Cutaneous reactions to heparin therapy: when are they caused by heparin allergy?

Directory of Open Access Journals (Sweden)

Giuliana Zisa

2013-03-01

Full Text Available Introduction: Little is known about the incidence and causes of heparin-induced skin lesions. The most commonly reported causes are delayed-type hypersensitivity reactions. We describe 3 patients who were referred to our staff between March and October 2009 for suspected heparin allergies. All were scheduled to undergo major surgery (cardiovascular or orthopedic. Materials and methods: All 3 patients reported the development of itchy, erythematous rashes a few days after the subcutaneous administration of heparin (nadroparin calcium in cases 1 and 2, unspecified in case 3. Each of them underwent a diagnostic work-up for heparin allergy, which included prick and intradermal tests with commonly used heparins and patch testing with undiluted heparins and disinfectants. Results: Patch tests with disinfectants were negative in all 3 cases. In case 2, all allergological tests were negative. In cases 1 and 3, delayed positivity emerged for nadroparin calcium and at least one other heparin tested. Intravenous and/or subcutaneous provocation testing was done with an alternative heparin which produced negative results in skin tests (heparin sodium in case 1, pentasaccharide fondaparinux in case 3. In both cases the alternative drug was tolerated. After our evaluation, all 3 patients underwent surgery with no heparin-related complications. Discussion: The presenting clinical features in these 3 cases provided no information on which reactions were likely to be allergic: all 3 patients presented with similar local delayed reaction. The allergic reactions were identified only after cutaneous testing.

Chitosan-capped gold nanoparticles for selective and colorimetric sensing of heparin

International Nuclear Information System (INIS)

Chen, Zhanguang; Wang, Zhen; Chen, Xi; Xu, Haixiong; Liu, Jinbin

2013-01-01

In this contribution, novel chitosan-stabilized gold nanoparticles (AuNPs) were prepared by mixing chitosan with citrate-reductive AuNPs under appropriate conditions. The as-prepared chitosan-stabilized AuNPs were positively charged and highly stably dispersed in aqueous solution. They exhibited weak resonance light scattering (RLS) intensity and a wine red color. In addition, the chitosan-stabilized AuNPs were successfully utilized as novel sensitive probes for the detection of heparin for the first time. It was found that the addition of heparin induced a strong increase of RLS intensity for AuNPs and the color change from red to blue. The increase in RLS intensity and the color change of chitosan-stabilized AuNPs caused by heparin allowed the sensitive detection of heparin in the range of 0.2–60 μM (∼6.7 U/mL). The detection limit for heparin is 0.8 μM at a signal-to-noise ratio of 3. The present sensor for heparin detection possessed a low detection limit and wide linear range. Additionally, the proposed method was also applied to the detection of heparin in biological media with satisfactory results

Chitosan-capped gold nanoparticles for selective and colorimetric sensing of heparin

Energy Technology Data Exchange (ETDEWEB)

Chen, Zhanguang, E-mail: kqlu@stu.edu.cn; Wang, Zhen; Chen, Xi [Shantou University, Department of Chemistry (China); Xu, Haixiong [Shantou Central Hospital, Affiliated Shantou Hospital of SUN YAT-SEN University (China); Liu, Jinbin [University of Texasat Dallas, Department of Chemistry (United States)

2013-09-15

In this contribution, novel chitosan-stabilized gold nanoparticles (AuNPs) were prepared by mixing chitosan with citrate-reductive AuNPs under appropriate conditions. The as-prepared chitosan-stabilized AuNPs were positively charged and highly stably dispersed in aqueous solution. They exhibited weak resonance light scattering (RLS) intensity and a wine red color. In addition, the chitosan-stabilized AuNPs were successfully utilized as novel sensitive probes for the detection of heparin for the first time. It was found that the addition of heparin induced a strong increase of RLS intensity for AuNPs and the color change from red to blue. The increase in RLS intensity and the color change of chitosan-stabilized AuNPs caused by heparin allowed the sensitive detection of heparin in the range of 0.2-60 {mu}M ({approx}6.7 U/mL). The detection limit for heparin is 0.8 {mu}M at a signal-to-noise ratio of 3. The present sensor for heparin detection possessed a low detection limit and wide linear range. Additionally, the proposed method was also applied to the detection of heparin in biological media with satisfactory results.

Harmonic Mode-Locked Fiber Laser based on Photonic Crystal Fiber Filled with Topological Insulator Solution

Directory of Open Access Journals (Sweden)

Yu-Shan Chen

2015-04-01

Full Text Available We reported that the photonic crystal fiber (PCF filled with TI:Bi2Te3 nanosheets solution could act as an effective saturable absorber (SA. Employing this TI-PCF SA device; we constructed an ytterbium-doped all-fiber laser oscillator and achieved the evanescent wave mode-locking operation. Due to the large cavity dispersion; the fundamental mode-locking pulse had the large full width at half maximum (FWHM of 2.33 ns with the repetition rate of ~1.11 MHz; and the radio frequency (RF spectrum with signal-to-noise ratio (SNR of 61 dB. In addition; the transition dynamics from a bunched state of pulses to harmonic mode-locking (HML was also observed; which was up to 26th order.

Interactions between nattokinase and heparin/GAGs.

Science.gov (United States)

Zhang, Fuming; Zhang, Jianhua; Linhardt, Robert J

2015-12-01

Nattokinase (NