pregnancy, and relative risk for carrier of mutation to develop preeclampsia, IUGR and placental abruption. MATERIAL AND METHODS: Prospective cohort study is implemented at University Clinic for Obstetric and Gynecology in Skopje, Republic of Macedonia. The study included 109 delivered patients: 40 with preeclapmsia, 22 with IUGR, 17 with placental abruption and 30 as control group with normal pregnancy. The amount of 3 ml venous blood has been used for detection of these point mutations using ThromboStrip -Opegen, QIAGEN kit manufactured for thrombotic risk. RESULTS: The highest frequency was found: in the group with preeclampsia 35% were MTHFR homozygous, IUGR -MTHFR heterozygous 45%, Placental abruption- 52.9% MTHFR heterozygous, and in the control group without thrombophilia 56.7%. There were combined thrombophilia in 3 patients. There aren`t statistical significance in presence of thrombophilia among groups (p > 0.05). Statistical significance (p < 0.05) was found between carriers of MTHFR homozygous in preeclampsia and group with placental abruption and control group. Relative risk in IUGR group for MTHFR homozygous was 5.54 (1.37

Effect of N-acetylcysteine on the accuracy of the prothrombin time assay of plasma coagulation factor II+VII+X activity in subjects infused with the drug. Influence of time and temperature.

PubMed

Thorsen, Sixtus; Teisner, Ane; Jensen, Søren Astrup; Philips, Malou; Dalhoff, Kim; Bendtsen, Flemming

2009-01-01

The prothrombin time (PT) assay of factor II+VII+X activity is an important predictor of liver damage in paracetamol poisoned patients. It complicates interpretation of results that the antidote, acetylcysteine (NAC) depresses this activity. The aim was to investigate if NAC influences the accuracy of the plasma PT assay. The accuracy of Nycotest PT was studied using plasma added NAC in vitro and plasma from subjects infused with NAC. The latter results were compared with those obtained by analysis of PT by CoaguChek S. Therapeutic NAC concentrations added to plasma in vitro decreased factor II+VII+X activity at 37 degrees C in a time-dependent manner. This effect was quenched at temperatures <24 degrees C. Activity lost at 37 degrees C could partly be recovered by subsequent incubation at 5 or 20 degrees C. Incubation at 37 degrees C prior to assay led to a significant additional depression of factor II+VII+X activity in plasma from subjects infused with NAC during the first 3h of infusion indicating that it contained reactive NAC. The risk that this NAC interfered with the accuracy of the PT assay was considered minimal with samples stored below 24 degrees C. This was supported by similarity of results obtained by analysis of appropriately stored plasma and simultaneously drawn blood by CoaguChek S. Residual reactive NAC does not interfere with the accuracy of the PT assay of plasma stored below 24 degrees C, but NAC-induced loss in activity at 37 degrees C may be partly recovered during subsequent storage below 24 degrees C.

Simultaneous generation of aptamers to multiple gamma-carboxyglutamic acid proteins from a focused aptamer library using DeSELEX and convergent selection.

PubMed

Layzer, Juliana M; Sullenger, Bruce A

2007-01-01

By using the in vitro selection method SELEX against the complex mixture of GLA proteins and utilizing methods to deconvolute the resulting ligands, we were able to successfully generate 2'-ribo purine, 2'-fluoro pyrimidine aptamers to various individual targets in the GLA protein proteome that ranged in concentration from 10 nM to 1.4 microM in plasma. Perhaps not unexpectedly, the majority of the aptamers isolated following SELEX bind the most abundant protein in the mixture, prothrombin (FII), with high affinity. We show that by deselecting the dominant prothrombin aptamer the selection can be redirected. By using this DeSELEX approach, we were able to shift the selection toward other sequences and to less abundant protein targets and obtained an aptamer to Factor IX (FIX). We also demonstrate that by using an RNA library that is focused around a proteome, purified protein targets can then be used to rapidly generate aptamers to the protein targets that are rare in the initial mixture such as Factor VII (FVII) and Factor X (FX). Moreover, for all four proteins targeted (FII, FVII, FIX, and FX), aptamers were identified that could inhibit the individual protein's activitity in coagulation assays. Thus, by applying the concepts of DeSELEX and focused library selection, aptamers specific for any protein in a particular proteome can theoretically be generated, even when the proteins in the mixture are present at very different concentrations.

Direct Oral Anticoagulant- or Warfarin-Related Major Bleeding: Characteristics, Reversal Strategies, and Outcomes From a Multicenter Observational Study.

PubMed

Xu, Yan; Schulman, Sam; Dowlatshahi, Dar; Holbrook, Anne M; Simpson, Christopher S; Shepherd, Lois E; Wells, Philip S; Giulivi, Antonio; Gomes, Tara; Mamdani, Muhammad; Khuu, Wayne; Frymire, Eliot; Johnson, Ana P

2017-07-01

Direct oral anticoagulants (DOACs) have expanded the armamentarium for antithrombotic therapy. Although DOAC-related major bleeding was associated with favorable outcomes compared with warfarin in clinical trials, warfarin effects were reversed in < 40% of cases, raising concerns about the generalizability of this finding. Consecutive patients ≥ 66 years presented to five tertiary care hospitals across three cities in Ontario, Canada from October 2010 to March 2015 with diagnoses that included hemorrhage. Charts were screened for association with DOAC or warfarin use; eligible cases were abstracted and linked to administrative databases. Among 19,061 records screened, 2,002 (460 receiving DOAC, 1,542 receiving warfarin) were eligible. Reversal agents (72.9% vitamin K, 40.7% prothrombin complex concentrates) were frequently used in warfarin bleeding events. Red blood cell transfusions occurred more often in DOAC bleeding events than in warfarin events (52.0% vs 39.5%; adjusted relative risk [aRR], 1.32; 95% CI, 1.19-2.47). However, units of blood products transfused were not different between the two groups. Thirty-four DOAC cases (7.4%) received activated prothrombin complex concentrates or recombinant factor VIIa. In-hospital mortality was lower following DOAC bleeding events (9.8% vs 15.2%; aRR, 0.66; 95% CI, 0.49-0.89), although differences in 30-day mortality did not reach statistical significance (12.6% vs 16.3%; aRR, 0.79; 95% CI, 0.61-1.03). In this unselected cohort of patients with oral anticoagulant-related hemorrhage with high rates of warfarin reversal, in-hospital mortality was lower among DOAC-associated bleeding events. These findings support the safety of DOACs in routine care and present useful baseline measures for evaluations of DOAC-specific reversal agents. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Insights into the complex association of bovine factor Va with acidic-lipid-containing synthetic membranes.

PubMed Central

Cutsforth, G A; Koppaka, V; Krishnaswamy, S; Wu, J R; Mann, K G; Lentz, B R

1996-01-01

The mechanism of binding of blood coagulation cofactor factor Va to acidic-lipid-containing membranes has been addressed. Binding isotherms were generated at room temperature using the change in fluorescence anisotropy of pyrene-labeled bovine factor Va to detect binding to sonicated membrane vesicles containing either bovine brain phosphatidylserine (PS) or 1,2-dioleoyl-3-sn-phosphatidylglycerol (DOPG) in combination with 1-palmitoyl-2-oleoyl-3-sn-phosphatidylcholine (POPC). The composition of the membranes was varied from 0 to 40 mol% for PS/POPC and from 0 to 65 mol % for DOPG/POPC membranes. Fitting the data to a classical Langmuir adsorption model yielded estimates of the dissociation constant (Kd) and the stoichiometry of binding. The values of Kd defined in this way displayed a maximum at low acidic lipid content but were nearly constant at intermediate to high fractions of acidic lipid. Fitting the binding isotherms to a two-process binding model (nonspecific adsorption in addition to binding of acidic lipids to sites on the protein) suggested a significant acidic-lipid-independent binding affinity in addition to occupancy of three protein sites that bind PS in preference to DOPG. Both analyses indicated that interaction of factor Va with an acidic-lipid-containing membrane is much more complex than those of factor Xa or prothrombin. Furthermore, a change in the conformation of bound pyrene-labeled factor Va with surface concentration of acidic lipid was implied by variation of both the saturating fluorescence anisotropy and the binding parameters with the acidic lipid content of the membrane. Finally, the results cannot support the contention that binding occurs through nonspecific adsorption to a patch or domain of acidic lipids in the membrane. Factor Va is suggested to associate with membranes by a complex process that includes both acidic-lipid-specific and acidic-lipid-independent sites and a protein structure change induced by occupancy of acidic

Thrombophilic mutations in pre-eclampsia and pregnancy-induced hypertension.

PubMed

Omar, Siti Z; Qvist, Rajes; Khaing, Si L; Muniandy, Sekaran; Bhalla, Sunil

2008-04-01

The aim of the present study was to determine the existence or prevalence of thrombophilic markers such as Factor V Leiden, prothrombin G20210A, protein S, protein C, activated protein C and anti-thrombin in pre-eclampsia and pregnancy-induced hypertensive patients. Blood samples were collected from a total number of 124 women at the maternity unit, University of Malaya Medical Center. These included 49 patients with pre-eclampsia, 63 patients with pregnancy-induced hypertension and 12 normal pregnant women. DNA was extracted from the blood samples. Factor V Leiden (Taq I) and prothrombin G20210A (Hind III) genotyping was done on polymerase chain reaction-restriction fragment length polymorphism. Anti-thrombin activity and the concentrations of protein C, protein S and activated protein C were measured using the IL Coagulation System (Hemosil). Of the 124 subjects, one pre-eclampsia patient was homozygous for Factor V Leiden mutation but prothrombin G20210A mutation was not present in any of the subjects. The subject with Factor V Leiden mutation also had a low activated protein C resistance and a low protein S concentration. Factor V Leiden mutation is present in the Asian population and may very well serve as one of the genetic factors responsible for pre-eclampsia and other adverse pregnancy outcomes.

Recovery of fibrinogen concentrate after intraosseous application is equivalent to the intravenous route in a porcine model of hemodilution

PubMed Central

Schlimp, Christoph J.; Solomon, Cristina; Keibl, Claudia; Zipperle, Johannes; Nürnberger, Sylvia; Öhlinger, Wolfgang; Redl, Heinz; Schöchl, Herbert

2014-01-01

BACKGROUND Fibrinogen concentrate is increasingly considered as a hemostatic agent for trauma patients experiencing bleeding. Placing a venous access is sometimes challenging during severe hemorrhage. Intraosseous access may be considered instead. Studies of intraosseous infusion of coagulation factor concentrates are limited. We investigated in vivo recovery following intraosseous administration of fibrinogen concentrate and compared the results with intravenous administration. METHODS This study was performed on 12 pigs (mean [SD] body weight, 34.1 [2.8] kg). Following controlled blood loss (35 mL/kg) and fluid replacement with balanced crystalloid solution, intraosseous (n = 6) administration of fibrinogen concentrate (80 mg per kilogram of bodyweight) in the proximal tibia was compared with intravenous (n = 6) administration of the same dose (fibrinogen infusion time approximately 5 minutes in both groups). The following laboratory parameters were assessed: blood cell count, prothrombin time index, activated partial thromboplastin time, and plasma fibrinogen concentration (Clauss assay). Coagulation status was also assessed by thromboelastometry. RESULTS All tested laboratory parameters were comparable between the intraosseous and intravenous groups at baseline, hemodilution, and 30 minutes after fibrinogen concentrate administration. In vivo recovery of fibrinogen was also similar in the two groups (89% [23%] and 91% [22%], respectively). There were no significant between-group differences in any of the thromboelastometric parameters. Histologic examination indicated no adverse effects on the tissue surrounding the intraosseous administration site. CONCLUSION This study suggests that intraosseous administration of fibrinogen concentrate results in a recovery of fibrinogen similar to that of intravenous administration. The intraosseous route of fibrinogen concentrate could be a valuable alternative in situations where intravenous access is not feasible or would

Effective concentration as a tool for quantitatively addressing preorganization in multicomponent assemblies: application to the selective complexation of lanthanide cations.

PubMed

Canard, Gabriel; Koeller, Sylvain; Bernardinelli, Gérald; Piguet, Claude

2008-01-23

The beneficial entropic effect, which may be expected from the connection of three tridentate binding units to a strain-free covalent tripod for complexing nine-coordinate cations (Mz+ = Ca2+, La3+, Eu3+, Lu3+), is quantitatively analyzed by using a simple thermodynamic additive model. The switch from pure intermolecular binding processes, characterizing the formation of the triple-helical complexes [M(L2)3]z+, to a combination of inter- and intramolecular complexation events in [M(L8)]z+ shows that the ideal structural fit observed in [M(L8)]z+ indeed masks large energetic constraints. This limitation is evidenced by the faint effective concentrations, ceff, which control the intramolecular ring-closing reactions operating in [M(L8)]z+. This predominence of the thermodynamic approach over the usual structural analysis agrees with the hierarchical relationships linking energetics and structures. Its simple estimation by using a single microscopic parameter, ceff, opens novel perspectives for the molecular tuning of specific receptors for the recognition of large cations, a crucial point for the programming of heterometallic f-f complexes under thermodynamic control.

Synergism between urinary prothrombin fragment 1 and urine: a comparison of inhibitory activities in stone-prone and stone-free population groups.

PubMed

Webber, Dawn; Rodgers, Allen L; Sturrock, Edward D

2002-09-01

South African blacks rarely form kidney stones compared with whites. This study investigated whether purified urinary prothrombin fragment 1 (UPTF1) derived from blacks is a more potent inhibitor of calcium oxalate crystallisation than that from whites. UPTF1 was purified from the urine of both population groups and their inhibitory activities were compared in a cross-over design in which each protein was tested in ultrafiltered urine from both population groups. Coulter Multisizer, [14C]-oxalate deposition and scanning electron microscopy experiments were used to monitor crystallisation. The study has demonstrated for the first time that UPTF1 promotes nucleation and that inhibitory activity is synergistically dependent upon urine composition. The activity of the whites' UPTF1 was greater than that of the blacks in the whites' urine (e.g. particle size decrease: 31.7% vs. 25.2%), while the blacks' UPTF1 was superior to that of the whites in the blacks' urine (e.g. particle size decrease: 46.5% vs. 32.4%). In addition, when tested in their respective endogenous urines, the blacks' UPTF1 demonstrated superior inhibitory activity on an absolute scale (e.g. particle size decrease: 46.5% vs. 31.7%). Thus, the urine composition of black South Africans may influence their UPTF1 conformation, conferring greater efficacy for inhibition of calcium oxalate crystallisation.

Diagnostic accuracy of des-gamma-carboxy prothrombin for hepatocellular carcinoma in a French cohort using the Lumipulse® G600 analyzer.

PubMed

Sultanik, P; Ginguay, A; Vandame, J; Popovici, T; Meritet, J-F; Cynober, L; Pol, S; Bories, P-N

2017-01-01

The increasing incidence of hepatocellular carcinoma (HCC) in Western countries requests reliable tumour markers for preclinical diagnosis. We evaluated the diagnostic accuracy of des-gamma-carboxy prothrombin (DCP), in comparison with alpha-fetoprotein (AFP) in a French cohort using a new analyser. One hundred and sixty-two patients with virus-related cirrhosis (46 HCC patients and 116 controls) were recruited in this retrospective proof-of-concept study. DCP was measured on new Lumipulse ® G600 analyzer and AFP on usual Cobas e602 analyzer in serum samples that were collected at the time of HCC diagnosis for HCC patients or during follow-up for controls. DCP and AFP levels were higher in HCC patients. The area under receiver operating characteristic curve was larger for DCP than for AFP (0.89 vs 0.77, P=.03). At the cut-off value of 128 mAU/mL, sensitivity and specificity for DCP were 74% and 92%. At the cut-off value of 20 μg/L, sensitivity and specificity for AFP were 63% and 82%. NRI >0 for the association of "AFP+DCP" were 101%, P<.0001, and 23%, P=.03, compared to "AFP" or "DCP" alone, respectively. We conclude that DCP outperformed AFP for the detection of HCC. © 2016 John Wiley & Sons Ltd.

Influence of domestic pets on soil concentrations of dissolved organic carbon, nitrogen, and phosphorus under turfgrass in apartment complexes of Central Texas, USA

NASA Astrophysics Data System (ADS)

Steele, M.; Aitkenhead-Peterson, J. A.

2009-12-01

High nitrogen (N) and phosphorus (P) watershed loading rates increases the concentration and loads present in urban streams and rivers, resulting in eutrophication and degradation of surface water quality. Domestic pet animal feed may represent a significant proportion of nitrogen loading in urban watersheds, and because it is deposited directly on the watershed surface may have a large effect on N loads in urban surface waters (Baker et al. 2001). Animal manure has long been used to increase soil N and phosphorus concentrations for the purpose of growing agricultural crops; however, little is known about unintentional urban manuring resulting from a high density of domesticated pets. The purpose of this study is to determine if the presence of domesticated animals in high density urban developments results in increased concentrations of soil dissolved organic carbon (DOC), N, and P and the potential to contribute to loading of urban streams. Composite soil samples from the 0 to 5 cm and 5 to 10 cm soil depth were collected from apartment complexes in Bryan/College Station (BCS) and San Antonio, Texas during August, 2009. Apartment complexes were randomly located around the city and were chosen based on their rules regarding pet ownership. Four apartment complexes that allowed all domestic pets were compared to four that did not allow any domestic pets on the property. A 10:1 water extraction of field moist soil was conducted immediately after sampling. Soil water extracts were analyzed for DOC, total dissolved nitrogen (TDN), nitrate-N, ammonium-N, dissolved organic N, and orthophosphate-P. Results indicated significantly increased concentrations of DOC and N species at both depths in BCS apartments that allowed pets compared to those that did not; however, opposite trends were found in San Antonio. There is a trend for increased concentrations of orthophosphate-P at both locations. Baker, L.A., D. Hope, Y. Xu, et al. 2001. Nitrogen balance for the central Arizona

At clinically relevant concentrations the anaesthetic/amnesic thiopental but not the anticonvulsant phenobarbital interferes with hippocampal sharp wave-ripple complexes

PubMed Central

Papatheodoropoulos, Costas; Sotiriou, Evangelos; Kotzadimitriou, Dimitrios; Drimala, Panagiota

2007-01-01

Background Many sedative agents, including anesthetics, produce explicit memory impairment by largely unknown mechanisms. Sharp-wave ripple (SPW-R) complexes are network activity thought to represent the neuronal substrate for information transfer from the hippocampal to neocortical circuits, contributing to the explicit memory consolidation. In this study we examined and compared the actions of two barbiturates with distinct amnesic actions, the general anesthetic thiopental and the anticonvulsant phenobarbital, on in vitro SPW-R activity. Results Using an in vitro model of SPW-R activity we found that thiopental (50–200 μM) significantly and concentration-dependently reduced the incidence of SPW-R events (it increased the inter-event period by 70–430 %). At the concentration of 25 μM, which clinically produces mild sedation and explicit memory impairment, thiopental significantly reduced the quantity of ripple oscillation (it reduced the number of ripples and the duration of ripple episodes by 20 ± 5%, n = 12, P < 0.01), and suppressed the rhythmicity of SPWs by 43 ± 15% (n = 6, P < 0.05). The drug disrupted the synchrony of SPWs within the CA1 region at 50 μM (by 19 ± 12%; n = 5, P < 0.05). Similar effects of thiopental were observed at higher concentrations. Thiopental did not affect the frequency of ripple oscillation at any of the concentrations tested (10–200 μM). Furthermore, the drug significantly prolonged single SPWs at concentrations ≥50 μM (it increased the half-width and the duration of SPWs by 35–90 %). Thiopental did not affect evoked excitatory synaptic potentials and its results on SPW-R complexes were also observed under blockade of NMDA receptors. Phenobarbital significantly accelerated SPWs at 50 and 100 μM whereas it reduced their rate at 200 and 400 μM. Furthermore, it significantly prolonged SPWs, reduced their synchrony and reduced the quantity of ripples only at the clinically very high concentration of 400 �

Establishment of reference values for various coagulation tests in healthy Florida manatees (Trichechus manatus latirostris) and evaluation of coagulation in debilitated manatees during rehabilitation.

PubMed

Gerlach, Trevor J; Bandt, Carsten; Conner, Bobbi; Ball, Ray L

2015-11-01

To establish reference ranges for coagulation parameters in healthy Florida manatees (Trichechus manatus latirostris) and compare results with those for debilitated manatees undergoing treatment at a rehabilitation facility. Prospective study. 29 healthy manatees and 45 debilitated manatees with various diseases. Manatees considered healthy on the basis of results of physical examination, CBC, and serum biochemical analysis underwent coagulation testing including measurement of prothrombin time, partial thromboplastin time, D-dimer concentration, platelet count, and fibrinogen concentration to establish reference ranges. For comparison, a group of manatees undergoing rehabilitation was also tested, and the results were compared. Thromboelastography was also performed on some animals. Values for D-dimer concentration were significantly higher in debilitated versus healthy animals. There was no significant difference for prothrombin time, partial thromboplastin time, platelet count, or fibrinogen concentration between groups. Thromboelastography was performed on 8 healthy animals. Reference ranges were established for various tests of coagulation that may assist clinicians during the initial evaluation and rehabilitation of Florida manatees. Future research to evaluate the effect of specific disease processes on the coagulation cascade is recommended.

Analytical methods for determination of free metal ion concentration, labile species fraction and metal complexation capacity of environmental waters: a review.

PubMed

Pesavento, Maria; Alberti, Giancarla; Biesuz, Raffaela

2009-01-12

Different experimental approaches have been suggested in the last few decades to determine metal species in complex matrices of unknown composition as environmental waters. The methods are mainly focused on the determination of single species or groups of species. The more recent developments in trace elements speciation are reviewed focusing on methods for labile and free metal determination. Electrochemical procedures with low detection limit as anodic stripping voltammetry (ASV) and the competing ligand exchange with adsorption cathodic stripping voltammetry (CLE-AdCSV) have been widely employed in metal distribution studies in natural waters. Other electrochemical methods such as stripping chronopotentiometry and AGNES seem to be promising to evaluate the free metal concentration at the low levels of environmental samples. Separation techniques based on ion exchange (IE) and complexing resins (CR), and micro separation methods as the Donnan membrane technique (DMT), diffusive gradients in thin-film gels (DGT) and the permeation liquid membrane (PLM), are among the non-electrochemical methods largely used in this field and reviewed in the text. Under appropriate conditions such techniques make possible the evaluation of free metal ion concentration.

Formation and stability of water-soluble, molecular polyelectrolyte complexes: effects of charge density, mixing ratio, and polyelectrolyte concentration.

PubMed

Shovsky, Alexander; Varga, Imre; Makuska, Ricardas; Claesson, Per M

2009-06-02

The formation of complexes with stoichiometric (1:1) as well as nonstoichiometric (2:1) and (1:2) compositions between oppositely charged synthetic polyelectrolytes carrying strong ionic groups and significantly different molecular weights is reported in this contribution. Poly(sodium styrenesulfonate) (NaPSS) was used as polyanion, and a range of copolymers with various molar ratios of the poly(methacryloxyethyltrimethylammonium) chloride, poly(METAC), and the nonionic poly(ethylene oxide) ether methacrylate, poly(PEO45MEMA), were used as polycations. Formation and stability of PECs have been investigated by dynamic and static light scattering (LS), turbidity, and electrophoretic mobility measurements as a function of polyelectrolyte solution concentration, charge density of the cationic polyelectrolyte, and mixing ratio. The data obtained demonstrate that in the absence of PEO45 side chains the 100% charged polymer (polyMETAC) formed insoluble PECs with PSS that precipitate from solution when exact stoichiometry is achieved. In nonstoichiometric complexes (1:2) and (2:1) large colloidally stable aggregates were formed. The presence of even a relatively small amount of PEO45 side chains (25%) in the cationic copolymer was sufficient for preventing precipitation of the formed stoichiometric and nonstoichiometric complexes. These PEC's are sterically stabilized by the PEO45 chains. By further increasing the PEO45 side-chain content (50 and 75%) of the cationic copolymer, small, water-soluble molecular complexes could be formed. The data suggest that PSS molecules and the charged backbone of the cationic brush form a compact core, and with sufficiently high PEO45 chain density (above 25%) molecular complexes are formed that are stable over prolonged times.

Venom Concentrations and Clotting Factor Levels in a Prospective Cohort of Russell's Viper Bites with Coagulopathy.

PubMed

Isbister, Geoffrey K; Maduwage, Kalana; Scorgie, Fiona E; Shahmy, Seyed; Mohamed, Fahim; Abeysinghe, Chandana; Karunathilake, Harendra; O'Leary, Margaret A; Gnanathasan, Christeine A; Lincz, Lisa F

2015-01-01

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,<0.01 g/L; IQR: <0.01-0.9 g/L), low factor V levels [median,<5%; IQR: <5-4%], low factor VIII levels [median,40%; IQR: 12-79%] and low factor X levels [median, 48%; IQR: 29-67%]. There were smaller reductions in factors II, IX and VII over time. All factors recovered over 48 h post-antivenom. The median INR remained >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.

The role of hydrothermal processes in concentrating high-field strength elements in the Strange Lake peralkaline complex, northeastern Canada

NASA Astrophysics Data System (ADS)

Salvi, Stefano; Williams-Jones, Anthony E.

1996-06-01

The middle-Proterozoic peralkaline pluton at Strange Lake, Quebec/Labrador, comprises hypersolvus to subsolvus phases which are unusually enriched in Zr, Y, REEs, Nb, Be, and F, as exotic alkali and alkaline-earth silicate minerals. The highest concentrations of these elements are in subsolvus granite, which underwent intense low temperature (≤200°C) hydrothermal alteration involving hematization and the replacement of alkali high-field strength element (HFSE) minerals by calcic equivalents. This alteration is interpreted to have been caused by meteoric or formational waters. High temperature (≥ 350°C) alteration, attributed to orthomagmatic fluids, is evident in other parts of the subsolvus granite by the replacement of arfvedsonite by aegirine. Comparisons of the chemical compositions of fresh and altered rocks indicate that rocks subjected to high temperature alteration were chemically unaffected, except for depletion in Zr, Y, and HREEs. These elements were appreciably enriched in rocks that underwent low temperature alteration. Other elements affected by low temperature alteration include Ca and Mg, which were added and Na, which was removed. Available data on HFSE speciation in aqueous fluids and the chemistry of the pluton, suggest that the HFSEs were transported as fluoride complexes. If this was the case, the low temperature fluid could not have been responsible for HFSE transport, because the high concentration of Ca and low solubility of fluorite would have buffered F - activity to levels too low to permit significant complexation. We propose that HFSE mineralization and accompanying alteration were the result of mixing, in the apical parts of the pluton, of a F-rich, essentially Ca-free orthomagmatic fluid containing significant concentrations of HFSEs, with an externally derived meteoric-dominated fluid, enriched in Ca as a result of interaction with calc-silicate gneisses and gabbros. According to this interpretation, the latter fluid was

Inversion of In Situ Light Absorption and Attenuation Measurements to Estimate Constituent Concentrations in Optically Complex Shelf Seas

NASA Astrophysics Data System (ADS)

Ramírez-Pérez, M.; Twardowski, M.; Trees, C.; Piera, J.; McKee, D.

2018-01-01

A deconvolution approach is presented to use spectral light absorption and attenuation data to estimate the concentration of the major nonwater compounds in complex shelf sea waters. The inversion procedure requires knowledge of local material-specific inherent optical properties (SIOPs) which are determined from natural samples using a bio-optical model that differentiates between Case I and Case II waters and uses least squares linear regression analysis to provide optimal SIOP values. A synthetic data set is used to demonstrate that the approach is fundamentally consistent and to test the sensitivity to injection of controlled levels of artificial noise into the input data. Self-consistency of the approach is further demonstrated by application to field data collected in the Ligurian Sea, with chlorophyll (Chl), the nonbiogenic component of total suspended solids (TSSnd), and colored dissolved organic material (CDOM) retrieved with RMSE of 0.61 mg m-3, 0.35 g m-3, and 0.02 m-1, respectively. The utility of the approach is finally demonstrated by application to depth profiles of in situ absorption and attenuation data resulting in profiles of optically significant constituents with associated error bar estimates. The advantages of this procedure lie in the simple input requirements, the avoidance of error amplification, full exploitation of the available spectral information from both absorption and attenuation channels, and the reasonably successful retrieval of constituent concentrations in an optically complex shelf sea.

Relationship and interaction between serum sodium concentration and portal hemodynamics in patients with cirrhosis.

PubMed

Maruyama, Hitoshi; Kondo, Takayuki; Kiyono, Soichiro; Sekimoto, Tadashi; Takahashi, Masanori; Okugawa, Hidehiro; Yokosuka, Osamu

2015-11-01

To examine the relationship between hyponatremia and portal hemodynamics and their effect on the prognosis of cirrhosis. Portal hemodynamic parameters measured by Doppler ultrasound and serum sodium concentrations were examined in 153 cirrhosis patients (mean age 62.2 ± 12.0 years; median observation period, 34.1 m). Study participants included 16 patients with hyponatremia (Na < 135 mEq/L), who showed a significantly greater frequency of possessing a splenorenal shunt (SRS; P = 0.0068), and 137 patients without hyponatremia. Serum sodium concentrations were significantly lower in patients with SRS than in those without (P = 0.0193). An increased prothrombin time-international normalized ratio was a significant predictive factor for developing hyponatremia a year later (8/96; Hazard ratio 14.415; P = 0.028). The cumulative survival rate was significantly lower in patients with hyponatremia (46.7% at 1 and 3 years) than in those without (91.8% at 1 year, 76.8% at 3 years; P < 0.001). The cumulative survival rate was significantly lower in patients who had developed hyponatremia after 1 year (100% at 1 year, 62.5% at 3 years) than those who had not (100% at 1 year, 89.0% at 3 years; P < 0.001). The cumulative survival rate was significantly worse in patients with both hyponatremia and SRS (20% at 1 year). There was a close linkage between the serum sodium concentration and portal hemodynamic abnormality, presence of SRS, and their interaction may negatively influence the prognoses in cirrhosis. © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Radioisotope trithiol complexes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jurisson, Silvia S.; Cutler, Cathy S.; Degraffenreid, Anthony J.

The present invention is directed to a series of stable radioisotope trithiol complexes that provide a simplified route for the direct complexation of radioisotopes present in low concentrations. In certain embodiments, the complex contains a linking domain configured to conjugate the radioisotope trithiol complex to a targeting vector. The invention is also directed to a novel method of linking the radioisotope to a trithiol compound to form the radioisotope trithiol complex. The inventive radioisotope trithiol complexes may be utilized for a variety of applications, including diagnostics and/or treatment in nuclear medicine.

The effect of membrane composition on the hemostatic balance.

PubMed

Smirnov, M D; Ford, D A; Esmon, C T; Esmon, N L

1999-03-23

The phospholipid composition requirements for optimal prothrombin activation and factor Va inactivation by activated protein C (APC) anticoagulant were examined. Vesicles composed of phosphatidylethanolamine (PE) and phosphatidylcholine (PC) supported factor Va inactivation relatively well. However, optimal factor Va inactivation still required relatively high concentrations of phosphatidylserine (PS). In addition, at a fixed concentration of phospholipid, PS, and APC, vesicles devoid of PE never attained a rate of factor Va inactivation achievable with vesicles containing PE. Polyunsaturation of any vesicle component also contributed significantly to APC inactivation of factor Va. Thus, PE makes an important contribution to factor Va inactivation that cannot be mimicked by PS. In the absence of polyunsaturation in the other membrane constituents, this contribution was dependent upon the presence of both the PE headgroup per se and unsaturation of the 1,2 fatty acids. Although PE did not affect prothrombin activation rates at optimal PS concentrations, PE reduced the requirement for PS approximately 10-fold. The Km(app) for prothrombin and the Kd(app) for factor Xa-factor Va decreased as a function of increasing PS concentration, reaching optimal values at 10-15% PS in the absence of PE but only 1% PS in the presence of PE. Fatty acid polyunsaturation had minimal effects. A lupus anticoagulant immunoglobulin was more inhibitory to both prothrombinase and factor Va inactivation in the presence of PE. The degree of inhibition of APC was significantly greater and much more dependent on the phospholipid composition than that of prothrombinase. Thus, subtle changes in the phospholipid composition of cells may control procoagulant and anticoagulant reactions differentially under both normal and pathological conditions.

Mechanism of action of recombinant activated factor VII: an update.

PubMed

Hedner, Ulla

2006-01-01

Bleeding episodes in patients with hemophilia and inhibitors must be managed using agents that are hemostatically active in the absence of factor VIII or IX. Activated prothrombin complex concentrates have long been used in this context. However, the search for safer and more effective agents has led to the development of recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark). This paper presents an update on the mechanism of action of rFVIIa, and describes how pharmacologic doses of this agent enhance thrombin production and thus contribute to the development of a stable, lysis-resistant fibrin plug at the site of vessel damage. This mechanism explains the reported efficacy of rFVIIa in a range of clinical situations characterized by impaired thrombin generation.

Hemophilia and von Willebrand's disease: 2. Management. Association of Hemophilia Clinic Directors of Canada.

PubMed Central

1995-01-01

OBJECTIVE: To present current strategies for the treatment of hemophilia and von Willebrand's disease. OPTIONS: Prophylactic and corrective therapy with hemostatic and adjunctive agents: DDAVP (1-desamino-8-D-arginine vasopressin [desmopressin acetate]), recombinant coagulation products (human Factor VIII and human Factor VIIa) or virally inactivated plasma-derived products (high- or ultra-high-purity human Factor VIII or human Factor VIII concentrate containing von Willebrand factor activity, porcine Factor VIII, high-purity human Factor IX, human prothrombin-complex concentrate, human activated prothrombin-complex concentrate), adjunctive antifibrinolytic agents, topical thrombin and fibrin sealant. The induction of immune tolerance in patients in whom inhibitors develop should also be considered. OUTCOMES: Morbidity and quality of life associated with bleeding and treatment. EVIDENCE: Relevant clinical studies and reports published from 1974 to 1994 were examined. A search was conducted of our reprint files, MEDLINE, citations in the articles reviewed and references provided by colleagues. In the MEDLINE search the following terms were used singly or in combination: "hemophilia," "von Willebrand's disease," "Factor VIII," "Factor IX," "von Willebrand factor," "diagnosis," "management," "home care," "comprehensive care," "inhibitor," "AIDS," "hepatitis," "life expectancy," "complications," "practice guidelines," "consensus statement" and "controlled trial." The in-depth review included only articles written in English from North America and Europe that were relevant to human disease and pertinent to a predetermined outline. The availability of treatment products in Canada was also considered. VALUES: Minimizing morbidity and maximizing functional status and quality of life were given a high value. BENEFITS, HARMS AND COSTS: Proper prophylactic or early treatment with appropriate hemostatic agents minimizes morbidity and functional disability and improves quality

Concentration of clarithromycin and 14-R-hydroxy-clarithromycin in plasma of patients with Mycobacterium avium complex infection, before and after the addition of rifampicin.

PubMed

Yamamoto, F; Harada, S; Mitsuyama, T; Harada, Y; Kitahara, Y; Yoshida, M; Nakanishi, Y

2004-02-01

Clarithromycin (CAM) and rifampicin (RFP) have both been recognized to be effective antibiotic agents against Mycobacterium avium complex (MAC) infection. Rifamycin derivatives including RFP and rifabutin modulate the CAM metabolism by inducing the hepatic cytochrome p-450 3A4. To clarify the effect of RFP on the CAM metabolism, we measured the plasma concentration of CAM and 14-R-hydroxyclarithromycin (M-5), the major metabolite of CAM, in 9 patients suffering from MAC infection before and after the addition of RFP. After the addition of RFP, the mean plasma concentration of CAM significantly decreased, while that of M-5 did not. In addition, the amount of CAM + M-5 concentration also significantly decreased. As M-5 is less effective against MAC infection than CAM, more attention should thus be paid to the plasma CAM concentration in patients administered CAM and RFP concomitantly.

Charge carrier effective mass and concentration derived from combination of Seebeck coefficient and Te 125 NMR measurements in complex tellurides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Levin, E. M.

Thermoelectric materials utilize the Seebeck effect to convert heat to electrical energy. The Seebeck coefficient (thermopower), S, depends on the free (mobile) carrier concentration, n, and effective mass, m*, as S ~ m*/n 2/3. The carrier concentration in tellurides can be derived from 125Te nuclear magnetic resonance (NMR) spin-lattice relaxation measurements. The NMR spin-lattice relaxation rate, 1/T 1, depends on both n and m* as 1/T 1~(m*) 3/2n (within classical Maxwell-Boltzmann statistics) or as 1/T1~(m*) 2n 2/3 (within quantum Fermi-Dirac statistics), which challenges the correct determination of the carrier concentration in some materials by NMR. Here it is shown thatmore » the combination of the Seebeck coefficient and 125Te NMR spin-lattice relaxation measurements in complex tellurides provides a unique opportunity to derive the carrier effective mass and then to calculate the carrier concentration. This approach was used to study Ag xSb xGe 50–2xTe 50, well-known GeTe-based high-efficiency tellurium-antimony-germanium-silver thermoelectric materials, where the replacement of Ge by [Ag+Sb] results in significant enhancement of the Seebeck coefficient. Thus, values of both m* and n derived using this combination show that the enhancement of thermopower can be attributed primarily to an increase of the carrier effective mass and partially to a decrease of the carrier concentration when the [Ag+Sb] content increases.« less

Charge carrier effective mass and concentration derived from combination of Seebeck coefficient and Te 125 NMR measurements in complex tellurides

DOE PAGES

Levin, E. M.

2016-06-27

Thermoelectric materials utilize the Seebeck effect to convert heat to electrical energy. The Seebeck coefficient (thermopower), S, depends on the free (mobile) carrier concentration, n, and effective mass, m*, as S ~ m*/n 2/3. The carrier concentration in tellurides can be derived from 125Te nuclear magnetic resonance (NMR) spin-lattice relaxation measurements. The NMR spin-lattice relaxation rate, 1/T 1, depends on both n and m* as 1/T 1~(m*) 3/2n (within classical Maxwell-Boltzmann statistics) or as 1/T1~(m*) 2n 2/3 (within quantum Fermi-Dirac statistics), which challenges the correct determination of the carrier concentration in some materials by NMR. Here it is shown thatmore » the combination of the Seebeck coefficient and 125Te NMR spin-lattice relaxation measurements in complex tellurides provides a unique opportunity to derive the carrier effective mass and then to calculate the carrier concentration. This approach was used to study Ag xSb xGe 50–2xTe 50, well-known GeTe-based high-efficiency tellurium-antimony-germanium-silver thermoelectric materials, where the replacement of Ge by [Ag+Sb] results in significant enhancement of the Seebeck coefficient. Thus, values of both m* and n derived using this combination show that the enhancement of thermopower can be attributed primarily to an increase of the carrier effective mass and partially to a decrease of the carrier concentration when the [Ag+Sb] content increases.« less

Chromatography of blood-clotting factors and serum proteins on columns of diatomaceous earth.

PubMed

MILSTONE, J H

1955-07-20

1. In batch adsorptions with prothrombin solutions, hyflo was the weakest adsorbent, standard super-cel intermediate, and filter-cel strongest. Of these three grades of diatomaceous earth, hyflo has the smallest surface area per gram and filter-cel the largest. In parallel breakthrough experiments, a column of standard super-cel had a capacity almost six times that of a hyflo column. 2. After partial removal of impurities by diatomaceous earth, prothrombin preparations contained less thrombokinase, were more stable, and displayed less tendency to form thrombin "spontaneously." Thrombokinase (or its precursor) was removed from a preparation of prothrombin by passage through a filter cake of standard super-cel. The specific activity of the prothrombin was increased; and 62 per cent of the activity was recovered. 3. Prothrombin was adsorbed from an ammonium sulfate solution at pH 5.26 by columns of hyflo or standard super-cel. When eluted by phosphate solutions, the protein moved down the columns more readily at higher pH and higher concentration of phosphate salts, within the pH range 5.0 to 6.6, and within the phosphate range 0.1 to 1.0 M. 4. Thrombin was adsorbed on a column of standard super-cel at pH 5.11. As successive eluents passed through the column, the thrombin emerged between two bands of impurities. The specific activity of the thrombin was raised; and 83 per cent of the activity was recovered. 5. With a column of standard super-cel, and with a series of eluents within the pH range 5.1 to 6.3, total serum proteins were separated into four major bands. About 94 per cent of the protein was recovered.

CHROMATOGRAPHY OF BLOOD-CLOTTING FACTORS AND SERUM PROTEINS ON COLUMNS OF DIATOMACEOUS EARTH

PubMed Central

Milstone, J. H.

1955-01-01

1. In batch adsorptions with prothrombin solutions, hyflo was the weakest adsorbent, standard super-cel intermediate, and filter-cel strongest. Of these three grades of diatomaceous earth, hyflo has the smallest surface area per gram and filter-cel the largest. In parallel breakthrough experiments, a column of standard super-cel had a capacity almost six times that of a hyflo column. 2. After partial removal of impurities by diatomaceous earth, prothrombin preparations contained less thrombokinase, were more stable, and displayed less tendency to form thrombin "spontaneously." Thrombokinase (or its precursor) was removed from a preparation of prothrombin by passage through a filter cake of standard super-cel. The specific activity of the prothrombin was increased; and 62 per cent of the activity was recovered. 3. Prothrombin was adsorbed from an ammonium sulfate solution at pH 5.26 by columns of hyflo or standard super-cel. When eluted by phosphate solutions, the protein moved down the columns more readily at higher pH and higher concentration of phosphate salts, within the pH range 5.0 to 6.6, and within the phosphate range 0.1 to 1.0 M. 4. Thrombin was adsorbed on a column of standard super-cel at pH 5.11. As successive eluents passed through the column, the thrombin emerged between two bands of impurities. The specific activity of the thrombin was raised; and 83 per cent of the activity was recovered. 5. With a column of standard super-cel, and with a series of eluents within the pH range 5.1 to 6.3, total serum proteins were separated into four major bands. About 94 per cent of the protein was recovered. PMID:13242761

Monoclonal antibody to trivalent chromium chelate complex and its application to measurement of the total chromium concentration.

PubMed

Sasaki, Kazuhiro; Oguma, Shinichi; Namiki, Yukie; Ohmura, Naoya

2009-05-15

Isothiocyanobenzyl group-appended ethylenediamine tetraacetic acid (EDTA) was used to covalently couple Cr(III) x EDTA to keyhole limpet hemocyanin for use as an immunogen. An obtained monoclonal antibody (RD3G4) bound to Cr(III) x EDTA with an equilibrium dissociation constant (K(d)) of 9.7 nM, which was 100-fold tighter than the K(d)s for the other tested EDTA-metal complex. In particular, there was an over 2000-fold affinity difference between Cr(III) x EDTA and Fe(III) x EDTA, although the ion radius of trivalent chromium (0.76 A) was quite close to that of ferric ion (0.79 A). Hexavalent chromium could be detected by the antibody after being reduced into trivalent form. An immunoassay format showed an IC50 of 87 nM for hexavalent chromium, with a detection limit of 30 nM (1.6 microg/L). Therefore, the addition of reducing agents to the mixture of tri- and hexavalent chromium allows determination of the total chromium concentration by the immunoassay. Hexavalent chromium could be isolated from trivalent chromium by an anion-exchange column, and thus, the concentration of hexavalent chromium in tri- and hexa- mixture can also be estimated by the immunoassay.

Complex Terahertz and Direct Current Inverse Spin Hall Effect in YIG/Cu1-xIrx Bilayers Across a Wide Concentration Range.

PubMed

Cramer, Joel; Seifert, Tom; Kronenberg, Alexander; Fuhrmann, Felix; Jakob, Gerhard; Jourdan, Martin; Kampfrath, Tobias; Kläui, Mathias

2018-02-14

We measure the inverse spin Hall effect of Cu 1-x Ir x thin films on yttrium iron garnet over a wide range of Ir concentrations (0.05 ⩽ x ⩽ 0.7). Spin currents are triggered through the spin Seebeck effect, either by a continuous (dc) temperature gradient or by ultrafast optical heating of the metal layer. The spin Hall current is detected by electrical contacts or measurement of the emitted terahertz radiation. With both approaches, we reveal the same Ir concentration dependence that follows a novel complex, nonmonotonous behavior as compared to previous studies. For small Ir concentrations a signal minimum is observed, whereas a pronounced maximum appears near the equiatomic composition. We identify this behavior as originating from the interplay of different spin Hall mechanisms as well as a concentration-dependent variation of the integrated spin current density in Cu 1-x Ir x . The coinciding results obtained for dc and ultrafast stimuli provide further support that the spin Seebeck effect extends to terahertz frequencies, thus enabling a transfer of established spintronic measurement schemes into the terahertz regime. Our findings also show that the studied material allows for efficient spin-to-charge conversion even on ultrafast time scales.

[Transport of dinitrosyl iron complexes into animal lungs].

PubMed

Mojokina, G N; Elistratova, N A; Mikoyan, V D; Vanin, A F

2015-01-01

Effective accumulation of binuclear dinitrosyl iron complexes with glutathione was shown after a subcutaneous para lymphatic injection of an aqueous solution of a dinitrosyl-iron complex into animal lung tissue at a single-dose of 2 micromoles per kilogram two times a day with a 2-h interval. Two hours later after the administration was repeated the concentration of these complexes was 16 micromoles per kilogram of tissue dropping down for the last two hours to 7 micromoles per kilogram of tissue. At one dose injection of binuclear dinitrosyl iron complexes with glutathione their concentration in 2 and 4 hours was two times lower than in the previous experiments. Presumably at the obtained concentration of dinitrosyl iron complexes a bactericidal effect in lungs can be observed against mycobacterium tuberculosis and rapidly proliferating lung tumors.

Analysis of ambient SO 2 concentrations and winds in the complex surroundings of a thermal power plant

NASA Astrophysics Data System (ADS)

Mlakar, P.

2004-11-01

in order to find the correlation between winds and pollutant concentrations. The analyses made provide a better insight into air pollution over complex terrain.

Effect of Low-Dose Ferrous Sulfate vs Iron Polysaccharide Complex on Hemoglobin Concentration in Young Children With Nutritional Iron-Deficiency Anemia: A Randomized Clinical Trial.

PubMed

Powers, Jacquelyn M; Buchanan, George R; Adix, Leah; Zhang, Song; Gao, Ang; McCavit, Timothy L

2017-06-13

Iron-deficiency anemia (IDA) affects millions of persons worldwide, and is associated with impaired neurodevelopment in infants and children. Ferrous sulfate is the most commonly prescribed oral iron despite iron polysaccharide complex possibly being better tolerated. To compare the effect of ferrous sulfate with iron polysaccharide complex on hemoglobin concentration in infants and children with nutritional IDA. Double-blind, superiority randomized clinical trial of infants and children aged 9 to 48 months with nutritional IDA (assessed by history and laboratory criteria) that was conducted in an outpatient hematology clinic at a US tertiary care hospital from September 2013 through November 2015; 12-week follow-up ended in January 2016. Three mg/kg of elemental iron once daily as either ferrous sulfate drops or iron polysaccharide complex drops for 12 weeks. Primary outcome was change in hemoglobin over 12 weeks. Secondary outcomes included complete resolution of IDA (defined as hemoglobin concentration >11 g/dL, mean corpuscular volume >70 fL, reticulocyte hemoglobin equivalent >25 pg, serum ferritin level >15 ng/mL, and total iron-binding capacity <425 μg/dL at the 12-week visit), changes in serum ferritin level and total iron-binding capacity, adverse effects. Of 80 randomized infants and children (median age, 22 months; 55% male; 61% Hispanic white; 40 per group), 59 completed the trial (28 [70%] in ferrous sulfate group; 31 [78%] in iron polysaccharide complex group). From baseline to 12 weeks, mean hemoglobin increased from 7.9 to 11.9 g/dL (ferrous sulfate group) vs 7.7 to 11.1 g/dL (iron complex group), a greater difference of 1.0 g/dL (95% CI, 0.4 to 1.6 g/dL; P < .001) with ferrous sulfate (based on a linear mixed model). Proportion with a complete resolution of IDA was higher in the ferrous sulfate group (29% vs 6%; P = .04). Median serum ferritin level increased from 3.0 to 15.6 ng/mL (ferrous sulfate) vs 2.0 to 7.5 ng/mL (iron complex) over

Triggers for β-sheet formation at the hydrophobic-hydrophilic interface: high concentration, in-plane orientational order, and metal ion complexation.

PubMed

Hoernke, Maria; Falenski, Jessica A; Schwieger, Christian; Koksch, Beate; Brezesinski, Gerald

2011-12-06

Amyloid formation plays a causative role in neurodegenerative diseases such as Alzheimer's disease or Parkinson's disease. Soluble peptides form β-sheets that subsequently rearrange into fibrils and deposit as amyloid plaques. Many parameters trigger and influence the onset of the β-sheet formation. Early stages are recently discussed to be cell-toxic. Aiming at understanding various triggers such as interactions with hydrophobic-hydrophilic interfaces and metal ion complexation and their interplay, we investigated a set of model peptides at the air-water interface. We are using a general approach to a variety of diseases such as Alzheimer's disease, Parkinson's disease, and type II diabetes that are connected to amyloid formation. Surface sensitive techniques combined with film balance measurements have been used to assess the conformation of the peptides and their orientation at the air-water interface (IR reflection-absorption spectroscopy). Additionally, the structures of the peptide layers were characterized by grazing incidence X-ray diffraction and X-ray reflectivity. The peptides adsorb to the air-water interface and immediately adopt an α-helical conformation. This helical intermediate transforms into β-sheets upon further triggering. The factors that result in β-sheet formation are dependent on the peptide sequence. In general, the interface has the strongest effect on peptide conformation compared to high concentrations or metal ions. Metal ions are able to prevent aggregation in bulk but not at the interface. At the interface, metal ion complexation has only minor effects on the peptide secondary structure, influencing the in-plane structure that is formed in two dimensions. At the air-water interface, increased concentrations or a parallel arrangement of the α-helical intermediates are the most effective triggers. This study reveals the role of various triggers for β-sheet formation and their complex interplay. Our main finding is that the

Plasminogen activator inhibitor-1 4G/5G polymorphism, factor V Leiden, prothrombin mutations and the risk of VTE recurrence.

PubMed

Sundquist, Kristina; Wang, Xiao; Svensson, Peter J; Sundquist, Jan; Hedelius, Anna; Larsson Lönn, Sara; Zöller, Bengt; Memon, Ashfaque A

2015-11-25

Plasminogen-activator inhibitor (PAI)-1 is an important inhibitor of the plasminogen/plasmin system. PAI-1 levels are influenced by the 4G/5G polymorphism in the PAI-1 promoter. We investigated the relationship between the PAI-1 polymorphism and VTE recurrence, and its possible modification by factor V Leiden (FVL) and prothrombin (PTM) mutations. Patients (n=1,069) from the Malmö Thrombophilia Study were followed from discontinuation of anticoagulant treatment until diagnosis of VTE recurrence or the end of the study (maximum follow-up 9.8 years). One hundred twenty-seven patients (11.9 %) had VTE recurrence. PAI-1 was genotyped by TaqMan PCR. Cox regression analysis adjusted for age, sex and acquired risk factors of VTE showed no evidence of an association between PAI-1 genotype and risk of VTE recurrence in the study population as a whole. However, by including an interaction term in the analysis we showed that FVL but not PTM modified the effect of PAI-1 genotype: patients with the 4G allele plus FVL had a higher risk of VTE recurrence [hazard ratio (HR) =2.3, 95 % confidence interval (CI) =1.5-3.3] compared to patients with the 4G allele but no FVL (reference group) or FVL irrespective of PAI-1 genotype (HR=1.8, 95 % CI=1.3-2.5). Compared to reference group, 5G allele irrespective of FVL was associated with lower risk of VTE recurrence only when compared with 4G allele together with FVL. In conclusion, FVL has a modifying effect on PAI-1 polymorphism in relation to risk of VTE recurrence. The role of PAI-1 polymorphism as a risk factor of recurrent VTE may be FVL dependent.

Thermal regeneration of an electrochemical concentration cell

DOEpatents

Krumpelt, Michael; Bates, John K.

1981-01-01

A system and method for thermally regenerating an electrochemical concentration cell having first and second aluminum electrodes respectively positioned in contact with first and second electrolytes separated by an ion exchange member, the first and second electrolytes being composed of different concentrations of an ionic solvent and a salt, preferably an aluminum halide. The ionic solvent may be either organic or inorganic with a relatively low melting point, the ionic solvent and the salt form a complex wherein the free energy of formation of said complex is less than about -5 Kcal/mole. A distillation column using solar heat or low grade industrial waste heat receives the first and second electrolytes and thermally decomposes the salt-solvent complex to provide feed material for the two half cells.

Crystal structure of prethrombin-1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Zhiwei; Pelc, Leslie A.; Di Cera, Enrico

2010-11-15

Prothrombin is the zymogen precursor of the clotting enzyme thrombin, which is generated by two sequential cleavages at R271 and R320 by the prothrombinase complex. The structure of prothrombin is currently unknown. Prethrombin-1 differs from prothrombin for the absence of 155 residues in the N-terminal domain and is composed of a single polypeptide chain containing fragment 2 (residues 156-271), A chain (residues 272-320), and B chain (residues 321-579). The X-ray crystal structure of prethrombin-1 solved at 2.2-{angstrom} resolution shows an overall conformation significantly different (rmsd = 3.6 {angstrom}) from that of its active form meizothrombin desF1 carrying a cleavage atmore » R320. Fragment 2 is rotated around the y axis by 29{sup o} and makes only few contacts with the B chain. In the B chain, the oxyanion hole is disrupted due to absence of the I16-D194 ion pair and the Na{sup +} binding site and adjacent primary specificity pocket are highly perturbed. A remarkable feature of the structure is that the autolysis loop assumes a helical conformation enabling W148 and W215, located 17 {angstrom} apart in meizothrombin desF1, to come within 3.3 {angstrom} of each other and completely occlude access to the active site. These findings suggest that the zymogen form of thrombin possesses conformational plasticity comparable to that of the mature enzyme and have significant implications for the mechanism of prothrombin activation and the zymogen {yields} protease conversion in trypsin-like proteases.« less

Metal Complexation in Xylem Fluid 1

PubMed Central

White, Michael C.; Chaney, Rufus L.; Decker, A. Morris

1981-01-01

The capacity of ligands in xylem fluid to form metal complexes was tested with a series of in vitro experiments using paper electrophoresis and radiographs. The xylem fluid was collected hourly for 8 hours from soybean (Glycine max L. Merr.) and tomato (Lycopersicon esculentum Mill.) plants grown in normal and Zn-phytotoxic nutrient solutions. Metal complexation was assayed by anodic or reduced cathodic movement of radionuclides (63Ni, 65Zn, 109Cd, 54Mn) that were presumed to have formed negatively charged complexes. Electrophoretic migration of Ni, Zn, Cd, and Mn added to xylem exudate and spotted on KCl- or KNO3-wetted paper showed that stable Ni, Zn, and Cd metal complexes were formed by exudate ligands. No anodic Mn complexes were observed in this test system. Solution pH, plant species, exudate collection time, and Zn phytotoxicity all affected the amount of metal complex formed in exudate. As the pH increased, there was increased anodic metal movement. Soybean exudate generally bound more of each metal than did tomato exudate. Metal binding usually decreased with increasing exudate collection time, and less metal was bound by the high-Zn exudate. Ni, Zn, Cd, and Mn in exudate added to exudate-wetted paper demonstrated the effect of ligand concentration on stable metal complex formation. Complexes for each metal were demonstratable with this method. Cathodic metal movement increased with time of exudate collection, and it was greater in the high-Zn exudate than in the normal-Zn exudate. A model study illustrated the effect of ligand concentration on metal complex stability in the electrophoretic field. Higher ligand (citric acid) concentrations increased the stability for all metals tested. Images PMID:16661666

Thermal regeneration of an electrochemical concentration cell

DOEpatents

Krumpelt, M.; Bates, J.K.

1980-05-09

A system and method are described for thermally regenerating an electrochemical concentration cell having first and second aluminum electrodes respectively positioned in contact with first and second electrolytes separated by an ion exchange member, the first and second electrolytes being composed of different concentrations of an ionic solvent and a salt, preferably an aluminum halide. The ionic solvent may be either organic or inorganic with a relatively low melting point, the ionic solvent and the salt form a complex wherein the free energy of formation of said complex is less than about -5 kcal/mole. A distillation column using solar heat or low grade industrial waste heat receives the first and second electrolytes and thermally decomposes the salt-solvent complex to provide feed material for the two half cells.

Efficient quantum repeater with respect to both entanglement-concentration rate and complexity of local operations and classical communication

NASA Astrophysics Data System (ADS)

Su, Zhaofeng; Guan, Ji; Li, Lvzhou

2018-01-01

Quantum entanglement is an indispensable resource for many significant quantum information processing tasks. However, in practice, it is difficult to distribute quantum entanglement over a long distance, due to the absorption and noise in quantum channels. A solution to this challenge is a quantum repeater, which can extend the distance of entanglement distribution. In this scheme, the time consumption of classical communication and local operations takes an important place with respect to time efficiency. Motivated by this observation, we consider a basic quantum repeater scheme that focuses on not only the optimal rate of entanglement concentration but also the complexity of local operations and classical communication. First, we consider the case where two different two-qubit pure states are initially distributed in the scenario. We construct a protocol with the optimal entanglement-concentration rate and less consumption of local operations and classical communication. We also find a criterion for the projective measurements to achieve the optimal probability of creating a maximally entangled state between the two ends. Second, we consider the case in which two general pure states are prepared and general measurements are allowed. We get an upper bound on the probability for a successful measurement operation to produce a maximally entangled state without any further local operations.

Reduced anticoagulation variability in patients on warfarin monitored with Fiix-prothrombin time associates with reduced thromboembolism: The Fiix-trial.

PubMed

Oskarsdóttir, Alma Rut; Gudmundsdottir, Brynja R; Indridason, Olafur S; Lund, Sigrun H; Arnar, David O; Bjornsson, Einar S; Magnusson, Magnus K; Jensdottir, Hulda M; Vidarsson, Brynjar; Francis, Charles W; Onundarson, Pall T

2017-05-01

Fiix-prothrombin time (Fiix-PT) differs from traditional PT in being affected by reduced factor (F) II or FX only. In the randomized controlled Fiix-trial, patients on warfarin monitored with Fiix-PT (Fiix-warfarin patients) had fewer thromboembolisms (TE), similar major bleeding (MB) and more stable anticoagulation than patients monitored with PT (PT-warfarin patients). In the current Fiix-trial report we analyzed how reduced anticoagulation variability during Fiix-PT monitoring was reflected in patients with TE or bleeding. Data from 1143 randomized patients was used. We analyzed the groups for anticoagulation intensity (time within target range; TTR), international normalized ratio (INR) variability (variance growth rate B 1 ; VGR) and dose adjustment frequency. We assessed how these parameters associated with clinically relevant vascular events (CRVE), ie TE or MB or clinically relevant non-MB. TTR was highest in Fiix-warfarin patients without CRVE (median 82%;IQR 72-91) and lowest in PT-warfarin patients with TE (62%;56-81). VGR was lowest in Fiix-warfarin patients without CRVE (median VGR B 1 0.17; 95% CI 0.08-0.38) and with TE (0.20;0.07-0.26) and highest in PT-warfarin patients with TE (0.50;0.27-0.90) or MB (0.59;0.07-1.36). The mean annual dose adjustment frequency was lowest in Fiix-warfarin patients with TE (mean 5.4;95% CI 3.9-7.3) and without CRVE (mean 6.0; 5.8-6.2) and highest in PT-warfarin patients with TE (14.2;12.2-16.3). Frequent dose changes predicted MB in both study arms. Compared to patients monitored with PT, high anticoagulation stability in Fiix-warfarin patients coincided with their low TE rate. Those with bleeding had high variability irrespective of monitoring method. Thus, although further improvements are needed to reduce bleeding, stabilization of anticoagulation by Fiix-PT monitoring associates with reduced TE.

Error-Tolerant Quasi-Paraboloidal Solar Concentrator

NASA Technical Reports Server (NTRS)

Wagner, Howard A.

1988-01-01

Scalloping reflector surface reduces sensitivity to manufacturing and aiming errors. Contrary to intuition, most effective shape of concentrating reflector for solar heat engine is not perfect paraboloid. According to design studies for Space Station solar concentrator, scalloped, nonimaging approximation to perfect paraboloid offers better overall performance in view of finite apparent size of Sun, imperfections of real equipment, and cost of accommodating these complexities. Scalloped-reflector concept also applied to improve performance while reducing cost of manufacturing and operation of terrestrial solar concentrator.

Aggregation behavior and complex structure between triblock copolymer and anionic surfactants

NASA Astrophysics Data System (ADS)

Li, Yiming; Bao, Mutai; Wang, Zhining; Zhang, Haixia; Xu, Guiying

2011-01-01

The aggregation behavior and complex structure of ABA triblock copolymer EO 76PO 30EO 76 (F68) with sodium dodecyl sulfate (SDS) and sodium bis(2-ethylhexyl)sulfonate (AOT) in aqueous solution were investigated by surface tension, fluorescence techniques and dynamic light-scattering (DLS) measurements. It is revealed that in certain regions of binding, surfactant/F68 complexes are formed. Structural informations and size of complexes are evaluated. When F68 is present in its nonassociated state, F68/micellar SDS complexes are formed at SDS concentrations above its critical aggregation concentration (cac). The cac is well below the critical micellar concentration (cmc) of pure SDS, and a model suggesting how complexes are formed at the cac in the presence of F68 is described. Experimental results show that SDS interacts with F68 mainly through hydrophobic forces, polypropylene oxide (PPO) groups of F68 are solubilized into SDS micellar cores and poly(ethylene oxide) (PEO) groups interact with SDS micelles. This interaction mechanism results in a "pearl-necklace" complex structure. However, a different structure occurs for F68/AOT complex at lower F68 concentrations, as nonassociated F68 interacts with AOT mainly through ion-dipole interactions. Complexes with a "wrapping" structure at lower F68 concentrations are formed.

A fluorescence anisotropy method for measuring protein concentration in complex cell culture media.

PubMed

Groza, Radu Constantin; Calvet, Amandine; Ryder, Alan G

2014-04-22

The rapid, quantitative analysis of the complex cell culture media used in biopharmaceutical manufacturing is of critical importance. Requirements for cell culture media composition profiling, or changes in specific analyte concentrations (e.g. amino acids in the media or product protein in the bioprocess broth) often necessitate the use of complicated analytical methods and extensive sample handling. Rapid spectroscopic methods like multi-dimensional fluorescence (MDF) spectroscopy have been successfully applied for the routine determination of compositional changes in cell culture media and bioprocess broths. Quantifying macromolecules in cell culture media is a specific challenge as there is a need to implement measurements rapidly on the prepared media. However, the use of standard fluorescence spectroscopy is complicated by the emission overlap from many media components. Here, we demonstrate how combining anisotropy measurements with standard total synchronous fluorescence spectroscopy (TSFS) provides a rapid, accurate quantitation method for cell culture media. Anisotropy provides emission resolution between large and small fluorophores while TSFS provides a robust measurement space. Model cell culture media was prepared using yeastolate (2.5 mg mL(-1)) spiked with bovine serum albumin (0 to 5 mg mL(-1)). Using this method, protein emission is clearly discriminated from background yeastolate emission, allowing for accurate bovine serum albumin (BSA) quantification over a 0.1 to 4.0 mg mL(-1) range with a limit of detection (LOD) of 13.8 μg mL(-1). Copyright © 2014. Published by Elsevier B.V.

Time-dependent changes in extra-domain A-fibronectin concentration and relative amounts of fibronectin-fibrin complexes in plasma of patients with peripheral arterial disease after endovascular revascularisation.

PubMed

Pupek, Małgorzata; Krzyżanowska-Gołąb, Dorota; Kotschy, Daniel; Witkiewicz, Wojciech; Kwiatkowska, Wiesława; Kotschy, Maria; Kątnik-Prastowska, Iwona

2018-03-13

Fibronectin (FN) may be involved in time- and stage-dependent and inter-related controlled processes of inflammation, coagulation, and wound healing accompanying peripheral arterial disease (PAD). In the present study, FN and FN-containing extra-domain A (EDA-FN), macromolecular FN-fibrin complexes, and FN monomer were analysed in the plasma of 142 PAD patients, including 37 patients with restenosis, for 37 months after revascularisation. FN concentration increased significantly in the plasma of PAD patients within 7 to 12 months after revascularisation, whereas the high concentration of EDA-FN was maintained up to 24 months, significantly higher in the group 7 to 12 months after revascularisation with recurrence of stenosis and lower in the PAD groups 1 to 3 months and 4 to 6 months after revascularisation with comorbid diabetes and ulceration, respectively. The relative amounts of FN-fibrin complexes up to 1600 kDa and FN monomer were significantly higher, within intervals of 4 to 24 months and 4 to 6 months after revascularisation, respectively. Moreover, the relative amounts of 750 to 1600 kDa FN-fibrin complexes within 13 to 24 months after revascularisation were higher in comparison with those in the group without restenosis. In conclusion, high levels of EDA-FN and FN-fibrin complexes could have potential diagnostic value in the management of PAD patients after revascularisation, predicting restenosis risk. © 2018 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Experimental study of the complex resistivity and dielectric constant of chrome-contaminated soil

NASA Astrophysics Data System (ADS)

Liu, Haorui; Yang, Heli; Yi, Fengyan

2016-08-01

Heavy metals such as arsenic and chromium often contaminate soils near industrialized areas. Soil samples, made with different water content and chromate pollutant concentrations, are often needed to test soil quality. Because complex resistivity and complex dielectric characteristics of these samples need to be measured, the relationship between these measurement results and chromium concentration as well as water content was studied. Based on soil sample observations, the amplitude of the sample complex resistivity decreased with an increase of contamination concentration and water content. The phase of complex resistivity takes on a tendency of initially decrease, and then increase with the increasing of contamination concentration and water content. For a soil sample with the same resistivity, the higher the amplitude of complex resistivity, the lower the water content and the higher the contamination concentration. The real and imaginary parts of the complex dielectric constant increase with an increase in contamination concentration and water content. Note that resistivity and complex resistivity methods are necessary to adequately evaluate pollution at various sites.

Vacancy-hydrogen complexes in ammonothermal GaN

NASA Astrophysics Data System (ADS)

Tuomisto, F.; Kuittinen, T.; Zając, M.; Doradziński, R.; Wasik, D.

2014-10-01

We have applied positron annihilation spectroscopy to study in-grown vacancy defects in bulk GaN crystals grown by the ammonothermal method. We observe a high concentration of Ga vacancy related defects in n-type samples with varying free electron and oxygen content. The positron lifetimes found in these samples suggest that the Ga vacancies are complexed with hydrogen impurities. The number of hydrogen atoms in each vacancy decreases with increasing free electron concentration and oxygen and hydrogen content. The local vibrational modes observed in infrared absorption support this conclusion. Growth of high-quality ammonothermal GaN single crystals with varying electron concentrations. Identification of defect complexes containing a Ga vacancy and 1 or more hydrogen atoms, and possibly O. These vacancy complexes provide a likely explanation for electrical compensation in ammonothermal GaN.

Global gene expression analysis reveals pathway differences between teratogenic and non-teratogenic exposure concentrations of bisphenol A and 17β-estradiol in embryonic zebrafish

PubMed Central

Saili, Katerine S.; Tilton, Susan C.; Waters, Katrina M.; Tanguay, Robert L.

2013-01-01

Transient developmental exposure to 0.1 μM bisphenol A (BPA) results in larval zebrafish hyperactivity and learning impairments in the adult, while exposure to 80 μM BPA results in teratogenic responses, including craniofacial abnormalities and edema. The mode of action underlying these effects is unclear. We used global gene expression analysis to identify candidate genes and signaling pathways that mediate BPA’s developmental toxicity in zebrafish. Exposure concentrations were selected and anchored to the positive control, 17β-estradiol (E2), based on previously determined behavioral or teratogenic phenotypes. Functional analysis of differentially expressed genes revealed distinct expression profiles at 24 hours post fertilization for 0.1 versus 80 μM BPA and 0.1 versus 15 μM E2 exposure, identification of prothrombin activation as a top canonical pathway impacted by both 0.1 μM BPA and 0.1 μM E2 exposure, and suppressed expression of several genes involved in nervous system development and function following 0.1 μM BPAexposure. PMID:23557687

Effect of pH and sulfur precursor concentration on electrochemically deposited CZTS thin films using glycine as the complexing agent

NASA Astrophysics Data System (ADS)

Paraye, Akanksha; Sani, Rabiya; Ramachandran, Manivannan; Selvam, Noyel Victoria

2018-03-01

Copper zinc tin sulfide (CZTS) a promising quaternary chalcogenide material was deposited using single step electrodeposition using glycine as the complexing agent. The deposition was studied at different sulfur concentrations and at different pH. The pH of the electrolyte was found to influence the stoichiometry of the deposits significantly. The deposits formed at pH 2.5 showed satisfactory stoichiometry. The thickness of the deposits was observed to decrease with increase in sulfur concentration and pH. The transmission electron spectroscopy analysis showed the formation of flower shaped core shell particles from the electrolyte that contained 80 mM sulfur precursor at pH 2.5. The band gap of the deposits was found to be in the range from 1.57 eV to 2.1 eV. X-ray diffraction analysis showed that the as synthesized particles were amorphous in nature, the crystallinity of which improved with annealing. The Mott Schottky analysis of the deposits in 0.1 M sodium perchlorate showed that the particles exhibited p-type conductivity.

Generative complexity of Gray-Scott model

NASA Astrophysics Data System (ADS)

Adamatzky, Andrew

2018-03-01

In the Gray-Scott reaction-diffusion system one reactant is constantly fed in the system, another reactant is reproduced by consuming the supplied reactant and also converted to an inert product. The rate of feeding one reactant in the system and the rate of removing another reactant from the system determine configurations of concentration profiles: stripes, spots, waves. We calculate the generative complexity-a morphological complexity of concentration profiles grown from a point-wise perturbation of the medium-of the Gray-Scott system for a range of the feeding and removal rates. The morphological complexity is evaluated using Shannon entropy, Simpson diversity, approximation of Lempel-Ziv complexity, and expressivity (Shannon entropy divided by space-filling). We analyse behaviour of the systems with highest values of the generative morphological complexity and show that the Gray-Scott systems expressing highest levels of the complexity are composed of the wave-fragments (similar to wave-fragments in sub-excitable media) and travelling localisations (similar to quasi-dissipative solitons and gliders in Conway's Game of Life).

Concentration and purification of plutonium or thorium

DOEpatents

Hayden, John A.; Plock, Carl E.

1976-01-01

In this invention a first solution obtained from such as a plutonium/thorium purification process or the like, containing plutonium (Pu) and/or thorium (Th) in such as a low nitric acid (HNO.sub.3) concentration may have the Pu and/or Th separated and concentrated by passing an electrical current from a first solution having disposed therein an anode to a second solution having disposed therein a cathode and separated from the first solution by a cation permeable membrane, the Pu or Th cation permeating the cation membrane and forming an anionic complex within the second solution, and electrical current passage affecting the complex formed to permeate an anion membrane separating the second solution from an adjoining third solution containing disposed therein an anode, thereby effecting separation and concentration of the Pu and/or Th in the third solution.

Indoor air-assessment: Indoor concentrations of environmental carcinogens

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gold, K.W.; Naugle, D.F.; Berry, M.A.

1991-01-01

In the report, indoor concentration data are presented for the following general categories of air pollutants: radon-222, environmental tobacco smoke (ETS), asbestos, gas phase organic compounds, formaldehyde, polycyclic aromatic hydrocarbons (PAH), pesticides, and inorganic compounds. These pollutants are either known or suspect carcinogens (i.e., radon-222, asbestos) or more complex mixtures or classes of compounds which contain known or suspect carcinogens. Concentration data for individual carcinogenic compounds in complex mixtures are usually far from complete. The data presented for complex mixtures often include compounds which are not carcinogenic or for which data are insufficient to evaluate carcinogenicity. Their inclusion is justified,more » however, by the possibility that further work may show them to be carcinogens, cocarcinogens, initiators or promotors, or that they may be employed as markers (e.g., nicotine, acrolein) for the estimation of exposure to complex mixtures.« less

Prothrombin time (PT)

MedlinePlus

... of a blood clotting or bleeding disorder Normal Results PT is measured in seconds. Most of the ... meaning of your specific test results. What Abnormal Results Mean If you are not taking blood thinning ...

Generating a heated fluid using an electromagnetic radiation-absorbing complex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Halas, Nancy J.; Nordlander, Peter; Neumann, Oara

A vessel including a concentrator configured to concentrate electromagnetic (EM) radiation received from an EM radiation source and a complex configured to absorb EM radiation to generate heat. The vessel is configured to receive a cool fluid from the cool fluid source, concentrate the EM radiation using the concentrator, apply the EM radiation to the complex, and transform, using the heat generated by the complex, the cool fluid to the heated fluid. The complex is at least one of consisting of copper nanoparticles, copper oxide nanoparticles, nanoshells, nanorods, carbon moieties, encapsulated nanoshells, encapsulated nanoparticles, and branched nanostructures. Further, the EMmore » radiation is at least one of EM radiation in an ultraviolet region of an electromagnetic spectrum, in a visible region of the electromagnetic spectrum, and in an infrared region of the electromagnetic spectrum.« less

Polyaspartic Acid Concentration Controls the Rate of Calcium Phosphate Nanorod Formation in High Concentration Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krogstad, Daniel V.; Wang, Dongbo; Lin-Gibson, Sheng

Polyelectrolytes are known to greatly affect calcium phosphate (CaP) mineralization. The reaction kinetics as well as the CaP phase, morphology and aggregation state depend on the relative concentrations of the polyelectrolyte and the inorganic ions in a complex, nonlinear manner. This study examines the structural evolution and kinetics of polyaspartic acid (pAsp) directed CaP mineralization at high concentrations of polyelectrolytes, calcium, and total phosphate (19–30 mg/mL pAsp, 50–100 mM Ca2+, Ca/P = 2). Using a novel combination of characterization techniques including cryogenic transmission electron microscopy (cryo-TEM), spectrophotometry, X-ray total scattering pair distribution function analysis, and attenuated total reflectance Fourier transformmore » infrared spectroscopy (ATR-FTIR), it was determined that the CaP mineralization occurred over four transition steps. The steps include the formation of aggregates of pAsp stabilized CaP spherical nanoparticles (sNP), crystallization of sNP, oriented attachment of the sNP into nanorods, and further crystallization of the nanorods. The intermediate aggregate sizes and the reaction kinetics were found to be highly polymer concentration dependent while the sizes of the particles were not concentration dependent. This study demonstrates the complex role of pAsp in controlling the mechanism as well as the kinetics of CaP mineralization.« less

Role of hepsin in factor VII activation in zebrafish.

PubMed

Khandekar, Gauri; Jagadeeswaran, Pudur

2014-01-01

Factor VII, the initiator of the extrinsic coagulation cascade, circulates in human plasma mainly in its zymogen form, factor VII and in small amounts in its activated form, factor VIIa. However, the mechanism of initial generation of factor VIIa is not known despite intensive research using currently available model systems. Earlier findings suggested serine proteases factor VII activating protease and hepsin play a role in activating factor VII, however, it has remained controversial. In this paper we estimated the levels of factor VIIa and factor VII for the first time in zebrafish adult population and also reevaluated the role of the above two serine proteases in activating factor VII in vivo using zebrafish as a model system. Knockdown of factor VII activating protease and hepsin was performed followed by assaying for their effect on factor VIIa concentration and extrinsic coagulation as measured by the kinetic prothrombin time. Factor VII activating protease knockdown showed no change in kinetic prothrombin time and no effect on factor VIIa levels while hepsin knockdown increased the kinetic prothrombin time and significantly reduced the factor VIIa plasma levels. Our results thus indicate that hepsin plays a physiologically important role in factor VII activation and hemostasis in zebrafish. © 2013.

Acute Coagulopathy of Trauma in the Rat

DTIC Science & Technology

2013-01-01

coagulation and include prothrombin complex con- centrate, recombinant activated FVII , tranexamic acid, and fibrinogen (13, 14). The degree of coagulopathy...extrinsic pathway using tissue factor to initiate coagulation as would be expected following tissue injury. Cytochalasin D (inhibit platelet function in...chalasin D. ! Angle was elevated, and clotting time was shortened, suggesting that coagulation factors were activated and adequate to support thrombin

Elevated prothrombin time on routine preoperative laboratory results in a healthy infant undergoing craniosynostosis repair: Diagnosis and perioperative management of congenital factor VII deficiency.

PubMed

Jones, Kareen L; Greenberg, Robert S; Ahn, Edward S; Kudchadkar, Sapna R

2016-01-01

Congenital factor VII deficiency is a rare bleeding disorder with high phenotypic variability. It is critical that children with congenital Factor VII deficiency be identified early when high-risk surgery is planned. Cranial vault surgery is common for children with craniosynostosis, and these surgeries are associated with significant morbidity mostly secondary to the risk of massive blood loss. A two-month old infant who presented for elective craniosynostosis repair was noted to have an elevated prothrombin time (PT) with a normal activated partial thromboplastin time (aPTT) on preoperative labs. The infant had no clinical history or reported family history of bleeding disorders, therefore a multidisciplinary decision was made to repeat the labs under general anesthesia and await the results prior to incision. The results confirmed the abnormal PT and the case was canceled. Hematologic workup during admission revealed factor VII deficiency. The patient underwent an uneventful endoscopic strip craniectomy with perioperative administration of recombinant Factor VIIa. Important considerations for perioperative laboratory evaluation and management in children with factor VII deficiency are discussed. Anesthetic and surgical management of the child with factor VII deficiency necessitates meticulous planning to prevent life threatening bleeding during the perioperative period. A thorough history and physical examination with a high clinical suspicion are vital in preventing hemorrhage during surgeries in children with coagulopathies. Abnormal preoperative lab values should always be confirmed and addressed before proceeding with high-risk surgery. A multidisciplinary discussion is essential to optimize the risk-benefit ratio during the perioperative period. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Only minor changes in thrombin generation of children and adolescents with type 1 diabetes mellitus - A case-control study.

PubMed

Cimenti, Christina; Schlagenhauf, Axel; Leschnik, Bettina; Fröhlich-Reiterer, Elke; Jasser-Nitsche, Hildegard; Haidl, Harald; Suppan, Elisabeth; Weinhandl, Gudrun; Leberl, Maximilian; Borkenstein, Martin; Muntean, Wolfgang E

2016-12-01

Micro- and macrovascular diseases are frequent complications in patients with diabetes. Hypercoagulability may contribute to microvascular alterations. In this study, we investigated whether type 1 diabetes in children is associated with a hypercoagulable state by performing a global function test of coagulation - the thrombin generation assay. 75 patients with type 1 diabetes aged between 2 and 19years were compared to an age-matched healthy control group. Diabetes patients were divided into high-dose and low-dose insulin cohorts with a cut-off at 0.8Ukg -1 d -1 . Measurements were performed with platelet poor plasma using Calibrated Automated Thrombography and 1 pM or 5 pM tissue factor. Additionally, we quantified prothrombin fragments F1+2, thrombin-antithrombin complex, prothrombin, tissue factor pathway inhibitor, and antithrombin. Patients with type 1 diabetes exhibited a significantly shorter of lag time as well as decreased thrombin peak and endogenous thrombin potential compared to control subjects with 5 pM but not with 1 pM tissue factor. In high-dose insulin patients peak thrombin generation was higher and time to peak shorter than in low-dose patients. Thrombin-antithrombin complex was decreased in patients with type 1 diabetes, whereas prothrombin fragments F1+2 was comparable in both groups. Thrombin generation parameters did not correlate with parameters of metabolic control and the duration of diabetes. Taken together, we found only minor changes of thrombin generation in children and adolescents with type 1 diabetes which - in contrast to type 2 diabetes - do not argue for a hypercoagulable state. Copyright © 2016 Elsevier Ltd. All rights reserved.

Synthesis of nutrient and sediment export patterns in the Chesapeake Bay watershed: Complex and non-stationary concentration-discharge relationships.

PubMed

Zhang, Qian

2018-03-15

Derived from river monitoring data, concentration-discharge (C-Q) relationships are useful indicators of riverine export dynamics. A top-down synthesis of C-Q patterns was conducted for suspended sediment (SS), total phosphorus (TP), and total nitrogen (TN) for nine major tributaries (15 monitoring sites) to Chesapeake Bay, which represent diverse characteristics in terms of land use, physiography, and hydrological settings. Model coefficients from the recently-developed Weighted Regressions on Time, Discharge, and Season (WRTDS) method were used to make informative interpretation of C-Q relationships. Unlike many previous C-Q studies that focused on stormflow conditions, this approach allows simultaneous examination of various discharge conditions within an uncertainty framework. This synthesis on WRTDS coefficients (i.e., the sensitivity of concentration to discharge) has offered new insights on the complexity of watershed function. Results show that watershed export has been dominated by mobilization patterns for SS and TP (particulate-dominated species) and chemostasis patterns for TN (dissolved-dominated species) under many river discharge conditions. Among nine possible modalities of low-flow vs. high-flow patterns, the three most frequent modalities are mobilization vs. mobilization (17 cases), chemostasis vs. mobilization (13 cases), and chemostasis vs. chemostasis (7 cases), representing 82% of all 45 watershed-constituent pairs. The general lack of dilution patterns may suggest that none of these constituents has been supply-limited in these watersheds. For many watershed-constituent combinations, results show clear temporal non-stationarity in C-Q relationships under selected time-invariant discharges, reflecting major changes in dominant watershed sources due to anthropogenic actions. These results highlight the potential pitfalls of assuming fixed C-Q relationships in the record. Overall, this work demonstrates the utility of WRTDS model coefficients

Studies on a family with combined functional deficiencies of vitamin K-dependent coagulation factors.

PubMed Central

Goldsmith, G H; Pence, R E; Ratnoff, O D; Adelstein, D J; Furie, B

1982-01-01

Two siblings with m ild hemorrhagic symptoms had combined functional deficiencies of vitamin K-dependent clotting factors. Prothrombin (0.18-0.20 U/ml) and Stuart factor (Factor X, 0.18-0.20 U/ml) and Stuart factor (Factor X, 0.18-0.20 U/ml) were most severely affected. Antigenic amounts of affected coagulation factors were normal and normal generation of thrombin activity occurred in the patients' plasmas after treatment with nonophysiologic activators that do not require calcium for prothrombin activation. Hepatobilary disease, malabsorptive disorders, and plasma warfarin were not present. Both parents had normal levels of all coagulation factors. The patients' plasmas contained prothrombin that reacted both with antibody directed against des-gamma-carboxyprothrombin and native prothrombin. Crossed immunoelectrophoresis of patients' plasmas and studies of partially purified patient prothrombin suggested the presence of a relatively homogeneous species of dysfunctional prothrombin, distinct from the heterologous species found in the plasma of warfarin-treated persons. These studies are most consistent with a posttranslational defect in hepatic carboxylation of vitamin K-dependent factors. This kindred uniquely possesses an autosomal recessive disorder of vitamin K-dependent factor formation that causes production of an apparently homogeneous species of dysfunctional prothrombin; the functional deficiencies in clotting factors are totally corrected by oral or parenteral administration of vitamin K1. Images PMID:7085873

Administration of recombinant activated factor VII in the intensive care unit after complex cardiovascular surgery: clinical and economic outcomes.

PubMed

Uber, Walter E; Toole, John M; Stroud, Martha R; Haney, Jason S; Lazarchick, John; Crawford, Fred A; Ikonomidis, John S

2011-06-01

Refractory bleeding after complex cardiovascular surgery often leads to increased length of stay, cost, morbidity, and mortality. Recombinant activated factor VII administered in the intensive care unit can reduce bleeding, transfusion, and surgical re-exploration. We retrospectively compared factor VII administration in the intensive care unit with reoperation for refractory bleeding after complex cardiovascular surgery. From 1501 patients who underwent cardiovascular procedures between December 2003 and September 2007, 415 high-risk patients were identified. From this cohort, 24 patients were divided into 2 groups based on whether they either received factor VII in the intensive care unit (n = 12) or underwent reoperation (n = 12) for refractory bleeding. Preoperative and postoperative data were collected to compare efficacy, safety, and economic outcomes. In-hospital survival for both groups was 100%. Factor VII was comparable with reoperation in achieving hemostasis, with both groups demonstrating decreases in chest tube output and need for blood products. Freedom from reoperation was achieved in 75% of patients receiving factor VII, whereas reoperation was effective in achieving hemostasis alone in 83.3% of patients. Prothrombin time, international normalized ratio, and median operating room time were significantly less (P < .05) in patients who received factor VII. Both groups had no statistically significant differences in other efficacy, safety, or economic outcomes. Factor VII administration in the intensive care unit appears comparable with reoperation for refractory bleeding after complex cardiovascular surgical procedures and might represent an alternative to reoperation in selected patients. Future prospective, randomized controlled trials might further define its role. Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Complexation of tocotrienol with gamma-cyclodextrin enhances intestinal absorption of tocotrienol in rats.

PubMed

Ikeda, Saiko; Uchida, Tomono; Ichikawa, Tomio; Watanabe, Takashi; Uekaji, Yukiko; Nakata, Daisuke; Terao, Keiji; Yano, Tomohiro

2010-01-01

To determine the bioavailability of tocotrienol complex with gamma-cyclodextrin, the effects of tocotrienol/gamma-cyclodextrin complex on tocotrienol concentration in rat plasma and tissues were studied. Rats were administered by oral gavage an emulsion containing tocotrienol, tocotrienol with gamma-cyclodextrin, or tocotrienol/gamma-cyclodextrin complex. At 3 h after administration, the plasma gamma-tocotrienol concentration of the rats administered tocotrienol/gamma-cyclodextrin complex was higher than that of the rats administered tocotrienol and gamma-cyclodextrin. In order to determine the effect of complexation on tocotrienol absorption, rats were injected with Triton WR1339, which prevents the catabolism of triacylglycerol-rich lipoprotein by lipoprotein lipase, and then administered by oral gavage an emulsion containing tocotrienol, tocotrienol with gamma-cyclodextrin, or tocotrienol/gamma-cyclodextrin complex. The plasma gamma-tocotrienol concentration of the Triton-treated rats administered tocotrienol/gamma-cyclodextrin complex was higher than that of the other Triton-treated rats. These results suggest that complexation of tocotrienol with gamma-cyclodextrin elevates plasma and tissue tocotrienol concentrations by enhancing intestinal absorption.

Amorphic complexity

NASA Astrophysics Data System (ADS)

Fuhrmann, G.; Gröger, M.; Jäger, T.

2016-02-01

We introduce amorphic complexity as a new topological invariant that measures the complexity of dynamical systems in the regime of zero entropy. Its main purpose is to detect the very onset of disorder in the asymptotic behaviour. For instance, it gives positive value to Denjoy examples on the circle and Sturmian subshifts, while being zero for all isometries and Morse-Smale systems. After discussing basic properties and examples, we show that amorphic complexity and the underlying asymptotic separation numbers can be used to distinguish almost automorphic minimal systems from equicontinuous ones. For symbolic systems, amorphic complexity equals the box dimension of the associated Besicovitch space. In this context, we concentrate on regular Toeplitz flows and give a detailed description of the relation to the scaling behaviour of the densities of the p-skeletons. Finally, we take a look at strange non-chaotic attractors appearing in so-called pinched skew product systems. Continuous-time systems, more general group actions and the application to cut and project quasicrystals will be treated in subsequent work.

Testing of Intravenous Hemostatic Agents in a Novel Swine Model of Bleeding: Preliminary Results With FXa-PCPs

DTIC Science & Technology

2005-08-01

proceeds through a prothrombinase complex (prothrombin, factor Va, calcium, and phospholipid). Thrombin is the final product in the coagulation cascade...we report preliminary data on the efficacy of mixtures of highly purified blood coagulation factors (FVIIa and FXa) and phospholipids vesicles (PCPS...testing. Further study of these drugs for the use of traumatic hemorrhage is not warranted. 15. SUBJECT TERMS Recombinant Factor VI~a, factor Xa

The complexity of hair/blood mercury concentration ratios and its implications.

PubMed

Liberda, Eric N; Tsuji, Leonard J S; Martin, Ian D; Ayotte, Pierre; Dewailly, Eric; Nieboer, Evert

2014-10-01

The World Health Organization (WHO) recommends a mercury (Hg) hair-to-blood ratio of 250 for the conversion of Hg hair levels to those in whole blood. This encouraged the selection of hair as the preferred analyte because it minimizes collection, storage, and transportation issues. In spite of these advantages, there is concern about inherent uncertainties in the use of this ratio. To evaluate the appropriateness of the WHO ratio, we investigated total hair and total blood Hg concentrations in 1333 individuals from 9 First Nations (Aboriginal) communities in northern Québec, Canada. We grouped participants by sex, age, and community and performed a 3-factor (M)ANOVA for total Hg in hair (0-2 cm), total Hg in blood, and their ratio. In addition, we calculated the percent error associated with the use of the WHO ratio in predicting blood Hg concentrations from hair Hg. For group comparisons, Estimated Marginal Means (EMMS) were calculated following ANOVA. At the community level, the error in blood Hg estimated from hair Hg ranged -25% to +24%. Systematic underestimation (-8.4%) occurred for females and overestimation for males (+5.8%). At the individual level, the corresponding error range was -98.7% to 1040%, with observed hair-to-blood ratios spanning 3 to 2845. The application of the ratio endorsed by the WHO would be unreliable for determining individual follow-up. We propose that Hg exposure be assessed by blood measurements when there are human health concerns, and that the singular use of hair and the hair-to-blood concentration conversion be discouraged in establishing individual risk. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

Rhodamine-123: a p-glycoprotein marker complex with sodium lauryl sulfate.

PubMed

Al-Mohizea, Abdullah M; Al-Jenoobi, Fahad Ibrahim; Alam, Mohd Aftab

2015-03-01

Aim of this study was to investigate the role of sodium lauryl sulfate (SLS) as P-glycoprotein inhibitor. The everted rat gut sac model was used to study in-vitro mucosal to serosal transport of Rhodamine-123 (Rho-123). Surprisingly, SLS decreases the serosal absorption of Rho-123 at all investigated concentrations. Investigation reveals complex formation between Rhodamine-123 and sodium lauryl sulfate. Interaction profile of SLS & Rho-123 was studied at variable SLS concentrations. The SLS concentration higher than critical micelle concentration (CMC) increases the solubility of Rho-123 but could not help in serosal absorption, on the contrary the absorption of Rho-123 decreased. Rho-123 and SLS form pink color complex at sub-CMC. The SLS concentrations below CMC decrease the solubility of Rho-123. For further studies, Rho-123 & SLS complex was prepared by using solvent evaporation technique and characterized by using differential scanning calorimeter (DSC). Thermal analysis also proved the formation of complex between SLS & Rho-123. The P values were found to be significant (<0.05) except group comprising 0.0001% SLS, and that is because 0.0001% SLS is seems to be very low to affect the solubility or complexation of Rho-123.

Detection and Estimation of 2-D Distributions of Greenhouse Gas Source Concentrations and Emissions over Complex Urban Environments and Industrial Sites

NASA Astrophysics Data System (ADS)

Zaccheo, T. S.; Pernini, T.; Dobler, J. T.; Blume, N.; Braun, M.

2017-12-01

This work highlights the use of the greenhouse-gas laser imaging tomography experiment (GreenLITETM) data in conjunction with a sparse tomography approach to identify and quantify both urban and industrial sources of CO2 and CH4. The GreenLITETM system provides a user-defined set of time-sequenced intersecting chords or integrated column measurements at a fixed height through a quasi-horizontal plane of interest. This plane, with unobstructed views along the lines of sight, may range from complex industrial facilities to a small city scale or urban sector. The continuous time phased absorption measurements are converted to column concentrations and combined with a plume based model to estimate the 2-D distribution of gas concentration over extended areas ranging from 0.04-25 km2. Finally, these 2-D maps of concentration are combined with ancillary meteorological and atmospheric data to identify potential emission sources and provide first order estimates of their associated fluxes. In this presentation, we will provide a brief overview of the systems and results from both controlled release experiments and a long-term system deployment in Paris, FR. These results provide a quantitative assessment of the system's ability to detect and estimate CO2 and CH4 sources, and demonstrate its ability to perform long-term autonomous monitoring and quantification of either persistent or sporadic emissions that may have both health and safety as well as environmental impacts.

Properties of a recombinant bovine tissue factor expressed by Silkworm pupae and its performance as an Owren-type prothrombin time reagent for warfarin monitoring.

PubMed

Okuda, Masahiro; Taniguchi, Tomokuni; Takamiya, Osamu

2012-09-01

Tissue factor (TF), or thromboplastin, is a glycoprotein that triggers the extrinsic coagulation pathway. In blood coagulation testing, TF has been used as a natural source for determining Quick prothrombin time (PT) or the Owren PT (OBT). Currently, natural sources are being replaced with recombinant proteins because of their uniform characteristics and the possibility of stable mass production of PT reagents. Because bovine spongiform encephalopathy (BSE)-infected cows are widespread in Japan, we prepared a recombinant bovine TF (rbTF) with a baculovirus expression system using silkworms. To overcome the limitations of natural TF, especially in bovine brain, we expressed a full-length rbTF protein in Silkworm pupae with a baculovirus expression system. Baculovirus inactivation and the presence of DNA fragments in the rbTF fraction were confirmed using Reed-Muench and polymerase chain reaction methods after inactivation with a detergent. The rbTF fraction prepared by an immobilized anti-Silkworm pupae fluid protein Sepharose 4B column was identified as a visible band on western blots with a polyclonal antibody against human TF with cross-reactivity with TFs. The inhibition of the polyclonal antibody against human TF by the clotting assay for PT was identified, and amidolytic biological activity through activated factor VII on S-2288 substrate was observed. In conclusion, the rbTF expressed by the baculovirus system using Silkworm pupae was uniformly specific for bovine TF. The OBT reagent incorporated by this rbTF was similar to those of commercial reagents. It also showed a suitable International Sensitivity Index and reproducibility precision, thereby allowing for diagnostic use. Copyright © 2012 Elsevier Ltd. All rights reserved.

Women with Red Hair Report A Slightly Increased Rate of Bruising, but Have Normal Coagulation Tests

PubMed Central

Liem, Edwin B.; Hollensead, Sandra C.; Joiner, Teresa V.

2005-01-01

There is an anecdotal impression that redheads experience more perioperative bleeding complications than those with other hair colors. We, therefore, tested the hypothesis that perceived problems with hemostasis could be detected with commonly used coagulation tests. Se studied healthy female Caucasian volunteers, 18 to 40 years, comparable in terms of height, weight, and age, with natural bright red (n = 25) or black or dark brown (n = 26) hair. Volunteers were questioned about their bleeding history and the following tests were performed: complete blood count, prothrombin time/international normalized ratio, activated partial thromboplastin time, platelet function analysis (PFA-100), and platelet aggregation using standard turbidimetric methodology. Agonists for aggregation were adenosine diphosphate, arachidonic acid, collagen, epinephrine, and two concentrations of ristocetin. The red-haired volunteers reported significantly more bruising, but there were no significant differences between the red- and dark-haired groups in hemoglobin concentration, platelet numbers, prothrombin time/international normalized ratio, or activated partial thromboplastin time. Furthermore, no significant differences in platelet function, as measured with the PFA-100 or with platelet aggregometry, were observed. We conclude that if redheads have hemostasis abnormalities, they are subtle. PMID:16368849

Chemical synthesis of water-soluble, chiral conducting-polymer complexes

DOEpatents

Wang, Hsing-Lin; McCarthy, Patrick A.; Yang, Sze Cheng

2003-01-01

The template-guided synthesis of water-soluble, chiral conducting polymer complexes is described. Synthesis of water-soluble polyaniline complexes is achieved by carefully controlling the experimental parameters such as; acid concentration, ionic strength, monomer/template ratio, total reagent concentration, and order of reagent addition. Chiral (helical) polyaniline complexes can be synthesized by addition of a chiral inducing agent (chiral acid) prior to polymerization, and the polyaniline helix can be controlled by the addition of the (+) or (-) form of the chiral acid. Moreover the quantity of chiral acid and the salt content has a significant impact on the degree of chirality in the final polymer complexes. The polyaniline and the template have been found to be mixed at the molecular level which results in chiral complexes that are robust through repeated doping and dedoping cycles.

Rapid and early α-fetoprotein and des-γ-carboxy prothrombin responses to initial arterial infusion chemotherapy predict treatment outcomes of advanced hepatocellular carcinoma

PubMed Central

OYAMA, KENJI; KODA, MASAHIKO; SUGIHARA, TAKAAKI; KISHINA, MANABU; MIYOSHI, KENICHI; OKAMOTO, TOSHIAKI; HODOTSUKA, MASANORI; FUJISE, YUKI; MATONO, TOMOMITSU; TOKUNAGA, SHIHO; OKAMOTO, KINYA; HOSHO, KEIKO; OKANO, JUNICHI; MURAWAKI, YOSHIKAZU

2015-01-01

The aim of the present study was to predict the effects of transarterial infusion (TAI) chemotherapy based on early changes in α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) in patients with advanced hepatocellular carcinoma (HCC). Seventy-four patients who underwent TAI with cisplatin, 5-fluorouracil, mitomycin C and epirubicin for advanced HCC were enrolled. Antitumor responses were evaluated 6 months after TAI. Rapid and early responses were defined as the ratio of AFP or DCP after 1 week and 1 month compared to baseline. A total of 5, 10, 17 and 42 patients had complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD), respectively. Early AFP response was significantly lower in the CR+PR compared to the SD+PD groups (P<0.01). The early DCP response was significantly lower in the CR+PR compared to the SD+PD. The sensitivity and specificity of rapid and early AFP responses in the CR+PR were 0.78 and 0.72, and 0.80 and 0.73, respectively, and those of rapid and early DCP responses were 0.67 and 0.65, and 0.77 and 0.71, respectively. The combination of AFP and DCP responses had higher specificity compared to AFP or DCP alone responses. Patients were divided into responder and non-responder groups to evaluate the prediction of survival outcome. Early responders of AFP, DCP and AFP+DCP, who were divided based on the cut-off values of CR+PR survived significantly longer than the non-responders (P<0.05). In conclusion, rapid or early responses of AFP and/or DCP levels 1 and 4 weeks after TAI chemotherapy helped to predict the treatment effects. PMID:26137283

Soluble ST2 Plasma Concentrations Predict Mortality in HBV-Related Acute-on-Chronic Liver Failure

PubMed Central

Mo, Zhishuo; Zhu, Jianyun; Pang, Xiuqing; Wu, Zhebin; Wang, Ke; Li, Xinhua; Xie, Dongying; Gao, Zhiliang

2015-01-01

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a rapidly progressing and frequently fatal condition. The aim of this study was to determine whether interleukin- (IL-) 33 and soluble ST2 (sST2) were associated with disease severity and mortality in HBV-ACLF. We found that plasma levels of sST2 but not IL-33 were higher in HBV-ACLF patients compared with chronic hepatitis B (CHB) patients and healthy controls. However, plasma levels of IL-33, TNF-α, IFN-γ, and IL-10 did not correlate with sST2 levels. Similarly, immunohistochemistry revealed low IL-33 expression and high ST2 expression in liver sections of patients with HBV-ACLF. Evaluation of dynamic changes of sST2 in HBV-ACLF showed that plasma sST2 levels increased over time in patients who died during the 180-day follow-up but decreased in those who survived. In addition, plasma sST2 level after week 1 correlated with disease severity, as assessed by total bilirubin, prothrombin time, and model for end-stage liver disease score. Results of Kaplan-Meier survival analysis showed that higher sST2 concentration (≥87 ng/mL) at week 3 was associated with poor survival. These findings indicate the potential usefulness of sST2 as a predictor of disease severity and in making treatment decisions for patients with HBV-ACLF. PMID:25892854

REM-containing silicate concentrates

NASA Astrophysics Data System (ADS)

Pavlov, V. F.; Shabanova, O. V.; Pavlov, I. V.; Pavlov, M. V.; Shabanov, A. V.

2016-01-01

A new method of advanced complex processing of ores containing rare-earth elements (REE) is proposed to obtain porous X-ray amorphous aluminosilicate material with a stable chemical composition which concentrates oxides of rare-earth metals (REM). The ferromanganese oxide ores of Chuktukon deposit (Krasnoyarsk Region, RF) were used for the experiment. The obtained aluminosilicate material is appropriate for treatment with 5 - 15% solutions of mineral acids to leach REM.

Interpolymer complexation: comparisons of bulk and interfacial structures.

PubMed

Cattoz, Beatrice; de Vos, Wiebe M; Cosgrove, Terence; Crossman, Martin; Espidel, Youssef; Prescott, Stuart W

2015-04-14

The interactions between the strong polyelectrolyte sodium poly(styrenesulfonate), NaPSS, and the neutral polymer poly(vinylpyrrolidone), PVP, were investigated in bulk and at the silica/solution interface using a combination of diffusion nuclear magnetic resonance spectroscopy (NMR), small-angle neutron scattering (SANS), solvent relaxation NMR, and ellipsometry. We show for the first time that complex formation occurs between NaPSS and PVP in solution; the complexes formed were shown not to be influenced by pH variation, whereas increasing the ionic strength increases the complexation of NaPSS but does not influence the PVP directly. The complexes formed contained a large proportion of NaPSS. Study of these interactions at the silica interface demonstrated that complexes also form at the nanoparticle interface where PVP is added in the system prior to NaPSS. For a constant PVP concentration and varying NaPSS concentration, the system remains stable until NaPSS is added in excess, which leads to depletion flocculation. Surface complex formation using the layer-by-layer technique was also reported at a planar silica interface.

Application of a UV-Vis submersible probe for capturing changes in DOC concentrations across a mire complex during the snowmelt and summer periods

NASA Astrophysics Data System (ADS)

Avagyan, Armine; Runkle, Benjamin; Kutzbach, Lars

2013-04-01

An accurate quantification of dissolved organic carbon (DOC) is crucial for understanding changes in water resources under the influence of climate, land use and urbanization. However, the conventionally used methods do not allow high frequency in situ analyses in remote or hostile environments (e.g., industrial wastewater or during environmental high-flow events, such as snowmelt or floods). In particular, missing measurements during the snowmelt period in landscapes of the boreal region can lead to significant miscalculations in regional carbon budgets. Therefore, the aim of the study was to test the performance of a portable, submersible UV-Vis spectrophotometer (spectro::lyser, s::can Messtechnik GmbH, Austria) during the snowmelt period in a boreal mire-forest catchment, and to provide a conceptual understanding of the spatial and temporal dynamics of DOC concentrations during and after snowmelt. During 2011, water samples were collected from the near-pristine Ust-Pojeg mire complex in northwestern Russia (61° 56'N, 50° 13'E). Sampling started during the spring snowmelt period and continued until late fall. The mire presented a mosaic of different landscape units. The mire consisted of minerogeous (fen), ombrogenous (bog), and transitional forest-mire (lagg) zones. Water samples were taken from the surface across the mire (22 points at 50-m intervals). DOC concentrations were analyzed directly at the study site using a portable, submersible UV-Vis spectrophotometer, which uses high-resolution absorbance measurements over the wavelength range 200-742.5 nm at 2.5-nm intervals as a proxy for DOC content. Because the DOC composition of fluids varies by site, a local calibration replaced the default settings of the spectro::lyser (Global Calibration) to enhance the accuracy of the measurements. To evaluate the local calibration and correct for drift, the same samples (n = 157) were additionally analyzed using the wet persulfate oxidation method (O

Detection of Labile Low-Molecular-Mass Transition Metal Complexes in Mitochondria

PubMed Central

McCormick, Sean P.; Moore, Michael J.; Lindahl, Paul A.

2015-01-01

Liquid chromatography was used with an on-line inductively coupled plasma mass spectrometer to detect low-molecular-mass (LMM) transition metal complexes in mitochondria isolated from fermenting yeast cells, human Jurkat cells, and mouse brain and liver. These complexes constituted 20 – 40% of total mitochondrial Mn, Fe, Zn, and Cu ions. The major LMM Mn complex in yeast mitochondria had a mass of ca. 1100 Da and a concentration of ~ 2 μM. Mammalian mitochondria contained a second Mn species with a mass of ca. 2000 Da at a comparable concentration. The major Fe complex in mitochondria isolated from exponentially growing yeast cells had a mass of ca. 580 Da; the concentration of Fe580 in mitochondria was ca. 100 μM. When mitochondria were isolated from fermenting cells in post-exponential phase, the mass of the dominant LMM Fe complex was ca. 1100 Da. Upon incubation, the intensity of Fe1100 declined and Fe580 increased, suggesting that the two are interrelated. Mammalian mitochondria contained Fe580 and 2 other Fe species (Fe2000 and Fe1100) at concentrations of ca. 50 μM each. The dominant LMM Zn species in mitochondria had a mass of ca. 1200 Da and a concentration of ca. 110 μM. Mammalian mitochondria contained a second major LMM Zn species at 1500 Da. The dominant LMM Cu species in yeast mitochondria had a mass of ca. 5000 Da and a concentration in yeast mitochondria of ca. 16 μM; Cu5000 was not observed in mammalian mitochondria. The dominant Co species in mitochondria, Co1200, had a concentration of 20 nM and was probably a cobalamin. Mammalian but not yeast mitochondria contained a LMM Mo species, Mo730, at ca. 1 μM concentration. Increasing Mn, Fe, Cu, and Zn concentrations 10 fold in the medium increased the concentration of the same element in the corresponding isolated mitochondria. Treatment with metal chelators confirmed that these LMM species were labile. The dominant S species at 1100 Da was not free GSH or GSSG. PMID:26018429

Gel phase formation in dilute triblock copolyelectrolyte complexes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Srivastava, Samanvaya; Andreev, Marat; Levi, Adam E.

Assembly of oppositely charged triblock copolyelectrolytes into phase-separated gels at low polymer concentrations (<1% by mass) has been observed in scattering experiments and molecular dynamics simulations. Here we show that in contrast to uncharged, amphiphilic block copolymers that form discrete micelles at low concentrations and enter a phase of strongly interacting micelles in a gradual manner with increasing concentration, the formation of a dilute phase of individual micelles is prevented in polyelectrolyte complexation-driven assembly of triblock copolyelectrolytes. Gel phases form and phase separate almost instantaneously on solvation of the copolymers. Furthermore, molecular models of self-assembly demonstrate the presence of oligo-chainmore » aggregates in early stages of copolyelectrolyte assembly, at experimentally unobservable polymer concentrations. Our discoveries contribute to the fundamental understanding of the structure and pathways of complexation-driven assemblies, and raise intriguing prospects for gel formation at extraordinarily low concentrations, with applications in tissue engineering, agriculture, water purification and theranostics.« less

Gel phase formation in dilute triblock copolyelectrolyte complexes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Srivastava, Samanvaya; Andreev, Marat; Levi, Adam E.

Assembly of oppositely charged triblock copolyelectrolytes into phase-separated gels at low polymer concentrations (<1% by mass) has been observed in scattering experiments and molecular dynamics simulations. Here we show that in contrast to uncharged, amphiphilic block copolymers that form discrete micelles at low concentrations and enter a phase of strongly interacting micelles in a gradual manner with increasing concentration, the formation of a dilute phase of individual micelles is prevented in polyelectrolyte complexation-driven assembly of triblock copolyelectrolytes. Gel phases form and phase separate almost instantaneously on solvation of the copolymers. Furthermore, molecular models of self-assembly demonstrate the presence of oligo-chainmore » aggregates in early stages of copolyelectrolyte assembly, at experimentally unobservable polymer concentrations. Finally, our discoveries contribute to the fundamental understanding of the structure and pathways of complexation-driven assemblies, and raise intriguing prospects for gel formation at extraordinarily low concentrations, with applications in tissue engineering, agriculture, water purification and theranostics.« less

Gel phase formation in dilute triblock copolyelectrolyte complexes

DOE PAGES

Srivastava, Samanvaya; Andreev, Marat; Levi, Adam E.; ...

2017-02-23

Assembly of oppositely charged triblock copolyelectrolytes into phase-separated gels at low polymer concentrations (<1% by mass) has been observed in scattering experiments and molecular dynamics simulations. Here we show that in contrast to uncharged, amphiphilic block copolymers that form discrete micelles at low concentrations and enter a phase of strongly interacting micelles in a gradual manner with increasing concentration, the formation of a dilute phase of individual micelles is prevented in polyelectrolyte complexation-driven assembly of triblock copolyelectrolytes. Gel phases form and phase separate almost instantaneously on solvation of the copolymers. Furthermore, molecular models of self-assembly demonstrate the presence of oligo-chainmore » aggregates in early stages of copolyelectrolyte assembly, at experimentally unobservable polymer concentrations. Finally, our discoveries contribute to the fundamental understanding of the structure and pathways of complexation-driven assemblies, and raise intriguing prospects for gel formation at extraordinarily low concentrations, with applications in tissue engineering, agriculture, water purification and theranostics.« less

Gel Phase Formation in Dilute Triblock Copolyelectrolyte Complexes

NASA Astrophysics Data System (ADS)

Srivastava, Samanvaya; Andreev, Marat; Prabhu, Vivek; de Pablo, Juan; Tirrell, Matthew

Assembly of oppositely charged triblock copolyelectrolytes into phase-separated gels at extremely low polymer concentrations (<1 % by mass) has been observed in scattering experiments and molecular dynamics simulations. In contrast to uncharged, amphiphilic block copolymers that form discrete micelles at low concentrations and enter a phase of strongly interacting micelles in a gradual manner with increasing polymer concentrations, the formation of a dilute phase of individual micelles is prevented in polyelectrolyte complexation-driven assemblies of triblock copolyelectrolytes. Gel phases form and phase separate almost instantaneously upon solvation of the copolymers. Furthermore, molecular models of self-assembly demonstrate the presence of oligo-chain aggregates in early stages of triblock copolyelectrolyte assembly, at experimentally unobservable polymer concentrations. Our discoveries not only contribute to our fundamental understanding of the structure and pathways of complexation driven assemblies, but also raise intriguing prospects for formation of gel structures at extraordinarily low concentrations, with applications in tissue engineering, agriculture, water purification and theranostics.

Gel phase formation in dilute triblock copolyelectrolyte complexes

NASA Astrophysics Data System (ADS)

Srivastava, Samanvaya; Andreev, Marat; Levi, Adam E.; Goldfeld, David J.; Mao, Jun; Heller, William T.; Prabhu, Vivek M.; de Pablo, Juan J.; Tirrell, Matthew V.

2017-02-01

Assembly of oppositely charged triblock copolyelectrolytes into phase-separated gels at low polymer concentrations (<1% by mass) has been observed in scattering experiments and molecular dynamics simulations. Here we show that in contrast to uncharged, amphiphilic block copolymers that form discrete micelles at low concentrations and enter a phase of strongly interacting micelles in a gradual manner with increasing concentration, the formation of a dilute phase of individual micelles is prevented in polyelectrolyte complexation-driven assembly of triblock copolyelectrolytes. Gel phases form and phase separate almost instantaneously on solvation of the copolymers. Furthermore, molecular models of self-assembly demonstrate the presence of oligo-chain aggregates in early stages of copolyelectrolyte assembly, at experimentally unobservable polymer concentrations. Our discoveries contribute to the fundamental understanding of the structure and pathways of complexation-driven assemblies, and raise intriguing prospects for gel formation at extraordinarily low concentrations, with applications in tissue engineering, agriculture, water purification and theranostics.

Complex equiangular tight frames

NASA Astrophysics Data System (ADS)

Tropp, Joel A.

2005-08-01

A complex equiangular tight frame (ETF) is a tight frame consisting of N unit vectors in Cd whose absolute inner products are identical. One may view complex ETFs as a natural geometric generalization of an orthonormal basis. Numerical evidence suggests that these objects do not arise for most pairs (d, N). The goal of this paper is to develop conditions on (d, N) under which complex ETFs can exist. In particular, this work concentrates on the class of harmonic ETFs, in which the components of the frame vectors are roots of unity. In this case, it is possible to leverage field theory to obtain stringent restrictions on the possible values for (d, N).

Comparative toxicity of diphacinone to northern bobwhite (Colinus virginianus) and American kestrels (Falco sparverius)

USGS Publications Warehouse

Rattner, Barnett A.; Horak, Katherine E.; Warner, Sarah E.; Day, Daniel D.; Johnston, John J.

2010-01-01

The acute oral toxicity of the anticoagulant rodenticide diphacinone was found to be about 20 times greater to American kestrels (LD50=97 mg/kg) than to northern bobwhite (LD50=2,014 mg/kg). Several precise and sensitive clotting assays (prothrombin time, Russell's Viper venom time, thrombin clotting time) were adapted for use in these species, and this combination of assays is recommended to detect effects of diphacinone and other rodenticides on coagulation. Oral administration of diphacinone over a range of doses (sublethal to the extrapolated LD15) prolonged prothrombin time and Russell's Viper venom time within 24 to 48 hrs post-exposure. Prolongation of in vitro clotting time reflects impaired coagulation complex activity and was detected before or at the onset of overt signs of toxicity and lethality. These data will assist in the development of a pharmacodynamic model to assess and predict rodenticide toxicity to non-target avian species.

An evaluation of patient self-testing competency of prothrombin time for managing anticoagulation: pre-randomization results of VA Cooperative Study #481--The Home INR Study (THINRS).

PubMed

Dolor, Rowena J; Ruybalid, R Lynne; Uyeda, Lauren; Edson, Robert G; Phibbs, Ciaran; Vertrees, Julia E; Shih, Mei-Chiung; Jacobson, Alan K; Matchar, David B

2010-10-01

Prior studies suggest patient self-testing (PST) of prothrombin time (PT) can improve the quality of anticoagulation (AC) and reduce complications (e.g., bleeding and thromboembolic events). "The Home INR Study" (THINRS) compared AC management with frequent PST using a home monitoring device to high-quality AC management (HQACM) with clinic-based monitoring on major health outcomes. A key clinical and policy question is whether and which patients can successfully use such devices. We report the results of Part 1 of THINRS in which patients and caregivers were evaluated for their ability to perform PST. Study-eligible patients (n = 3643) were trained to use the home monitoring device and evaluated after 2-4 weeks for PST competency. Information about demographics, medical history, warfarin use, medications, plus measures of numeracy, literacy, cognition, dexterity, and satisfaction with AC were collected. Approximately 80% (2931 of 3643) of patients trained on PST demonstrated competency; of these, 8% (238) required caregiver assistance. Testers who were not competent to perform PST had higher numbers of practice attempts, higher cuvette wastage, and were less able to perform a fingerstick or obtain blood for the cuvette in a timely fashion. Factors associated with failure to pass PST training included increased age, previous stroke history, poor cognition, and poor manual dexterity. A majority of patients were able to perform PST. Successful home monitoring of PT with a PST device required adequate levels of cognition and manual dexterity. Training a caregiver modestly increased the proportion of patients who can perform PST.

A network property necessary for concentration robustness

NASA Astrophysics Data System (ADS)

Eloundou-Mbebi, Jeanne M. O.; Küken, Anika; Omranian, Nooshin; Kleessen, Sabrina; Neigenfind, Jost; Basler, Georg; Nikoloski, Zoran

2016-10-01

Maintenance of functionality of complex cellular networks and entire organisms exposed to environmental perturbations often depends on concentration robustness of the underlying components. Yet, the reasons and consequences of concentration robustness in large-scale cellular networks remain largely unknown. Here, we derive a necessary condition for concentration robustness based only on the structure of networks endowed with mass action kinetics. The structural condition can be used to design targeted experiments to study concentration robustness. We show that metabolites satisfying the necessary condition are present in metabolic networks from diverse species, suggesting prevalence of this property across kingdoms of life. We also demonstrate that our predictions about concentration robustness of energy-related metabolites are in line with experimental evidence from Escherichia coli. The necessary condition is applicable to mass action biological systems of arbitrary size, and will enable understanding the implications of concentration robustness in genetic engineering strategies and medical applications.

A network property necessary for concentration robustness.

PubMed

Eloundou-Mbebi, Jeanne M O; Küken, Anika; Omranian, Nooshin; Kleessen, Sabrina; Neigenfind, Jost; Basler, Georg; Nikoloski, Zoran

2016-10-19

Maintenance of functionality of complex cellular networks and entire organisms exposed to environmental perturbations often depends on concentration robustness of the underlying components. Yet, the reasons and consequences of concentration robustness in large-scale cellular networks remain largely unknown. Here, we derive a necessary condition for concentration robustness based only on the structure of networks endowed with mass action kinetics. The structural condition can be used to design targeted experiments to study concentration robustness. We show that metabolites satisfying the necessary condition are present in metabolic networks from diverse species, suggesting prevalence of this property across kingdoms of life. We also demonstrate that our predictions about concentration robustness of energy-related metabolites are in line with experimental evidence from Escherichia coli. The necessary condition is applicable to mass action biological systems of arbitrary size, and will enable understanding the implications of concentration robustness in genetic engineering strategies and medical applications.

Significance of the concentration of chelating ligands on Fe3+-solubility, bioavailability, and uptake in rice plant.

PubMed

Hasegawa, Hiroshi; Rahman, M Mamunur; Kadohashi, Kouta; Takasugi, Yui; Tate, Yousuke; Maki, Teruya; Rahman, M Azizur

2012-09-01

Present study investigated the significance of the concentration of chelating ligand on Fe(3+)-solubility in growth medium and its influence on Fe bioavailability and uptake in rice plant. Rice seedlings were grown in modified Murashige and Skoog (MS) hydroponic growth medium with moderate (250 μM) and high (500 μM) concentrations of ethylenediaminetetraacetate (EDTA) and hydroxyiminodisuccinate (HIDS) under sterile and non-sterile conditions. Concentrations of soluble Fe in the growth medium increased with increasing ligand concentrations, and the growth of rice seedlings was higher at moderate ligand concentration than at control (without chelant) and high ligand concentration. This explains the relationship between Fe solubility and bioavailability in the growth medium, and its effect on Fe uptake in rice plant. Fe exists in the growth medium predominantly as particulate (insoluble) forms at low ligand concentration, and as soluble [Fe(OH)(2+), Fe(OH)(2)(+), Fe-L complex] and apparently soluble (colloidal) forms at moderate ligand concentration. At high ligand concentration, most of the Fe(3+) in the growth medium forms soluble Fe-L complex, however, the bioavailability of Fe from Fe-L complex decreased due to lopsided complex formation equilibrium reaction (CFER) between Fe and the ligands. Also, Fe is solubilized forming stable and soluble Fe-L complex, which is then detached as less stable, but soluble and bioavailable substance(s) after (time-dependent) biodegradation. Therefore- i) ligand concentration and stability constant of Fe-L complex (K(Fe-L)) influence Fe bioavailability and uptake in rice plant, and ii) the biodegradable ligands (e.g., HIDS) would be more effective Fe fertilizer than the environmentally persistent and less biodegradable ligands (e.g., EDTA). Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Concentrations, profiles, and estimated human exposures for polychlorinated dibenzo-p-dioxins and dibenzofurans from electronic waste recycling facilities and a chemical industrial complex in Eastern China

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, J.; Kannan, K.; Cheng, J.

2008-11-15

Electronic shredder waste and dust from e-waste facilities, and leaves and surface soil collected in the vicinity of a large scale e-waste recycling facility in Taizhou, Eastern China, were analyzed for total dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) including 2,3,7,8-substituted congeners. We also determined PCDD/Fs in surface agricultural soils from several provinces in China for comparison with soils from e-waste facilities. Concentrations of total PCDD/Fs were high in all of the matrices analyzed and ranged from 30.9 to 11,400 pg/g for shredder waste, 3460 to 9820 pg/g dry weight for leaves, 2560 to 148,000 pg/g dry weight for workshop-floor dust, and 854more » to 10200 pg/g dry weight for soils. We also analyzed surface soils from a chemical industrial complex (a coke-oven plant, a coal-fired power plant, and a chlor-alkali plant) in Shanghai. Concentrations of total PCDD/Fs in surface soil from the chemical industrial complex were lower than the concentrations found in soils from e-waste recycling plants, but higher than the concentrations found in agricultural soils. Agricultural soils from six cities in China contained low levels of total PCDD/Fs. Profiles of dioxin toxic equivalents (TEQs) of 2,3,7,8-PCDD/Fs in soils from e-waste facilities in Taizhou differed from the profiles found in agricultural soils. The estimated daily intakes of TEQs of PCDD/Fs via soil/dust ingestion and dermal exposure were 2 orders of magnitude higher in people at e-waste recycling facilities than in people at the chemical industrial site, implying greater health risk for humans from dioxin exposures at e-waste recycling facilities. The calculated TEQ exposures for e-waste workers from dust and soil ingestion alone were 2-3 orders of magnitude greater than the exposures from soils in reference locations. 37 refs., 1 fig., 2 tabs.« less

The scaling of crime concentration in cities

PubMed Central

Bastos-Filho, Carmelo; Menezes, Ronaldo

2017-01-01

Crime is a major threat to society’s well-being but lacks a statistical characterization that could lead to uncovering some of its underlying mechanisms. Evidence of nonlinear scaling of urban indicators in cities, such as wages and serious crime, has motivated the understanding of cities as complex systems—a perspective that offers insights into resources limits and sustainability, but that usually neglects details of the indicators themselves. Notably, since the nineteenth century, criminal activities have been known to occur unevenly within a city; crime concentrates in such way that most of the offenses take place in few regions of the city. Though confirmed by different studies, this concentration lacks broad analyses on its characteristics, which hinders not only the comprehension of crime dynamics but also the proposal of sounding counter-measures. Here, we developed a framework to characterize crime concentration which divides cities into regions with the same population size. We used disaggregated criminal data from 25 locations in the U.S. and the U.K., spanning from 2 to 15 years of longitudinal data. Our results confirmed that crime concentrates regardless of city and revealed that the level of concentration does not scale with city size. We found that the distribution of crime in a city can be approximated by a power-law distribution with exponent α that depends on the type of crime. In particular, our results showed that thefts tend to concentrate more than robberies, and robberies more than burglaries. Though criminal activities present regularities of concentration, we found that criminal ranks have the tendency to change continuously over time—features that support the perspective of crime as a complex system and demand analyses and evolving urban policies covering the city as a whole. PMID:28800604

The scaling of crime concentration in cities.

PubMed

Oliveira, Marcos; Bastos-Filho, Carmelo; Menezes, Ronaldo

2017-01-01

Crime is a major threat to society's well-being but lacks a statistical characterization that could lead to uncovering some of its underlying mechanisms. Evidence of nonlinear scaling of urban indicators in cities, such as wages and serious crime, has motivated the understanding of cities as complex systems-a perspective that offers insights into resources limits and sustainability, but that usually neglects details of the indicators themselves. Notably, since the nineteenth century, criminal activities have been known to occur unevenly within a city; crime concentrates in such way that most of the offenses take place in few regions of the city. Though confirmed by different studies, this concentration lacks broad analyses on its characteristics, which hinders not only the comprehension of crime dynamics but also the proposal of sounding counter-measures. Here, we developed a framework to characterize crime concentration which divides cities into regions with the same population size. We used disaggregated criminal data from 25 locations in the U.S. and the U.K., spanning from 2 to 15 years of longitudinal data. Our results confirmed that crime concentrates regardless of city and revealed that the level of concentration does not scale with city size. We found that the distribution of crime in a city can be approximated by a power-law distribution with exponent α that depends on the type of crime. In particular, our results showed that thefts tend to concentrate more than robberies, and robberies more than burglaries. Though criminal activities present regularities of concentration, we found that criminal ranks have the tendency to change continuously over time-features that support the perspective of crime as a complex system and demand analyses and evolving urban policies covering the city as a whole.

Long-term changes of heavy metal and sulphur concentrations in ecosystems of the Taymyr Peninsula (Russian Federation) North of the Norilsk Industrial Complex.

PubMed

Zhulidov, Alexander V; Robarts, Richard D; Pavlov, Dmitry F; Kämäri, J; Gurtovaya, Tatiana Yu; Meriläinen, J J; Pospelov, Igor N

2011-10-01

The Norilsk industrial ore smelting complex (Taymyr Peninsula, Russian Federation) has significantly impacted many components of local terrestrial and aquatic environments. Whether it has had a major impact on the wider Russian Arctic remains controversial as studies are scarce. From 1986 to 2004, data on heavy metal (Cu, Ni, Zn, Hg, Cd and Hg) concentrations in fish (burbot), moss, lichens, periphyton, hydric soils and snow in and around Norilsk and the most northern parts of the Taymyr Peninsula were analysed. Very high concentrations of Cu (203 μg L⁻¹ ± 51 μg L⁻¹) and Ni (113 μg L⁻¹ ± 15 μg L⁻¹) were found in the water of the Schuchya River close to Norilsk. Heavy metal concentrations in burbot liver were highest in Lake Pyasino near Norilsk compared to other study regions that were >100 km distant. From 1989-1996, Cu (121 μg L⁻¹ ± 39 μg L⁻¹ SD), Zn (150 μg L⁻¹) ± 70 μg L⁻¹) and Ni (149 μg L⁻¹ ± 72 μg L⁻¹) snow concentrations were greatest in Norilsk, but were low elsewhere. By 2004, these concentrations had dropped significantly, especially for Cu-74 μg L⁻¹ (±18.7 μg L⁻¹ SD), Zn-81.7 μg L⁻¹ (± 31.3 μg L⁻¹ SD) and Ni-80 μg L⁻¹(±18.0 μg L⁻¹ SD). Norilsk and its surroundings are subject to heavy pollution from the Norilsk metallurgical industry but these are absent from the greater Arctic region due to the prevailing winds and the Byrranga Mountains. Pollution abatement measures have been made so further investigations are necessary in order to assess their efficiency.

Dilution of protein-surfactant complexes: a fluorescence study.

PubMed

Azadi, Glareh; Chauhan, Anuj; Tripathi, Anubhav

2013-09-01

Dilution of protein-surfactant complexes is an integrated step in microfluidic protein sizing, where the contribution of free micelles to the overall fluorescence is reduced by dilution. This process can be further improved by establishing an optimum surfactant concentration and quantifying the amount of protein based on the fluorescence intensity. To this end, we study the interaction of proteins with anionic sodium dodecyl sulfate (SDS) and cationic hexadecyl trimethyl ammonium bromide (CTAB) using a hydrophobic fluorescent dye (sypro orange). We analyze these interactions fluourometrically with bovine serum albumin, carbonic anhydrase, and beta-galactosidase as model proteins. The fluorescent signature of protein-surfactant complexes at various dilution points shows three distinct regions, surfactant dominant, breakdown, and protein dominant region. Based on the dilution behavior of protein-surfactant complexes, we propose a fluorescence model to explain the contribution of free and bound micelles to the overall fluorescence. Our results show that protein peak is observed at 3 mM SDS as the optimum dilution concentration. Furthermore, we study the effect of protein concentration on fluorescence intensity. In a single protein model with a constant dye quantum yield, the peak height increases with protein concentration. Finally, addition of CTAB to the protein-SDS complex at mole fractions above 0.1 shifts the protein peak from 3 mM to 4 mM SDS. The knowledge of protein-surfactant interactions obtained from these studies provides significant insights for novel detection and quantification techniques in microfluidics. © 2013 The Protein Society.

Computer simulations of dendrimer-polyelectrolyte complexes.

PubMed

Pandav, Gunja; Ganesan, Venkat

2014-08-28

We carry out a systematic analysis of static properties of the clusters formed by complexation between charged dendrimers and linear polyelectrolyte (LPE) chains in a dilute solution under good solvent conditions. We use single chain in mean-field simulations and analyze the structure of the clusters through radial distribution functions of the dendrimer, cluster size, and charge distributions. The effects of LPE length, charge ratio between LPE and dendrimer, the influence of salt concentration, and the dendrimer generation number are examined. Systems with short LPEs showed a reduced propensity for aggregation with dendrimers, leading to formation of smaller clusters. In contrast, larger dendrimers and longer LPEs lead to larger clusters with significant bridging. Increasing salt concentration was seen to reduce aggregation between dendrimers as a result of screening of electrostatic interactions. Generally, maximum complexation was observed in systems with an equal amount of net dendrimer and LPE charges, whereas either excess LPE or dendrimer concentrations resulted in reduced clustering between dendrimers.

Diagnostic Evaluation of Des-Gamma-Carboxy Prothrombin versus α-Fetoprotein for Hepatitis B Virus-Related Hepatocellular Carcinoma in China: A Large-Scale, Multicentre Study

PubMed Central

Zheng, Lei; Yin, Yuepeng; Zou, Zhenzhen; Zhou, Feiguo; Zhou, Weiping; Shen, Feng; Gao, Chunfang

2016-01-01

An efficient serum marker for hepatocellular carcinoma (HCC) is currently lacking and requires intensive exploration. We aimed to evaluate the performance of des-gamma-carboxy prothrombin (DCP) for identifying hepatitis B virus-related HCC in a large, multicentre study in China. A total of 1034 subjects in three cohorts (A, B, and C) including HCC and various non-HCC controls were enrolled from 4 academic medical centers in China from January 2011 to February 2014. Blind parallel detections were conducted for DCP and AFP. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic efficacies. In cohort A, which comprised 521 subjects, including patients with HCC, liver metastasis, liver cirrhosis (LC), and liver hemangiomas as well as healthy controls (HCs), the accuracy of DCP for distinguishing HCC from various controls was 6.2–9.7% higher than that of AFP. In cohort B, which comprised 447 subjects, including patients with HCC, LC, and chronic hepatitis B as well as HC, the accuracy of DCP was further elevated (12.3–20.67% higher than that of AFP). The superiority of DCP to AFP was more profound in the surveillance of early HCC [AUC 0.837 (95% CI: 0.771–0.903) vs. 0.650 (0.555–0.745)] and AFP-negative HCC [AUC: 0.856 (0.798–0.914)] and in discriminating HCC from LC (accuracy: 92.9% vs.64.71%). Higher DCP levels were associated with worse clinical behaviors and shorter disease-free survival. DCP not only is complementary to AFP in identifying AFP-negative HCC and in excluding AFP-positive non-HCC (liver cirrhosis), but also demonstrates improved performance in HCC surveillance, early diagnosis, treatment response and recurrence monitoring in the HBV-related population. PMID:27070780

Using nitrogen concentration and isotopic composition in lichens to spatially assess the relative contribution of atmospheric nitrogen sources in complex landscapes.

PubMed

Pinho, P; Barros, C; Augusto, S; Pereira, M J; Máguas, C; Branquinho, C

2017-11-01

Reactive nitrogen (Nr) is an important driver of global change, causing alterations in ecosystem biodiversity and functionality. Environmental assessments require monitoring the emission and deposition of both the amount and types of Nr. This is especially important in heterogeneous landscapes, as different land-cover types emit particular forms of Nr to the atmosphere, which can impact ecosystems distinctively. Such assessments require high spatial resolution maps that also integrate temporal variations, and can only be feasibly achieved by using ecological indicators. Our aim was to rank land-cover types according to the amount and form of emitted atmospheric Nr in a complex landscape with multiple sources of N. To do so, we measured and mapped nitrogen concentration and isotopic composition in lichen thalli, which we then related to land-cover data. Results suggested that, at the landscape scale, intensive agriculture and urban areas were the most important sources of Nr to the atmosphere. Additionally, the ocean greatly influences Nr in land, by providing air with low Nr concentration and a unique isotopic composition. These results have important consequences for managing air pollution at the regional level, as they provide critical information for modeling Nr emission and deposition across regional as well as continental scales. Copyright © 2017 Elsevier Ltd. All rights reserved.

A network property necessary for concentration robustness

PubMed Central

Eloundou-Mbebi, Jeanne M. O.; Küken, Anika; Omranian, Nooshin; Kleessen, Sabrina; Neigenfind, Jost; Basler, Georg; Nikoloski, Zoran

2016-01-01

Maintenance of functionality of complex cellular networks and entire organisms exposed to environmental perturbations often depends on concentration robustness of the underlying components. Yet, the reasons and consequences of concentration robustness in large-scale cellular networks remain largely unknown. Here, we derive a necessary condition for concentration robustness based only on the structure of networks endowed with mass action kinetics. The structural condition can be used to design targeted experiments to study concentration robustness. We show that metabolites satisfying the necessary condition are present in metabolic networks from diverse species, suggesting prevalence of this property across kingdoms of life. We also demonstrate that our predictions about concentration robustness of energy-related metabolites are in line with experimental evidence from Escherichia coli. The necessary condition is applicable to mass action biological systems of arbitrary size, and will enable understanding the implications of concentration robustness in genetic engineering strategies and medical applications. PMID:27759015

Delivery of fullerene-containing complexes via microgel swelling and shear-induced release.

PubMed

Tarabukina, Elena; Zoolshoev, Zoolsho; Melenevskaya, Elena; Budtova, Tatiana

2010-01-15

The absorption and release of poly(vinylpyrrolidone)-fullerene C60 complexes (PVP/C60) from a model microgel is studied. A dry microgel based on a chemically cross-linked sodium polyacrylate was swollen in the aqueous solutions of complexes which were afterwards released under shear stress. First, gel swelling degree in static conditions in the excess of PVP/C60 solutions was studied: the degree of swelling decreases with the increase in PVP/C60 concentration. While pure PVP is homogeneously distributed between the gel and the surrounding solution, a slight concentration of complexes outside the gel was recorded. It was attributed to PVP/C60 hydrophobicity leading to the decrease in the thermodynamic quality of fullerene-containing solution being gel solvent. The release of PVP/C60 solutions induced by shear was studied with counter-rotating rheo-optical technique and compared with PVP solution release under the same conditions. The amount of solution released depends on polymer concentration and shear strain. Contrary to pure PVP solutions in which rate of release decreases with the increase in polymer concentration, PVP/C60 complexes are released faster when fullerene concentration inside the gel is higher.

Evidence supporting oral sensitivity to complex carbohydrates independent of sweet taste sensitivity in humans.

PubMed

Low, Julia Y Q; Lacy, Kathleen E; McBride, Robert L; Keast, Russell S J

2017-01-01

Compared to simple sugars, complex carbohydrates have been assumed invisible to taste. However, two recent studies proposed that there may be a perceivable taste quality elicited by complex carbohydrates independent of sweet taste. There is precedent with behavioural studies demonstrating that rats are very attracted to complex carbohydrates, and that complex carbohydrates are preferred to simple sugars at low concentrations. This suggests that rats may have independent taste sensors for simple sugars and complex carbohydrates. The aim of this paper is to investigate oral sensitivities of two different classes of complex carbohydrates (a soluble digestible and a soluble non-digestible complex carbohydrate), and to compare these to other caloric and non-nutritive sweeteners in addition to the prototypical tastes using two commonly used psychophysical measures. There were strong correlations between the detection thresholds and mean intensity ratings for complex carbohydrates (maltodextrin, oligofructose) (r = 0.94, P < 0.001). There were no significant correlations between the detection thresholds of the complex carbohydrates (maltodextrin, oligofructose) and the sweeteners (glucose, fructose, sucralose, Rebaudioside A, erythritol) (all P > 0.05). However, moderate correlations were observed between perceived intensities of complex carbohydrates and sweeteners (r = 0.48-0.61, P < 0.05). These data provide evidence that complex carbohydrates can be sensed in the oral cavity over a range of concentrations independent of sweet taste sensitivity at low concentrations, but with partial overlap with sweet taste intensity at higher concentrations.

Evidence supporting oral sensitivity to complex carbohydrates independent of sweet taste sensitivity in humans

PubMed Central

Lacy, Kathleen E.; Keast, Russell S. J.

2017-01-01

Compared to simple sugars, complex carbohydrates have been assumed invisible to taste. However, two recent studies proposed that there may be a perceivable taste quality elicited by complex carbohydrates independent of sweet taste. There is precedent with behavioural studies demonstrating that rats are very attracted to complex carbohydrates, and that complex carbohydrates are preferred to simple sugars at low concentrations. This suggests that rats may have independent taste sensors for simple sugars and complex carbohydrates. The aim of this paper is to investigate oral sensitivities of two different classes of complex carbohydrates (a soluble digestible and a soluble non-digestible complex carbohydrate), and to compare these to other caloric and non-nutritive sweeteners in addition to the prototypical tastes using two commonly used psychophysical measures. There were strong correlations between the detection thresholds and mean intensity ratings for complex carbohydrates (maltodextrin, oligofructose) (r = 0.94, P < 0.001). There were no significant correlations between the detection thresholds of the complex carbohydrates (maltodextrin, oligofructose) and the sweeteners (glucose, fructose, sucralose, Rebaudioside A, erythritol) (all P > 0.05). However, moderate correlations were observed between perceived intensities of complex carbohydrates and sweeteners (r = 0.48–0.61, P < 0.05). These data provide evidence that complex carbohydrates can be sensed in the oral cavity over a range of concentrations independent of sweet taste sensitivity at low concentrations, but with partial overlap with sweet taste intensity at higher concentrations. PMID:29281655

1. West facade of Plutonium Concentration Facility (Building 233S), ReductionOxidation ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

1. West facade of Plutonium Concentration Facility (Building 233-S), Reduction-Oxidation Building (REDOX-202-S) to the right. Looking east. - Reduction-Oxidation Complex, Plutonium Concentration Facility, 200 West Area, Richland, Benton County, WA

The dome-shaped Fresnel-Köhler concentrator

NASA Astrophysics Data System (ADS)

Zamora, P.; Benitez, P.; Li, Y.; Miñano, J. C.; Mendes-Lopes, J.; Araki, K.

2012-10-01

Manufacturing tolerances, along with a high concentration ratio, are key issues in order to obtain cheap CPV systems for mass production. Consequently, this manuscript presents a novel tolerant and cost effective concentrator optic: the domed-shaped Fresnel-Köhler, presenting a curved Fresnel lens as Primary Optical Element (POE). This concentrator is based on two previous successful CPV designs: the FK concentrator, based on a flat Fresnel lens, and the dome-shaped Fresnel lens system developed by Daido Steel, resulting on a superior concentrator. The manuscript shows outstanding simulation results for geometrical concentration factor of Cg = 1,230x: high tolerance and high optical efficiency, achieving acceptance angles of 1.18° (dealing to a CAP*=0.72) and efficiencies over 85% (without any anti-reflective coating). Moreover, Köhler integration provides good irradiance uniformity on the cell surface without increasing system complexity by means of any extra element. Daido Steel advanced technique for demolding injected plastic pieces will allow for easy manufacture of the dome-shaped POE of DFK concentrator.

Active control of complex, multicomponent self-assembly processes

NASA Astrophysics Data System (ADS)

Schulman, Rebecca

The kinetics of many complex biological self-assembly processes such as cytoskeletal assembly are precisely controlled by cells. Spatiotemporal control over rates of filament nucleation, growth and disassembly determine how self-assembly occurs and how the assembled form changes over time. These reaction rates can be manipulated by changing the concentrations of the components needed for assembly by activating or deactivating them. I will describe how we can use these principles to design driven self-assembly processes in which we assemble and disassemble multiple types of components to create micron-scale networks of semiflexible filaments assembled from DNA. The same set of primitive components can be assembled into many different, structures depending on the concentrations of different components and how designed, DNA-based chemical reaction networks manipulate these concentrations over time. These chemical reaction networks can in turn interpret environmental stimuli to direct complex, multistage response. Such a system is a laboratory for understanding complex active material behaviors, such as metamorphosis, self-healing or adaptation to the environment that are ubiquitous in biological systems but difficult to quantitatively characterize or engineer.

Study of five cell salvage machines in coronary artery surgery.

PubMed

Burman, J F; Westlake, A S; Davidson, S J; Rutherford, L C; Rayner, A S; Wright, A M; Morgan, C J; Pepper, J R

2002-06-01

We evaluated the effectiveness, ease of use and safety of five machines for blood salvage during coronary artery surgery. All were equally effective in concentrating red cells. We measured haemoglobin, packed cell volume, free haemoglobin, white cells, neutrophil elastase, platelets, thrombin-antithrombin complex (TAT), prothrombin activation peptide F1.2, fibrin degradation product (d-dimers), tissue plasminogen activator (tPA) and heparin in wound blood, in washed cell suspensions and in a unit of bank blood prepared for each patient. All machines were equally safe and easy to use and were equally effective in removing heparin and the physiological components measured. There were no adverse effects on patients. Clotting factors are severely depleted both in salvaged blood, even before washing, and in bank blood. Cell savers are a valuable adjunct to coronary artery surgery, but careful monitoring of coagulation is required when the volumes of either bank blood or salvaged blood are large.

Myelofibrosis and acquired hemophilia A: a case report.

PubMed

Wrobel, Marie; Comio, Emilie; Gay, Valerie; Baroudi, Noureddine; Meyer, Pascal; Chuniaud-Louche, Christine; Hacini, Maya; Pica, Gian Matteo

2016-05-07

Myelofibrosis and acquired hemophilia A is a rare association. To the best of our knowledge only one case of myelofibrosis and acquired hemophilia A has been previously described. A 66-year-old Caucasian man diagnosed with myelofibrosis evolving in acute myeloid leukemia was referred to us for postoperative bleeding. Hemostatic studies showed prolonged activated partial thromboplastin time, decreased factor VIII coagulation, and a high factor VIII inhibitor titer; these findings led to a diagnosis of acquired hemophilia A for which he was treated with methylprednisolone and recombinant activated factor VII on admission. Due to a lack of response he was subsequently treated with rituximab combined with activated prothrombin complex concentrates. Furthermore, he received azacytidine to treat the underlying hematological malignancies. Immunosuppressive rituximab therapy resolved acquired hemophilia A with marked efficacy. Rapid and accurate diagnosis, effective hemostatic therapy, and timely treatment for underlying disease are important in the management of acquired hemophilia A secondary to hematological malignancy.

The crystallogenesis of a human estradiol dehydrogenase-substrate complex

NASA Astrophysics Data System (ADS)

Zhu, Dao-Wei; Azzi, Arezki; Rehse, Peter; Lin, Sheng-Xiang

1996-10-01

Human 17β-hydroxysteroid dehydrogenase type 1 is an important steroidogenic enzyme catalyzing the synthesis of the most active estrogen: estradiol. The enzyme is formed by two identical subunits (34.5 kDa). In this paper, we report the preparation of a stoichiometric 17β-HSD1-estradiol complex sample at a much higher concentration than the solubility of the free substrate, using a gradual concentration of the enzyme-substrate mixture starting at low concentration. The complex is successfully crystallized by vapor diffusion at pH 7.5 with polyethyleneglycol 4000 as the precipitating agent. The space group is C2 with a = 123.56 Å, b = 45.21 Å, c = 61.30 Å and β = 99.06°. There is one monomer in the asymmetric unit and two molecules of the enzyme in a unit cell. A diffraction data set to 2.5 Å has been collected to 86% completeness on native crystals. The high quality of the electronic density map of estradiol supports the full occupancy of the binding site, thus confirming the efficiency of the complex preparation. This method will also be useful in crystallizing other steroid-dehydrogenase complexes.

Rheology of polyelectrolyte complex materials

NASA Astrophysics Data System (ADS)

Tirrell, Matthew

Fluid polyelectrolyte complexes, sometimes known as complex coacervates, have rheological properties that are very sensitive to structure and salt concentration. Dynamic moduli of such viscoelastic materials very many orders of magnitude between solutions of no added salt to of order tenth molar salt, typical, for example of physiological saline. Indeed, salt plays a role in the rheology of complex coacervates analogous to that which temperature plays on polymer melts, leading to an empirical observation of what may be termed time-salt or frequency salt superposition. Block copolymers containing complexing ionic blocks also exhibit strong salt sensitivity of their rheological properties. Data representing these phenomena will be presented and discussed. Support from NIST, Department of Commerce, via the Center for Hierarchical Materials Design at Northwestern University and the University of Chicago is gratefully acknowledged.

Prognostic roles of preoperative α-fetoprotein and des-γ-carboxy prothrombin in hepatocellular carcinoma patients

PubMed Central

Meguro, Makoto; Mizuguchi, Toru; Nishidate, Toshihiko; Okita, Kenji; Ishii, Masayuki; Ota, Shigenori; Ueki, Tomomi; Akizuki, Emi; Hirata, Koichi

2015-01-01

AIM: To clarify the utility of using des-γ-carboxy prothrombin (DCP) and α-fetoprotein (AFP) levels to predict the prognosis of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV) and the hepatitis C virus (HCV) infections. METHODS: A total of 205 patients with HCC (105 patients with HBV infection 100 patients with HCV infection) who underwent primary hepatectomy between January 2004 and May 2012 were enrolled retrospectively. Preoperative AFP and DCP levels were used to create interactive dot diagrams to predict recurrence within 2 years after hepatectomy, and cutoff levels were calculated. Patients in the HBV and HCV groups were classified into three groups: a group with low AFP and DCP levels (LL group), a group in which one of the two parameters was high and the other was low (HL group), and a group with high AFP and DCP levels (HH group). Liver function parameters, the postoperative recurrence-free survival rate, and postoperative overall survival were compared between groups. The survival curves were compared by log-rank test using the Kaplan-Meier method. Multivariate analysis using a Cox forward stepwise logistic regression model was conducted for a prognosis. RESULTS: The preoperative AFP cutoff levels for recurrence within 2 years after hepatectomy in the HBV and HCV groups were 529.8 ng/mL and 60 mAU/mL, respectively; for preoperative DCP levels, the cutoff levels were 21.0 ng/mL in the HBV group and 67 mAU/mL in the HCV group. The HBV group was significantly different from the other groups in terms of vascular invasion, major hepatectomy, volume of intraoperative blood loss, and surgical duration. Significant differences were found between the LL group, the HL group, and the HH group in terms of both mean disease-free survival time (MDFST) and mean overall survival time (MOST): 64.81 ± 7.47 vs 36.63 ± 7.62 vs 18.98 ± 6.17 mo (P = 0.001) and 85.30 ± 6.55 vs 59.44 ± 7.87 vs 46.57 ± 11.20 mo (P = 0.018). In contrast, the HCV

Concentrator hot-spot testing, phase 1

NASA Technical Reports Server (NTRS)

Gonzalez, C. C.

1987-01-01

Results of a study to determine the hot-spot susceptibility of concentrator cells, to provide a hot-spot qualification test for concentrator modules, and to provide guidelines for reducing hot-spot susceptibility are presented. Hot-spot heating occurs in a photovoltaic module when the short-circuit current of a cell is lower than the string operating current forcing the cell into reverse bias with a concurrent power dissipation. Although the basis for the concentrator module hot-spot qualification test is the test developed for flat-plate modules, issues, such as providing cell illumination, introduce additional complexities into the testing procedure. The same general guidelines apply for protecting concentrator modules from hot-spot stressing as apply to flat-plate modules. Therefore, recommendations are made on the number of bypass diodes required per given number of series cells per module or source circuit. In addition, a new method for determining the cell temperature in the laboratory or in the field is discussed.

Influence of an americium solid phase on americium concentrations in solutions

NASA Astrophysics Data System (ADS)

Rai, Dhanpat; Strickert, R. G.; Moore, D. A.; Serne, R. J.

1981-11-01

Americium-241 concentrations in solutions contacting contaminated sediments for up to 2 yr were measured as a function of pH. Steady-state concentrations were reached within a few days. The solubility-limited Am concentration was found to decrease approximately 10-fold with one unit increase in pH. The log equilibrium constant for the solubility of Am (soil) solid [Am (soil) + H + ⇌ Am (aq complex)+] was found to be -4.12. The predictions based upon thermodynamic data suggest that Am (aq complex)+ is likely to be Am(OH) 2+. Although the chemical formula of Am (soil) was not determined, it does not appear to be Am(OH) 3(a). Published data on sorption coefficients of Am by different rocks, soils, and minerals were critically evaluated. Final Am solution concentrations calculated from the sorption coefficients of a variety of earth materials with several solutions agreed well with the concentrations predicted from the solubility of Am (soil) solid, indicating that the sorption coefficient data are controlled by Am precipitation.

Anti-Leishmania activity of new ruthenium(II) complexes: Effect on parasite-host interaction.

PubMed

Costa, Mônica S; Gonçalves, Yasmim G; Nunes, Débora C O; Napolitano, Danielle R; Maia, Pedro I S; Rodrigues, Renata S; Rodrigues, Veridiana M; Von Poelhsitz, Gustavo; Yoneyama, Kelly A G

2017-10-01

Leishmaniasis is a parasitic disease caused by protozoa of the genus Leishmania. The many complications presented by the current treatment - including high toxicity, high cost and parasite resistance - make the development of new therapeutic agents indispensable. The present study aims to evaluate the anti-Leishmania potential of new ruthenium(II) complexes, cis‑[Ru II (η 2 -O 2 CR)(dppm) 2 ]PF 6 , with dppm=bis(diphenylphosphino)methane and R=4-butylbenzoate (bbato) 1, 4-(methylthio)benzoate (mtbato) 2 and 3-hydroxy-4-methoxybenzoate (hmxbato) 3, in promastigote cytotoxicity and their effect on parasite-host interaction. The cytotoxicity of complexes was analyzed by MTT assay against Leishmania (Leishmania) amazonensis, Leishmania (Viannia) braziliensis, Leishmania (Leishmania) infantum promastigotes and the murine macrophage (RAW 264.7). The effect of complexes on parasite-host interaction was evaluated by in vitro infectivity assay performed in the presence of two different concentrations of each complex: the promastigote IC 50 value and the concentration nontoxic to 90% of RAW 264.7 macrophages. Complexes 1-3 exhibited potent cytotoxic activity against all Leishmania species assayed. The IC 50 values ranged from 7.52-12.59μM (complex 1); 0.70-3.28μM (complex 2) and 0.52-1.75μM (complex 3). All complexes significantly inhibited the infectivity index at both tested concentrations. The infectivity inhibitions ranged from 37 to 85%. Interestingly, the infectivity inhibitions due to complex action did not differ significantly at either of the tested concentrations, except for the complex 1 against Leishmania (Leishmania) infantum. The infectivity inhibitions resulted from reductions in both percentage of infected macrophages and number of parasites per macrophage. Taken together the results suggest remarkable leishmanicidal activity in vitro by these new ruthenium(II) complexes. Copyright © 2017 Elsevier Inc. All rights reserved.

Soil mercury levels in the area surrounding the Cerro Prieto geothermal complex, MEXICO.

PubMed

Pastrana-Corral, M A; Wakida, F T; García-Flores, E; Rodriguez-Mendivil, D D; Quiñonez-Plaza, A; Piñon-Colin, T D J

2016-08-01

Even though geothermal energy is a renewable energy source that is seen as cost-effective and environmentally friendly, emissions from geothermal plants can impact air, soil, and water in the vicinity of geothermal power plants. The Cerro Prieto geothermal complex is located 30 km southeast of the city of Mexicali in the Mexican state of Baja California. Its installed electricity generation capacity is 720 MW, being the largest geothermal complex in Mexico. The objective of this study was to evaluate whether the emissions generated by the geothermal complex have increased the soil mercury concentration in the surrounding areas. Fifty-four surface soil samples were collected from the perimeter up to an approximate distance of 7660 m from the complex. Additionally, four soil depth profiles were performed in the vicinity of the complex. Mercury concentration in 69 % of the samples was higher than the mercury concentration found at the baseline sites. The mercury concentration ranged from 0.01 to 0.26 mg/kg. Our results show that the activities of the geothermal complex have led to an accumulation of mercury in the soil of the surrounding area. More studies are needed to determine the risk to human health and the ecosystems in the study area.

Freezing-Out Technique Applied to the Concentration of Biologically Active Materials

PubMed Central

Wilson, T. E.; Evans, D. J.; Theriot, Mary L.

1964-01-01

When applied to a dilute solution of folic acid and glucose, a freezing-out (with agitation) technique was shown to be an effective method of achieving a 20-fold reduction in volume with a loss of 10% of the active material being concentrated. Concentration of a stimulatory factor for Lactobacillus casei produced by Candida albicans in a complex medium was limited by the total solute concentration. Salts in the medium were concentrated to levels inhibitory for L. casei. The process is not selective and all solutes are concentrated. Images FIG. 2 FIG. 3 PMID:14131370

Sorption behavior of the Pt(II) complex anion on manganese dioxide (δ-MnO2): a model reaction to elucidate the mechanism by which Pt is concentrated into a marine ferromanganese crust

NASA Astrophysics Data System (ADS)

Maeno, Mamiko Yamashita; Ohashi, Hironori; Yonezu, Kotaro; Miyazaki, Akane; Okaue, Yoshihiro; Watanabe, Koichiro; Ishida, Tamao; Tokunaga, Makoto; Yokoyama, Takushi

2016-02-01

It is difficult to directly investigate the chemical state of Pt in marine ferromanganese crusts (a mixture of hydrous iron(III) oxide and manganese dioxide (δ-MnO2)) because it is present at extremely low concentration levels. This paper attempts to elucidate the mechanism by which Pt is concentrated into marine ferromanganese crust from the Earth's continental crust through ocean water. In this investigation, the sorption behavior of the Pt(II) complex ions on the surface of the δ-MnO2 that is a host of Pt was examined as a model reaction. The δ-MnO2 sorbing Pt was characterized by X-ray photoelectron spectroscopy (XPS) and X-ray absorption fine structure (XAFS) to determine the chemical state of the Pt. Hydrolytic Pt(II) complex ions were specifically sorbed above pH 6 by the formation of a Mn-O-Pt bond. XPS spectra and XANES spectra for δ-MnO2 sorbing Pt showed that the sorbed Pt(II) was oxidized to Pt(IV) on δ-MnO2. The extended X-ray absorption fine structure (EXAFS) analysis showed that the coordination structure of Pt sorbed on δ-MnO2 is almost the same as that of the [Pt(OH)6]2- complex ion used as a standard. Therefore, the mechanism for the concentration of Pt in marine ferromanganese crust may be an oxidative substitution (penetration of Pt(IV) into structure of δ-MnO2) by a reduction-oxidation reaction between Pt(II) in [PtCl4-n(OH)n]2- and Mn(IV) in δ-MnO2 through a Mn-O-Pt bond.

Metal-organic complexes in geochemical processes: temperature dependence of the standard thermodynamic properties of aqueous complexes between metal cations and dicarboxylate ligands

NASA Astrophysics Data System (ADS)

Prapaipong, Panjai; Shock, Everett L.; Koretsky, Carla M.

1999-10-01

By combining results from regression and correlation methods, standard state thermodynamic properties for aqueous complexes between metal cations and divalent organic acid ligands (oxalate, malonate, succinate, glutarate, and adipate) are evaluated and applied to geochemical processes. Regression of experimental standard-state equilibrium constants with the revised Helgeson-Kirkham-Flowers (HKF) equation of state yields standard partial molal entropies (S¯°) of aqueous metal-organic complexes, which allow determination of thermodynamic properties of the complexes at elevated temperatures. In cases where S¯° is not available from either regression or calorimetric measurement, the values of S¯° can be estimated from a linear correlation between standard partial molal entropies of association (ΔS¯°r) and standard partial molal entropies of aqueous cations (S¯°M). The correlation is independent of cation charge, which makes it possible to predict S¯° for complexes between divalent organic acids and numerous metal cations. Similarly, correlations between standard Gibbs free energies of association of metal-organic complexes (ΔḠ°r) and Gibbs free energies of formation (ΔḠ°f) for divalent metal cations allow estimates of standard-state equilibrium constants where experimental data are not available. These correlations are found to be a function of ligand structure and cation charge. Predicted equilibrium constants for dicarboxylate complexes of numerous cations were included with those for inorganic and other organic complexes to study the effects of dicarboxylate complexes on the speciation of metals and organic acids in oil-field brines. Relatively low concentrations of oxalic and malonic acids affect the speciation of cations more than similar concentrations of succinic, glutaric, and adipic acids. However, the extent to which metal-dicarboxylate complexes contribute to the speciation of dissolved metals depends on the type of dicarboxylic acid

Predictors of Serum Chlorinated Pesticide Concentrations among Prepubertal Russian Boys

PubMed Central

Williams, Paige L.; Burns, Jane S.; Sergeyev, Oleg; Korrick, Susan A.; Lee, Mary M.; Birnbaum, Linda S.; Revich, Boris; Altshul, Larisa M.; Patterson, Donald G.; Turner, Wayman E.; Hauser, Russ

2013-01-01

Background: Few studies have evaluated predictors of childhood exposure to organochlorine pesticides (OCPs), a class of lipophilic persistent chemicals. Objectives: Our goal was to identify predictors of serum OCP concentrations—hexachlorobenzene (HCB), β-hexachlorocyclohexane (β-HCH), and p,p-dichlorodiphenyldichloroethylene (p,p´-DDE)—among boys in Chapaevsk, Russia. Methods: Between 2003 and 2005, 499 boys 8–9 years of age were recruited in a prospective cohort. The initial study visit included a physical examination; blood collection; health, lifestyle, and food-frequency questionnaires; and determination of residential distance from a local factory complex that produced HCB and β-HCH. Fasting serum samples were analyzed for OCPs at the U.S. Centers for Disease Control and Prevention. General linear regression models were used to identify predictors of the boys’ serum HCB, β-HCH, and p,p´-DDE concentrations. Results: Among 355 boys with OCP measurements, median serum HCB, β-HCH, and p,p´-DDE concentrations were 158, 167, and 284 ng/g lipid, respectively. Lower body mass index, longer breastfeeding duration, and local dairy consumption were associated with higher concentrations of OCPs. Boys who lived < 2 km from the factory complex had 64% (95% CI: 37, 96) and 57% (95% CI: 32, 87) higher mean HCB and β-HCH concentrations, respectively, than boys who lived ≥ 5 km away. Living > 3 years in Chapaevsk predicted higher β-HCH concentrations, and having parents who lacked a high school education predicted higher p,p´-DDE concentrations. Conclusions: Among this cohort of prepubertal Russian boys, predictors of serum OCPs included consumption of local dairy products, longer local residence, and residential proximity to the local factory complex. Citation: Lam T, Williams PL, Burns JS, Sergeyev O, Korrick SA, Lee MM, Birnbaum LS, Revich B, Altshul LM, Patterson DG Jr, Turner WE, Hauser R. 2013. Predictors of serum chlorinated pesticide concentrations

Complex analysis of concentrated antibody-gold nanoparticle conjugates' mixtures using asymmetric flow field-flow fractionation.

PubMed

Safenkova, Irina V; Slutskaya, Elvira S; Panferov, Vasily G; Zherdev, Anatoly V; Dzantiev, Boris B

2016-12-16

Conjugates of gold nanoparticles (GNPs) with antibodies are powerful analytical tools. It is crucial to know the conjugates' state in both the concentrated and mixed solutions used in analytical systems. Herein, we have applied asymmetrical flow field-flow fractionation (AF4) to identify the conjugates' state. The influence of a conjugate's composition and concentration on aggregation was studied in a true analytical solution (a concentrated mixture with stabilizing components). GNPs with an average diameter of 15.3±1.2nm were conjugated by adsorption with eight antibodies of different specificities. We found that, while the GNPs have a zeta potential of -31.6mV, the conjugates have zeta potentials ranging from -5.8 to -11.2mV. Increased concentrations (up to 184nM, OD 520 =80) of the mixed conjugate (mixture of eight conjugates) did not change the form of fractograms, and the peak areas' dependence on concentration was strongly linear (R 2 values of 0.99919 and 0.99845 for absorption signal and light scattering, respectively). Based on the gyration (R g ) and hydrodynamic (R h ) radii measured during fractionation, we found that the nanoparticles were divided into two populations: (1) those with constant radii (R g =9.9±0.9nm; R h =14.3±0.5nm); and (2) those with increased radii from 9.9 to 24.4nm for R g and from 14.3 to 28.1nm for R h . These results confirm that the aggregate state of the concentrated and mixed conjugates' preparations is the same as that of diluted preparations and that AF4 efficiently characterizes the conjugates' state in a true analytical solution. Copyright © 2016 Elsevier B.V. All rights reserved.

Gold nanoparticles as a factor of influence on doxorubicin-bovine serum albumin complex

NASA Astrophysics Data System (ADS)

Goncharenko, N. A.; Pavlenko, O. L.; Dmytrenko, O. P.; Kulish, M. P.; Lopatynskyi, A. M.; Chegel, V. I.

2018-04-01

The interaction between doxorubicin (Dox) and bovine serum albumin (BSA) complex with gold nanoparticles (AuNPs) was investigated by optical spectroscopy. The optical absorption of Dox and BSA solutions was studied. The formation of Dox-BSA complexes with a binding constant K = 7.56 × 106 M-2 and the number of binding sites n = 2 was found out. With pH 6.9, the concentration of complexes is an order of magnitude lower than the concentration of unbound antibiotic molecules. Optical absorption in solutions of Dox-BSA conjugates in the presence of AuNPs undergoes a significant rearrangement, which manifests the changes in the magnitude of the hydrophobic interaction of BSA with Dox, changes in the conformational state of antibiotic, and, as a consequence, a plasmon-induced change in the mechanism of complex formation. The aggregation of the Dox-AuNPs conjugate depends on the presence and concentration of BSA and in the case of formation of the Dox-BSA complex is minimal.

Mechanism of host-guest complexation by cucurbituril.

PubMed

Márquez, César; Hudgins, Robert R; Nau, Werner M

2004-05-12

The factors affecting host-guest complexation between the molecular container compound cucurbit[6]uril (CB6) and various guests in aqueous solution are studied, and a detailed complexation mechanism in the presence of cations is derived. The formation of the supramolecular complex is studied in detail for cyclohexylmethylammonium ion as guest. The kinetics and thermodynamics of complexation is monitored by NMR as a function of temperature, salt concentration, and cation size. The binding constants and the ingression rate constants decrease with increasing salt concentration and cation-binding constant, in agreement with a competitive binding of the ammonium site of the guest and the metal cation with the ureido carbonyl portals of CB6. Studies as a function of guest size indicate that the effective container volume of the CB6 cavity is approximately 105 A(3). It is suggested that larger guests are excluded for two reasons: a high activation barrier for ingression imposed by the tight CB6 portals and a destabilization of the complex due to steric repulsion inside. For example, in the case of the nearly spherical azoalkane homologues 2,3-diazabicyclo[2.2.1]hept-2-ene (DBH, volume ca. 96 A(3)) and 2,3-diazabicyclo[2.2.2]oct-2-ene (DBO, volume ca. 110 A(3)), the former forms the CB6 complex promptly with a sizable binding constant (1300 M(-1)), while the latter does not form a complex even after several months at optimized complexation conditions. Molecular mechanics calculations are performed for several CB6/guest complexes. A qualitative agreement is found between experimental and calculated activation energies for ingression as a function of both guest size and state of protonation. The potential role of constrictive binding by CB6 is discussed.

Age-related changes in factor VII proteolysis in vivo.

PubMed

Ofosu, F A; Craven, S; Dewar, L; Anvari, N; Andrew, M; Blajchman, M A

1996-08-01

Previous studies have reported that pre-operative plasmas of patients over the age of 40 years who developed post-operative deep vein thrombosis (DVT) had approximately twice the amount of proteolysed factor VII found in plasmas of patients in whom prophylaxis with heparin or low M(r) heparin was successful. These and other studies also reported higher concentrations of thrombin-antithrombin III in pre- and post-operative plasmas of patients who developed post-operative thrombosis than in plasmas of patients in whom prophylaxis was successful. Whether the extent of factor VII proteolysis seen in the patients who developed post-operative DVT is related to the severity of their disease or age is not known. This report investigated age-related changes in the concentrations of total factor VII protein, factor VII zymogen, factor VIIa, tissue factor pathway inhibitor, thrombin-antithrombin III, and prothrombin fragment 1 + 2 in normal plasmas and the relationships between these parameters. With the exception of thrombin-antithrombin III, statistically significant increases in the concentrations of these parameters with age were found. Additionally, the differences between the concentrations of total factor VII protein and factor VII zymogen, an index factor VII proteolysis in vivo, were statistically significant only for individuals over age 40. Using linear regression analysis, a significant correlation was found to exist between the concentrations of plasma factor VIIa and prothrombin fragment 1 + 2. Since factor VIIa-tissue factor probably initiates coagulation in vivo, we hypothesize that the elevated plasma factor VIIa (reflecting a less tightly regulated tissue factor activity and therefore increased thrombin production in vivo) accounts for the high risk for post-operative thrombosis seen in individuals over the age of 40.

Metal complexes of diisopropylthiourea: synthesis, characterization and antibacterial studies.

PubMed

Ajibade, Peter A; Zulu, Nonkululeko H

2011-01-01

Co(II), Cu(II), Zn(II) and Fe(III) complexes of diisopropylthiourea have been synthesized and characterized by elemental analyses, molar conductivity, magnetic susceptibility, FTIR and electronic spectroscopy. The compounds are non-electrolytes in solution and spectroscopic data of the complexes are consistent with 4-coordinate geometry for the metal(II) complexes and six coordinate octahedral for Fe(III) complex. The complexes were screened for their antibacterial activities against six bacteria: Escherichia coli, Pseudomonas auriginosa, Klebsiella pneumoniae, Bacillus cereus, Staphylococcus aureus and Bacillus pumilus. The complexes showed varied antibacterial activities and their minimum inhibitory concentrations (MICs) were determined.

A concentration-independent micro/nanofluidic active diode using an asymmetric ion concentration polarization layer.

PubMed

Lee, Hyekyung; Kim, Junsuk; Kim, Hyeonsoo; Kim, Ho-Young; Lee, Hyomin; Kim, Sung Jae

2017-08-24

Over the past decade, nanofluidic diodes that rectify ionic currents (i.e. greater current in one direction than in the opposite direction) have drawn significant attention in biomolecular sensing, switching and energy harvesting devices. To obtain current rectification, conventional nanofluidic diodes have utilized complex nanoscale asymmetry such as nanochannel geometry, surface charge density, and reservoir concentration. Avoiding the use of sophisticated nano-asymmetry, micro/nanofluidic diodes using microscale asymmetry have been recently introduced; however, their diodic performance is still impeded by (i) low (even absent) rectification effects at physiological concentrations over 100 mM and strong dependency on the bulk concentration, and (ii) the fact that they possess only passive predefined rectification factors. Here, we demonstrated a new class of micro/nanofluidic diode with an ideal perm-selective nanoporous membrane based on ion concentration polarization (ICP) phenomenon. Thin side-microchannels installed near a nanojunction served as mitigators of the amplified electrokinetic flows generated by ICP and induced convective salt transfer to the nanoporous membrane, leading to actively controlled micro-scale asymmetry. Using this device, current rectifications were successfully demonstrated in a wide range of electrolytic concentrations (10 -5 M to 3 M) as a function of the fluidic resistance of the side-microchannels. Noteworthily, it was confirmed that the rectification factors were independent from the bulk concentration due to the ideal perm-selectivity. Moreover, the rectification of the presenting diode was actively controlled by adjusting the external convective flows, while that of the previous diode was passively determined by invariant nanoscale asymmetry.

Effect of fish gelatin-gum arabic interactions on structural and functional properties of concentrated emulsions.

PubMed

Anvari, Mohammad; Joyner Melito, Helen S

2017-12-01

Concentrated emulsions containing both proteins and polysaccharides are the basis for many commercial products; however, the effects of protein-polysaccharide interactions on the functional properties of these complex systems are often poorly understood from a fundamental standpoint. Hence, the objective of this study was to determine the effects of fish gelatin (FG)-gum arabic (GA) complexation at different aqueous phase pH (3.6, 5.0, and 9.0) on concentrated emulsion structure-function relationships. Concentrated emulsions were prepared using FG-GA mixtures and characterized by rheometry and confocal scanning laser microscopy (CSLM). CSLM images showed that all samples were O/W emulsions; emulsions with lower pH showed smaller oil droplets, greater homogeneity in size distribution, and higher stability. This was attributed to an increased number of FG-GA complexes in the emulsification. Electrostatic attractive interactions and charge neutralization created biopolymer associations with increased emulsification capacity. Samples with FG-GA mixtures at lower pH showed higher elastic moduli under small deformation and exhibited greater deviation between apparent and complex viscosities under the Cox-Merz rule, indicating increased gel network extension and greater intermolecular connectivity between adsorbed layers of adjacent oil droplets. These results can be used to incorporate protein-polysaccharide complexes as a suitable emulsifier in materials comprising concentrated emulsions. Copyright © 2017 Elsevier Ltd. All rights reserved.

The absorption spectra of the complexes of uranium (VI) with some β-diketones

USGS Publications Warehouse

Feinstein, H.I.

1956-01-01

The absorption spectra of the complexes of uranium (VI) with four β-dike tones were determined under various conditions of pH, concentration of uranium, and alcohol concentration. Under optimum conditions, the maximum molar absorptivity (31,200) is obtained using 2-furoyltrifluoroacetone. This compares with about 4,000 and 19,000 for the thiocyanate and dibenzoylmethane complexes, respectively.

Effect of CMC Molecular Weight on Acid-Induced Gelation of Heated WPI-CMC Soluble Complex.

PubMed

Huan, Yan; Zhang, Sha; Vardhanabhuti, Bongkosh

2016-02-01

Acid-induced gelation properties of heated whey protein isolate (WPI) and carboxymethylcellulose (CMC) soluble complex were investigated as a function of CMC molecular weight (270, 680, and 750 kDa) and concentrations (0% to 0.125%). Heated WPI-CMC soluble complex with 6% protein was made by heating biopolymers together at pH 7.0 and 85 °C for 30 min and diluted to 5% protein before acid-induced gelation. Acid-induced gel formed from heated WPI-CMC complexes exhibited increased hardness and decreased water holding capacity with increasing CMC concentrations but gel strength decreased at higher CMC content. The highest gel strength was observed with CMC 750 k at 0.05%. Gels with low CMC concentration showed homogenous microstructure which was independent of CMC molecular weight, while increasing CMC concentration led to microphase separation with higher CMC molecular weight showing more extensive phase separation. When heated WPI-CMC complexes were prepared at 9% protein the acid gels showed improved gel hardness and water holding capacity, which was supported by the more interconnected protein network with less porosity when compared to complexes heated at 6% protein. It is concluded that protein concentration and biopolymer ratio during complex formation are the major factors affecting gel properties while the effect of CMC molecular weight was less significant. © 2016 Institute of Food Technologists®

Study of the adsorption of Cd and Zn onto an activated carbon: Influence of pH, cation concentration, and adsorbent concentration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seco, A.; Marzal, P.; Gabaldon, C.

1999-06-01

The single adsorption of Cd and Zn from aqueous solutions has been investigated on Scharlau Ca 346 granular activated carbon in a wide range of experimental conditions: pH, metal concentration, and carbon concentration. The results showed the efficiency of the activated carbon as sorbent for both metals. Metal removals increase on raising the pH and carbon concentration, and decrease on raising the initial metal concentration. The adsorption processes have been modeled using the surface complex formation (SCF) Triple Layer Model (TLM). The adsorbent TLM parameters were determined. Modeling has been performed assuming a single surface bidentate species or an overallmore » surface species with fractional stoichiometry. The bidentate stoichiometry successfully predicted cadmium and zinc removals in all the experimental conditions. The Freundlich isotherm has been also checked.« less

Chirality sensing with stereodynamic copper(I) complexes.

PubMed

De Los Santos, Zeus A; Legaux, Nicholas M; Wolf, Christian

2017-11-01

Three Cu(I) complexes derived from stereodynamic diphosphine ligands were synthesized and used for chirality sensing. The coordination of diamines and amino acids to these complexes generates distinct circular dichroism signals. The chiroptical sensor response allows determination of the absolute configuration and the enantiomeric excess of the analyte at low concentrations. This method is operationally simple, fast, and attractive for high-throughput sensing applications. © 2017 Wiley Periodicals, Inc.

Self-assembly of concentric quantum double rings.

PubMed

Mano, Takaaki; Kuroda, Takashi; Sanguinetti, Stefano; Ochiai, Tetsuyuki; Tateno, Takahiro; Kim, Jongsu; Noda, Takeshi; Kawabe, Mitsuo; Sakoda, Kazuaki; Kido, Giyuu; Koguchi, Nobuyuki

2005-03-01

We demonstrate the self-assembled formation of concentric quantum double rings with high uniformity and excellent rotational symmetry using the droplet epitaxy technique. Varying the growth process conditions can control each ring's size. Photoluminescence spectra emitted from an individual quantum ring complex show peculiar quantized levels that are specified by the carriers' orbital trajectories.

Design and Implementation of a Biomolecular Concentration Tracker

PubMed Central

2015-01-01

As a field, synthetic biology strives to engineer increasingly complex artificial systems in living cells. Active feedback in closed loop systems offers a dynamic and adaptive way to ensure constant relative activity independent of intrinsic and extrinsic noise. In this work, we use synthetic protein scaffolds as a modular and tunable mechanism for concentration tracking through negative feedback. Input to the circuit initiates scaffold production, leading to colocalization of a two-component system and resulting in the production of an inhibitory antiscaffold protein. Using a combination of modeling and experimental work, we show that the biomolecular concentration tracker circuit achieves dynamic protein concentration tracking in Escherichia coli and that steady state outputs can be tuned. PMID:24847683

Thrombin Generating Capacity and Phenotypic Association in ABO Blood Groups.

PubMed

Kremers, Romy M W; Mohamed, Abdulrahman B O; Pelkmans, Leonie; Hindawi, Salwa; Hemker, H Coenraad; de Laat, H Bas; Huskens, Dana; Al Dieri, Raed

2015-01-01

Individuals with blood group O have a higher bleeding risk than non-O blood groups. This could be explained by the lower levels of FVIII and von Willebrand Factor (VWF) levels in O individuals. We investigated the relationship between blood groups, thrombin generation (TG), prothrombin activation and thrombin inactivation. Plasma levels of VWF, FVIII, antithrombin, fibrinogen, prothrombin and α2Macroglobulin (α2M) levels were determined. TG was measured in platelet rich (PRP) and platelet poor plasma (PPP) of 217 healthy donors and prothrombin conversion and thrombin inactivation were calculated. VWF and FVIII levels were lower (75% and 78%) and α2M levels were higher (125%) in the O group. TG is 10% lower in the O group in PPP and PRP. Less prothrombin was converted in the O group (86%) and the thrombin decay capacity was lower as well. In the O group, α2M plays a significantly larger role in the inhibition of thrombin (126%). In conclusion, TG is lower in the O group due to lower prothrombin conversion, and a larger contribution of α2M to thrombin inactivation. The former is unrelated to platelet function because it is similar in PRP and PPP, but can be explained by the lower levels of FVIII.

Thrombin Generating Capacity and Phenotypic Association in ABO Blood Groups

PubMed Central

Hindawi, Salwa; Hemker, H. Coenraad; de Laat, H. Bas; Huskens, Dana; Al Dieri, Raed

2015-01-01

Individuals with blood group O have a higher bleeding risk than non-O blood groups. This could be explained by the lower levels of FVIII and von Willebrand Factor (VWF) levels in O individuals. We investigated the relationship between blood groups, thrombin generation (TG), prothrombin activation and thrombin inactivation. Plasma levels of VWF, FVIII, antithrombin, fibrinogen, prothrombin and α2Macroglobulin (α2M) levels were determined. TG was measured in platelet rich (PRP) and platelet poor plasma (PPP) of 217 healthy donors and prothrombin conversion and thrombin inactivation were calculated. VWF and FVIII levels were lower (75% and 78%) and α2M levels were higher (125%) in the O group. TG is 10% lower in the O group in PPP and PRP. Less prothrombin was converted in the O group (86%) and the thrombin decay capacity was lower as well. In the O group, α2M plays a significantly larger role in the inhibition of thrombin (126%). In conclusion, TG is lower in the O group due to lower prothrombin conversion, and a larger contribution of α2M to thrombin inactivation. The former is unrelated to platelet function because it is similar in PRP and PPP, but can be explained by the lower levels of FVIII. PMID:26509437

Hot-spot qualification testing of concentrator modules

NASA Technical Reports Server (NTRS)

Gonzalez, C. C.; Sugimura, R. S.; Ross, R. G., Jr.

1987-01-01

Results of a study to determine the hot-spot susceptibility of concentrator cells, to provide a hot-spot qualification test for concentrator modules, and to provide guidelines for reducing hot-spot susceptibility are presented. Hot-spot heating occurs in a photovoltaic module when the short-circuit current of a cell is lower than the string operating current, forcing the cell into reverse bias with a concurrent power dissipation. Although the basis for the concentrator-module hot-spot qualification test is the test developed for flat-plate modules, issues such as providing cell illumination introduce additional complexities into the testing procedure. The results indicate that the same general guidelines apply to protecting concentrator modules from hot-spot stressing as apply to flat-plate modules, and recommendations are made on the number of bypass diodes required per given number of series cells per module or source circuit. A method for determining the cell temperature in the laboratory or in the field is discussed.

Low-Complexity Noncoherent Signal Detection for Nanoscale Molecular Communications.

PubMed

Li, Bin; Sun, Mengwei; Wang, Siyi; Guo, Weisi; Zhao, Chenglin

2016-01-01

Nanoscale molecular communication is a viable way of exchanging information between nanomachines. In this investigation, a low-complexity and noncoherent signal detection technique is proposed to mitigate the inter-symbol-interference (ISI) and additive noise. In contrast to existing coherent detection methods of high complexity, the proposed noncoherent signal detector is more practical when the channel conditions are hard to acquire accurately or hidden from the receiver. The proposed scheme employs the molecular concentration difference to detect the ISI corrupted signals and we demonstrate that it can suppress the ISI effectively. The difference in molecular concentration is a stable characteristic, irrespective of the diffusion channel conditions. In terms of complexity, by excluding matrix operations or likelihood calculations, the new detection scheme is particularly suitable for nanoscale molecular communication systems with a small energy budget or limited computation resource.

Chansporter complexes in cell signaling.

PubMed

Abbott, Geoffrey W

2017-09-01

Ion channels facilitate diffusion of ions across cell membranes for such diverse purposes as neuronal signaling, muscular contraction, and fluid homeostasis. Solute transporters often utilize ionic gradients to move aqueous solutes up their concentration gradient, also fulfilling a wide variety of tasks. Recently, an increasing number of ion channel-transporter ('chansporter') complexes have been discovered. Chansporter complex formation may overcome what could otherwise be considerable spatial barriers to rapid signal integration and feedback between channels and transporters, the ions and other substrates they transport, and environmental factors to which they must respond. Here, current knowledge in this field is summarized, covering both heterologous expression structure/function findings and potential mechanisms by which chansporter complexes fulfill contrasting roles in cell signaling in vivo. © 2017 Federation of European Biochemical Societies.

Toxic Hazards Research Unit Annual Technical Report: 1975

DTIC Science & Technology

1975-10-01

by different sampling rates 160 21 Particle size distribution curves 167 22 Effect of 03 or N02 concentrations on rat lung weight 177 23 Relationship...previously, consisted of female C57 black/6 mice obtained from Jackson Laboratories, male CDF (Fischer 344 derived) albino rats from Charles River...the exposure phase of the study but made at the conclusion of the 5 ppm and 0. 5 ppm experiments were: Blood urea nitrogen SGOT Chloride Prothrombin

Elimination of interleukin 6 attenuates coagulation activation in experimental endotoxemia in chimpanzees

PubMed Central

1994-01-01

The role of interleukin 6 (IL-6) in the toxic sequelae of sepsis is controversial. To assess the part of IL-6 in inflammatory responses to endotoxin, we investigated eight chimpanzees after either a bolus intravenous injection of Escherichia coli endotoxin (n = 4; 4 ng/kg) or after the same dose of endotoxin with a simultaneous bolus intravenous injection of an anti-IL-6 mAb (30 mg; n = 4). Anti-IL-6 did not affect the induction of the cytokine network (tumor necrosis factor [TNF], soluble TNF receptors types I and II, and IL-8) by endotoxin, nor did it influence the occurrence of a neutrophilic leukocytosis and neutrophil degranulation, as monitored by the measurement of elastase- alpha 1-antitrypsin complexes. In contrast, anti-IL-6 markedly attenuated endotoxin-induced activation of coagulation, monitored with the plasma levels of the prothrombin fragment F1+2 and thrombin- antithrombin III complexes, whereas activation of fibrinolysis, determined with the plasma concentrations of plasmin-alpha 2- antiplasmin complexes, remained unaltered. We conclude that IL-6 does not have a feedback effect on the release of other cytokines after injection of endotoxin, and that it is not involved in endotoxin- induced neutrophilia or neutrophil degranulation. IL-6 is, however, an important intermediate factor in activation of coagulation in low grade endotoxemia in chimpanzees. PMID:8145042

[Generation of Superoxide Radicals by Complex III in Heart Mitochondria and Antioxidant Effect of Dinitrosyl Iron Complexes at Different Partial Pressure of Oxygen].

PubMed

Dudylina, A L; Ivanova, M V; Shumaev, K B; Ruuge, E K

2016-01-01

The EPR spin-trapping technique and EPR-oximetry were used to study generation of superoxide radicals in heart mitochondria isolated from Wistar rats under conditions of variable oxygen concentration. Lithium phthalocyanine and TEMPONE-15N-D16 were chosen to determine oxygen content in a gas-permeable capillary tube containing mitochondria. TIRON was used as a spin trap. We investigated the influence of different oxygen concentrations in incubation mixture and demonstrated that heart mitochondria can generate superoxide in complex III at different partial pressure of oxygen as well as under the conditions of deep hypoxia (< 5% O2). Dinitrosyl iron complexes with glutathione (the pharmaceutical drug "Oxacom") exerted an antioxidant effect, regardless of the value of the partial pressure of oxygen, but the magnitude and kinetic characteristics of the effect depended on the concentration of the drug.

Performance of a Prototype Stationary Catadioptric Concentrating Photovoltaic Module

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lloyd, John V.; Kozodoy, Peter; Gladden, Christopher

A stationary catadioptric concentrating photovoltaic module with aperture area over 100 cm2, geometric concentration of 180x, and collection within 60° of polar incidence was designed, prototyped, and characterized. The module performance followed modeling closely with a peak power conversion efficiency of 26% for direct irradiance. Tracking of the sun is accomplished via translational micro-tracking completely internal to the module, avoiding the cost and complexity of mechanical two-axis trackers that point towards the sun. This study demonstrates the potential for concentrating photovoltaic modules with significantly higher efficiency than industry standard silicon photovoltaic modules that could be installed in stationary configurations onmore » rooftops.« less

Performance of a Prototype Stationary Catadioptric Concentrating Photovoltaic Module

DOE PAGES

Lloyd, John V.; Kozodoy, Peter; Gladden, Christopher; ...

2018-03-28

A stationary catadioptric concentrating photovoltaic module with aperture area over 100 cm2, geometric concentration of 180x, and collection within 60° of polar incidence was designed, prototyped, and characterized. The module performance followed modeling closely with a peak power conversion efficiency of 26% for direct irradiance. Tracking of the sun is accomplished via translational micro-tracking completely internal to the module, avoiding the cost and complexity of mechanical two-axis trackers that point towards the sun. This study demonstrates the potential for concentrating photovoltaic modules with significantly higher efficiency than industry standard silicon photovoltaic modules that could be installed in stationary configurations onmore » rooftops.« less

Using complexation for the microencapsulation of nisin in biopolymer matrices by spray-drying.

PubMed

Ben Amara, Chedia; Kim, Lanhee; Oulahal, Nadia; Degraeve, Pascal; Gharsallaoui, Adem

2017-12-01

The aim of this study is to investigate the potential of complexation to encapsulate nisin (5g/L concentration) using spray-drying technique and to evaluate how complexation with pectin or alginate (2g/L concentration) can preserve nisin structure and antimicrobial activity. Spray-drying of nisin-low methoxyl pectin or nisin-alginate electrostatic complexes has led to the microencapsulation of the peptide in different networks that were highly influenced by the polysaccharide type. Turbidity and particle size measurements indicated that while spray-drying promoted the aggregation of nisin-pectin complexes, it favored the dissociation of nisin-alginate aggregates to form individual complexes. Structural changes of nisin induced by complexation with pectin or alginate and spray-drying were studied by using UV-Vis absorption and fluorescence spectroscopy. The results showed that complexation with pectin or alginate preserved nisin structure as well as its antimicrobial activity during spray-drying. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of an antiandrogenic oral contraceptive pill compared with metformin on blood coagulation tests and endothelial function in women with the polycystic ovary syndrome: influence of obesity and smoking.

PubMed

Luque-Ramírez, Manuel; Mendieta-Azcona, Covandonga; del Rey Sánchez, José M; Matíes, Milagro; Escobar-Morreale, Héctor F

2009-03-01

To study the blood clotting tests and endothelial function of polycystic ovary syndrome (PCOS) patients and non-hyperandrogenic women, and their changes during PCOS treatment, as a function of the presence of obesity and smoking. Case-control study followed by a randomized clinical trial. Blood clotting and endothelial function were analyzed in 40 PCOS patients and 20 non-hyperandrogenic women. Thirty-four PCOS women were randomized to an oral contraceptive containing 35 microg ethinyl-estradiol plus 2 mg cyproterone acetate (Diane(35)Diario) or metformin (850 mg twice daily), monitoring the changes on these parameters during 24 weeks of treatment. The influence of obesity and smoking was also analyzed. Blood clotting and endothelial function tests were similar among PCOS patients and controls with the exception of a higher platelet count in the former. Obesity increased circulating fibrinogen levels, prothrombin activity and platelet counts, and reduced prothrombin and activated partial thromboplastin times. Smoking increased fibrinogen levels, platelet counts, and prothrombin activity, and reduced prothrombin time, in relation to the larger waist circumference of smokers. Irrespective of the treatment received, PCOS patients showed a decrease in prothrombin time and an increase in prothrombin activity, with a parallel increase in homocysteine levels in metformin users. The activated partial thromboplastin time decreased markedly in the patients treated with Diane(35)Diario. Finally, flow-mediated dilation improved in non-smokers irrespective of the drug received, but worsened in smokers. Oral contraceptives and metformin may exert deleterious effects on blood clotting tests of PCOS women, yet the effects of metformin appear to be milder. Because smoking potentiates some of these effects and deteriorates endothelial function, smoking cessation should be promoted in PCOS patients.

Complex-formation between reduced xanthine oxidase and purine substrates demonstrated by electron paramagnetic resonance

PubMed Central

Pick, Frances M.; Bray, R. C.

1969-01-01

The origin of the Rapid molybdenum electron-paramagnetic-resonance signals, which are obtained on reducing xanthine oxidase with purine or with xanthine, and whose parameters were measured by Bray & Vänngård (1969), was studied. It is concluded that these signals represent complexes of reduced enzyme with substrate molecules. Xanthine forms one complex at high concentrations and a different one at low concentrations. Purine forms a complex indistinguishable from the low-concentration xanthine complex. There are indications that some other substrates also form complexes, but uric acid, a reaction product, does not appear to do so. The possible significance of the complexes in the catalytic cycle of the enzyme is discussed and it is suggested that they represent substrate molecules bound at the reduced active site, waiting their turn to react there, when the enzyme has been reoxidized. Support for this role for the complexes was deduced from experiments in which frozen samples of enzyme–xanthine mixtures, prepared by the rapid-freezing method, were warmed until the signals began to change. Under these conditions an increase in amplitude of the Very Rapid signal took place. Data bearing on the origin of the Slow molybdenum signal are also discussed. This signal disappears only slowly in the presence of oxygen, and its appearance rate is unaffected by change in the concentration of dithionite. It is concluded that, like other signals from the enzyme, it is due to Mov but that a slow change of ligand takes place before it is seen. The Slow species, like the Rapid, seems capable of forming complexes with purines. PMID:4310056

Measurement of protein HC (alpha 1 microglobulin) and protein HC-IgA complex in different body fluids.

PubMed Central

Fernández-Luna, J L; Leyva-Cobián, F; Méndez, E

1988-01-01

Protein HC and protein HC-IgA complex were measured in 18 different types of fluid sample from healthy subjects and patients with different illnesses to determine if the concentrations of protein HC and protein HC-IgA complexes could be used to monitor certain diseases, when measured separately. The normal values for HC ranged from between 0.30 mg/l in saliva and 11.7 mg/l in blood plasma. HC-IgA complex has a greater range, from undetectable concentrations (urine, colostrum, and cervical mucus) up to 59.2 mg/l in blood plasma. Undetectable concentrations of HC-IgA complex were also shown in serum from patients with IgA immune deficiency and in cerebrospinal fluid from patients with multiple sclerosis. Increased concentrations of HC were noted in bronchoalveolar fluid from a patient with pulmonary alveolar proteinosis, serum from patients with Behcet's syndrome, and in synovial fluid from patients with gout, chondrocalcinosis, and rheumatoid arthritis. On the other hand, the concentrations of HC-IgA complex were raised only in those patients with pulmonary alveolar proteinosis or rheumatoid arthritis. PMID:2463270

Complex numbers in chemometrics: examples from multivariate impedance measurements on lipid monolayers.

PubMed

Geladi, Paul; Nelson, Andrew; Lindholm-Sethson, Britta

2007-07-09

Electrical impedance gives multivariate complex number data as results. Two examples of multivariate electrical impedance data measured on lipid monolayers in different solutions give rise to matrices (16x50 and 38x50) of complex numbers. Multivariate data analysis by principal component analysis (PCA) or singular value decomposition (SVD) can be used for complex data and the necessary equations are given. The scores and loadings obtained are vectors of complex numbers. It is shown that the complex number PCA and SVD are better at concentrating information in a few components than the naïve juxtaposition method and that Argand diagrams can replace score and loading plots. Different concentrations of Magainin and Gramicidin A give different responses and also the role of the electrolyte medium can be studied. An interaction of Gramicidin A in the solution with the monolayer over time can be observed.

Thermodynamic characterization of hydrogen interaction with iridium polyhydride complexes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zidan, R.A.; Rocheleau, R.E.

1999-01-01

Hydrogen interaction with solid iridium complexes IrXH{sub 2}(PPr3{sup i}){sub 2} (X=Cl, I) was investigated. Gaseous hydrogen was found to react reversibly with solid chloro-iridium complex IrClH{sub 2}(PPr3{sup i}){sub 2} forming IrClH{sub 2}(PPr3{sup i}){sub 2}H{sub 2}. The relative partial molal enthalpy and entropy were obtained from equilibrium isotherms at different hydrogen concentrations. The decrease in entropy with increasing hydrogen concentration and the absence of plateaus in the equilibrium isotherms were consistent with a single phase solid solution with two chemical components. Hydrogen release from solid iodo-iridium complex IrIH{sub 2}(PPr3{sup i}){sub 2}H{sub 2} was not observed at temperatures up to 350 K,more » indicating stronger hydrogen bonding. {copyright} {ital 1999 Materials Research Society.}« less

Vitamin K epoxide reductase complex subunit 1 (Vkorc1) haplotype diversity in mouse priority strains

PubMed Central

Song, Ying; Vera, Nicole; Kohn, Michael H

2008-01-01

Background Polymorphisms in the vitamin K-epoxide reductase complex subunit 1 gene, Vkorc1, could affect blood coagulation and other vitamin K-dependent proteins, such as osteocalcin (bone Gla protein, BGP). Here we sequenced the Vkorc1 gene in 40 mouse priority strains. We analyzed Vkorc1 haplotypes with respect to prothrombin time (PT) and bone mineral density and composition (BMD and BMC); phenotypes expected to be vitamin K-dependent and represented by data in the Mouse Phenome Database (MPD). Findings In the commonly used laboratory strains of Mus musculus domesticus we identified only four haplotypes differing in the intron or 5' region sequence of the Vkorc1. Six haplotypes differing by coding and non-coding polymorphisms were identified in the other subspecies of Mus. We detected no significant association of Vkorc1 haplotypes with PT, BMD and BMC within each subspecies of Mus. Vkorc1 haplotype sequences divergence between subspecies was associated with PT, BMD and BMC. Conclusion Phenotypic variation in PT, BMD and BMC within subspecies of Mus, while substantial, appears to be dominated by genetic variation in genes other than the Vkorc1. This was particularly evident for M. m. domesticus, where a single haplotype was observed in conjunction with virtually the entire range of PT, BMD and BMC values of all 5 subspecies of Mus included in this study. Differences in these phenotypes between subspecies also should not be attributed to Vkorc1 variants, but should be viewed as a result of genome wide genetic divergence. PMID:19046458

Population pharmacokinetics and pharmacodynamics of rivaroxaban in patients with non-valvular atrial fibrillation: results from ROCKET AF.

PubMed

Girgis, I G; Patel, M R; Peters, G R; Moore, K T; Mahaffey, K W; Nessel, C C; Halperin, J L; Califf, R M; Fox, K A A; Becker, R C

2014-08-01

Two once-daily rivaroxaban dosing regimens were compared with warfarin for stroke prevention in patients with non-valvular atrial fibrillation in ROCKET AF: 20 mg for patients with normal/mildly impaired renal function and 15 mg for patients with moderate renal impairment. Rivaroxaban population pharmacokinetic (PK)/pharmacodynamic (PD) modeling data from ROCKET AF patients (n = 161) are reported and are used to confirm established rivaroxaban PK and PK/PD models and to re-estimate values of the models' parameters for the current AF population. An oral one-compartment model with first-order absorption adequately described rivaroxaban PK. Age, renal function, and lean body mass influenced the PK model. Prothrombin time and prothrombinase-induced clotting time exhibited a near-linear relationship with rivaroxaban plasma concentration; inhibitory effects were observed through to 24 hours post-dose. Rivaroxaban plasma concentration and factor Xa activity had an inhibitory maximum-effect (Emax ) relationship. Renal function (on prothrombin time; prothrombinase-induced clotting time) and age (on factor Xa activity) had moderate effects on PK/PD models. PK and PK/PD models were shown to be adequate for describing the current dataset. These findings confirm the modeling and empirical results that led to the selection of doses tested against warfarin in ROCKET AF. © 2014, The American College of Clinical Pharmacology.

Ratio of mean platelet volume to platelet count is a potential surrogate marker predicting liver cirrhosis.

PubMed

Iida, Hiroya; Kaibori, Masaki; Matsui, Kosuke; Ishizaki, Morihiko; Kon, Masanori

2018-01-27

To provide a simple surrogate marker predictive of liver cirrhosis (LC). Specimens from 302 patients who underwent resection for hepatocellular carcinoma between January 2006 and December 2012 were retrospectively analyzed. Based on pathologic findings, patients were divided into groups based on whether or not they had LC. Parameters associated with hepatic functional reserve were compared in these two groups using Mann-Whitney U -test for univariate analysis. Factors differing significantly in univariate analyses were entered into multivariate logistic regression analysis. There were significant differences between the LC group ( n = 100) and non-LC group ( n = 202) in prothrombin activity, concentrations of alanine aminotransferase, aspartate aminotransferase, total bilirubin, albumin, cholinesterase, type IV collagen, hyaluronic acid, indocyanine green retention rate at 15 min, maximal removal rate of technitium-99m diethylene triamine penta-acetic acid-galactosyl human serum albumin and ratio of mean platelet volume to platelet count (MPV/PLT). Multivariate analysis showed that prothrombin activity, concentrations of alanine aminotransferase, aspartate aminotransferase, total bilirubin and hyaluronic acid, and MPV/PLT ratio were factors independently predictive of LC. The area under the curve value for MPV/PLT was 0.78, with a 0.8 cutoff value having a sensitivity of 65% and a specificity of 78%. The MPV/PLT ratio, which can be determined simply from the complete blood count, may be a simple surrogate marker predicting LC.

Complex Fluids and Hydraulic Fracturing.

PubMed

Barbati, Alexander C; Desroches, Jean; Robisson, Agathe; McKinley, Gareth H

2016-06-07

Nearly 70 years old, hydraulic fracturing is a core technique for stimulating hydrocarbon production in a majority of oil and gas reservoirs. Complex fluids are implemented in nearly every step of the fracturing process, most significantly to generate and sustain fractures and transport and distribute proppant particles during and following fluid injection. An extremely wide range of complex fluids are used: naturally occurring polysaccharide and synthetic polymer solutions, aqueous physical and chemical gels, organic gels, micellar surfactant solutions, emulsions, and foams. These fluids are loaded over a wide range of concentrations with particles of varying sizes and aspect ratios and are subjected to extreme mechanical and environmental conditions. We describe the settings of hydraulic fracturing (framed by geology), fracturing mechanics and physics, and the critical role that non-Newtonian fluid dynamics and complex fluids play in the hydraulic fracturing process.

Complex mixtures, complex responses: Assessing pharmaceutical mixtures using field and laboratory approaches

USGS Publications Warehouse

Schoenfuss, Heiko L.; Furlong, Edward T.; Phillips, Patrick J.; Scott, Tia-Marie; Kolpin, Dana W.; Cetkovic-Cvrlje, Marina; Lesteberg, Kelsey E.; Rearick, Daniel C.

2016-01-01

Pharmaceuticals are present in low concentrations (<100 ng/L) in most municipal wastewater effluents but may be elevated locally because of factors such as input from pharmaceutical formulation facilities. Using existing concentration data, the authors assessed pharmaceuticals in laboratory exposures of fathead minnows (Pimephales promelas) and added environmental complexity through effluent exposures. In the laboratory, larval and mature minnows were exposed to a simple opioid mixture (hydrocodone, methadone, and oxycodone), an opioid agonist (tramadol), a muscle relaxant (methocarbamol), a simple antidepressant mixture (fluoxetine, paroxetine, venlafaxine), a sleep aid (temazepam), or a complex mixture of all compounds. Larval minnow response to effluent exposure was not consistent. The 2010 exposures resulted in shorter exposed minnow larvae, whereas the larvae exposed in 2012 exhibited altered escape behavior. Mature minnows exhibited altered hepatosomatic indices, with the strongest effects in females and in mixture exposures. In addition, laboratory-exposed, mature male minnows exposed to all pharmaceuticals (except the selective serotonin reuptake inhibitor mixture) defended nest sites less rigorously than fish in the control group. Tramadol or antidepressant mixture exposure resulted in increased splenic T lymphocytes. Only male minnows exposed to whole effluent responded with increased plasma vitellogenin concentrations. Female minnows exposed to pharmaceuticals (except the opioid mixture) had larger livers, likely as a compensatory result of greater prominence of vacuoles in liver hepatocytes. The observed alteration of apical endpoints central to sustaining fish populations confirms that effluents containing waste streams from pharmaceutical formulation facilities can adversely impact fish populations but that the effects may not be temporally consistent. The present study highlights the importance of including diverse biological endpoints spanning

Oleic acid is a key cytotoxic component of HAMLET-like complexes.

PubMed

Permyakov, Sergei E; Knyazeva, Ekaterina L; Khasanova, Leysan M; Fadeev, Roman S; Zhadan, Andrei P; Roche-Hakansson, Hazeline; Håkansson, Anders P; Akatov, Vladimir S; Permyakov, Eugene A

2012-01-01

HAMLET is a complex of α-lactalbumin (α-LA) with oleic acid (OA) that selectively kills tumor cells and Streptococcus pneumoniae. To assess the contribution of the proteinaceous component to cytotoxicity of HAMLET, OA complexes with proteins structurally and functionally distinct from α-LA were prepared. Similar to HAMLET, the OA complexes with bovine β-lactoglobulin (bLG) and pike parvalbumin (pPA) (bLG-OA-45 and pPA-OA-45, respectively) induced S. pneumoniae D39 cell death. The activation mechanisms of S. pneumoniae death for these complexes were analogous to those for HAMLET, and the cytotoxicity of the complexes increased with OA content in the preparations. The half-maximal inhibitory concentration for HEp-2 cells linearly decreased with rise in OA content in the preparations, and OA concentration in the preparations causing HEp-2 cell death was close to the cytotoxicity of OA alone. Hence, the cytotoxic action of these complexes against HEp-2 cells is induced mostly by OA. Thermal stabilization of bLG upon association with OA implies that cytotoxicity of bLG-OA-45 complex cannot be ascribed to molten globule-like conformation of the protein component. Overall, the proteinaceous component of HAMLET-like complexes studied is not a prerequisite for their activity; the cytotoxicity of these complexes is mostly due to the action of OA.

Aptamer-based detection of plasma proteins by an electrochemical assay coupled to magnetic beads.

PubMed

Centi, Sonia; Tombelli, Sara; Minunni, Maria; Mascini, Marco

2007-02-15

The DNA thrombin aptamer has been extensively investigated, and the coupling of this aptamer to different transduction principles has demonstrated the wide applicability of aptamers as bioreceptors in bioanalytical assays. The goal of this work was to design an aptamer-based sandwich assay with electrochemical detection for thrombin analysis in complex matrixes, using a simple target capturing step by aptamer-functionalized magnetic beads. The conditions for the aptamer immobilization and for the protein binding have been first optimized by surface plasmon resonance, and then transferred to the electrochemical-based assay performed onto screen-printed electrodes. The assay was then applied to the analysis of thrombin in buffer, spiked serum, and plasma and high sensitivity and specificity were found. Moreover, thrombin was generated in situ in plasma by the conversion of its precursor prothrombin, and the formation of thrombin was followed at different times. The concentrations detected by the electrochemical assay were in agreement with a simulation software that mimics the formation of thrombin over time (thrombogram). The proposed work demonstrates that the high specificity of aptamers together with the use of magnetic beads are the key features for aptamer-based analysis in complex matrixes, opening the possibility of a real application to diagnostics or medical investigation.

Carbonate Complexation of Mn2+ in Aqueous Phase

PubMed Central

Dasgupta, Jyotishman; Tyryshkin, Alexei M.; Kozlov, Yuri N.; Klimov, Vyacheslav V.; Dismukes, G. Charles

2008-01-01

The chemical speciation of Mn2+ within cells is critical for its transport, availability and redox properties. Herein we investigate the redox behavior and complexation equilibria of Mn2+ in aqueous solutions of bicarbonate by voltametry and electron paramagnetic resonance (EPR) spectroscopy, and discuss the implications for the uptake of Mn2+ by mangano-cluster enzymes like photosystem II (PSII). Both the electrochemical reduction of Mn2+ to Mn0 at an Hg electrode and EPR (in the absence of a polarizing electrode), revealed formation of 1:1 and 1:2 Mn-(bi)carbonate complexes as a function of Mn2+ and bicarbonate concentrations. Pulsed EPR spectroscopy, including ENDOR, ESEEM and 2D-HYSCORE, were used to probe the hyperfine couplings to 1H and 13C nuclei of the ligand(s) bound to Mn2+. For the 1:2 complex the complete 13C hyperfine tensor for one of the (bi)carbonate ligands was determined and it was established that this ligand coordinates to Mn2+ in bidentate mode with 13C-Mn distance of 2.85 ± 0.1 Å. The second (bi)carbonate ligand in the 1:2 complex coordinates possibly in monodentate mode, which is structurally less defined, and its 13C signal is broad and unobservable. 1H ENDOR reveals that 1-2 water ligands are lost upon binding of one bicarbonate ion in the 1:1 complex while 3-4 water ligands are lost upon forming the 1:2 complex. Thus, we deduce that the dominant species above 0.1 M bicarbonate concentration is the 1:2 complex, [Mn(CO3)(HCO3)(OH2)3]-. PMID:16526753

Effects of molecular composition of natural organic matter on ferric iron complexation at circumneutral pH.

PubMed

Fujii, Manabu; Imaoka, Akira; Yoshimura, Chihiro; Waite, T D

2014-04-15

Thermodynamic and kinetic parameters for ferric iron (Fe[III]) complexation by well-characterized humic substances (HS) from various origins were determined by a competitive ligand method with 5-sulfosalicylic acid at circumneutral pH (6.0-8.0) and an ionic strength of ∼0.06 M. The measured Fe binding properties including conditional stability constants and complexation capacities ranged over more than 2 orders of magnitude, depending on the origin and the particular operationally defined fraction of HS examined. Statistical comparison of the complexation parameters to a range of chemical properties of the HS indicated a strong positive correlation between Fe(III) complexation capacity and aromatic carbon content in the HS at all pHs examined. In contrast, the complexation capacity was determined to be up to a few orders of magnitude smaller than the concentration of carboxylic and phenolic groups present. Therefore, specific functional groups including those resident in the proximity of aromatic structures within the HS are likely preferable for Fe(III) coordination under the conditions examined. Overall, our results suggest that the concentration of dissolved Fe(III) complexes in natural waters is substantially influenced by variation in HS characteristics in addition to other well-known factors such as HS concentration and nature and concentration of competing cations present.

Complexation and molecular modeling studies of europium(III)-gallic acid-amino acid complexes.

PubMed

Taha, Mohamed; Khan, Imran; Coutinho, João A P

2016-04-01

With many metal-based drugs extensively used today in the treatment of cancer, attention has focused on the development of new coordination compounds with antitumor activity with europium(III) complexes recently introduced as novel anticancer drugs. The aim of this work is to design new Eu(III) complexes with gallic acid, an antioxida'nt phenolic compound. Gallic acid was chosen because it shows anticancer activity without harming health cells. As antioxidant, it helps to protect human cells against oxidative damage that implicated in DNA damage, cancer, and accelerated cell aging. In this work, the formation of binary and ternary complexes of Eu(III) with gallic acid, primary ligand, and amino acids alanine, leucine, isoleucine, and tryptophan was studied by glass electrode potentiometry in aqueous solution containing 0.1M NaNO3 at (298.2 ± 0.1) K. Their overall stability constants were evaluated and the concentration distributions of the complex species in solution were calculated. The protonation constants of gallic acid and amino acids were also determined at our experimental conditions and compared with those predicted by using conductor-like screening model for realistic solvation (COSMO-RS) model. The geometries of Eu(III)-gallic acid complexes were characterized by the density functional theory (DFT). The spectroscopic UV-visible and photoluminescence measurements are carried out to confirm the formation of Eu(III)-gallic acid complexes in aqueous solutions. Copyright © 2016 Elsevier Inc. All rights reserved.

Irradiation-induced damage evolution in concentrated Ni-based alloys

DOE PAGES

Velisa, Gihan; Ullah, Mohammad Wali; Xue, Haizhou; ...

2017-06-06

Understanding the effects of chemical complexity from the number, type and concentration of alloying elements in single-phase concentred solid-solution alloys (SP-CSAs) on defect dynamics and microstructure evolution is pivotal for developing next-generation radiation-tolerant structural alloys. A specially chosen set of SP-CSAs with different chemical complexity (Ni 80Fe 20, Ni 80Cr 20 and Ni 40Fe 40Cr 20) are investigated using 1.5 MeV Mn ions over a wide fluence range, from 2 × 10 13 to 1 × 10 16 ions cm –2 at room temperature. Based on an integrated study of Rutherford backscattering spectroscopy in channeling geometry and molecular dynamics simulations,more » the results demonstrate that Ni 40Fe 40Cr 20 is more radiation tolerant than Ni 80Fe 20, Ni 80Cr 20 and elemental Ni in the low fluence regime. While chemical complexity of this set of SP-CSAs is clearly demonstrated to affect defect evolution through suppressed defect production and enhanced recombination at early stages, the effect of the mixed ferro- and anti-ferromagnetic interactions is not the only controlling factor responsible for the improved radiation performance. As a result, the observed strong alloying effect on defect evolution is attributed to the altered defect migration mobilities of defect clusters in these alloys, an intrinsic characteristic of the complex energy landscapes in CSAs.« less

Irradiation-induced damage evolution in concentrated Ni-based alloys

DOE Office of Scientific and Technical Information (OSTI.GOV)

Velisa, Gihan; Ullah, Mohammad Wali; Xue, Haizhou

Understanding the effects of chemical complexity from the number, type and concentration of alloying elements in single-phase concentred solid-solution alloys (SP-CSAs) on defect dynamics and microstructure evolution is pivotal for developing next-generation radiation-tolerant structural alloys. A specially chosen set of SP-CSAs with different chemical complexity (Ni 80Fe 20, Ni 80Cr 20 and Ni 40Fe 40Cr 20) are investigated using 1.5 MeV Mn ions over a wide fluence range, from 2 × 10 13 to 1 × 10 16 ions cm –2 at room temperature. Based on an integrated study of Rutherford backscattering spectroscopy in channeling geometry and molecular dynamics simulations,more » the results demonstrate that Ni 40Fe 40Cr 20 is more radiation tolerant than Ni 80Fe 20, Ni 80Cr 20 and elemental Ni in the low fluence regime. While chemical complexity of this set of SP-CSAs is clearly demonstrated to affect defect evolution through suppressed defect production and enhanced recombination at early stages, the effect of the mixed ferro- and anti-ferromagnetic interactions is not the only controlling factor responsible for the improved radiation performance. As a result, the observed strong alloying effect on defect evolution is attributed to the altered defect migration mobilities of defect clusters in these alloys, an intrinsic characteristic of the complex energy landscapes in CSAs.« less

Echinacea complex--chemical view and anti-asthmatic profile.

PubMed

Šutovská, Martina; Capek, Peter; Kazimierová, Ivana; Pappová, Lenka; Jošková, Marta; Matulová, Mária; Fraňová, Soňa; Pawlaczyk, Izabela; Gancarz, Roman

2015-12-04

Echinacea purpurea (L.) Moench is one of the mostly used herbs in the traditional medicine for the treatment of respiratory diseases. Modern interest in Echinacea is directed to its immunomodulatory activity. Recent studies have shown that secretion of asthma-related cytokines in the bronchial epithelial cells can be reversed by Echinacea preparations. To examine the pharmacodynamics profile of Echinacea active principles, a complex has been isolated from its flowers by alkaline extraction and has been tested using an animal model of allergic asthma. The structural features of Echinacea purpurea complex was determined using chemical and spectroscopic methods. Allergic inflammation of the airways was induced by repetitive exposure of guinea pigs to ovalbumin. Echinacea complex was then administered 14 days in 50mg/kg b.w. daily dose perorally. Bronchodilatory effect was verified as decrease in the specific airway resistance (sRaw) in vivo and by reduced contraction amplitude (mN) of tracheal and pulmonary smooth muscle to cumulative concentrations of acetylcholine and histamine in vitro. The impact on mucociliary clearance evaluated measurement of ciliary beat frequency (CBF) in vitro using LabVIEW™ Software. Anti-inflammatory effect of Echinacea complex was verified by changes in exhaled NO levels and by Bio-Plex® assay of Th2 cytokine concentrations (IL-4, IL-5, IL-13 and TNF-alpha) in serum and bronchoalveolar lavage fluid (BALF). Chemical and spectroscopic studies confirmed the presence of carbohydrates, phenolic compounds and proteins, as well as the dominance of rhamnogalacturonan and arabinogalactan moieties in Echinacea complex. The significant decrease in sRaw values and suppressed histamine and acetylcholine-induced contractile amplitude of isolated airways smooth muscle that were similar to effects of control drug salbutamol confirmed Echinacea complex bronchodilatory activity. The anti-inflammatory effect was comparable with that of control agent

Characterization of complexes between phenethylamine enantiomers and β-cyclodextrin derivatives by capillary electrophoresis-Determination of binding constants and complex mobilities.

PubMed

Wahl, Joachim; Furuishi, Takayuki; Yonemochi, Etsuo; Meinel, Lorenz; Holzgrabe, Ulrike

2017-04-01

To optimize chiral separation conditions and to improve the knowledge of enantioseparation, it is important to know the binding constants K between analytes and cyclodextrins and the electrophoretic mobilities of the temporarily formed analyte-cyclodextrin-complexes. K values for complexes between eight phenethylamine enantiomers, namely ephedrine, pseudoephedrine, methylephedrine and norephedrine, and four different β-cyclodextrin derivatives were determined by affinity capillary electrophoresis. The binding constants were calculated from the electrophoretic mobility values of the phenethylamine enantiomers at increasing concentrations of cyclodextrins in running buffer. Three different linear plotting methods (x-reciprocal, y-reciprocal, double reciprocal) and nonlinear regression were used for the determination of binding constants with β-cyclodextrin, (2-hydroxypropyl)-β-cyclodextrin, methyl-β-cyclodextrin and 6-O-α-maltosyl-β-cyclodextrin. The cyclodextrin concentration in a 50 mM phosphate buffer pH 3.0 was varied from 0 to 12 mM. To investigate the influence of the binding constant values on the enantioseparation the observed electrophoretic selectivities were compared with the obtained K values and the calculated enantiomer-cyclodextrin-complex mobilities. The different electrophoretic mobilities of the temporarily formed complexes were crucial factors for the migration order and enantioseparation of ephedrine derivatives. To verify the apparent binding constants determined by capillary electrophoresis, a titration process using ephedrine enantiomers and β-cyclodextrin was carried out. Furthermore, the isothermal titration calorimetry measurements gave information about the thermal properties of the complexes. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Quantitative trace analysis of complex mixtures using SABRE hyperpolarization.

PubMed

Eshuis, Nan; van Weerdenburg, Bram J A; Feiters, Martin C; Rutjes, Floris P J T; Wijmenga, Sybren S; Tessari, Marco

2015-01-26

Signal amplification by reversible exchange (SABRE) is an emerging nuclear spin hyperpolarization technique that strongly enhances NMR signals of small molecules in solution. However, such signal enhancements have never been exploited for concentration determination, as the efficiency of SABRE can strongly vary between different substrates or even between nuclear spins in the same molecule. The first application of SABRE for the quantitative analysis of a complex mixture is now reported. Despite the inherent complexity of the system under investigation, which involves thousands of competing binding equilibria, analytes at concentrations in the low micromolar range could be quantified from single-scan SABRE spectra using a standard-addition approach. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effect of stress concentrations in composite structures

NASA Technical Reports Server (NTRS)

Babcock, G. D.; Knauss, W. G.

1984-01-01

The goal of achieving a better understanding of the failure of complex composite structure is sought. This type of structure requires a thorough understanding of the behavior under load both on a macro and micro scale if failure mechanisms are to be understood. The two problems being studied are the failure at a panel/stiffener interface and a generic problem of failure at a stress concentration.

Low-concentration exposure to glyphosate-based herbicide modulates the complexes of the mitochondrial respiratory chain and induces mitochondrial hyperpolarization in the Danio rerio brain.

PubMed

Pereira, Aline G; Jaramillo, Michael L; Remor, Aline P; Latini, Alexandra; Davico, Carla E; da Silva, Mariana L; Müller, Yara M R; Ammar, Dib; Nazari, Evelise M

2018-06-11

Glyphosate (N-phosphonomethyl-glycine) (GLY) is the active ingredient of the most used herbicides in the world. GLY is applied in formulated products known as glyphosate-based herbicides (GBH), which could induce effects that are not predicted by toxicity assays with pure GLY. This herbicide is classified as organophosphorus compound, which is known to induce neurotoxic effects. Although this compound is classified as non-neurotoxic by regulatory agencies, acute exposure to GBH causes neurological symptoms in humans. However, there is no consensus in relation to neurotoxic effects of GBH. Thus, the aim of this study was to investigate the neurotoxic effects of the GBH in the zebrafish Danio rerio, focusing on acute toxicity, the activity and transcript levels of mitochondrial respiratory chain complexes, mitochondrial membrane potential, reactive species (RS) formation, and behavioral repertoire. Adult zebrafish were exposed in vivo to three concentrations of GBH Scout ® , which contained GLY in formulation (fGLY) (0.065, 1.0 and 10.0 mg L -1 fGLY) for 7 d, and an in vitro assay was performed using also pure GLY. Our results show that GBH induced in zebrafish brain a decrease in cell viability, inhibited mitochondrial complex enzymatic activity, modulated gene expression related to mitochondrial complexes, induced an increase in RS production, promoted hyperpolarization of mitochondrial membrane, and induced behavioral impairments. Together, our data contributes to the knowledge of the neurotoxic effects of GBH. Mitochondrial dysfunction has been recognized as a relevant cellular response that should not be disregarded. Moreover, this study pointed to the mitochondria as an important target of GBH. Copyright © 2018 Elsevier Ltd. All rights reserved.

Concentrations, profiles, and estimated human exposures for polychlorinated dibenzo-p-dioxins and dibenzofurans from electronic waste recycling facilities and a chemical industrial complex in Eastern China.

PubMed

Ma, Jing; Kannan, Kurunthachalam; Cheng, Jinping; Horii, Yuichi; Wu, Qian; Wang, Wenhua

2008-11-15

Environmental pollution arising from electronic waste (e-waste) disposal and recycling has received considerable attention in recent years. Treatment, at low temperatures, of e-wastes that contain polyvinylchloride and related polymers can release polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs). Although several studies have reported trace metals and polybrominated diphenyl ethers (PBDEs) released from e-waste recycling operations, environmental contamination and human exposure to PCDD/Fs from e-waste recycling operations are less well understood. In this study, electronic shredder waste and dust from e-waste facilities, and leaves and surface soil collected in the vicinity of a large scale e-waste recycling facility in Taizhou, Eastern China, were analyzed for total PCDD/ Fs including 2,3,7,8-substituted congeners. We also determined PCDD/Fs in surface agricultural soils from several provinces in China for comparison with soils from e-waste facilities. Concentrations of total PCDD/Fs were high in all of the matrices analyzed and ranged from 30.9 to 11400 pg/g for shredder waste, 3460 to 9820 pg/g dry weight for leaves, 2560 to 148000 pg/g dry weight for workshop-floor dust, and 854 to 10200 pg/g dry weight for soils. We also analyzed surface soils from a chemical industrial complex (a coke-oven plant, a coal-fired power plant, and a chlor-alkali plant) in Shanghai. Concentrations of total PCDD/Fs in surface soil (44.5-531 pg/g dry wt) from the chemical industrial complex were lower than the concentrations found in soils from e-waste recycling plants, but higher than the concentrations found in agricultural soils. Agricultural soils from six cities in China contained low levels (3.44-33.8 pg/g dry wt) of total PCDD/Fs. Profiles of dioxin toxic equivalents (TEQs) of 2,3,7,8-PCDD/Fs in soils from e-waste facilities in Taizhou differed from the profiles found in agricultural soils. The estimated daily intakes of TEQs of PCDD/ Fs via soil/dust ingestion

Surface effects and desorption of tetracycline supramolecular complex on bovine dentine.

PubMed

Pataro, A L; Franco, C F; Santos, V R; Cortés, M E; Sinisterra, R D

2003-03-01

The aim of this in vitro study was to evaluate the antimicrobial activity, the substantivity, and surface effects of the inclusion compound tetracycline: beta-cyclodextrin on bovine roots. The antimicrobial activity was assessed by dentine slabs which had been immersed in the inclusion complex in concentrations 8.0%, 4.0%, 2.0%, 1.0%, 0.5% and 0.25% for 5min compared to a control of tetracycline hydrochloride. Each slab was tested in a broth of overnight culture of Actinobacillus actinomycetemcomitans (Y4-FDC). The inclusion complex significantly inhibited the A. actinomycetemcomitans (p<0.01) verified at concentrations from 1.0% to 8.0%. The substantivity of tetracycline was evaluated by the measure of desorption from the slabs previously immersed in solution samples and removed at 24h intervals. The tetracycline encapsulated in beta-cyclodextrin showed a flow rate near to zero order in comparison to free tetracycline. The surface morphology determined by SEM showed a more homogeneous and integrated layer with the complex compared to the effect of free tetracycline. We concluded that the root surfaces treated with tetracycline: beta-cyclodextrin release lower concentrations of active drug over 5 days at inhibitory concentrations against A. actinomycetemcomitans with enhanced disponibility in comparison to tetracycline.

Concentration Measurements in a Cold Flow Model Annular Combustor Using Laser Induced Fluorescence

NASA Technical Reports Server (NTRS)

Morgan, Douglas C.

1996-01-01

A nonintrusive concentration measurement method is developed for determining the concentration distribution in a complex flow field. The measurement method consists of marking a liquid flow with a water soluble fluorescent dye. The dye is excited by a two dimensional sheet of laser light. The fluorescent intensity is shown to be proportional to the relative concentration level. The fluorescent field is recorded on a video cassette recorder through a video camera. The recorded images are analyzed with image processing hardware and software to obtain intensity levels. Mean and root mean square (rms) values are calculated from these intensity levels. The method is tested on a single round turbulent jet because previous concentration measurements have been made on this configuration by other investigators. The previous results were used to comparison to qualify the current method. These comparisons showed that this method provides satisfactory results. 'Me concentration measurement system was used to measure the concentrations in the complex flow field of a model gas turbine annular combustor. The model annular combustor consists of opposing primary jets and an annular jet which discharges perpendicular to the primary jets. The mixing between the different jet flows can be visualized from the calculated mean and rms profiles. Concentration field visualization images obtained from the processing provide further qualitative information about the flow field.

Comparison of AERMOD and CALPUFF models for simulating SO2 concentrations in a gas refinery.

PubMed

Atabi, Farideh; Jafarigol, Farzaneh; Moattar, Faramarz; Nouri, Jafar

2016-09-01

In this study, concentration of SO2 from a gas refinery located in complex terrain was calculated by the steady-state, AERMOD model, and nonsteady-state CALPUFF model. First, in four seasons, SO2 concentrations emitted from 16 refinery stacks, in nine receptors, were obtained by field measurements, and then the performance of both models was evaluated. Then, the simulated results for SO2 ambient concentrations made by each model were compared with the results of the observed concentrations, and model results were compared among themselves. The evaluation of the two models to simulate SO2 concentrations was based on the statistical analysis and Q-Q plots. Review of statistical parameters and Q-Q plots has shown that, according to the evaluation of estimations made, performance of both models to simulate the concentration of SO2 in the region can be considered acceptable. The results showed the AERMOD composite ratio between simulated values made by models and the observed values in various receptors for all four average times is 0.72, whereas CALPUFF's ratio is 0.89. However, in the complex conditions of topography, CALPUFF offers better agreement with the observed concentrations.

Formation of lactoferrin/sodium caseinate complexes and their adsorption behaviour at the air/water interface.

PubMed

Li, Quanyang; Zhao, Zhengtao

2017-10-01

This research investigated the complexation behaviour between lactoferrin (Lf) and sodium caseinate (NaCas) before and after heat treatment. The results showed that heating facilitated their interaction and different complexes were formed at different Lf/NaCas ratios. The presence of low concentrations of NaCas resulted in the rapid precipitation of Lf, while no precipitation was observed at the NaCas concentrations higher than Lf/NaCas ratio of 2:1. The formed complexes at the ratio of 2:1 have an average diameter of 194±9.0nm and they exhibited a great capacity in lowering the air/water interfacial tension. Further increase of NaCas concentration to ratios of 1:1 and 1:2 resulted in the formation of smaller complexes with average diameters of 60±2.5nm. The complexes formed at these two ratios showed similar adsorption behaviour at the air/water interface and they exhibited lower capacity in decreasing the interfacial tension than the ratio of 2:1. Copyright © 2017 Elsevier Ltd. All rights reserved.

Influence of Hydrophobicity on Polyelectrolyte Complexation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sadman, Kazi; Wang, Qifeng; Chen, Yaoyao

Polyelectrolyte complexes are a fascinating class of soft materials that can span the full spectrum of mechanical properties from low-viscosity fluids to glassy solids. This spectrum can be accessed by modulating the extent of electrostatic association in these complexes. However, to realize the full potential of polyelectrolyte complexes as functional materials, their molecular level details need to be clearly correlated with their mechanical response. The present work demonstrates that by making simple amendments to the chain architecture, it is possible to affect the salt responsiveness of polyelectrolyte complexes in a systematic manner. This is achieved by quaternizing poly(4-vinylpyridine) (QVP) withmore » methyl, ethyl, and propyl substituents—thereby increasing the hydrophobicity with increasing side chain length—and complexing them with a common anionic polyelectrolyte, poly(styrenesulfonate). The mechanical behavior of these complexes is compared to the more hydrophilic system of poly(styrenesulfonate) and poly(diallyldimethylammonium) by quantifying the swelling behavior in response to salt stimuli. More hydrophobic complexes are found to be more resistant to doping by salt, yet the mechanical properties of the complex remain contingent on the overall swelling ratio of the complex itself, following near universal swelling–modulus master curves that are quantified in this work. Furthermore, the rheological behaviors of QVP complex coacervates are found to be approximately the same, only requiring higher salt concentrations to overcome strong hydrophobic interactions, demonstrating that hydrophobicity can be used as an important parameter for tuning the stability of polyelectrolyte complexes in general, while still preserving the ability to be processed “saloplastically”.« less

Influence of Hydrophobicity on Polyelectrolyte Complexation

DOE PAGES

Sadman, Kazi; Wang, Qifeng; Chen, Yaoyao; ...

2017-11-16

Polyelectrolyte complexes are a fascinating class of soft materials that can span the full spectrum of mechanical properties from low-viscosity fluids to glassy solids. This spectrum can be accessed by modulating the extent of electrostatic association in these complexes. However, to realize the full potential of polyelectrolyte complexes as functional materials, their molecular level details need to be clearly correlated with their mechanical response. The present work demonstrates that by making simple amendments to the chain architecture, it is possible to affect the salt responsiveness of polyelectrolyte complexes in a systematic manner. This is achieved by quaternizing poly(4-vinylpyridine) (QVP) withmore » methyl, ethyl, and propyl substituents—thereby increasing the hydrophobicity with increasing side chain length—and complexing them with a common anionic polyelectrolyte, poly(styrenesulfonate). The mechanical behavior of these complexes is compared to the more hydrophilic system of poly(styrenesulfonate) and poly(diallyldimethylammonium) by quantifying the swelling behavior in response to salt stimuli. More hydrophobic complexes are found to be more resistant to doping by salt, yet the mechanical properties of the complex remain contingent on the overall swelling ratio of the complex itself, following near universal swelling–modulus master curves that are quantified in this work. Furthermore, the rheological behaviors of QVP complex coacervates are found to be approximately the same, only requiring higher salt concentrations to overcome strong hydrophobic interactions, demonstrating that hydrophobicity can be used as an important parameter for tuning the stability of polyelectrolyte complexes in general, while still preserving the ability to be processed “saloplastically”.« less

A comparative study of the biosorption of iron(III)-cyanide complex anions to Rhizopus arrhizus and Chlorella vulgaris

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aksu, Z.; Calik, A.

1999-03-01

In this study a comparative biosorption of iron(III)-cyanide complex anions from aqueous solutions to Rhizopus arrhizus and Chlorella vulgaris was investigated. The iron(III)-cyanide complex ion-binding capacities of the biosorbents were shown as a function of initial pH, initial iron(III)-cyanide complex ion, and biosorbent concentrations. The results indicated that a significant reduction of iron(III)-cyanide complex ions was achieved at pH 13, a highly alkaline condition for both the biosorbents. The maximum loading capacities of the biosorbents were found to be 612.2 mg/g for R.arrhizus at 1,996.2 mg/L initial iron(III)-cyanide complex ion concentration and 387.0 mg/g for C. vulgaris at 845.4 mg/Lmore » initial iron(III)-cyanide complex ion concentration at this pH. The Freundlich, Langmuir, and Redlich-Peterson adsorption models were fitted to the equilibrium data at pH 3, 7, and 13. The equilibrium data of the biosorbents could be best fitted by all the adsorption models over the entire concentration range at pH 13.« less

Influence of novel gallium complexes on the homeostasis of some biochemical and hematological parameters in rats.

PubMed

Gârban, Gabriela; Silaghi-Dumitrescu, Radu; Ioniţă, Hortensia; Gârban, Zeno; Hădărugă, Nicoleta-Gabriela; Ghibu, George-Daniel; Baltă, Cornel; Simiz, Florin-Dan; Mitar, Carmen

2013-12-01

The aim of this study was to detect possible homeostasis changes in some biochemical and hematological parameters after the administration of gallium (Ga) complexes C (24) and C (85) on an experimental animal model (Wistar strain rats). In order to observe chronobiological aspects, a morning (m) and an evening (e) animal series were constituted. Further on, each series were divided into three groups: control (C), experimental I (EI), and experimental II (EII). Both Ga complexes were solubilized in a carrier solution containing polyethylene glycol (PEG) 400, water, and ethanol. Animals of the C groups received the carrier solution by intraperitoneal injection, those from the EI groups received the solubilized C(24) gallium complex, and those of the EII groups received the solubilized C(85) gallium complex. At the end of the experiment, blood and tissue samples were taken and the following parameters were determined: serum concentration of the nonprotein nitrogenous compounds (uric acid, creatinine, and blood urea nitrogen), hematological parameters (erythrocytes, hemoglobin, leukocytes, and platelets), and the kidney tissue concentration of three essential trace elements (Fe, Cu, and Zn). With the exception of uric acid, the results revealed increased concentrations of the nonprotein nitrogenous compounds both in the morning and in the evening experimental groups. Hematological data showed increased levels of erythrocytes, hemoglobin, and leukocytes and decreased platelet levels in the experimental group given the C(24) gallium complex in the morning (EI-m) group; increased levels of leukocytes and decreased levels of the other parameters in the experimental group given the C(24) gallium complex in the evening (EI-e) group; and increased levels of all hematological parameters in the experimental groups receiving the C(85) gallium complex in the morning (EII-m) group and in the evening (EII-e) group. Decreased kidney tissue concentrations of metals were found in all

Chemical behavior of Cu, Zn, Cd, and Pb in a eutrophic reservoir: speciation and complexation capacity.

PubMed

Tonietto, Alessandra Emanuele; Lombardi, Ana Teresa; Choueri, Rodrigo Brasil; Vieira, Armando Augusto Henriques

2015-10-01

This research aimed at evaluating cadmium (Cd), copper (Cu), lead (Pb), and zinc (Zn) speciation in water samples as well as determining water quality parameters (alkalinity, chlorophyll a, chloride, conductivity, dissolved organic carbon, dissolved oxygen, inorganic carbon, nitrate, pH, total suspended solids, and water temperature) in a eutrophic reservoir. This was performed through calculation of free metal ions using the chemical equilibrium software MINEQL+ 4.61, determination of labile, dissolved, and total metal concentrations via differential pulse anodic stripping voltammetry, and determination of complexed metal by the difference between the total concentration of dissolved and labile metal. Additionally, ligand complexation capacities (CC), such as the strength of the association of metals-ligands (logK'ML) and ligand concentrations (C L) were calculated via Ruzic's linearization method. Water samples were taken in winter and summer, and the results showed that for total and dissolved metals, Zn > Cu > Pb > Cd concentration. In general, higher concentrations of Cu and Zn remained complexed with the dissolved fraction, while Pb was mostly complexed with particulate materials. Chemical equilibrium modeling (MINEQL+) showed that Zn(2+) and Cd(2+) dominated the labile species, while Cu and Pb were complexed with carbonates. Zinc was a unique metal for which a direct relation between dissolved species with labile and complexed forms was obtained. The CC for ligands indicated a higher C L for Cu, followed by Pb, Zn, and Cd in decreasing amounts. Nevertheless, the strength of the association of all metals and their respective ligands was similar. Factor analysis with principal component analysis as the extraction procedure confirmed seasonal effects on water quality parameters and metal speciation. Total, dissolved, and complexed Cu and total, dissolved, complexed, and labile Pb species were all higher in winter, whereas in summer, Zn was mostly present in the

Groundwater cleanup demonstrations at Complex 34, CCAS

NASA Technical Reports Server (NTRS)

2000-01-01

At Launch Complex 34, the Six-Phase Soil Heating site that is involved in a groundwater cleanup project can be seen. The project involves the Department of Defense, Environmental Protection Agency, Department of Energy and NASA. Concentrations of trichloroethylene solvent have been identified in the soil at the complex as a result of cleaning methods for rocket parts during the Apollo Program, which used the complex, in the 60s. The group formed the Interagency NDAPL Consortium (IDC) to study three contamination cleanup technologies: Six-Phase Soil Heating, Steam Injection and In Situ Oxidation with Potassium Permanganate. All three methods may offer a way to remove the contaminants in months instead of decades. In the background is the block house for the complex. KSC hosted a two-day conference that presented information and demonstrations of the three technologies being tested at the site.

The kinetics of lanthanide complexation by EDTA and DTPA in lactate media.

PubMed

Nash, K L; Brigham, D; Shehee, T C; Martin, A

2012-12-28

The interaction of trivalent lanthanide and actinide cations with polyaminopolycarboxylic acid complexing agents in lactic acid buffer systems is an important feature of the chemistry of the TALSPEAK process for the separation of trivalent actinides from lanthanides. To improve understanding of metal ion coordination chemistry in this process, the results of an investigation of the kinetics of lanthanide complexation by ethylenediamine-N,N,N',N'-tetraacetic acid (EDTA) and diethylenetriamine-N,N,N',N'',N''-pentaacetic acid (DTPA) in 0.3 M lactic acid/0.3 M ionic strength solution are reported. Progress of the reaction was monitored using the distinctive visible spectral changes attendant to lanthanide complexation by the colorimetric indicator ligand Arsenazo III, which enables the experiment but plays no mechanistic role. Under the conditions of these experiments, the reactions occur in a time regime suitable for study by stopped-flow spectrophotometric techniques. Experiments have been conducted as a function of EDTA/DTPA ligand concentration, total lactic acid concentration, and pH. The equilibrium perturbation reaction proceeds as a first order approach to equilibrium over a wide range of conditions, allowing the simultaneous determination of complex formation and dissociation rate constants. The rate of the complexation reaction has been determined for the entire lanthanide series (except Pm(3+)). The predominant pathway for lanthanide-EDTA and lanthanide-DTPA dissociation is inversely dependent on the total lactate concentration; the complex formation reaction demonstrates a direct dependence on [H(+)]. Unexpectedly, the rate of the complex formation reaction is seen in both ligand systems to be fastest for Gd(3+). Correlation of these results indicates that in 0.3 M lactate solutions the exchange of lanthanide ions between lactate complexes and the polyaminopolycarboxylate govern the process.

Improving permeability and oral absorption of mangiferin by phospholipid complexation.

PubMed

Ma, Hequn; Chen, Hongming; Sun, Le; Tong, Lijin; Zhang, Tianhong

2014-03-01

Mangiferin is an active ingredient of medicinal plant with poor hydrophilicity and lipophilicity. Many reports focused on improving aqueous solubility, but oral bioavailability of mangiferin was still limited. In this study, we intended to increase not only solubility, but also membrane permeability of mangiferin by a phospholipid complexation technique. The new complex's physicochemical properties were characterized in terms of scanning electron microscopy (SEM), differential scanning calorimetry (DSC), infrared absorption spectroscopy (IR), aqueous solubility, oil-water partition coefficient and in vitro dissolution. The intestinal absorption of the complex was studied by the rat in situ intestinal perfusion model. After oral administration of mangiferin-phospholipid complex and crude mangiferin in rats, the concentrations of mangiferin were determined by a validated RP-HPLC method. Results showed that the solubility of the complex in water and in n-octanol was enhanced and the oil-water partition coefficient was improved by 6.2 times and the intestinal permeability in rats was enhanced significantly. Peak plasma concentration and AUC of mangiferin from the complex (Cmax: 377.66 μg/L, AUC: 1039.94 μg/L*h) were higher than crude mangiferin (Cmax: 180 μg/L, AUC: 2355.63 μg/L*h). In view of improved solubility and enhanced permeability, phospholipid complexation technique can increase bioavailability of mangiferin by 2.3 times in comparison to the crude mangiferin. Copyright © 2013 Elsevier B.V. All rights reserved.

Establishment of a rat model of thrombosis induced by intravenous injection of anti-phosphatidylserine-prothrombin complex antibody.

PubMed

Yamada, Mai; Kawakami, Tamihiro; Takashima, Kohei; Nishioka, Yusuke; Nishibata, Yuka; Masuda, Sakiko; Yoshida, Shigeru; Tomaru, Utano; Ishizu, Akihiro

2017-06-01

Recent studies have suggested that aPS-PT antibody is one of the most relevant autoantibodies to APS. This study aimed to demonstrate the pathogenicity of aPS-PT antibody in vivo . At first, cultured rat vascular endothelial cells (RECs) were exposed to calf thymus-derived histones. Two hours later, lactate dehydrogenase release from the RECs and expression of PS on the cell surface were assessed. Next, we administered an i.v. injection of calf thymus-derived histones into Wistar rats (12.5 µg/g weight of 8-week-old female rats), and 2 h later they were given an i.v. injection of aPS-PT mAb (1.25 mg/g weight, n = 6) or an equal dose of rat IgM as controls (n = 5). Three days later, histological examination was conducted. Calf thymus-derived histones (>12.5 µg/ml) could injure RECs in vitro . Simultaneously, annexin V could bind to the RECs; thereby, this result indicated that cell-free histone exposure of vascular endothelial cells induced cell surface expression of PS, which is naturally present inside the plasma membrane. Thrombosis developed with higher frequency in the rats given an i.v. injection of aPS-PT mAb than in controls. We established a rat model of thrombosis induced by i.v. injection of aPS-PT mAb. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology.

A framework for evaluating complex networks measurements

NASA Astrophysics Data System (ADS)

Comin, Cesar H.; Silva, Filipi N.; Costa, Luciano da F.

2015-06-01

A good deal of current research in complex networks involves the characterization and/or classification of the topological properties of given structures, which has motivated several respective measurements. This letter proposes a framework for evaluating the quality of complex-network measurements in terms of their effective resolution, degree of degeneracy and discriminability. The potential of the suggested approach is illustrated with respect to comparing the characterization of several model and real-world networks by using concentric and symmetry measurements. The results indicate a markedly superior performance for the latter type of mapping.

Modeling the CAPTEX Vertical Tracer Concentration Profiles.

NASA Astrophysics Data System (ADS)

Draxler, Roland R.; Stunder, Barbara J. B.

1988-05-01

Perfluorocarbon tracer concentration profiles measured by aircraft 600-900 km downwind of the release locations during CAPTEX are discussed and compared with some model results. In general, the concentrations decreased with height in the upper half of the boundary layer where the aircraft measurements were made. The results of a model sensitivity study suggested that the shape of the profile was primarily due to winds increasing with height and relative position of the sampling with respect to the upwind and downwind edge of the plume. Further modeling studies showed that relatively simple vertical mixing parameterizations could account for the complex vertical plume structure when the model had sufficient vertical resolution. In general, the model performed better with slower winds and corresponding longer transport times.

Antibacterial, antibiofilm and antioxidant screening of copper(II)-complexes with some S-alkyl derivatives of thiosalicylic acid. Crystal structure of the binuclear copper(II)-complex with S-propyl derivative of thiosalicylic acid

NASA Astrophysics Data System (ADS)

Bukonjić, Andriana M.; Tomović, Dušan Lj.; Nikolić, Miloš V.; Mijajlović, Marina Ž.; Jevtić, Verica V.; Ratković, Zoran R.; Novaković, Slađana B.; Bogdanović, Goran A.; Radojević, Ivana D.; Maksimović, Jovana Z.; Vasić, Sava M.; Čomić, Ljiljana R.; Trifunović, Srećko R.; Radić, Gordana P.

2017-01-01

The spectroscopically predicted structure of the obtained copper(II)-complex with S-propyl derivative of thiosalicylic acid was confirmed by X-ray structural study. The binuclear copper(II)-complex with S-propyl derivative of thiosalicylic acid crystallized in two polymorphic forms with main structural difference in the orientation of phenyl rings relative to corresponding carboxylate groups. The antibacterial activity was tested determining the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) by using microdilution method. The influence on bacterial biofilm formation was determined by tissue culture plate method. In general, the copper(II)-complexes manifested a selective and moderate activity. The most sensitive bacteria to the effects of Cu(II)-complexes was a clinical isolate of Pseudomonas aeruginosa. For this bacteria MIC and biofilm inhibitory concentration (BIC) values for all tested complexes were in the range or better than the positive control, doxycycline. Also, for the established biofilm of clinical isolate Staphylococcus aureus, BIC values for the copper(II)-complex with S-ethyl derivative of thiosalicylic acid,[Cu2(S-et-thiosal)4(H2O)2] (C3) and copper(II)-complex with S-butyl derivative of thiosalicylic acid, [Cu2(S-bu-thiosal)4(H2O)2] (C5) were in range or better than the positive control. All the complexes acted better against Gram-positive bacteria (Staphylococcus aureus and Staphylococcus aureus ATCC 25923) than Gram-negative bacteria (Proteus mirabilis ATCC 12453, Pseudomonas aeruginosa, and P. aeruginosa ATCC 27855). The complexes showed weak antioxidative properties tested by two methods (1,1-diphenyl-2-picrylhydrazyl (DPPH) and reducing power assay).

Chirality-selected phase behaviour in ionic polypeptide complexes

DOE PAGES

Perry, Sarah L.; Leon, Lorraine; Hoffmann, Kyle Q.; ...

2015-01-14

In this study, polyelectrolyte complexes present new opportunities for self-assembled soft matter. Factors determining whether the phase of the complex is solid or liquid remain unclear. Ionic polypeptides enable examination of the effects of stereochemistry on complex formation. Here we demonstrate that chirality determines the state of polyelectrolyte complexes, formed from mixing dilute solutions of oppositely charged polypeptides, via a combination of electrostatic and hydrogen-bonding interactions. Fluid complexes occur when at least one of the polypeptides in the mixture is racemic, which disrupts backbone hydrogen-bonding networks. Pairs of purely chiral polypeptides, of any sense, form compact, fibrillar solids with amore » β-sheet structure. Analogous behaviour occurs in micelles formed from polypeptide block copolymers with polyethylene oxide, where assembly into aggregates with either solid or fluid cores, and eventually into ordered phases at high concentrations, is possible. Chirality is an exploitable tool for manipulating material properties in polyelectrolyte complexation.« less

Complexation of Nickel Ions by Boric Acid or (Poly)borates.

PubMed

Graff, Anais; Barrez, Etienne; Baranek, Philippe; Bachet, Martin; Bénézeth, Pascale

2017-01-01

An experiment based on electrochemical reactions and pH monitoring was performed in which nickel ions were gradually formed by oxidation of a nickel metal electrode in a solution of boric acid. Based on the experimental results and aqueous speciation modeling, the evolution of pH showed the existence of significant nickel-boron complexation. A triborate nickel complex was postulated at high boric acid concentrations when polyborates are present, and the equilibrium constants were determined at 25, 50 and 70 °C. The calculated enthalpy and entropy at 25 °C for the formation of the complex from boric acid and Ni 2+ ions are respectively equal to (65.6 ± 3.1) kJ·mol -1 and (0.5 ± 11.1) J·K -1 ·mol -1 . The results of this study suggest that complexation of nickel ions by borates can significantly enhance the solubility of nickel metal and nickel oxide depending on the concentration of boric acid and pH. First principles calculations were investigated and tend to show that the complex is thermodynamically stable and the nickel cation in solution should interact more strongly with the [Formula: see text] than with boric acid.

The impact of tertiary wastewater treatment on copper and zinc complexation.

PubMed

Constantino, C; Gardner, M; Comber, S D W; Scrimshaw, M D; Ellor, B

2015-01-01

Tightening quality standards for European waters has seen a move towards enhanced wastewater treatment technologies such as granulated organic carbon treatment and ozonation. Although these technologies are likely to be successful in degrading certain micro-organic contaminants, these may also destroy compounds which would otherwise complex and render metals significantly less toxic. This study examined the impact of enhanced tertiary treatment on the capacity of organic compounds within sewage effluents to complex copper and zinc. The data show that granulated organic carbon treatment removes a dissolved organic carbon (DOC) fraction that is unimportant to complexation such that no detrimental impact on complexation or metal bioavailability is likely to occur from this treatment type. High concentrations of ozone (>1 mg O3/mg DOC) are, however, likely to impact the complexation capacity for copper although this is unlikely to be important at the concentrations of copper typically found in effluent discharges or in rivers. Ozone treatment did not affect zinc complexation capacity. The complexation profiles of the sewage effluents show these to contain a category of non-humic ligand that appears unaffected by tertiary treatment and which displays a high affinity for zinc, suggesting these may substantially reduce the bioavailability of zinc in effluent discharges. The implication is that traditional metal bioavailability assessment approaches such as the biotic ligand model may overestimate zinc bioavailability in sewage effluents and effluent-impacted waters.

In vitro biopharmaceutical evaluation of ciprofloxacin/metal cation complexes for pulmonary administration.

PubMed

Brillault, J; Tewes, F; Couet, W; Olivier, J C

2017-01-15

Pulmonary delivery of fluoroquinolones (FQs) is an interesting approach to treat lung infections as it may lead to high local concentrations while minimizing systemic exposure. However, FQs have a rapid diffusion through the lung epithelium giving the pulmonary route no advantage compared to the oral route. Interactions between FQs and metal cations form complexes which limit the diffusion through the epithelial barrier and would reduce the absorption of FQs and maintain high concentrations in the lung. The effects of this complexation depend on the FQ and the metal cations and optimum partners should be selected through in vitro experiments prior to aerosol drug formulation. In this study, CIP was chosen as a representative FQ and 5 cations (Ca 2+ , Mg 2+ , Zn 2+ , Al 3+ , Cu 2+ ) were selected to study the complexation and its effects on permeability, antimicrobial efficacy and cell toxicity. The results showed that the apparent association constants between CIP and cations ranked with the descending order: Cu 2+ >Al 3+ >Zn 2+ >Mg 2+ >Ca 2+ . When a target of 80% complexation was reached with the adequate concentrations of cations, the CIP permeability through the Calu-3 lung epithelial cells was decreased of 50%. Toxicity of the CIP on the Calu-3 cells, with an EC50 evaluated at 7μM, was not significantly affected by the presence of the cations. The minimum inhibitory concentration of CIP for Pseudomonas aeruginosa was not affected or slightly increased in the range of cation concentrations tested, except for Mg 2+ . In conclusion, permeability was the main parameter that was affected by the metal cation complexation while cell toxicity and antimicrobial activity were not or slightly modified. Cu 2+ , with the highest apparent constant of association and with no effect on cell toxicity and antimicrobial activity of the CIP, appeared as a promising cation for the development of a controlled-permeability formulation of CIP for lung treatment. Copyright © 2016

Dissolved metals and associated constituents in abandoned coal-mine discharges, Pennsylvania, USA. Part 2: Geochemical controls on constituent concentrations

USGS Publications Warehouse

Cravotta, C.A.

2008-01-01

Water-quality data for discharges from 140 abandoned mines in the Anthracite and Bituminous Coalfields of Pennsylvania reveal complex relations among the pH and dissolved solute concentrations that can be explained with geochemical equilibrium models. Observed values of pH ranged from 2.7 to 7.3 in the coal-mine discharges (CMD). Generally, flow rates were smaller and solute concentrations were greater for low-pH CMD samples; pH typically increased with flow rate. Although the frequency distribution of pH was similar for the anthracite and bituminous discharges, the bituminous discharges had smaller median flow rates; greater concentrations of SO4, Fe, Al, As, Cd, Cu, Ni and Sr; comparable concentrations of Mn, Cd, Zn and Se; and smaller concentrations of Ba and Pb than anthracite discharges with the same pH values. The observed relations between the pH and constituent concentrations can be attributed to (1) dilution of acidic water by near-neutral or alkaline ground water; (2) solubility control of Al, Fe, Mn, Ba and Sr by hydroxide, sulfate, and/or carbonate minerals; and (3) aqueous SO4-complexation and surface-complexation (adsorption) reactions. The formation of AlSO4+ and AlHSO42 + complexes adds to the total dissolved Al concentration at equilibrium with Al(OH)3 and/or Al hydroxysulfate phases and can account for 10-20 times greater concentrations of dissolved Al in SO4-laden bituminous discharges compared to anthracite discharges at pH of 5. Sulfate complexation can also account for 10-30 times greater concentrations of dissolved FeIII concentrations at equilibrium with Fe(OH)3 and/or schwertmannite (Fe8O8(OH)4.5(SO4)1.75) at pH of 3-5. In contrast, lower Ba concentrations in bituminous discharges indicate that elevated SO4 concentrations in these CMD sources could limit Ba concentrations by the precipitation of barite (BaSO4). Coprecipitation of Sr with barite could limit concentrations of this element. However, concentrations of dissolved Pb, Cu, Cd, Zn

Reactivity of the cadmium ion in concentrated phosphoric acid solutions.

PubMed

De Gyves, J; Gonzales, J; Louis, C; Bessiere, J

1989-07-01

The solvation transfer coefficients which characterize the changes of ion reactivity with phosphoric acid concentration have been calculated for cadmium from the constants of the successive chloride complexes, and for silver and diethyldithiophosphate from potentiometric measurements. They evidence the strong desolvation of the cadmium species in concentrated phosphoric acid media, causing a remarkable increase of its reactivity. They allow the results of liquid-liquid extraction, precipitation and flotation reactions to be correctly interpreted and their changes to be foreseen when the reagents are modified.

Evidence for Carbonate Surface Complexation during Forsterite Carbonation in Wet Supercritical Carbon Dioxide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Loring, John S.; Chen, Jeffrey; Benezeth, Pascale

Continental flood basalts are attractive formations for geologic sequestration of carbon dioxide because of their reactive divalent-cation containing silicates, such as forsterite (Mg2SiO4), suitable for long-term trapping of CO2 mineralized as metal carbonates. The goal of this study was to investigate at a molecular level the carbonation products formed during the reaction of forsterite with supercritical CO2 (scCO2) as a function of the concentration of H2O adsorbed to the forsterite surface. Experiments were performed at 50 °C and 90 bar using an in situ IR titration capability, and post-reaction samples were examined by ex situ techniques, including SEM, XPS, FIB-TEM,more » TGA-MS, and MAS-NMR. Carbonation products and reaction extents varied greatly with adsorbed H2O. We show for the first time evidence of Mg-carbonate surface complexation under wet scCO2 conditions. Carbonate is found to be coordinated to Mg at the forsterite surface in a predominately bidentate fashion at adsorbed H2O concentrations below 27 µmol/m2. Above this concentration and up to 76 µmol/m2, monodentate coordinated complexes become dominant. Beyond a threshold adsorbed H2O concentration of 76 µmol/m2, crystalline carbonates continuously precipitate as magnesite, and the particles that form are hundreds of times larger than the estimated thicknesses of the adsorbed water films of about 7 to 15 Å. At an applied level, the implication of these results is that mineral trapping in scCO2 dominated fluids will be insignificant and limited to surface complexation unless adsorbed H2O concentrations are high enough to promote crystalline carbonate formation. At a fundamental level, the surface complexes and their dependence on adsorbed H2O concentration give insights regarding forsterite dissolution processes and magnesite nucleation and growth.« less

Actin-related protein 2/3 complex-based actin polymerization is critical for male fertility.

PubMed

Lee, J S; Kwon, W S; Rahman, M S; Yoon, S J; Park, Y J; Pang, M G

2015-09-01

The actin-related protein 2/3 (Arp2/3) complex is critical for regulation of actin polymerization, which is associated with sperm motility and capacitation status. However, the function of the Arp2/3 complex in male fertility has not yet been fully elucidated. Therefore, this study was designed to investigate the role of the Arp2/3 complex in different processes in spermatozoa and its consequences on fertilization and early embryonic development. In this in vitro study, mouse spermatozoa were incubated with different concentrations (10, 100, and 500 μm) of CK-636, an Arp2/3 complex antagonist. Our results demonstrated that inhibition of the Arp2/3 complex by high concentrations (100 and 500 μm) of CK-636 induced hyper-activated motility and acrosomal reaction, whereas intracellular calcium and tyrosine phosphorylation levels in spermatozoa were inhibited. Moreover, exposure of spermatozoa to the highest concentration of CK-636 reduced fertilization and embryo development. Interestingly, fertilization was significantly increased after treatment with 100 μm CK-636, whereas embryonic development was significantly decreased. Therefore, we conclude that the Arp2/3 complex plays a decisive role in regulation of sperm function and male fertility via actin polymerization. We anticipate that the Arp2/3 complex may have clinical application as marker for male fertility and male contraceptive targeting. © 2015 American Society of Andrology and European Academy of Andrology.

Influence of Hydrophobicity on Polyelectrolyte Complexation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sadman, Kazi; Wang, Qifeng; Chen, Yaoyao

Polyelectrolyte complexes are a fascinating class of soft materials that can span the full spectrum of mechanical properties from low viscosity fluids to glassy solids. This spectrum can be accessed by modulating the extent of electrostatic association in these complexes. However, to realize the full potential of polyelectrolyte complexes as functional materials their molecular level details need to be clearly correlated with their mechanical response. The present work demonstrates that by making simple amendments to the chain architecture it is possible to affect the salt responsiveness of polyelectrolyte complexes in a systematic manner. This is achieved by quaternizing poly(4-vinylpyridine) (QVP)more » with methyl, ethyl and propyl substituents– thereby increasing the hydrophobicity with increasing side chain length– and complexing them with a common anionic polyelectrolyte, poly(styrene sulfonate). The mechanical 1 ACS Paragon Plus Environment behavior of these complexes is compared to the more hydrophilic system of poly(styrene sulfonate) and poly(diallyldimethylammonium) by quantifying the swelling behavior in response to salt stimuli. More hydrophobic complexes are found to be more resistant to doping by salt, yet the mechanical properties of the complex remain contingent on the overall swelling ratio of the complex itself, following near universal swelling-modulus master curves that are quantified in this work. The rheological behavior of QVP complex coacervates are found to be approximately the same, only requiring higher salt concentrations to overcome strong hydrophobic interactions, demonstrating that hydrophobicity can be used as an important parameter for tuning the stability of polyelectrolyte complexes in general, while still preserving the ability to be processed “saloplastically”.« less

Complexation between carrageenan and methylene blue for sensor design

NASA Astrophysics Data System (ADS)

Ling, Yew Pei; Heng, Lee Yook

2013-11-01

Theoretical studies on the methylene blue (MB)-carrageenans complexation at solution and solid states have been carried out via ultraviolet spectrophotoscopy and reflectometry methods. The equilibrium constant (Ka) of the MBcarrageenans complexation follows the order of Iota > Lambda > Kappa carrageenans, which indicated Iota-carrageenan forms a stable complex. MB-carrageenan complexation reaction showed decrease in Ka value from 210.71 ppm-1 to 114.57 ppm-1 when the reaction temperature increased from 298 K to 323 K. Le Chatelier's principle and mass action law explained that the MB-carrageenan complexation was an exothermic reaction (ΔH=-18.54 kJmol-1) that release heat. Thus MB-carrageenan complex was less stable at high temperature and tend to dissociate into free MB and carrageenan molecules. It was also supported by the van't Hoff equation. The reaction is a spontaneous process (ΔG=-13.23 kJmol-1) where the randomness of the molecules reduced (ΔS=-17.83 Jmol-1K-1) due to complexation. Besides, linear regression of the concentration and absorption of the MB-carrageenan reaction obeys the Beer Lambert law, which elucidated that the complexation process was not affected by any concentration dependent factors such as aggregation and self-quenching. Moreover, linear Benesi Hilderbrend plot revealed that the interaction between MB and carrageenan was a reversible and stoichiometric reaction with 1:1 ratio. However, the molar extinction coefficient (ɛ) and molar adsorption coefficient (μa) of the MB-carrageenan complex were lower compared to free MB, described that the complex was less adsorptive. The sensor constructed based on these theoretical investigations showed response behavior that was similar with solution test as both have attraction for carrageenans in the sequence of Iota-, Lambda-, Kappa- carrageenans. Likewise, carrageenan sensor was more selective towards Iota-carrageenan than to Lambda- and Kappa-carrageenans, and no response observed when

Cost analysis of carbon dioxide concentrators

NASA Technical Reports Server (NTRS)

Yakut, M. M.

1973-01-01

Methodology and cost estimating relationships, for flight-type and prototype CO2 concentrators, have been developed and presented. A validity check was made by comparing the molecular sieves system considered here and that developed for Skylab. The system evaluated here is twice the size of the Skylab system and is also more complex as it desorbs CO2 thermally and stores it in an accumulator. The cost estimates developed were found to be approximately 50 to 70% higher than the actual cost of the Skylab unit.

Weak polyelectrolyte complexation driven by associative charging.

PubMed

Rathee, Vikramjit S; Zervoudakis, Aristotle J; Sidky, Hythem; Sikora, Benjamin J; Whitmer, Jonathan K

2018-03-21

Weak polyelectrolytes are relevant for a wide range of fields; in particular, they have been investigated as "smart" materials for chemical separations and drug delivery. The charges on weak polyelectrolytes are dynamic, causing polymer chains to adopt different equilibrium conformations even with relatively small changes to the surrounding environment. Currently, there exists no comprehensive picture of this behavior, particularly where polymer-polymer interactions have the potential to affect charging properties significantly. In this study, we elucidate the novel interplay between weak polyelectrolyte charging and complexation behavior through coupled molecular dynamics and Monte Carlo simulations. Specifically, we investigate a model of two equal-length and oppositely charging polymer chains in an implicit salt solution represented through Debye-Hückel interactions. The charging tendency of each chain, along with the salt concentration, is varied to determine the existence and extent of cooperativity in charging and complexation. Strong cooperation in the charging of these chains is observed at large Debye lengths, corresponding to low salt concentrations, while at lower Debye lengths (higher salt concentrations), the chains behave in apparent isolation. When the electrostatic coupling is long-ranged, we find that a highly charged chain strongly promotes the charging of its partner chain, even if the environment is unfavorable for an isolated version of that partner chain. Evidence of this phenomenon is supported by a drop in the potential energy of the system, which does not occur at the lower Debye lengths where both potential energies and charge fractions converge for all partner chain charging tendencies. The discovery of this cooperation will be helpful in developing "smart" drug delivery mechanisms by allowing for better predictions for the dissociation point of delivery complexes.

Weak polyelectrolyte complexation driven by associative charging

NASA Astrophysics Data System (ADS)

Rathee, Vikramjit S.; Zervoudakis, Aristotle J.; Sidky, Hythem; Sikora, Benjamin J.; Whitmer, Jonathan K.

2018-03-01

Weak polyelectrolytes are relevant for a wide range of fields; in particular, they have been investigated as "smart" materials for chemical separations and drug delivery. The charges on weak polyelectrolytes are dynamic, causing polymer chains to adopt different equilibrium conformations even with relatively small changes to the surrounding environment. Currently, there exists no comprehensive picture of this behavior, particularly where polymer-polymer interactions have the potential to affect charging properties significantly. In this study, we elucidate the novel interplay between weak polyelectrolyte charging and complexation behavior through coupled molecular dynamics and Monte Carlo simulations. Specifically, we investigate a model of two equal-length and oppositely charging polymer chains in an implicit salt solution represented through Debye-Hückel interactions. The charging tendency of each chain, along with the salt concentration, is varied to determine the existence and extent of cooperativity in charging and complexation. Strong cooperation in the charging of these chains is observed at large Debye lengths, corresponding to low salt concentrations, while at lower Debye lengths (higher salt concentrations), the chains behave in apparent isolation. When the electrostatic coupling is long-ranged, we find that a highly charged chain strongly promotes the charging of its partner chain, even if the environment is unfavorable for an isolated version of that partner chain. Evidence of this phenomenon is supported by a drop in the potential energy of the system, which does not occur at the lower Debye lengths where both potential energies and charge fractions converge for all partner chain charging tendencies. The discovery of this cooperation will be helpful in developing "smart" drug delivery mechanisms by allowing for better predictions for the dissociation point of delivery complexes.

Biases in field measurements of ice nuclei concentrations

NASA Astrophysics Data System (ADS)

Garimella, S.; Voigtländer, J.; Kulkarni, G.; Stratmann, F.; Cziczo, D. J.

2015-12-01

Ice nuclei (IN) play an important role in the climate system by influencing cloud properties, precipitation, and radiative transfer. Despite their importance, there are significant uncertainties in estimating IN concentrations because of the complexities of atmospheric ice nucleation processes. Field measurements of IN concentrations with Continuous Flow Diffusion Chamber (CFDC) IN counters have been vital to constrain IN number concentrations and have led to various parameterizations of IN number vs. temperature and particle concentration. These parameterizations are used in many global climate models, which are very sensitive to the treatment of cloud microphysics. However, due to non-idealities in CFDC behavior, especially at high relative humidity, many of these measurements are likely biased too low. In this study, the extent of this low bias is examined with laboratory experiments at a variety of instrument conditions using the SPectrometer for Ice Nucleation, a commercially-available CFDC-style chamber. These laboratory results are compared to theoretical calculations and computational fluid dynamics models to map the variability of this bias as a function of chamber temperature and relative humidity.

Analysis and generation of groundwater concentration time series

NASA Astrophysics Data System (ADS)

Crăciun, Maria; Vamoş, Călin; Suciu, Nicolae

2018-01-01

Concentration time series are provided by simulated concentrations of a nonreactive solute transported in groundwater, integrated over the transverse direction of a two-dimensional computational domain and recorded at the plume center of mass. The analysis of a statistical ensemble of time series reveals subtle features that are not captured by the first two moments which characterize the approximate Gaussian distribution of the two-dimensional concentration fields. The concentration time series exhibit a complex preasymptotic behavior driven by a nonstationary trend and correlated fluctuations with time-variable amplitude. Time series with almost the same statistics are generated by successively adding to a time-dependent trend a sum of linear regression terms, accounting for correlations between fluctuations around the trend and their increments in time, and terms of an amplitude modulated autoregressive noise of order one with time-varying parameter. The algorithm generalizes mixing models used in probability density function approaches. The well-known interaction by exchange with the mean mixing model is a special case consisting of a linear regression with constant coefficients.

Viscothermal Coupling Effects on Sound Attenuation in Concentrated Colloidal Dispersions.

NASA Astrophysics Data System (ADS)

Han, Wei

1995-11-01

This thesis describes a Unified Coupled Phase Continuum (UCPC) model to analyze sound propagation through aerosols, emulsions and suspensions in terms of frequency dependent attenuation coefficient and sound speed. Expressions for the viscous and thermal coupling coefficients explicitly account for the effects of particle size, shape factor, orientation as well as concentration and the sound frequency. The UCPC model also takes into account the intrinsic acoustic absorption within the fluid medium due to its viscosity and heat conductivity. The effective complex wave number as a function of frequency is derived. A frequency- and concentration-dependent complex Nusselt number for the interfacial thermal coupling coefficient is derived using an approximate similarity between the 'viscous skin drag' and 'heat conduction flux' associated with the discontinuous suspended phase, on the basis of a cell model. The theoretical predictions of attenuation spectra provide satisfactory agreement with reported experimental data on two concentrated suspensions (polystyrene latex and kaolin pigment), two concentrated emulsions (toluene -in-water, n-hexadecane-in-water), and two aerosols (oleic acid droplets-in-nitrogen, alumina-in-air), covering a wide range of relative magnitudes (from 10^ {-3} to 10^{3}) of thermal versus viscous contributions, for dispersed phase volume fractions as high as 50%. The relative differences between the additive result of separate viscous and thermal loss estimates and combined viscothermal absorption results are also presented. Effects of particle shape on viscous attenuation of sound in concentrated suspensions of non-spherical clay particles are studied. Attenuation spectra for 18 frequencies from 3 to 100 MHz are measured and analyzed for eleven kaolin clay slurries with solid concentrations ranging from 0.6% to 35% (w/w). A modified viscous drag coefficient that considers frequency, concentration, particle size, shape and orientation of

Influence of chemical disorder on energy dissipation and defect evolution in concentrated solid solution alloys

DOE PAGES

Zhang, Yanwen; Stocks, George Malcolm; Jin, Ke; ...

2015-10-28

A long-standing objective in materials research is to understand how energy is dissipated in both the electronic and atomic subsystems in irradiated materials, and how related non-equilibrium processes may affect defect dynamics and microstructure evolution. Here we show that alloy complexity in concentrated solid solution alloys having both an increasing number of principal elements and altered concentrations of specific elements can lead to substantial reduction in the electron mean free path and thermal conductivity, which has a significant impact on energy dissipation and consequentially on defect evolution during ion irradiation. Enhanced radiation resistance with increasing complexity from pure nickel tomore » binary and to more complex quaternary solid solutions is observed under ion irradiation up to an average damage level of 1 displacement per atom. Understanding how materials properties can be tailored by alloy complexity and their influence on defect dynamics may pave the way for new principles for the design of radiation tolerant structural alloys.« less

Evaluation of the stability of uranyl peroxo-carbonato complex ions in carbonate media at different temperatures.

PubMed

Kim, Kwang-Wook; Lee, Keun-Young; Chung, Dong-Yong; Lee, Eil-Hee; Moon, Jei-Kwon; Shin, Dong-Woo

2012-09-30

This work studied the stability of peroxide in uranyl peroxo carbonato complex ions in a carbonate solution with hydrogen peroxide using absorption and Raman spectroscopies, and evaluated the temperature dependence of the decomposition characteristics of uranyl peroxo carbonato complex ions in the solution. The uranyl peroxo carbonato complex ions self-decomposed more rapidly into uranyl tris-carbonato complex ions in higher temperature carbonate solutions. The concentration of peroxide in the solution without free hydrogen peroxide represents the concentration of uranyl peroxo carbonato complex ions in a mixture of uranyl peroxo carbonato complex and uranyl tris-carbonato complex ions. The self-decomposition of the uranyl peroxo carbonato complex ions was a first order reaction, and its activation energy was evaluated to be 7.144×10(3) J mol(-1). The precipitation of sodium uranium oxide hydroxide occurred when the amount of uranyl tris-carbonato complex ions generated from the decomposition of the uranyl peroxo carbonato complex ions exceeded the solubility of uranyl tris-carbonato ions in the solution at the solution temperature. Copyright © 2012 Elsevier B.V. All rights reserved.

Pneumatic tube system transport does not alter platelet function in optical and whole blood aggregometry, prothrombin time, activated partial thromboplastin time, platelet count and fibrinogen in patients on anti-platelet drug therapy

PubMed Central

Enko, Dietmar; Mangge, Harald; Münch, Andreas; Niedrist, Tobias; Mahla, Elisabeth; Metzler, Helfried; Prüller, Florian

2017-01-01

Introduction The aim of this study was to assess pneumatic tube system (PTS) alteration on platelet function by the light transmission aggregometry (LTA) and whole blood aggregometry (WBA) method, and on the results of platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen. Materials and methods Venous blood was collected into six 4.5 mL VACUETTE® 9NC coagulation sodium citrate 3.8% tubes (Greiner Bio-One International GmbH, Kremsmünster, Austria) from 49 intensive care unit (ICU) patients on dual anti-platelet therapy and immediately hand carried to the central laboratory. Blood samples were divided into 2 Groups: Group 1 samples (N = 49) underwent PTS (4 m/s) transport from the central laboratory to the distant laboratory and back to the central laboratory, whereas Group 2 samples (N = 49) were excluded from PTS forces. In both groups, LTA and WBA stimulated with collagen, adenosine-5’-diphosphate (ADP), arachidonic acid (AA) and thrombin-receptor-activated-peptide 6 (TRAP-6) as well as platelet count, PT, APTT, and fibrinogen were performed. Results No statistically significant differences were observed between blood samples with (Group 1) and without (Group 2) PTS transport (P values from 0.064 – 0.968). The AA-induced LTA (bias: 68.57%) exceeded the bias acceptance limit of ≤ 25%. Conclusions Blood sample transportation with computer controlled PTS in our hospital had no statistically significant effects on platelet aggregation determined in patients with anti-platelet therapy. Although AA induced LTA showed a significant bias, the diagnostic accuracy was not influenced. PMID:28392742

Acquired antiprothrombin antibodies: an unusual cause of bleeding.

PubMed

Carvalho, Cristiana; Viveiro, Carolina; Maia, Paulo; Rezende, Teresa

2013-01-07

Acquired inhibitors of coagulation causing bleeding manifestations are rare in children. They emerge, normally in the context of autoimmune diseases or drug ingestion, but transient and self-limiting cases can occur after viral infection. We describe, an otherwise healthy, 7-year-old girl who had gingival bleeding after a tooth extraction. The prothrombin time (PT) and the activated partial thromboplastin time (APTT) were both prolonged with evidence of an immediate acting inhibitor (lupic anticoagulant). Further coagulation studies demonstrated prothrombin (FII) deficiency and prothrombin directed (FII) antibodies. The serological tests to detect an underlying autoimmune disease were all negative. The coagulation studies normalised alongside the disappearance of the antibody. This article presents lupus anticoagulant hypoprothrombinaemia syndrome (LAHS) as a rare case of acquired bleeding diathesis in childhood.

Complexation of buffer constituents with neutral complexation agents: part I. Impact on common buffer properties.

PubMed

Riesová, Martina; Svobodová, Jana; Tošner, Zdeněk; Beneš, Martin; Tesařová, Eva; Gaš, Bohuslav

2013-09-17

The complexation of buffer constituents with the complexation agent present in the solution can very significantly influence the buffer properties, such as pH, ionic strength, or conductivity. These parameters are often crucial for selection of the separation conditions in capillary electrophoresis or high-pressure liquid chromatography (HPLC) and can significantly affect results of separation, particularly for capillary electrophoresis as shown in Part II of this paper series (Beneš, M.; Riesová, M.; Svobodová, J.; Tesařová, E.; Dubský, P.; Gaš, B. Anal. Chem. 2013, DOI: 10.1021/ac401381d). In this paper, the impact of complexation of buffer constituents with a neutral complexation agent is demonstrated theoretically as well as experimentally for the model buffer system composed of benzoic acid/LiOH or common buffers (e.g., CHES/LiOH, TAPS/LiOH, Tricine/LiOH, MOPS/LiOH, MES/LiOH, and acetic acid/LiOH). Cyclodextrins as common chiral selectors were used as model complexation agents. We were not only able to demonstrate substantial changes of pH but also to predict the general complexation characteristics of selected compounds. Because of the zwitterion character of the common buffer constituents, their charged forms complex stronger with cyclodextrins than the neutral ones do. This was fully proven by NMR measurements. Additionally complexation constants of both forms of selected compounds were determined by NMR and affinity capillary electrophoresis with a very good agreement of obtained values. These data were advantageously used for the theoretical descriptions of variations in pH, depending on the composition and concentration of the buffer. Theoretical predictions were shown to be a useful tool for deriving some general rules and laws for complexing systems.

Is it acceptable to use coagulation plasma samples stored at room temperature and 4°C for 24 hours for additional prothrombin time, activated partial thromboplastin time, fibrinogen, antithrombin, and D-dimer testing?

PubMed

Rimac, V; Coen Herak, D

2017-10-01

Coagulation laboratories are faced on daily basis with requests for additional testing in already analyzed fresh plasma samples. This prompted us to examine whether plasma samples stored at room temperature (RT), and 4°C for 24 hours can be accepted for additional prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen (Fbg), antithrombin (AT), and D-dimer testing. We measured PT, aPTT, Fbg in 50 and AT in 30 plasma samples with normal and pathological values, within 4 hours of blood collection (baseline results) and after 24-hours storage at RT (primary tubes), and 4°C (aliquots). D-dimer stability was investigated in 20 samples stored in primary tubes at 4°C. No statistically significant difference between baseline results and results in samples stored at RT and 4°C was observed for PT (P=.938), aPTT (P=.186), Fbg (P=.962), AT (P=.713), and D-dimers (P=.169). The highest median percentage changes were found for aPTT, being more pronounced for samples stored at 4°C (13.0%) than at RT (8.7%). Plasma samples stored both at RT and 4°C for 24 hours are acceptable for additional PT, Fbg, and AT testing. Plasma samples stored 24 hours in primary tubes at 4°C are suitable for D-dimer testing. © 2017 John Wiley & Sons Ltd.

Supercharging Protein Complexes from Aqueous Solution Disrupts their Native Conformations

NASA Astrophysics Data System (ADS)

Sterling, Harry J.; Kintzer, Alexander F.; Feld, Geoffrey K.; Cassou, Catherine A.; Krantz, Bryan A.; Williams, Evan R.

2012-02-01

The effects of aqueous solution supercharging on the solution- and gas-phase structures of two protein complexes were investigated using traveling-wave ion mobility-mass spectrometry (TWIMS-MS). Low initial concentrations of m-nitrobenzyl alcohol ( m-NBA) in the electrospray ionization (ESI) solution can effectively increase the charge of concanavalin A dimers and tetramers, but at higher m-NBA concentrations, the increases in charge are accompanied by solution-phase dissociation of the dimers and up to a ~22% increase in the collision cross section (CCS) of the tetramers. With just 0.8% m-NBA added to the ESI solution of a ~630 kDa anthrax toxin octamer complex, the average charge is increased by only ~4% compared with the "native" complex, but it is sufficiently destabilized so that extensive gas-phase fragmentation occurs in the relatively high pressure regions of the TWIMS device. Anthrax toxin complexes exist in either a prechannel or a transmembrane channel state. With m-NBA, the prechannel state of the complex has the same CCS/charge ratio in the gas phase as the transmembrane channel state of the same complex formed without m-NBA, yet undergoes extensive dissociation, indicating that destabilization from supercharging occurs in the ESI droplet prior to ion formation and is not a result of Coulombic destabilization in the gas phase as a result of higher charging. These results demonstrate that the supercharging of large protein complexes is the result of conformational changes induced by the reagents in the ESI droplets, where enrichment of the supercharging reagent during droplet evaporation occurs.

Humic acid protein complexation

NASA Astrophysics Data System (ADS)

Tan, W. F.; Koopal, L. K.; Weng, L. P.; van Riemsdijk, W. H.; Norde, W.

2008-04-01

Interactions of purified Aldrich humic acid (PAHA) with lysozyme (LSZ) are investigated. In solution LSZ is moderately positively and PAHA negatively charged at the investigated pH values. The proton binding of PAHA and of LSZ is determined by potentiometric proton titrations at various KCl concentrations. It is also measured for two mixtures of PAHA-LSZ and compared with theoretically calculated proton binding assuming no mutual interaction. The charge adaptation due to PAHA-LSZ interaction is relatively small and only significant at low and high pH. Next to the proton binding, the mass ratio PAHA/LSZ at the iso-electric point (IEP) of the complex at given solution conditions is measured together with the pH using the Mütek particle charge detector. From the pH changes the charge adaptation due to the interaction can be found. Also these measurements show that the net charge adaptation is weak for PAHA-LSZ complexes at their IEP. PAHA/LSZ mass ratios in the complexes at the IEP are measured at pH 5 and 7. At pH 5 and 50 mmol/L KCl the charge of the complex is compensated for 30-40% by K +; at pH 7, where LSZ has a rather low positive charge, this is 45-55%. At pH 5 and 5 mmol/L KCl the PAHA/LSZ mass ratio at the IEP of the complex depends on the order of addition. When LSZ is added to PAHA about 25% K + is included in the complex, but no K + is incorporated when PAHA is added to LSZ. The flocculation behavior of the complexes is also different. After LSZ addition to PAHA slow precipitation occurs (6-24 h) in the IEP, but after addition of PAHA to LSZ no precipitation can be seen after 12 h. Clearly, PAHA/LSZ complexation and the colloidal stability of PAHA-LSZ aggregates depend on the order of addition. Some implications of the observed behavior are discussed.

Conditions for duality between fluxes and concentrations in biochemical networks

PubMed Central

Fleming, Ronan M.T.; Vlassis, Nikos; Thiele, Ines; Saunders, Michael A.

2016-01-01

Mathematical and computational modelling of biochemical networks is often done in terms of either the concentrations of molecular species or the fluxes of biochemical reactions. When is mathematical modelling from either perspective equivalent to the other? Mathematical duality translates concepts, theorems or mathematical structures into other concepts, theorems or structures, in a one-to-one manner. We present a novel stoichiometric condition that is necessary and sufficient for duality between unidirectional fluxes and concentrations. Our numerical experiments, with computational models derived from a range of genome-scale biochemical networks, suggest that this flux-concentration duality is a pervasive property of biochemical networks. We also provide a combinatorial characterisation that is sufficient to ensure flux-concentration duality. The condition prescribes that, for every two disjoint sets of molecular species, there is at least one reaction complex that involves species from only one of the two sets. When unidirectional fluxes and molecular species concentrations are dual vectors, this implies that the behaviour of the corresponding biochemical network can be described entirely in terms of either concentrations or unidirectional fluxes. PMID:27345817

Conditions for duality between fluxes and concentrations in biochemical networks

DOE PAGES

Fleming, Ronan M. T.; Vlassis, Nikos; Thiele, Ines; ...

2016-06-23

Mathematical and computational modelling of biochemical networks is often done in terms of either the concentrations of molecular species or the fluxes of biochemical reactions. When is mathematical modelling from either perspective equivalent to the other? Mathematical duality translates concepts, theorems or mathematical structures into other concepts, theorems or structures, in a one-to-one manner. We present a novel stoichiometric condition that is necessary and sufficient for duality between unidirectional fluxes and concentrations. Our numerical experiments, with computational models derived from a range of genome-scale biochemical networks, suggest that this flux-concentration duality is a pervasive property of biochemical networks. We alsomore » provide a combinatorial characterisation that is sufficient to ensure flux-concentration duality.The condition prescribes that, for every two disjoint sets of molecular species, there is at least one reaction complex that involves species from only one of the two sets. When unidirectional fluxes and molecular species concentrations are dual vectors, this implies that the behaviour of the corresponding biochemical network can be described entirely in terms of either concentrations or unidirectional fluxes« less

Conditions for duality between fluxes and concentrations in biochemical networks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fleming, Ronan M. T.; Vlassis, Nikos; Thiele, Ines

Mathematical and computational modelling of biochemical networks is often done in terms of either the concentrations of molecular species or the fluxes of biochemical reactions. When is mathematical modelling from either perspective equivalent to the other? Mathematical duality translates concepts, theorems or mathematical structures into other concepts, theorems or structures, in a one-to-one manner. We present a novel stoichiometric condition that is necessary and sufficient for duality between unidirectional fluxes and concentrations. Our numerical experiments, with computational models derived from a range of genome-scale biochemical networks, suggest that this flux-concentration duality is a pervasive property of biochemical networks. We alsomore » provide a combinatorial characterisation that is sufficient to ensure flux-concentration duality.The condition prescribes that, for every two disjoint sets of molecular species, there is at least one reaction complex that involves species from only one of the two sets. When unidirectional fluxes and molecular species concentrations are dual vectors, this implies that the behaviour of the corresponding biochemical network can be described entirely in terms of either concentrations or unidirectional fluxes« less

Polydopamine-based concentric nanoshells with programmable architectures and plasmonic properties.

PubMed

Choi, Chun Kit K; Zhuo, Xiaolu; Chiu, Yee Ting Elaine; Yang, Hongrong; Wang, Jianfang; Choi, Chung Hang Jonathan

2017-11-09

Nanoshells, classically comprising gold as the metallic component and silica as the dielectric material, are important for fundamental studies in nanoplasmonics. They also empower a myriad of applications, including sensing, energy harvesting, and cancer therapy. Yet, laborious preparation precludes the development of next-generation nanoshells with structural complexity, compositional diversity, and tailorable plasmonic behaviors. This work presents an efficient approach to the bottom-up assembly of concentric nanoshells. By employing polydopamine as the dielectric material and exploiting its intrinsic adhesiveness and pH-tunable surface charge, the growth of each shell only takes 3-4 hours at room temperature. A series of polydopamine-based concentric nanoshells with programmable nanogap thickness, elemental composition (gold and silver), and geometrical configuration (number of layers) is prepared, followed by extensive structural characterization. Four of the silver-containing nanostructures are newly reported. Systematic investigations into the plasmonic properties of concentric nanoshells as a function of their structural parameters further reveal multiple Fano resonances and local-field "hot spots", infrequently reported plasmonic features for individual nanostructures fabricated using bottom-up wet chemistry. These results establish materials design rules for engineering complex plasmon-based systems originating from the integration of multiple plasmonic elements into defined locations within a compact nanostructure.

Potentiation of the anticoagulation effect of warfarin by the herbal remedy Shu-Jing-Hwo-Shiee-Tang in rats: The dosing regimen and pharmacokinetic interaction.

PubMed

Ueng, Yune-Fang; Lu, Chung-Kuang; Yang, Sien-Hung; Wang, Hong-Jaan; Huang, Chiung-Chiao

2017-02-01

The herbal remedy Shu-Jing-Hwo-Shiee-Tang (SJHST) has been used in traditional Chinese medical care for the treatment of osteoarthritis. This study aims to examine the influence of SJHST on the oxidation and anticoagulation effect of warfarin in male rats. In three SJHST preparations (S1-S3), hesperidin, gentiopicrin, and paeoniflorin were identified as chemical marker ingredients. The inhibition of liver microsomal warfarin 7-hydroxylation (WOH) activity by 50% methanolic extracts of SJHST was potentiated by β-glucosidase pretreatment, but not by NADPH-fortified microsomal preincubation. Among various ingredients and their β-glucosidase-hydrolyzed products, hesperetin caused the most potent inhibition of WOH. Oral administration of S2 to rats at 2 h after warfarin treatment (WS2 2-h post ), but not co-treatment (WS2 co ), decreased warfarin clearance and increased the maximal plasma concentration and the area under the curve (AUC 0-t , AUC 0-∞ ) of plasma concentration versus time of warfarin administration. S2 and S3 did not change the coagulation parameters. At 24 h after warfarin administration, the WS2 2-h post and WS3 2-h post groups had a prothrombin time longer than that of the warfarin group. These results demonstrate that a 2-h post-treatment of rats with SJHST caused pharmacokinetic interaction with warfarin, resulting in prothrombin time prolongation. Copyright © 2016 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

[Partial parenteral nutrition in severe virus hepatitis].

PubMed

Kleinberger, G; Schneeweiss, B; Druml, W; Laggner, A; Lenz, K

1984-03-01

Patients with severe virus hepatitis and a prothrombin concentration below 25% have a bad prognosis. This is due to direct consequences of hepatic failure and to the rather frequent complications of this disease. The clinical course of such patients is essentially dependent upon the degree of liver regeneration, which again is dependent upon the mass of hepatocytes which are able to regenerate and upon the so called hepatotrophic factors. Patients with severe hepatitis suffer during the first weeks rather frequently from nausea and loss of appetite and for that reason their nutrition is insufficient. In the study recorded here 9 cases were investigated (7 patients with hepatitis B, 2 patients with hepatitis non A non B). The question was asked, if partial parenteral nutrition in addition to a liver diet not containing meat would improve liver function. It could be shown that the prothrombin concentration, which could not be improved by vitamine K1 supplements, was increased during a 7 day parenteral nutrition period from 19,3 +/- 2,9% to 41,5 +/- 8,1% (p less than 0,05), serum albumine and cholinesterase activity improved as well. During the first day of treatment there was a significant fall of ammoniac from 115 +/- 10 mumol to 73 +/- 10 mumol/l (p less than 0,05), at the same time production of urea did not increase. All patients survived. The results show, that parenteral nutrition can improve liver function and decrease the catabolic status of metabolism.

Stochastic analysis of concentration field in a wake region.

PubMed

Yassin, Mohamed F; Elmi, Abdirashid A

2011-02-01

Identifying geographic locations in urban areas from which air pollutants enter the atmosphere is one of the most important information needed to develop effective mitigation strategies for pollution control. Stochastic analysis is a powerful tool that can be used for estimating concentration fluctuation in plume dispersion in a wake region around buildings. Only few studies have been devoted to evaluate applications of stochastic analysis to pollutant dispersion in an urban area. This study was designed to investigate the concentration fields in the wake region using obstacle model such as an isolated building model. We measured concentration fluctuations at centerline of various downwind distances from the source, and different heights with the frequency of 1 KHz. Concentration fields were analyzed stochastically, using the probability density functions (pdf). Stochastic analysis was performed on the concentration fluctuation and the pdf of mean concentration, fluctuation intensity, and crosswind mean-plume dispersion. The pdf of the concentration fluctuation data have shown a significant non-Gaussian behavior. The lognormal distribution appeared to be the best fit to the shape of concentration measured in the boundary layer. We observed that the plume dispersion pdf near the source was shorter than the plume dispersion far from the source. Our findings suggest that the use of stochastic technique in complex building environment can be a powerful tool to help understand the distribution and location of air pollutants.

Assessment of regional air quality by a concentration-dependent Pollution Permeation Index

PubMed Central

Liang, Chun-Sheng; Liu, Huan; He, Ke-Bin; Ma, Yong-Liang

2016-01-01

Although air quality monitoring networks have been greatly improved, interpreting their expanding data in both simple and efficient ways remains challenging. Therefore, needed are new analytical methods. We developed such a method based on the comparison of pollutant concentrations between target and circum areas (circum comparison for short), and tested its applications by assessing the air pollution in Jing-Jin-Ji, Yangtze River Delta, Pearl River Delta and Cheng-Yu, China during 2015. We found the circum comparison can instantly judge whether a city is a pollution permeation donor or a pollution permeation receptor by a Pollution Permeation Index (PPI). Furthermore, a PPI-related estimated concentration (original concentration plus halved average concentration difference) can be used to identify some overestimations and underestimations. Besides, it can help explain pollution process (e.g., Beijing’s PM2.5 maybe largely promoted by non-local SO2) though not aiming at it. Moreover, it is applicable to any region, easy-to-handle, and able to boost more new analytical methods. These advantages, despite its disadvantages in considering the whole process jointly influenced by complex physical and chemical factors, demonstrate that the PPI based circum comparison can be efficiently used in assessing air pollution by yielding instructive results, without the absolute need for complex operations. PMID:27731344

Spectroscopic and structural study of the newly synthesized heteroligand complex of copper with creatinine and urea.

PubMed

Gangopadhyay, Debraj; Singh, Sachin Kumar; Sharma, Poornima; Mishra, Hirdyesh; Unnikrishnan, V K; Singh, Bachcha; Singh, Ranjan K

2016-02-05

Study of copper complex of creatinine and urea is very important in life science and medicine. In this paper, spectroscopic and structural study of a newly synthesized heteroligand complex of copper with creatinine and urea has been discussed. Structural studies have been carried out using DFT calculations and spectroscopic analyses were carried out by FT-IR, Raman, UV-vis absorption and fluorescence techniques. The copper complex of creatinine and the heteroligand complex were found to have much increased water solubility as compared to pure creatinine. The analysis of FT-IR and Raman spectra helps to understand the coordination properties of the two ligands and to determine the probable structure of the heteroligand complex. The LIBS spectra of the heteroligand complex reveal that the complex is free from other metal impurities. UV-visible absorption spectra and the fluorescence emission spectra of the aqueous solution of Cu-Crn-urea heteroligand complex at different solute concentrations have been analyzed and the complex is found to be rigid and stable in its monomeric form at very low concentrations. Copyright © 2015 Elsevier B.V. All rights reserved.

Calculating the True and Observed Rates of Complex Heterogeneous Catalytic Reactions

NASA Astrophysics Data System (ADS)

Avetisov, A. K.; Zyskin, A. G.

2018-06-01

Equations of the theory of steady-state complex reactions are considered in matrix form. A set of stage stationarity equations is given, and an algorithm is described for deriving the canonic set of stationarity equations with appropriate corrections for the existence of fast stages in a mechanism. A formula for calculating the number of key compounds is presented. The applicability of the Gibbs rule to estimating the number of independent compounds in a complex reaction is analyzed. Some matrix equations relating the rates of dependent and key substances are derived. They are used as a basis to determine the general diffusion stoichiometry relationships between temperature, the concentrations of dependent reaction participants, and the concentrations of key reaction participants in a catalyst grain. An algorithm is described for calculating heat and mass transfer in a catalyst grain with respect to arbitrary complex heterogeneous catalytic reactions.

Increased Levels of Metalloproteinase 10 and Hemostatic Markers in Patients With Noncomplicated Primary Varicose Veins.

PubMed

Dzieciuchowicz, Lukasz; Espinosa, Gaudencio; Páramo, José A

2015-10-01

The purpose of the study was to analyze a systemic activation of hemostasis and concentration of matrix metalloproteinase 10 (MMP-10) in patients with primary varicose veins (PVVs). A study group consisted of 41 patients with noncomplicated PVVs. A control group consisted of 30 age- and sex-matched healthy individuals without varicose veins. The concentration of d-dimers (DD), prothrombin fragments 1 and 2 (F1+2), antigen of von Willebrand factor (vWF), and activity of plasminogen activator inhibitor (PAI-1) in plasma and concentration of MMP-10 in serum were analyzed. In patients with PVVs, higher concentrations of DD (P < .001), F1+2 (P < .001), vWF (P = .027), MMP-10 (P = .006), and higher activity of PAI-1 (P < .001) were observed. However, no correlation between the concentrations of MMP-10 and prothrombotic markers was found. Noncomplicated PVVs are associated with systemic, prothrombotic activation of hemostasis and increased concentration of MMP-10, suggesting a prothrombotic and proinflammatory state. © The Author(s) 2014.

In vitro/in vivo effect of Citrus limon (L. Burm. f.) juice on blood parameters, coagulation and anticoagulation factors in rabbits.

PubMed

Riaz, Azra; Khan, Rafeeq Alam; Mirza, Talat; Mustansir, Tazeen; Ahmed, Mansoor

2014-07-01

The genus Citrus of the family Rutaceae includes many species e.g. Citrus indica, Citrus aurantifolia and Citrus limon, among which Citrus limon L. Burm. f. has been reported to have highest antimicrobial activity. It is used as antidote against certain venom, due to its platelet inhibitory effect and also reported to have hypocholesterolemic effect. However its anticoagulant and thrombolytic effect were not been investigated, hence a prospective in-vitro/in-vivo study was designed to determine the effect of Citrus limon on blood parameters, coagulation and anticoagulation factors. In-vitro tests revealed highly significant increase in thrombin time and activated partial thromboplastin time by Citrus limon, whereas fibrinogen concentration was significantly reduced in comparison to control, however prothrombin time was not affected significantly. In-vivo testing of Citrus limon was done at three different doses i.e. 0.2ml/kg, 0.4ml/kg and 0.6ml/kg in healthy rabbits. Significant changes were observed in hematological parameters such as erythrocytes, hemoglobin and mean corpuscular hemoglobin concentration. Bleeding time and thrombin time was significantly prolonged and there was increase in protein C and thrombin antithrombin complex levels. These results may be due to inactivation of thrombin because it significantly decreases fibrinogen concentration and inhibit platelet aggregation. Citrus limon showed maximal anticoagulant effect at 0.4ml/kg, which suggest that Citrus limon possesses an anti-thrombin component and could prevent thrombosis playing a cardio protective role.

Airborne pollutant characteristics in an urban, industrial and agricultural complex metroplex with high emission loading and ammonia concentration.

PubMed

Tsai, Jiun-Horng; Chang, Li-Peng; Chiang, Hung-Lung

2014-10-01

The size distribution of particulate mass and water-soluble ionic constituents and their gaseous precursors was investigated in a subtropical area, southern Taiwan. Field sampling and chemical analysis of particulate matter (PM) were conducted using a Micro Orifice Uniform Deposition Impactor (MOUDI) and a Nano-MOUDI, and gaseous pollutants were determined by a denuder-filter pack system. PM size mass distribution, mass concentration and ionic species concentration were measured during the day and at night in the winter and summer. Average PM concentrations in the winter were as high as 132 ± 42 μg/m(3), and PM mass concentrations in the summer were as low as 38 ± 19 μg/m(3). Generally, PM concentration was 111 ± 60 μg/m(3) at night, which was 20% higher than that in the daytime. The size-segregated mass distribution of PM mass concentration was over 85% in the 0.1-3.2 μm range. Ammonium, nitrate, and sulfate were the dominant water-soluble ionic species in PM, contributing 34%-48% of PM mass. High ammonia (12.9-49 μg/m(3)) and SO2 (2.6-27 μg/m(3)) were observed in the gas precursors. The molar ratio [Formula: see text] was 3.18 ± 1.20 at PM1.0, which indicated that the PM was rich in ammonium. Therefore, the excess ammonium could neutralize nitrate to form ammonium nitrate, after the more stable ammonium sulfate and ammonium bisulfate formation. Copyright © 2014 Elsevier B.V. All rights reserved.

Complex conductivity response to silver nanoparticles in ...

EPA Pesticide Factsheets

The increase in the use of nanoscale materials in consumer products has resulted in a growing concern of their potential hazard to ecosystems and public health from their accidental or intentional introduction to the environment. Key environmental, health, and safety research needs include knowledge and methods for their detection, characterization, fate, and transport. Specifically, techniques available for the direct detection and quantification of their fate and transport in the environment are limited. Their small size, high surface area to volume ratio, interfacial, and electrical properties make metallic nanoparticles, such as silver nanoparticles, good targets for detection using electrical geophysical techniques. Here we measured the complex conductivity response to silver nanoparticles in sand columns under varying moisture conditions (0–30%), nanoparticle concentrations (0–10 mg/g), lithology (presence of clay), pore water salinity (0.0275 and 0.1000 S/m), and particle size (35, 90–210 and 1500–2500 nm). Based on the Cole-Cole relaxation models we obtained the chargeability and the time constant. We demonstrate that complex conductivity can detect silver nanoparticles in porous media with the response enhanced by higher concentrations of silver nanoparticles, moisture content, ionic strength, clay content and particle diameter. Quantification of the volumetric silver nanoparticles content in the porous media can also be obtained from complex co

Pore water distributions of dissolved copper and copper-complexing ligands in estuarine and coastal marine sediments

NASA Astrophysics Data System (ADS)

Skrabal, Stephen A.; Donat, John R.; Burdige, David J.

2000-06-01

The distributions and seasonal variability of total dissolved Cu (TDCu) and Cu-complexing ligands in sediment pore waters have been investigated at two contrasting sites in the Chesapeake Bay. Two ligand classes, which differ on the basis of the conditional stability constants ( K'cond) of their Cu complexes, were detected at all depths at both sites. At the sulfidic, muddy, mid-Bay Sta. M, concentrations and values of log K'cond ranged from 390-12,500 nM and ≥7.2->8.9, respectively, for the stronger ligand class ( L1 S) and 75-6,420 nM and 6.2-7.9 for the weaker ligand class ( L2 S). At the bioturbated, sandy Sta. S in the lower Bay, respective concentrations and values of log K'cond ranged from 135-807 nM and ≥7.6-≥10.2 for L1 S and 40-1,410 nM and 6.6-9.2 for L2 S. For comparison, one pore water profile from a slope station off of the Chesapeake Bay also showed the presence of two ligand classes, with respective concentrations and values of log K'cond of 140-270 nM and 8->11 for L1 S and 30-180 nM and 7-10 for L2 S. These ligands are in large excess relative to ambient TDCu concentrations (<0.1-24.3 nM), thereby maintaining very low inorganic Cu concentrations (typically <0.1 to <100 pM) and a high degree of organic complexation (87.2->99.9%) of Cu in Bay and slope sediment pore waters. Thus, virtually all TDCu fluxing from these sediments is complexed during sediment-water exchange. A relatively small fraction of the TDCu is exchanged as inorganic species, which are widely regarded as the most bioavailable form of Cu. Higher ligand concentrations at Sta. M suggest that sulfide or organic ligands containing reduced S contribute to the pool of complexing ligands; however, the exact nature and sources of the ligands in Bay pore waters are not known. The progressive increase in conditional stability constants of the CuL 2 S complexes from the mid-Bay to the slope sediments may reflect differences in biological or chemical processes at each site, as well as

Study of the formation of soluble complexes of sodium caseinate and xanthan in solution.

PubMed

Bouhannache, Bouchra; HadjSadok, Abdelkader; Touabet, Abdelkrim

2017-09-01

The main objective of this work was to determinate the optimum conditions for the formation of soluble complexes between sodium caseinate and xanthan in solution at neutral pH, in the presence of the NaCl. The study of the influence of the concentrations of these three substances showed that salt was the most influent factor. It worsens the thermodynamic incompatibility of the two biopolymers in solution, when they are present at large amounts. However, it contributes to soluble complexes formation, when sodium caseinate concentration is below 5.5%. In this case, gels with enhanced rheological properties were obtained. Infrared spectroscopy confirmed that the complexes formation within these gels involves hydrophobic interactions. On the other hand, dynamic light scattering revealed that dilution cause their dissociation. These soluble complexes are promising ingredients to ensure new texturing properties.

Synthesis, characterization and biological evaluation of ruthenium flavanol complexes against breast cancer

NASA Astrophysics Data System (ADS)

Singh, Ashok Kumar; Saxena, Gunjan; Sahabjada; Arshad, M.

2017-06-01

Four Ru(II) DMSO complexes (M1R-M4R) having substituted flavones viz. 3-Hydroxy-2-(4-methoxyphenyl)-4H-chromen-4-one (HL1), 3-Hydroxy-2-(4-nitrophenyl)-4H-chromen-4-one (HL2), 3-Hydroxy-2-(4-dimethylaminophenyl)-4H-chromen-4-one (HL3) and 3-Hydroxy-2-(4-chlorophenyl)-4H-chromen-4-one (HL4) were synthesized and characterized by elemental analysis, IR, UV-Vis, 1H NMR spectroscopies and ESI-MS. The molecular structures of the complexes were investigated by integrated spectroscopic and computational techniques (DFT). Both ligands as well as their complexes were screened for anticancer activities against breast cancer cell lines MCF-7. Cytotoxicity was assayed by MTT [3-(4, 5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide] assay. All ligands and their complexes exhibited significant cytotoxic potential of 5-40 μM concentration at incubation period of 24 h. The cell cytotoxicity increased significantly in a concentration-dependent manner. In this series of compounds, HL2 (IC50 17.2 μM) and its complex M2R (IC50 16 μM) induced the highest cytotoxicity.

Quantifying intracellular hydrogen peroxide perturbations in terms of concentration

PubMed Central

Huang, Beijing K.; Sikes, Hadley D.

2014-01-01

Molecular level, mechanistic understanding of the roles of reactive oxygen species (ROS) in a variety of pathological conditions is hindered by the difficulties associated with determining the concentration of various ROS species. Here, we present an approach that converts fold-change in the signal from an intracellular sensor of hydrogen peroxide into changes in absolute concentration. The method uses extracellular additions of peroxide and an improved biochemical measurement of the gradient between extracellular and intracellular peroxide concentrations to calibrate the intracellular sensor. By measuring peroxiredoxin activity, we found that this gradient is 650-fold rather than the 7–10-fold that is widely cited. The resulting calibration is important for understanding the mass-action kinetics of complex networks of redox reactions, and it enables meaningful characterization and comparison of outputs from endogenous peroxide generating tools and therapeutics across studies. PMID:25460730

The TF1-ATPase and ATPase activities of assembled alpha 3 beta 3 gamma, alpha 3 beta 3 gamma delta, and alpha 3 beta 3 gamma epsilon complexes are stimulated by low and inhibited by high concentrations of rhodamine 6G whereas the dye only inhibits the alpha 3 beta 3, and alpha 3 beta 3 delta complexes.

PubMed

Paik, S R; Yokoyama, K; Yoshida, M; Ohta, T; Kagawa, Y; Allison, W S

1993-12-01

The ATPase activity of the F1-ATPase from the thermophilic bacterium PS3 is stimulated at concentrations of rhodamine 6G up to about 10 microM where 70% stimulation is observed at 36 degrees C. Half maximal stimulation is observed at about 3 microM dye. At rhodamine 6G concentrations greater than 10 microM, ATPase activity declines with 50% inhibition observed at about 75 microM dye. The ATPase activities of the alpha 3 beta 3 gamma and alpha 3 beta 3 gamma delta complexes assembled from isolated subunits of TF1 expressed in E. coli deleted of the unc operon respond to increasing concentrations of rhodamine 6G nearly identically to the response of TF1. In contrast, the ATPase activities of the alpha 3 beta 3 and alpha 3 beta 3 delta complexes are only inhibited by rhodamine 6G with 50% inhibition observed, respectively, at 35 and 75 microM dye at 36 degrees C. The ATPase activity of TF1 is stimulated up to 4-fold by the neutral detergent, LDAO. In the presence of stimulating concentrations of LDAO, the ATPase activity of TF1 is no longer stimulated by rhodamine 6G, but rather, it is inhibited with 50% inhibition observed at about 30 microM dye at 30 degrees C. One interpretation of these results is that binding of rhodamine 6G to a high-affinity site on TF1 stimulates ATPase activity and unmasks a low-affinity, inhibitory site for the dye which is also exposed by LDAO.

Concentration and purification of HIV-1 virions by microfluidic separation of superparamagnetic nanoparticles

PubMed Central

Chen, Grace Dongqing; Alberts, Catharina Johanna

2009-01-01

The low concentration and complex sample matrix of many clinical and environmental viral samples presents a significant challenge in the development of low cost, point-of-care viral assays. To address this problem, we investigated the use of a microfluidic passive magnetic separator combined with on-chip mixer to both purify and concentrate whole particle HIV-1 virions. Virus-containing plasma samples are first mixed to allow specific binding of the viral particles with antibody-conjugated superparamagnetic nanoparticles, and several passive mixer geometries were assessed for their mixing efficiencies. The virus-nanoparticle complexes are then separated from the plasma in a novel magnetic separation chamber, where packed micron-sized ferromagnetic particles serve as high magnetic gradient concentrators for an externally applied magnetic field. Thereafter, a viral lysis buffer was flowed through the chip and the released HIV proteins were assayed off-chip. Viral protein extraction efficiencies of 62% and 45% were achieved at 10uL/min and 30uL/min throughputs respectively. More importantly, an 80-fold concentration was observed for an initial sample volume of 1mL, and a 44-fold concentration for an initial sample volume of 0.5mL. The system is broadly applicable to microscale sample preparation of any viral sample and can be used for nucleic acid extraction as well as 40–80 fold enrichment of target viruses. PMID:19954210

Polylogarithmic equilibrium treatment of molecular aggregation and critical concentrations.

PubMed

Michel, Denis; Ruelle, Philippe

2017-02-15

A full equilibrium treatment of molecular aggregation is presented for prototypes of 1D and 3D aggregates, with and without nucleation. By skipping complex kinetic parameters like aggregate size-dependent diffusion, the equilibrium treatment allows us to predict directly time-independent quantities such as critical concentrations. The relationships between the macroscopic equilibrium constants for different paths are first established by statistical corrections and so as to comply with the detailed balance constraints imposed by nucleation, and the composition of the mixture resulting from homogeneous aggregation is then analyzed using a polylogarithmic function. Several critical concentrations are distinguished: the residual monomer concentration at equilibrium (RMC) and the critical nucleation concentration (CNC), which is the threshold concentration of total subunits necessary for initiating aggregation. When increasing the concentration of total subunits, the RMC converges more strongly to its asymptotic value, the equilibrium constant of depolymerization, for 3D aggregates and in the case of nucleation. The CNC moderately depends on the number of subunits in the nucleus, but sharply increases with the difference between the equilibrium constants of polymerization and nucleation. As the RMC and CNC can be numerically but not analytically determined, ansatz equations connecting them to thermodynamic parameters are proposed.

Increased water resistance of paper treated with amylose-fatty ammonium salt inclusion complexes

USDA-ARS?s Scientific Manuscript database

Amylose inclusion complexes were prepared from high amylose corn starch and the HCl salts of hexadecylamine and octadecylamine. Solutions of the complexes were applied to paper at concentrations of 2-4%. After the treated papers were dried, sodium hydroxide solution was applied to convert the adsorb...

Ultraviolet-B radiation mobilizes uranium from uranium-dissolved organic carbon complexes in aquatic systems, demonstrated by asymmetrical flow field-flow fractionation.

PubMed

Nehete, Sachin Vilas; Christensen, Terje; Salbu, Brit; Teien, Hans-Christian

2017-05-05

Humic substances have a tendency to form complexes with metal ions in aquatic medium, impacting the metal mobility, decreasing bioavailability and toxicity. Ultraviolet-B (UV-B) radiation exposure degrades the humic substance, changes their molecular weight distribution and their metal binding capacity in aquatic medium. In this study, we experimented the effect of UV-B radiation on the uranium complexed with fulvic acids and humic acids in a soft water system at different pH, uranium concentrations and radiant exposure. The concentration and distribution of uranium in a complexed form were investigated by asymmetrical flow field-flow fractionation coupled to multi detection technique (AsFlFFF-UV-ICP-MS). The major concentration of uranium present in complexes was primarily associated with average and higher molecular weight fulvic and humic acids components. The concentration of uranium in a complexed form increased with increasing fulvic and humic acid concentrations as well as pH of the solution. The higher molecular weight fraction of uranium was degraded due to the UV-B exposure, transforming about 50% of the uranium-dissolved organic carbon complexes into low molecular weight uranium species in complex form with organic ligands and/or free form. The result also suggests AsFlFFF-UV-ICP-MS to be an important separation and detection technique for understanding the interaction of radionuclides with dissolved organic matter, tracking size distribution changes during degradation of organic complexes for understanding mobility, bioavailability and ecosystem transfer of radionuclides as well as metals. Copyright © 2017 Elsevier B.V. All rights reserved.

Branched-chain amino acids complex inhibits melanogenesis in B16F0 melanoma cells.

PubMed

Cha, Jae-Young; Yang, Hyun-Ju; Moon, Hyung-In; Cho, Young-Su

2012-04-01

Present study was investigated the effect of each or complex of three branched-chain amino acids (BCAAs; isoleucine, leucine, and valine) on melanin production in B16F0 melanoma cells treated with various concentrations (1-16 mM) for 72 h. Among the 20 amino acids, lysine and glycine showed the highest activities of DPPH radical scavenging and mushroom tyrosinase inhibition, respectively. Each and combination of BCAAs reduced melanogenesis in a concentration-dependent manner without any morphological changes and cell viability in melanoma cells. Present study was also investigated the inhibitory effects of each or complex of BCAAs at each 10 mM concentration on the 100 μM IBMX-mediated stimulation of melanogenesis in melanoma cells for 72 h and found that IBMX treatment was stimulated to enhance melanin synthesis and that the complex of BCAAs was the most effectively inhibited in the melanin amounts of cellular and extracellular and the whitening the cell pellet. When the inhibitory effect of BCAAs on tyrosinase was examined by intracellular tyrosinase assay, both isoleucine and valine exhibit slightly inhibition, but leucine and combination of BCAAs did not inhibit the cell-derived tyrosinase activity. Present study demonstrated that complex of BCAAs inhibited melanin production without changes intercellular tyrosinase activity. Thus, the complex of BCAAs may be used in development of safe potentially depigmenting agents.

Vanadium and nickel complexes in petroleum resid acid, base, and neutral fractions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pearson, C.D.; Green, J.D.

1993-01-01

Acid and base fractions from petroleum vacuum resids with no detectable (by visible spectrophotometry) quantities of porphyrinic Ni or V complexes were hydrotreated under various conditions to determine if significant amounts of porphyrinic metals were released, via disassociation or other means, upon hydrotreating. No significant quantities were observed, thereby indicating that nonporphyrinic metals were not simply associated, complexed or otherwise masked (in terms of visible spectrophotometric response) porphyrinic metal complexes. However, it is possible that hydrotreating was simply not effective in breaking up these associates and/or that some porphyrinic forms of metal were in fact released but were rapidly destroyedmore » by hydrotreating. In addition, three liquid chromatographic (LC) separation methods were sequentially applied to Cerro Negro (Orinoco belt Venezuelan heavy crude) >700[degree]C resid in an effort to separate and concentrate the metal complexes present. Nonaqueous ion exchange chromatography was used initially to separate the resid into acid, base and neutral types. Two concentrates containing 19,500 and 13,500 ppm total V, or an estimated 19 and 13 wt % V-containing compounds respectively, were obtained. The degree of enrichment of Ni compounds obtained was significantly lower. By visible spectrophotometry, using vanadyl etioporphyrin as a standard, each of the concentrates contained near a 1:1 ratio of porphyrinic:nonporphyrinic V complexes. Analogous separation behavior for porphyrinic versus nonporphyrinic metal forms was observed throughout much of the work, thereby suggesting that a comparable diversity of structures existed within each general class of metal compounds. The generally wide dispersion of both Ni and V over the LC separation scheme suggests a structural variety of metal complexes that is comparable to that observed for other heteroatoms (N, S, O) in petroleum.« less

Vanadium and nickel complexes in petroleum resid acid, base, and neutral fractions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pearson, C.D.; Green, J.D.

1993-01-01

Acid and base fractions from petroleum vacuum resids with no detectable (by visible spectrophotometry) quantities of porphyrinic Ni or V complexes were hydrotreated under various conditions to determine if significant amounts of porphyrinic metals were released, via disassociation or other means, upon hydrotreating. No significant quantities were observed, thereby indicating that nonporphyrinic metals were not simply associated, complexed or otherwise masked (in terms of visible spectrophotometric response) porphyrinic metal complexes. However, it is possible that hydrotreating was simply not effective in breaking up these associates and/or that some porphyrinic forms of metal were in fact released but were rapidly destroyedmore » by hydrotreating. In addition, three liquid chromatographic (LC) separation methods were sequentially applied to Cerro Negro (Orinoco belt Venezuelan heavy crude) >700{degree}C resid in an effort to separate and concentrate the metal complexes present. Nonaqueous ion exchange chromatography was used initially to separate the resid into acid, base and neutral types. Two concentrates containing 19,500 and 13,500 ppm total V, or an estimated 19 and 13 wt % V-containing compounds respectively, were obtained. The degree of enrichment of Ni compounds obtained was significantly lower. By visible spectrophotometry, using vanadyl etioporphyrin as a standard, each of the concentrates contained near a 1:1 ratio of porphyrinic:nonporphyrinic V complexes. Analogous separation behavior for porphyrinic versus nonporphyrinic metal forms was observed throughout much of the work, thereby suggesting that a comparable diversity of structures existed within each general class of metal compounds. The generally wide dispersion of both Ni and V over the LC separation scheme suggests a structural variety of metal complexes that is comparable to that observed for other heteroatoms (N, S, O) in petroleum.« less

Communication complexity and information complexity

NASA Astrophysics Data System (ADS)

Pankratov, Denis

Information complexity enables the use of information-theoretic tools in communication complexity theory. Prior to the results presented in this thesis, information complexity was mainly used for proving lower bounds and direct-sum theorems in the setting of communication complexity. We present three results that demonstrate new connections between information complexity and communication complexity. In the first contribution we thoroughly study the information complexity of the smallest nontrivial two-party function: the AND function. While computing the communication complexity of AND is trivial, computing its exact information complexity presents a major technical challenge. In overcoming this challenge, we reveal that information complexity gives rise to rich geometrical structures. Our analysis of information complexity relies on new analytic techniques and new characterizations of communication protocols. We also uncover a connection of information complexity to the theory of elliptic partial differential equations. Once we compute the exact information complexity of AND, we can compute exact communication complexity of several related functions on n-bit inputs with some additional technical work. Previous combinatorial and algebraic techniques could only prove bounds of the form theta( n). Interestingly, this level of precision is typical in the area of information theory, so our result demonstrates that this meta-property of precise bounds carries over to information complexity and in certain cases even to communication complexity. Our result does not only strengthen the lower bound on communication complexity of disjointness by making it more exact, but it also shows that information complexity provides the exact upper bound on communication complexity. In fact, this result is more general and applies to a whole class of communication problems. In the second contribution, we use self-reduction methods to prove strong lower bounds on the information

Evidence for Carbonate Surface Complexation during Forsterite Carbonation in Wet Supercritical Carbon Dioxide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Loring, John S.; Chen, Jeffrey; Benezeth Ep Gisquet, Pascale

Continental flood basalts are attractive formations for geologic sequestration of carbon dioxide because of their reactive divalent-cation containing silicates, such as forsterite (Mg2SiO4), suitable for long-term trapping of CO2 mineralized as metal carbonates. The goal of this study was to investigate at a molecular level the carbonation products formed during the reaction of forsterite with supercritical CO2 (scCO2) as a function of the concentration of H2O adsorbed to the forsterite surface. Experiments were performed at 50 °C and 90 bar using an in situ IR titration capability, and post-reaction samples were examined by ex situ techniques, including SEM, XPS, FIB-TEM,more » TGA-MS, and MAS-NMR. Carbonation products and reaction extents varied greatly with adsorbed H2O. We show for the first time evidence of Mg-carbonate surface complexation under wet scCO2 conditions. Carbonate is found to be coordinated to Mg at the forsterite surface in a predominately bidentate fashion at adsorbed H2O concentrations below 27 µmol/m2. Above this concentration and up to 76 µmol/m2, monodentate coordinated complexes become dominant. Beyond a threshold adsorbed H2O concentration of 76 µmol/m2, crystalline carbonates continuously precipitate as magnesite, and the particles that form are hundreds of times larger than the estimated thicknesses of the adsorbed water films of about 7 to 15 Å. At an applied level, these results suggest that mineral carbonation in scCO2 dominated fluids near the wellbore and adjacent to caprocks will be insignificant and limited to surface complexation, unless adsorbed H2O concentrations are high enough to promote crystalline carbonate formation. At a fundamental level, the surface complexes and their dependence on adsorbed H2O concentration give insights regarding forsterite dissolution processes and magnesite nucleation and growth.« less

Synthesis, antiproliferative activity and mechanism of gallium(III)-thiosemicarbazone complexes as potential anti-breast cancer agents.

PubMed

Qi, Jinxu; Yao, Qian; Qian, Kun; Tian, Liang; Cheng, Zhen; Yang, Dongmei; Wang, Yihong

2018-05-14

Five thiosemicarbazone ligands were synthesized and characterized by condensation with different aldehydes or ketones by 4-phenylthiosemicarbazone. The representative dichlorido[2-(Di-2-pyridinylmethylene)-Nphenylhydrazinecarbothioamide-N,N,S]-gallium(III) (Ga4) was characterized by X-ray single crystal diffraction, which was 1:1 ligand/Ga(III) complexes. The structure-activity relationship of these ligands and Ga (III) complexes have been investigated, and the results demonstrate that the formation of Ga (III) complexes have significant antiproliferative activity over the corresponding ligands. The anticancer mechanism of gallium (III) complexes has been studied in detail, which is typical agents that effect on the mitochondrial apoptotic pathway. The ability of gallium (III) complexes to inhibit the cell cycle does not enhanced with the increasing concentrations, whereas the ability to promote apoptosis is concentration-dependent. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Manipulation of Muscle Glycogen Concentrations Using High and Low Carbohydrate Diets and Exercise

DTIC Science & Technology

1987-08-01

high in carbohydrates in the form of simple sugars (i.e., sucrose, fructose , lactose) and complex carbohydrates (i.e., starches, dietary fiber...AD-A 187 732 REPORT NO T32-87 MANIPULATION OF MUSCLE GLYCOGEN CONCENTRATIONS USING HIGH AND LOW CARBOHYDRATE DIETS AND EXERCISE U S ARMY RESEARCH...Muscle Glycogen Concentrations Using High and Low Carbohydrate Diets and Exercise 12. PERSONAL AUTHOR(S) Buchbinder, J., Pocost, J., Hodgess, L., Roche

Use of Antibiotic-Impregnated Absorbable Beads and Tissue Coverage of Complex Wounds.

PubMed

White, Terris L; Culliford, Alfred T; Zomaya, Martin; Freed, Gary; Demas, Christopher P

2016-11-01

The treatment of complex wounds is commonplace for plastic surgeons. Standard management is debridement of infected and devitalized tissue and systemic antibiotic therapy. In cases where vital structures are exposed within the wound, coverage is obtained with the use of vascularized tissue using both muscle and fasciocutaneous flaps. The use of nondissolving polymethylmethacrylate and absorbable antibiotic-impregnated beads has been shown to deliver high concentrations of antibiotics with low systemic levels of the same antibiotic. We present a multicenter retrospective review of all cases that used absorbable antibiotic-impregnated beads for complex wound management from 2003 to 2013. A total of 104 cases were investigated, flap coverage was used in 97 cases (93.3%). Overall, 15 patients (14.4%) required reoperation with the highest groups involving orthopedic wounds and sternal wounds. The advantages of using absorbable antibiotic-impregnated beads in complex infected wounds have been demonstrated with minimal disadvantages. The utilization of these beads is expanding to a variety of complex infectious wounds requiring high concentrations of local antibiotics.

Complexation between sodium dodecyl sulfate and amphoteric polyurethane nanoparticles.

PubMed

Qiao, Yong; Zhang, Shifeng; Lin, Ouya; Deng, Liandong; Dong, Anjie

2007-09-27

The complexation between negatively charged sodium dodecyl sulfate (SDS) and positively charged amphoteric polyurethane (APU) self-assembled nanoparticles (NPs) containing nonionic hydrophobic segments is studied by dynamic light scattering, pyrene fluorescent probing, zeta-potential, and transmission electron microscopy (TEM) in the present paper. With increasing the mol ratio of SDS to the positive charges on the surface of APU NPs, the aqueous solution of APU NPs presents precipitation at pH 2, around stoichiometric SDS concentration, and then the precipitate dissociates with excess SDS to form more stable nanoparticles of ionomer complexes. Three stages of the complexation process are clearly shown by the pyrene I1/I3 variation of the complex systems, which only depends on the ratio of SDS/APU, and demonstrate that the process is dominated by electrostatic attraction and hydrophobic aggregation.

Groundwater cleanup demonstrations at Complex 34, CCAS

NASA Technical Reports Server (NTRS)

2000-01-01

At Launch Complex 34, Greg Beyke, with Current Environmental Solutions, talks to representatives from environmental and federal agencies about the environmental research project that involves the Department of Defense, Environmental Protection Agency, Department of Energy and NASA in a groundwater cleanup effort. Concentrations of trichloroethylene solvent have been identified in the soil at the complex as a result of cleaning methods for rocket parts during the Apollo Program, which used the complex, in the 60s. The group formed the Interagency NDAPL Consortium (IDC) to study three contamination cleanup technologies: Six Phase Soil Heating, Steam Injection and In Situ Oxidation with Potassium Permanganate. All three methods may offer a way to remove the contaminants in months instead of decades. KSC hosted a two-day conference that presented information and demonstrations of the three technologies being tested at the site.

Groundwater cleanup demonstrations at Complex 34, CCAS

NASA Technical Reports Server (NTRS)

2000-01-01

At Launch Complex 34, representatives from environmental and Federal agencies head for the block house during presentations about the environmental research project that involves the Department of Defense, Environmental Protection Agency, Department of Energy and NASA in a groundwater cleanup effort. Concentrations of trichloroethylene solvent have been identified in the soil at the complex as a result of cleaning methods for rocket parts during the Apollo Program, which used the complex, in the 60s. The group formed the Interagency NDAPL Consortium (IDC) to study three contamination cleanup technologies: Six Phase Soil Heating, Steam Injection and In Situ Oxidation with Potassium Permanganate. All three methods may offer a way to remove the contaminants in months instead of decades. KSC hosted a two-day conference that presented information and demonstrations of the three technologies being tested at the site.

Investigation of the hemostatic effect of a transdermal patch containing 0.55 mg ethinyl estradiol and 2.1 mg gestodene compared with a monophasic oral contraceptive containing 0.03 mg ethinyl estradiol and 0.15 mg levonorgestrel: an open-label, randomized, crossover study.

PubMed

Junge, Wolfgang; Heger-Mahn, Doris; Trummer, Dietmar; Merz, Martin

2013-09-01

Transdermal delivery of contraceptives offers several advantages over combined oral contraceptives (COCs), including effective absorption and the provision of relatively constant serum concentrations. Ethinyl estradiol (EE) and the progestin gestodene are well-absorbed through the skin and, therefore, well-suited for use in a transdermal contraceptive patch. The objective of this study was to investigate the impact of a once-weekly transparent, transdermal patch delivering low doses of EE and gestodene equivalent to a COC containing 0.02 mg EE and 0.06 mg gestodene on hemostasis parameters compared with a monophasic COC containing 0.03 mg EE and 0.15 mg levonorgestrel. In this single-center, open-label, randomized, crossover study, 30 women (aged 18-35 years) received three cycles of each treatment, separated by a two-cycle washout period. The primary outcome measure was the absolute change from baseline in prothrombin fragments 1 + 2 and D-dimer. For both treatments, prothrombin fragments 1 + 2 remained stable during the first treatment period, and increased only slightly in the second period (mean absolute change 0.025 and 0.028 nmol/L in the novel Bayer patch and COC groups, respectively). Increases in D-dimer were observed in both periods (mean absolute change 107.0 ± 147.2 ng/L for the novel Bayer patch and 113.7 ± 159.0 ng/L for the COC). There were no statistically significant treatment differences in prothrombin 1 + 2 or D-dimer (p = 0.667 and p = 0.884, respectively) and no statistically significant treatment sequence or period effects. A COC containing 0.03 mg EE and 0.15 mg levonorgestrel and the novel Bayer patch have comparable influence on hemostatic endpoints. Both treatments were well-tolerated by subjects.

Metal–organic complexation in the marine environment

PubMed Central

Luther, George W; Rozan, Timothy F; Witter, Amy; Lewis, Brent

2001-01-01

We discuss the voltammetric methods that are used to assess metal–organic complexation in seawater. These consist of titration methods using anodic stripping voltammetry (ASV) and cathodic stripping voltammetry competitive ligand experiments (CSV-CLE). These approaches and a kinetic approach using CSV-CLE give similar information on the amount of excess ligand to metal in a sample and the conditional metal ligand stability constant for the excess ligand bound to the metal. CSV-CLE data using different ligands to measure Fe(III) organic complexes are similar. All these methods give conditional stability constants for which the side reaction coefficient for the metal can be corrected but not that for the ligand. Another approach, pseudovoltammetry, provides information on the actual metal–ligand complex(es) in a sample by doing ASV experiments where the deposition potential is varied more negatively in order to destroy the metal–ligand complex. This latter approach gives concentration information on each actual ligand bound to the metal as well as the thermodynamic stability constant of each complex in solution when compared to known metal–ligand complexes. In this case the side reaction coefficients for the metal and ligand are corrected. Thus, this method may not give identical information to the titration methods because the excess ligand in the sample may not be identical to some of the actual ligands binding the metal in the sample. PMID:16759421

Concerted formation of macromolecular Suppressor–mutator transposition complexes

PubMed Central

Raina, Ramesh; Schläppi, Michael; Karunanandaa, Balasulojini; Elhofy, Adam; Fedoroff, Nina

1998-01-01

Transposition of the maize Suppressor–mutator (Spm) transposon requires two element-encoded proteins, TnpA and TnpD. Although there are multiple TnpA binding sites near each element end, binding of TnpA to DNA is not cooperative, and the binding affinity is not markedly affected by the number of binding sites per DNA fragment. However, intermolecular complexes form cooperatively between DNA fragments with three or more TnpA binding sites. TnpD, itself not a sequence-specific DNA-binding protein, binds to TnpA and stabilizes the TnpA–DNA complex. The high redundancy of TnpA binding sites at both element ends and the protein–protein interactions between DNA-bound TnpA complexes and between these and TnpD imply a concerted transition of the element from a linear to a protein crosslinked transposition complex within a very narrow protein concentration range. PMID:9671711

DIGE-based protein expression analysis of B[a]P-exposed hepatoma cells reveals a complex stress response including alterations in oxidative stress, cell cycle control, and cytoskeleton motility at toxic and subacute concentrations.

PubMed

Dautel, Franziska; Kalkhof, Stefan; Trump, Saskia; Michaelson, Jacob; Beyer, Andreas; Lehmann, Irina; von Bergen, Martin

2011-02-04

Although the effects of high concentrations of the carcinogen benzo[a]pyrene (B[a]P) have been studied extensively, little is known about its effects at subacute toxic concentrations, which are typical for environmental pollutants. We exposed murine Hepa1c1c7 cells to a toxic concentration (5 μM) and a subacute concentration (50 nM) of B[a]P over a period of 2-24 h to differentiate between acute and pseudochronic effects and conducted a time-course analysis of B[a]P-influenced protein expression by DIGE. In total, a set of 120 spots were found to be significantly altered due to B[a]P exposure of which 112 were subsequently identified by mass spectrometry. Clustering and principal component analysis were conducted to identify sets of proteins responding in a concerted manner to the exposure. Our results indicate an immediate response to the contaminant at the protein level and demonstrate that B[a]P exposure alters the cellular response by disturbing proteins involved in oxidative stress, cell cycle regulation, apoptosis, and cytoskeleton organization. Furthermore, network analysis of protein-protein interactions revealed a complex network of interacting, B[a]P-regulated proteins mostly belonging to the cytoskeleton organization and several signal transduction pathways.

Thermodynamic Modeling of Poorly Complexing Metals in Concentrated Electrolyte Solutions: An X-Ray Absorption and UV-Vis Spectroscopic Study of Ni(II) in the NiCl2-MgCl2-H2O System

PubMed Central

Zhang, Ning; Brugger, Joël; Etschmann, Barbara; Ngothai, Yung; Zeng, Dewen

2015-01-01

Knowledge of the structure and speciation of aqueous Ni(II)-chloride complexes is important for understanding Ni behavior in hydrometallurgical extraction. The effect of concentration on the first-shell structure of Ni(II) in aqueous NiCl2 and NiCl2-MgCl2 solutions was investigated by Ni K edge X-ray absorption (XAS) and UV-Vis spectroscopy at ambient conditions. Both techniques show that no large structural change (e.g., transition from octahedral to tetrahedral-like configuration) occurs. Both methods confirm that the Ni(II) aqua ion (with six coordinated water molecules at R Ni-O = 2.07(2) Å) is the dominant species over the whole NiCl2 concentration range. However, XANES, EXAFS and UV-Vis data show subtle changes at high salinity (> 2 mol∙kg-1 NiCl2), which are consistent with the formation of small amounts of the NiCl+ complex (up to 0.44(23) Cl at a Ni-Cl distance of 2.35(2) Å in 5.05 mol∙kg-1 NiCl2) in the pure NiCl2 solutions. At high Cl:Ni ratio in the NiCl2-MgCl2-H2O solutions, small amounts of [NiCl2]0 are also present. We developed a speciation-based mixed-solvent electrolyte (MSE) model to describe activity-composition relationships in NiCl2-MgCl2-H2O solutions, and at the same time predict Ni(II) speciation that is consistent with our XAS and UV-Vis data and with existing literature data up to the solubility limit, resolving a long-standing uncertainty about the role of chloride complexing in this system. PMID:25885410

The Organic Complexation of Iron in the Marine Environment: A Review

PubMed Central

Gledhill, Martha; Buck, Kristen N.

2012-01-01

Iron (Fe) is an essential micronutrient for marine organisms, and it is now well established that low Fe availability controls phytoplankton productivity, community structure, and ecosystem functioning in vast regions of the global ocean. The biogeochemical cycle of Fe involves complex interactions between lithogenic inputs (atmospheric, continental, or hydrothermal), dissolution, precipitation, scavenging, biological uptake, remineralization, and sedimentation processes. Each of these aspects of Fe biogeochemical cycling is likely influenced by organic Fe-binding ligands, which complex more than 99% of dissolved Fe. In this review we consider recent advances in our knowledge of Fe complexation in the marine environment and their implications for the biogeochemistry of Fe in the ocean. We also highlight the importance of constraining the dissolved Fe concentration value used in interpreting voltammetric titration data for the determination of Fe speciation. Within the published Fe speciation data, there appear to be important temporal and spatial variations in Fe-binding ligand concentrations and their conditional stability constants in the marine environment. Excess ligand concentrations, particularly in the truly soluble size fraction, seem to be consistently higher in the upper water column, and especially in Fe-limited, but productive, waters. Evidence is accumulating for an association of Fe with both small, well-defined ligands, such as siderophores, as well as with larger, macromolecular complexes like humic substances, exopolymeric substances, and transparent exopolymers. The diverse size spectrum and chemical nature of Fe ligand complexes corresponds to a change in kinetic inertness which will have a consequent impact on biological availability. However, much work is still to be done in coupling voltammetry, mass spectrometry techniques, and process studies to better characterize the nature and cycling of Fe-binding ligands in the marine environment. PMID

Using cyclodextrin complexation to enhance secondary photoprotection of topically applied ibuprofen.

PubMed

Godwin, Donald A; Wiley, Cody J; Felton, Linda A

2006-01-01

Each year millions of people are overexposed to the sun resulting in photodamage of the skin. Secondary photoprotection is the application of medicinal agents to the body after sun exposure to reduce this damage. The objective of this study was to determine the affects of hydroxypropyl-beta-cyclodextrin (HPCD) complexation on the secondary photoprotective properties of topically applied ibuprofen. Complexation of ibuprofen by HPCD was demonstrated by differential scanning calorimetry, while solubilities were determined using HPLC. A linear (r2>0.999) relationship was found between ibuprofen solubility and HPCD concentration. For subsequent experiments, the concentration of ibuprofen was held constant at the solubility in 10% HPCD (10.6 mg/ml), while the HPCD concentration varied from 0 to 20% (w/w). In vitro transdermal permeation experiments demonstrated a parabolic relationship between transdermal kinetic parameters and HPCD concentration, with maximum values for both flux and skin accumulation occurring with the 10% HPCD formulation. In vivo experiments were performed by exposing hairless mice to UV radiation and applying ibuprofen-HPCD formulations topically at various times following UV exposure. Edema and epidermal lipid damage data demonstrated that application of ibuprofen-HPCD formulations within 1h of UV exposure provided significant photoprotection.

Phase behaviour and structure of stable complexes of oppositely charged polyelectrolytes

NASA Astrophysics Data System (ADS)

Mengarelli, V.; Auvray, L.; Zeghal, M.

2009-03-01

We study the formation and structure of stable electrostatic complexes between oppositely charged polyelectrolytes, a long polymethacrylic acid and a shorter polyethylenimine, at low pH, where the polyacid is weakly charged. We explore the phase diagram as a function of the charge and concentration ratio of the constituents. In agreement with theory, turbidity and ζ potential measurements show two distinct regimes of weak and strong complexation, which appear successively as the pH is increased and are separated by a well-defined limit. Weak complexes observed by neutron scattering and contrast matching have an open, non-compact structure, while strong complexes are condensed.

STUDIES ON MAMMALIAN AND HUMAN PYRUVATE AND ALPHA-KETOGLUTARATE DEHYDROGENATION COMPLEXES.

DTIC Science & Technology

Enzyme systems that catalyze a coenzyme A- and nicotinamide adenine dinucleotide-linked oxidative decarboxylation of pyruvate and alpha - ketoglutarate ...The pig heart pyruvate dehydrogenase complex was strongly inhibited by EDTA at low concentration, but the pig heart alpha - ketoglutarate ...On the oxidative decarboxylation of alpha -keto acids in pig heart complexes, Ca(2+) was strongly stimulatory to the same or more extent than Mg(2

Suspected limbic encephalitis and seizure in cats associated with voltage-gated potassium channel (VGKC) complex antibody.

PubMed

Pakozdy, A; Halasz, P; Klang, A; Bauer, J; Leschnik, M; Tichy, A; Thalhammer, J G; Lang, B; Vincent, A

2013-01-01

Treatment-resistant complex partial seizures (CPS) with orofacial involvement recently were reported in cats in association with hippocampal pathology. The features had some similarity to those described in humans with limbic encephalitis and voltage-gated potassium channel (VGKC) complex antibody. The purpose of this pilot study was to evaluate cats with CPS and orofacial involvement for the presence of VGKC-complex antibody. Client-owned cats with acute orofacial CPS and control cats were investigated. Prospective study. Serum was collected from 14 cats in the acute stage of the disease and compared with 19 controls. VGKC-complex antibodies were determined by routine immunoprecipitation and by binding to leucine-rich glioma inactivated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2), the 2 main targets of VGKC-complex antibodies in humans. Five of the 14 affected cats, but none of the 19 controls, had VGKC-complex antibody concentrations above the cut-off concentration (>100 pmol/L) based on control samples and similar to those found in humans. Antibodies in 4 cats were directed against LGI1, and none were directed against CASPR2. Follow-up sera were available for 5 cats in remission and all antibody concentrations were within the reference range. Our study suggests that an autoimmune limbic encephalitis exists in cats and that VGKC-complex/LGI1 antibodies may play a role in this disorder, as they are thought to in humans. Copyright © 2012 by the American College of Veterinary Internal Medicine.

Synthesis of biocompatible nanoparticle drug complexes for inhibition of mycobacteria

NASA Astrophysics Data System (ADS)

Bhave, Tejashree; Ghoderao, Prachi; Sanghavi, Sonali; Babrekar, Harshada; Bhoraskar, S. V.; Ganesan, V.; Kulkarni, Anjali

2013-12-01

Tuberculosis (TB) is one of the most critical infectious diseases affecting the world today. Current TB treatment involves six months long daily administration of four oral doses of antibiotics. Due to severe side effects and the long treatment, a patient's adherence is low and this results in relapse of symptoms causing an alarming increase in the prevalence of multi-drug resistant (MDR) TB. Hence, it is imperative to develop a new drug delivery technology wherein these effects can be reduced. Rifampicin (RIF) is one of the widely used anti-tubercular drugs (ATD). The present study discusses the development of biocompatible nanoparticle-RIF complexes with superior inhibitory activity against both Mycobacterium smegmatis (M. smegmatis) and Mycobacterium tuberculosis (M. tuberculosis). Iron oxide nanoparticles (NPs) synthesized by gas phase condensation and NP-RIF complexes were tested against M. smegmatis SN2 strain as well as M. tuberculosis H37Rv laboratory strain. These complexes showed significantly better inhibition of M. smegmatis SN2 strain at a much lower effective concentration (27.5 μg ml-1) as compared to neat RIF (125 μg ml-1). Similarly M. tuberculosis H37Rv laboratory strain was susceptible to both nanoparticle-RIF complex and neat RIF at a minimum inhibitory concentration of 0.22 and 1 μg ml-1, respectively. Further studies are underway to determine the efficacy of NPs-RIF complexes in clinical isolates of M. tuberculosis as well as MDR isolates.

Elevated serum β₂-GPI-Lp(a) complexes levels in children with nephrotic syndrome.

PubMed

Zhang, Chunni; Luo, Yang; Huang, Zhongwei; Xia, Zhengkun; Cai, Xiaoyi; Yang, Yuhua; Niu, Dongmei; Wang, Junjun

2012-10-09

The complexes of β₂-glycoprotein I (β₂-GPI) with lipoprotein(a) [β₂-GPI-Lp(a)] exist in human circulation and are increased in serum from patients with some autoimmune diseases. This study aims to investigate the concentration of β₂-GPI-Lp(a) in serum of children with idiopathic nephrotic syndrome (NS) and its relationship with serum lipids, oxidized lipoprotein and renal function parameters to explore the potential of the complexes as an additional marker for evaluating pediatric NS. Serum concentrations of β₂-GPI-Lp(a) complexes and oxidized Lp(a) [ox-Lp(a)] were measured by "Sandwich" ELISAs in 80 NS children and 82 age/sex-matched healthy controls. The levels of serum lipids and kidney parameters were also determined. Multivariate logistic regression analysis was performed to identify correlate of β₂-GPI-Lp(a) and NS. The serum concentrations of β₂-GPI-Lp(a) complexes in children with NS were significantly higher than those in controls (median 0.95 U/ml vs 0.28 U/ml, P<0.0001). Ox-Lp(a) levels were also markedly elevated (median 14.55 mg/l vs 2.60 mg/l, P<0.0001] in NS children. The concentrations of β₂-GPI-Lp(a) were positively correlated with ox-Lp(a) (r=0.246, P=0.028), but not with Lp(a) level, and the concentrations of ox-Lp(a) were positively related with Lp(a) (r=0.301, P=0.007) in NS children. Multivariate logistic regression analysis identified a positive association between NS and β₂-GPI-Lp(a) (OR=13.694, 95% CI 6.400-29.299, P<0.0001), after adjusting for kidney function parameters, serum lipids and ox-Lp(a). Elevated β₂-GPI-Lp(a) level was an independent and significant risk factor for pediatric NS and, enhanced Lp(a) oxidation partly contributes to the formation of β₂-GPI-Lp(a) complexes. Copyright © 2012 Elsevier B.V. All rights reserved.

CarD stabilizes mycobacterial open complexes via a two-tiered kinetic mechanism

PubMed Central

Rammohan, Jayan; Ruiz Manzano, Ana; Garner, Ashley L.; Stallings, Christina L.; Galburt, Eric A.

2015-01-01

CarD is an essential and global transcriptional regulator in mycobacteria. While its biological role is unclear, CarD functions by interacting directly with RNA polymerase (RNAP) holoenzyme promoter complexes. Here, using a fluorescent reporter of open complex, we quantitate RPo formation in real time and show that Mycobacterium tuberculosis CarD has a dramatic effect on the energetics of RNAP bound complexes on the M. tuberculosis rrnAP3 ribosomal RNA promoter. The data reveal that Mycobacterium bovis RNAP exhibits an unstable RPo that is stabilized by CarD and suggest that CarD uses a two-tiered, concentration-dependent mechanism by associating with open and closed complexes with different affinities. Specifically, the kinetics of open-complex formation can be explained by a model where, at saturating concentrations of CarD, the rate of bubble collapse is slowed and the rate of opening is accelerated. The kinetics and open-complex stabilities of CarD mutants further clarify the roles played by the key residues W85, K90 and R25 previously shown to affect CarD-dependent gene regulation in vivo. In contrast to M. bovis RNAP, Escherichia coli RNAP efficiently forms RPo on rrnAP3, suggesting an important difference between the polymerases themselves and highlighting how transcriptional machinery can vary across bacterial genera. PMID:25697505

Experimental determination and modeling of arsenic complexation with humic and fulvic acids.

PubMed

Fakour, Hoda; Lin, Tsair-Fuh

2014-08-30

The complexation of humic acid (HA) and fulvic acid (FA) with arsenic (As) in water was studied. Experimental results indicate that arsenic may form complexes with HA and FA with a higher affinity for arsenate than for arsenite. With the presence of iron oxide based adsorbents, binding of arsenic to HA/FA in water was significantly suppressed, probably due to adsorption of As and HA/FA. A two-site ligand binding model, considering only strong and weak site types of binding affinity, was successfully developed to describe the complexation of arsenic on the two natural organic fractions. The model showed that the numbers of weak sites were more than 10 times those of strong sites on both HA and FA for both arsenic species studied. The numbers of both types of binding sites were found to be proportional to the HA concentrations, while the apparent stability constants, defined for describing binding affinity between arsenic and the sites, are independent of the HA concentrations. To the best of our knowledge, this is the first study to characterize the impact of HA concentrations on the applicability of the ligand binding model, and to extrapolate the model to FA. The obtained results may give insights on the complexation of arsenic in HA/FA laden groundwater and on the selection of more effective adsorption-based treatment methods for natural waters. Copyright © 2014 Elsevier B.V. All rights reserved.

Molecular Speciation of Trace Metal Organic Complexes in the Pacific Ocean

NASA Astrophysics Data System (ADS)

Repeta, D.; Boiteau, R. M.; Bundy, R. M.; Babcock-Adams, L.

2017-12-01

Microbial production across approximately one third of the surface ocean is limited by extraordinarily low (picomolar) concentrations of dissolved iron, essentially all of which is complexed to strong organic ligands of unknown composition. Other biologically important trace metals (cobalt, copper, zinc, nickel) are also complexed to strong organic ligands, which again have not been extensively characterized. Nevertheless, organic ligands exert a strong influence on metal bioavailability and toxicity. For example, amendment experiments using commercially available siderophores, organic compounds synthesized by microbes to facilitate iron uptake, show these ligands can both facilitate or impede iron uptake depending on the siderophore composition and available uptake pathways. Over the past few years we have developed analytical techniques using high pressure liquid chromatography interfaced with inductively coupled plasma and electrospray ionization mass spectrometry to identify and quantify trace metal organic complexes in laboratory cultures of marine microbes and in seawater. We found siderophores to be widely distributed in the ocean, particularly in regions characterized by low iron concentrations. We also find chemically distinct complexes of copper, zinc, colbalt and nickel that we have yet to fully characterize. We will discuss some of our recent work on trace metal organic speciation in seawater and laboratory cultures, and outline future efforts to better understand the microbial cycling of trace metal organic complexes in the sea.

Deep-level transient spectroscopy of Pd-H complexes in silicon

NASA Astrophysics Data System (ADS)

Sachse, J.-U.; Weber, J.; Lemke, H.

2000-01-01

The interaction of atomic hydrogen with substitutional palladium impurities is studied in n- and p-type Si by deep-level transient spectroscopy. After wet-chemical etching, we determine seven different electrically active and at least one passive palladium hydrogen complex. The levels belong to Pd complexes with different number of hydrogen atoms. The PdH1 complex exhibits one level E(200) at EC-0.43 eV. PdH2 has two levels E(60) at EC-0.10 eV and H(280) at EV+0.55 eV. Four levels are assigned to the PdH3 complex E(160) at EC-0.29 eV, H(140) at EV+0.23 eV, H(55) at EV+0.08 eV, and H(45) at EV+0.07 eV. An electrically passive complex is associated with a PdH4 complex. There is great similarity with the correspondent complexes in Pt-doped Si. Annealing above 650 K destroys all hydrogen related complexes and restores the original substitutional Pd concentration.

Effects of MASP-1 of the Complement System on Activation of Coagulation Factors and Plasma Clot Formation

PubMed Central

Hess, Katharina; Ajjan, Ramzi; Phoenix, Fladia; Dobó, József; Gál, Péter; Schroeder, Verena

2012-01-01

Background Numerous interactions between the coagulation and complement systems have been shown. Recently, links between coagulation and mannan-binding lectin-associated serine protease-1 (MASP-1) of the complement lectin pathway have been proposed. Our aim was to investigate MASP-1 activation of factor XIII (FXIII), fibrinogen, prothrombin, and thrombin-activatable fibrinolysis inhibitor (TAFI) in plasma-based systems, and to analyse effects of MASP-1 on plasma clot formation, structure and lysis. Methodology/Principal Findings We used a FXIII incorporation assay and specific assays to measure the activation products prothrombin fragment F1+2, fibrinopeptide A (FPA), and activated TAFI (TAFIa). Clot formation and lysis were assessed by turbidimetric assay. Clot structure was studied by scanning electron microscopy. MASP-1 activated FXIII and, contrary to thrombin, induced FXIII activity faster in the Val34 than the Leu34 variant. MASP-1-dependent generation of F1+2, FPA and TAFIa showed a dose-dependent response in normal citrated plasma (NCP), albeit MASP-1 was much less efficient than FXa or thrombin. MASP-1 activation of prothrombin and TAFI cleavage were confirmed in purified systems. No FPA generation was observed in prothrombin-depleted plasma. MASP-1 induced clot formation in NCP, affected clot structure, and prolonged clot lysis. Conclusions/Significance We show that MASP-1 interacts with plasma clot formation on different levels and influences fibrin structure. Although MASP-1-induced fibrin formation is thrombin-dependent, MASP-1 directly activates prothrombin, FXIII and TAFI. We suggest that MASP-1, in concerted action with other complement and coagulation proteins, may play a role in fibrin clot formation. PMID:22536427

The effects of numerical-model complexity and observation type on estimated porosity values

USGS Publications Warehouse

Starn, Jeffrey; Bagtzoglou, Amvrossios C.; Green, Christopher T.

2015-01-01

The relative merits of model complexity and types of observations employed in model calibration are compared. An existing groundwater flow model coupled with an advective transport simulation of the Salt Lake Valley, Utah (USA), is adapted for advective transport, and effective porosity is adjusted until simulated tritium concentrations match concentrations in samples from wells. Two calibration approaches are used: a “complex” highly parameterized porosity field and a “simple” parsimonious model of porosity distribution. The use of an atmospheric tracer (tritium in this case) and apparent ages (from tritium/helium) in model calibration also are discussed. Of the models tested, the complex model (with tritium concentrations and tritium/helium apparent ages) performs best. Although tritium breakthrough curves simulated by complex and simple models are very generally similar, and there is value in the simple model, the complex model is supported by a more realistic porosity distribution and a greater number of estimable parameters. Culling the best quality data did not lead to better calibration, possibly because of processes and aquifer characteristics that are not simulated. Despite many factors that contribute to shortcomings of both the models and the data, useful information is obtained from all the models evaluated. Although any particular prediction of tritium breakthrough may have large errors, overall, the models mimic observed trends.

Neighbor effect in complexation of a conjugated polymer.

PubMed

Sosorev, Andrey; Zapunidi, Sergey

2013-09-19

Charge-transfer complex (CTC) formation between a conjugated polymer and low-molecular-weight organic acceptor is proposed to be driven by the neighbor effect. Formation of a CTC on the polymer chain results in an increased probability of new CTC formation near the existing one. We present an analytical model for CTC distribution considering the neighbor effect, based on the principles of statistical mechanics. This model explains the experimentally observed threshold-like dependence of the CTC concentration on the acceptor content in a polymer:acceptor blend. It also allows us to evaluate binding energies of the complexes.

A general mechanism for competitor-induced dissociation of molecular complexes

PubMed Central

Paramanathan, Thayaparan; Reeves, Daniel; Friedman, Larry J.; Kondev, Jane; Gelles, Jeff

2014-01-01

The kinetic stability of non-covalent macromolecular complexes controls many biological phenomena. Here we find that physical models of complex dissociation predict that competitor molecules will in general accelerate the breakdown of isolated bimolecular complexes by occluding rapid rebinding of the two binding partners. This prediction is largely independent of molecular details. We confirm the prediction with single-molecule fluorescence experiments on a well-characterized DNA strand dissociation reaction. Contrary to common assumptions, competitor–induced acceleration of dissociation can occur in biologically relevant competitor concentration ranges and does not necessarily implyternary association of competitor with the bimolecular complex. Thus, occlusion of complex rebinding may play a significant role in a variety of biomolecular processes. The results also show that single-molecule colocalization experiments can accurately measure dissociation rates despite their limited spatio temporal resolution. PMID:25342513

Development of nanoscale structure in LAT-based signaling complexes

PubMed Central

2016-01-01

ABSTRACT The adapter molecule linker for activation of T cells (LAT) plays a crucial role in forming signaling complexes induced by stimulation of the T cell receptor (TCR). These multi-molecular complexes are dynamic structures that activate highly regulated signaling pathways. Previously, we have demonstrated nanoscale structure in LAT-based complexes where the adapter SLP-76 (also known as LCP2) localizes to the periphery of LAT clusters. In this study, we show that initially LAT and SLP-76 are randomly dispersed throughout the clusters that form upon TCR engagement. The segregation of LAT and SLP-76 develops near the end of the spreading process. The local concentration of LAT also increases at the same time. Both changes require TCR activation and an intact actin cytoskeleton. These results demonstrate that the nanoscale organization of LAT-based signaling complexes is dynamic and indicates that different kinds of LAT-based complexes appear at different times during T cell activation. PMID:27875277

Droplet-Based Segregation and Extraction of Concentrated Samples

DOE Office of Scientific and Technical Information (OSTI.GOV)

Buie, C R; Buckley, P; Hamilton, J

2007-02-23

Microfluidic analysis often requires sample concentration and separation techniques to isolate and detect analytes of interest. Complex or scarce samples may also require an orthogonal separation and detection method or off-chip analysis to confirm results. To perform these additional steps, the concentrated sample plug must be extracted from the primary microfluidic channel with minimal sample loss and dilution. We investigated two extraction techniques; injection of immiscible fluid droplets into the sample stream (''capping'''') and injection of the sample into an immiscible fluid stream (''extraction''). From our results we conclude that capping is the more effective partitioning technique. Furthermore, this functionalitymore » enables additional off-chip post-processing procedures such as DNA/RNA microarray analysis, realtime polymerase chain reaction (RT-PCR), and culture growth to validate chip performance.« less

The Purification and Concentration of Hog Cholera Virus*

PubMed Central

Cunliffe, H. R.; Rebers, P. A.

1968-01-01

Partial purification of hog cholera virus (HCV) using a simple batch-type chromatographic procedure with magnetic ferric oxide (MFO) is described. Infectious HCV was adsorbed from isotonic solutions to MFO and was eluted under conditions of low ionic strength and high pH. Aqueous solutions of 0.01 M sodium cyanide or 0.0003 M ammonium hydroxide effectively dissociated MFO-HCV complexes. The data indicate that 50 to 100% of the original HCV infectivity was recovered concomitant with a 90 to 95% reduction of extraneous organic nitrogen. MFO-purified HCV was concentrated by density gradient type centrifugations in buffered solutions of cesium chloride and sucrose. Prolonged isodensity centrifugations of concentrated MFO-purified HCV indicated a buoyant density of 1.14 to 1.15 gm/ml for the strain of virus used. PMID:15846899

The Electrochemical Performance of Silicon Nanoparticles in Concentrated Electrolyte.

PubMed

Chang, Zeng-Hua; Wang, Jian-Tao; Wu, Zhao-Hui; Gao, Min; Wu, Shuai-Jin; Lu, Shi-Gang

2018-06-11

Silicon is a promising material for anodes in energy-storage devices. However, excessive growth of a solid-electrolyte interphase (SEI) caused by the severe volume change during the (de)lithiation processes leads to dramatic capacity fading. Here, we report a super-concentrated electrolyte composed of lithium bis(fluorosulfonyl)imide (LiFSI) and propylene carbonate (PC) with a molar ratio of 1:2 to improve the cycling performance of silicon nanoparticles (SiNPs). The SiNP electrode shows a remarkably improved cycling performance with an initial delithiation capacity of approximately 3000 mAh g -1 and a capacity of approximately 2000 mAh g -1 after 100 cycles, exhibiting about 6.8 times higher capacity than the cells with dilute electrolyte LiFSI-(PC) 8 . Raman spectra reveal that most of the PC solvent and FSI anions are complexed by Li + to form a specific solution structure like a fluid polymeric network. The reduction of FSI anions starts to play an important role owing to the increased concentration of contact ion pairs (CIPs) or aggregates (AGGs), which contribute to the formation of a more mechanically robust and chemically stable complex SEI layer. The complex SEI layer can effectively suppress the morphology evolution of silicon particles and self-limit the excessive growth, which mitigates the crack propagation of the silicon electrode and the deterioration of the kinetics. This study will provide a new direction for screening cycling-stable electrolytes for silicon-based electrodes. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Heparin Cofactor II in Atherosclerotic Lesions from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Study

PubMed Central

Rau, Jill C.; Deans, Carolyn; Hoffman, Maureane R.; Thomas, David B.; Malcom, Gray T.; Zieske, Arthur W.; Strong, Jack P.; Koch, Gary G.; Church, Frank C.

2009-01-01

Heparin cofactor II (HCII) is a serine protease inhibitor (serpin) that has been shown to be a predictor of decreased atherosclerosis in the elderly and protective against atherosclerosis in mice. HCII inhibits thrombin in vitro and HCII-thrombin complexes have been detected in human plasma. Moreover, the mechanism of protection against atherosclerosis in mice was determined to be the inhibition of thrombin. Despite this evidence, the presence of HCII in human atherosclerotic tissue has not been reported. In this study, using samples of coronary arteries obtained from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study, we explore the local relationship between HCII and (pro)thrombin in atherosclerosis. We found that HCII and (pro)thrombin are co-localized in the lipid-rich necrotic core of atheromas. A significant positive correlation between each protein and the severity of the atherosclerotic lesion was present. These results suggest that HCII is in a position to inhibit thrombin in atherosclerotic lesions where thrombin can exert a proatherogenic inflammatory response. However, these results should be tempered by the additional findings from this, and other studies, that indicate the presence of other plasma proteins (antithrombin, albumin, and α1-protease inhibitor) in the same localized region of the atheroma. PMID:19747479

RNA stores tau reversibly in complex coacervates

PubMed Central

Lin, Yanxian; Eschmann, Neil A.; Zhou, Hongjun; Rauch, Jennifer N.; Hernandez, Israel; Guzman, Elmer; Kosik, Kenneth S.; Han, Songi

2017-01-01

Nonmembrane-bound organelles that behave like liquid droplets are widespread among eukaryotic cells. Their dysregulation appears to be a critical step in several neurodegenerative conditions. Here, we report that tau protein, the primary constituent of Alzheimer neurofibrillary tangles, can form liquid droplets and therefore has the necessary biophysical properties to undergo liquid-liquid phase separation (LLPS) in cells. Consonant with the factors that induce LLPS, tau is an intrinsically disordered protein that complexes with RNA to form droplets. Uniquely, the pool of RNAs to which tau binds in living cells are tRNAs. This phase state of tau is held in an approximately 1:1 charge balance across the protein and the nucleic acid constituents, and can thus be maximal at different RNA:tau mass ratios, depending on the biopolymer constituents involved. This feature is characteristic of complex coacervation. We furthermore show that the LLPS process is directly and sensitively tuned by salt concentration and temperature, implying it is modulated by both electrostatic interactions between the involved protein and nucleic acid constituents, as well as net changes in entropy. Despite the high protein concentration within the complex coacervate phase, tau is locally freely tumbling and capable of diffusing through the droplet interior. In fact, tau in the condensed phase state does not reveal any immediate changes in local protein packing, local conformations and local protein dynamics from that of tau in the dilute solution state. In contrast, the population of aggregation-prone tau as induced by the complexation with heparin is accompanied by large changes in local tau conformations and irreversible aggregation. However, prolonged residency within the droplet state eventually results in the emergence of detectable β-sheet structures according to thioflavin-T assay. These findings suggest that the droplet state can incubate tau and predispose the protein toward the

[Effects of various adsorbants on coagulation factors (author's transl)].

PubMed

Soulier, J P; Prou-Wartelle, O

1975-01-01

Adsorption of clotting factors by various adsorbants is studied (tricalcium phosphate, baryum sulfate or carbonate or citrate, calcium oxalate, aluminium hydroxyde and several silicate such as: kaolin, celite, bentonite, attapulgite, beidellite, asbestos). The main properties of each adsorbant are listed as well as several applications such as: selective adsorption of fibrinogen, separation between fibrinogen and factor VIII, separation of factor II from the other components of the prothrombin complex. Activation of factors XII and XI by the various silicates, as well as the activation of factor V by attapulgite are studied. Finally, the action of such adsorbants on the fibrinolytic system is summarized.

How Winter Time Atmospheric Stability Influences PM2.5 Concentration in Different Complex Terrains; Beijing in China vs Fairbanks in Alaska

NASA Astrophysics Data System (ADS)

Karandana Gamalathge, T. D.; Green, M.

2017-12-01

Consequences of air pollution is known to majority of the global population. Small particles or aerosols play a significant role in global climate change, and increasing the number of people suffer from poor health. Specially during winter seasons, people live in valleys or close to mountains experience hazy conditions and severe health problems. As a result, aerosol related research works have gained more attention over the last couple of decades. We considered PM2.5-particulate matter less than 2.5 µm of aerodynamic diameter, to see how PM2.5 varies with different atmospheric conditions during winter seasons over two different regions of the world. We selected five winter seasons from November to February from 2011 to 2015 both in Beijing and in Fairbanks. Both locations can be considered as complex terrains, as those regions are surrounded by or close to mountains. Using University of Wyoming's sounding data, we calculated a parameter called Heat Deficit (HD). Higher HD is associated with less turbulence, thus high PM2.5 concentration. On the other hand, low HD is associated with high turbulence, thus low PM2.5 concentration. So, we considered HD as a measure of stability in the region of interest. Despite geographical differences, Fairbanks was covered by snow every day over the study period while Beijing had almost no snow cover. Analysis was done in two ways, with and without paying attention to precipitation. HD was also evaluated with different levels of PM2.5, set up to multiples of average PM2.5 concentration. This was done to check whether HD correlates well with a particular range of PM2.5. A day of precipitation for Fairbanks was considered to be when the daily snowfall >1 inch, while for Beijing when any type of daily precipitation >0.1 inch. Precipitation for Beijing was rare and only 9 days were met even with the 0.1 inch criteria while Fairbanks had 61 days of exceeding the 1 inch criteria. Results revealed that precipitation doesn't impact the

Influence of chemical disorder on energy dissipation and defect evolution in concentrated solid solution alloys

PubMed Central

Zhang, Yanwen; Stocks, G. Malcolm; Jin, Ke; Lu, Chenyang; Bei, Hongbin; Sales, Brian C.; Wang, Lumin; Béland, Laurent K.; Stoller, Roger E.; Samolyuk, German D.; Caro, Magdalena; Caro, Alfredo; Weber, William J.

2015-01-01

A grand challenge in materials research is to understand complex electronic correlation and non-equilibrium atomic interactions, and how such intrinsic properties and dynamic processes affect energy transfer and defect evolution in irradiated materials. Here we report that chemical disorder, with an increasing number of principal elements and/or altered concentrations of specific elements, in single-phase concentrated solid solution alloys can lead to substantial reduction in electron mean free path and orders of magnitude decrease in electrical and thermal conductivity. The subsequently slow energy dissipation affects defect dynamics at the early stages, and consequentially may result in less deleterious defects. Suppressed damage accumulation with increasing chemical disorder from pure nickel to binary and to more complex quaternary solid solutions is observed. Understanding and controlling energy dissipation and defect dynamics by altering alloy complexity may pave the way for new design principles of radiation-tolerant structural alloys for energy applications. PMID:26507943

Prognosis and survival analysis of paraquat poisoned patients based on improved HPLC-UV method.

PubMed

Hong, Guangliang; Hu, Lufeng; Tang, Yahui; Zhang, Tao; Kang, Xiaowen; Zhao, Guangju; Lu, Zhongqiu

2016-01-01

Paraquat (PQ) has caused deaths of numerous people around the world. In order to assess the lethal plasma concentration, the patients who acquired acute PQ intoxication were analyzed by plasma concentration monitoring. The plasma PQ concentrations were determined by high performance liquid chromatography (HPLC) which used 5-bromopyrimidine as internal standard and trichloroacetic acid-methanol (1:9) as protein precipitant. The liver, kidney and coagulation function were determined by automatic biochemical analyzer. According to plasma PQ concentration, 90 patients were divided into four groups: trace PQ group (<50ng/mL), low PQ group (<1000ng/mL), medium PQ group (1000-5000ng/mL) and high PQ group (>5000ng/mL). The clinical data from the four groups was statistically analyzed. The results showed the developed HPLC methods exhibited a high degree of accuracy and good linearity within 50-25000ng/mL (R=0.9998). The Spearman's correlation analysis showed PQ concentration had a strong relationship to total bilirubin, direct bilirubin, aspartic transaminase, urea nitrogen, prothrombin time, prothrombin activity, and international normalized ratio (P<0.01). The cured or survival PQ poisoned patients among the trace PQ group, the low PQ group, the medium PQ group, and the high PQ group were 19/19 (100%), 19/21 (90.47%), 11/25 (44.0%), and 0/25 (0%) respectively. The mean hospital days were (10.37±8.04), (18.76±12.06), (16.76±14.44), and (4.04±5.41) days respectively. The Cox regression analysis indicated that plasma PQ concentration was highly related to prognosis (P<0.05). In conclusion, no patient presenting with a PQ concentration over 5000ng/mL survived. The plasma PQ level is related to liver, kidney and coagulation function, which can be used as an important clinical index to judge the prognosis of PQ poisoned patients. Paraquat (PubChem CID: 15938), 5-bromopyrimidine (PubChem CID: 78344), acetonitrile (PubChem CID: 6342), sodium dihydrogen phosphate (PubChem CID

Complexation facilitated reduction of aromatic N-oxides by aqueous Fe(II)-tiron complex: reaction kinetics and mechanisms.

PubMed

Chen, Yiling; Zhang, Huichun

2013-10-01

Rapid reduction of carbadox (CDX), olaquindox and several other aromatic N-oxides were investigated in aqueous solution containing Fe(II) and tiron. Consistent with previous work, the 1:2 Fe(II)-tiron complex, FeL2(6-), is the dominant reactive species as its concentration linearly correlates with the observed rate constant kobs under various conditions. The N-oxides without any side chains were much less reactive, suggesting direct reduction of the N-oxides is slow. UV-vis spectra suggest FeL2(6-) likely forms 5- or 7-membered rings with CDX and olaquindox through the N and O atoms on the side chain. The formed inner-sphere complexes significantly facilitated electron transfer from FeL2(6-) to the N-oxides. Reduction products of the N-oxides were identified by HPLC/QToF-MS to be the deoxygenated analogs. QSAR analysis indicated neither the first electron transfer nor N-O bond cleavage is the rate-limiting step. Calculations of the atomic spin densities of the anionic N-oxides confirmed the extensive delocalization between the aromatic ring and the side chain, suggesting complex formation can significantly affect the reduction kinetics. Our results suggest the complexation facilitated N-oxide reduction by Fe(II)-tiron involves a free radical mechanism, and the subsequent deoxygenation might also benefit from the weak complexation of Fe(II) with the N-oxide O atom.

Activity of amikacin against Mycobacterium avium complex under simulated in vivo conditions.

PubMed Central

Gangadharam, P R; Kesavalu, L; Rao, P N; Perumal, V K; Iseman, M D

1988-01-01

We studied the activity of amikacin against Mycobacterium avium complex strain 101 by using continuous-level, changing concentrations which simulated levels in serum in a patient, and pulsed exposures. Amikacin at a concentration of 5 or 15 micrograms/ml showed rapid bactericidal action following constant exposure of the organisms. With the in vitro model, using a peak concentration of 10 or 20 micrograms/ml, complete sterilization was obtained by day 7. In pulsed-exposure studies, a minimum period of contact of 72 or 96 h at a concentration of 10 micrograms/ml was needed for complete sterilization. PMID:3415209

Simultaneous separation of inorganic anions and metal-citrate complexes on a zwitterionic stationary phase with on-column complexation.

PubMed

Nesterenko, Ekaterina P; Nesterenko, Pavel N; Paull, Brett

2008-12-05

The retention and separation selectivity of inorganic anions and on-column derivatised negatively charged citrate or oxalate metal complexes on reversed-phase stationary phases dynamically coated with N-(dodecyl-N,N-dimethylammonio)undecanoate (DDMAU) has been investigated. The retention mechanism for the metal-citrate complexes was predominantly anion exchange, although the amphoteric/zwitterionic nature of the stationary phase coating undoubtedly also contributed to the unusual separation selectivity shown. A mixture of 10 inorganic anions and metal cations was achieved using a 20 cm monolithic DDMAU modified column and a 1 mM citrate eluent, pH 4.0, flow rate equal to 0.8 mL/min. Selectivity was found to be strongly pH dependent, allowing additional scope for manipulation of solute retention, and thus application to complex samples. This is illustrated with the analysis of an acidic mine drainage sample with a range of inorganic anions and transition metal cations, varying significantly in their concentrations levels.

Thermoelectric Properties of Complex Zintl Phases

NASA Astrophysics Data System (ADS)

Snyder, G. Jeffrey

2008-03-01

Complex Zintl phases make ideal thermoelectric materials because they can exhibit the necessary ``electron-crystal, phonon-glass'' properties required for high thermoelectric efficiency. Complex crystal structures can lead to high thermoelectric figure of merit (zT) by having extraordinarily low lattice thermal conductivity. A recent example is the discovery that Yb14MnSb11, a complex Zintl compound, has twice the zT as the SiGe based material currently in use at NASA. The high temperature (300K - 1300K) electronic properties of Yb14MnSb11 can be understood using models for heavily doped semiconductors. The free hole concentration, confirmed by Hall effect measurements, is set by the electron counting rules of Zintl and the valence of the transition metal (Mn^+2). Substitution of nonmagnetic Zn^+2 for the magnetic Mn^+2 reduces the spin-disorder scattering and leads to increased zT (10%). The reduction of spin-disorder scattering is consistent with the picture of Yb14MnSb11 as an underscreened Kondo lattice as derived from low temperature measurements. The hole concentration can be reduced by the substitution of Al^+3 for Mn^+2, which leads to an increase in the Seebeck coefficient and electrical resistivity consistent with models for degenerate semiconductors. This leads to further improvements (about 25%) in zT and a reduction in the temperature where the zT peaks. The peak in zT is due to the onset of minority carrier conduction and can be correlated with reduction in Seebeck coefficient, increase in electrical conductivity and increase in thermal conductivity due to bipolar thermal conduction.

Temporal evolution of cadmium, copper and lead concentration in the Venice Lagoon water in relation with the speciation and dissolved/particulate partition.

PubMed

Morabito, Elisa; Radaelli, Marta; Corami, Fabiana; Turetta, Clara; Toscano, Giuseppa; Capodaglio, Gabriele

2018-04-01

In order to study the role of sediment re-suspension and deposition versus the role of organic complexation, we investigated the speciation of cadmium (Cd), copper (Cu) and lead (Pb) in samples collected in the Venice Lagoon during several campaigns from 1992 to 2006. The increment in Cd and Pb concentration in the dissolved phases, observed in the central and northern basins, can be linked to important alterations inside the lagoon caused by industrial and urban factors. The study focuses on metal partition between dissolved and particulate phases. The analyses carried out in different sites illustrate the complex role of organic matter in the sedimentation process. While Cd concentration in sediments can be correlated with organic matter, no such correlation can be established in the case of Pb, whose particulate concentration is related only to the dissolved concentration. In the case of Cu, the role of organic complexation remains unclear. Copyright © 2017 Elsevier Ltd. All rights reserved.

Improved estimates of filtered total mercury loadings and total mercury concentrations of solids from potential sources to Sinclair Inlet, Kitsap County, Washington

USGS Publications Warehouse

Paulson, Anthony J.; Conn, Kathleen E.; DeWild, John F.

2013-01-01

Previous investigations examined sources and sinks of mercury to Sinclair Inlet based on historic and new data. This included an evaluation of mercury concentrations from various sources and mercury loadings from industrial discharges and groundwater flowing from the Bremerton naval complex to Sinclair Inlet. This report provides new data from four potential sources of mercury to Sinclair Inlet: (1) filtered and particulate total mercury concentrations of creek water during the wet season, (2) filtered and particulate total mercury releases from the Navy steam plant following changes in the water softening process and discharge operations, (3) release of mercury from soils to groundwater in two landfill areas at the Bremerton naval complex, and (4) total mercury concentrations of solids in dry dock sumps that were not affected by bias from sequential sampling. The previous estimate of the loading of filtered total mercury from Sinclair Inlet creeks was based solely on dry season samples. Concentrations of filtered total mercury in creek samples collected during wet weather were significantly higher than dry weather concentrations, which increased the estimated loading of filtered total mercury from creek basins from 27.1 to 78.1 grams per year. Changes in the concentrations and loading of filtered and particulate total mercury in the effluent of the steam plant were investigated after the water softening process was changed from ion-exchange to reverse osmosis and the discharge of stack blow-down wash began to be diverted to the municipal water-treatment plant. These changes reduced the concentrations of filtered and particulate total mercury from the steam plant of the Bremerton naval complex, which resulted in reduced loadings of filtered total mercury from 5.9 to 0.15 grams per year. Previous investigations identified three fill areas on the Bremerton naval complex, of which the western fill area is thought to be the largest source of mercury on the base

Modulating the protein content of complex proteomes using acetonitrile.

PubMed

Prates, João; Martins, Gonçalo; López-Fernández, Hugo; Lodeiro, Carlos; Capelo, J L; Santos, Hugo M

2018-05-15

In this work we present acetonitrile as a tool to modulate the dynamic range of the proteome of complex samples. Different concentrations of acetonitrile ranging from 15% v/v to 65% v/v were used to modulate the protein content of serum samples from healthy people and patients with lymphoma and myeloma. We show that the proteome above 70 kDa is pelleted as a function of the concentration of acetonitrile and that profiling with PCA or Clustering is only possible using the supernatants obtained for concentrations of acetonitrile higher than 45% v/v or the pellets for concentrations of acetonitrile of 35% and 45%. The differentiation and classification of the three groups of sera samples (healthy, lymphoma and myeloma) were possible using acetonitrile at 55% v/v concentration. This work opens new avenues for the application of acetonitrile as a cost-effective tool in proteomics applications. Copyright © 2018 Elsevier B.V. All rights reserved.

Environmentally relevant concentrations of aminopolycarboxylate chelating agents mobilize Cd from humic acid.

PubMed

North, Ashley E; Sarpong-Kumankomah, Sophia; Bellavie, Andrew R; White, Wade M; Gailer, Jürgen

2017-07-01

Although Cd is a pollutant of public health relevance, many dietary sources from which it can be absorbed into human tissues remain unknown. While it is well established that the biogeochemical cycle of Cd involves its complexation with environment-derived ligands (e.g., humic acids, HAs) and anthropogenic ones (e.g., chelating agents, CAs), the interaction of Cd with both of these ligands is less well understood. To gain insight, a HA-Cd complex was injected on a size-exclusion chromatography (SEC) column coupled on-line with a flame atomic absorption spectrometer (FAAS) using 10mmol/L Tris buffer (pH8.0) as the mobile phase. This approach allowed us to observe the intact HA-Cd complex and the retention behavior of Cd as a function of 2-20μmol/L concentrations of ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA) or methylglycinediacetic acid (MGDA) that were added to the mobile phase. An increase of the retention time of Cd was indicative of a partial or complete abstraction of Cd from HA. Our results revealed that all CAs abstracted Cd from the HA-Cd complex at concentrations of 5μmol/L, while MGDA and DTPA were effective at 2μmol/L. The bioavailability of some of the on-column formed CA-Cd complexes explains the previously reported increased accumulation of Cd in periphyton in the ecosystem downstream of wastewater treatment plants. In addition, our results imply that the use of effluents which contain CAs and Cd for the irrigation of food crops can introduce Cd into the food supply and compromise food safety. Copyright © 2017. Published by Elsevier B.V.

Silver(I) complexes with DNA and RNA studied by Fourier transform infrared spectroscopy and capillary electrophoresis.

PubMed Central

Arakawa, H; Neault, J F; Tajmir-Riahi, H A

2001-01-01

Ag(I) is a strong nucleic acids binder and forms several complexes with DNA such as types I, II, and III. However, the details of the binding mode of silver(I) in the Ag-polynucleotides remains unknown. Therefore, it was of interest to examine the binding of Ag(I) with calf-thymus DNA and bakers yeast RNA in aqueous solutions at pH 7.1-6.6 with constant concentration of DNA or RNA and various concentrations of Ag(I). Fourier transform infrared spectroscopy and capillary electrophoresis were used to analyze the Ag(I) binding mode, the binding constant, and the polynucleotides' structural changes in the Ag-DNA and Ag-RNA complexes. The spectroscopic results showed that in the type I complex formed with DNA, Ag(I) binds to guanine N7 at low cation concentration (r = 1/80) and adenine N7 site at higher concentrations (r = 1/20 to 1/10), but not to the backbone phosphate group. At r = 1/2, type II complexes formed with DNA in which Ag(I) binds to the G-C and A-T base pairs. On the other hand, Ag(I) binds to the guanine N7 atom but not to the adenine and the backbone phosphate group in the Ag-RNA complexes. Although a minor alteration of the sugar-phosphate geometry was observed, DNA remained in the B-family structure, whereas RNA retained its A conformation. Scatchard analysis following capillary electrophoresis showed two binding sites for the Ag-DNA complexes with K(1) = 8.3 x 10(4) M(-1) for the guanine and K(2) = 1.5 x 10(4) M(-1) for the adenine bases. On the other hand, Ag-RNA adducts showed one binding site with K = 1.5 x 10(5) M(-1) for the guanine bases. PMID:11509371

Solar Concentration for Electricity and Cooking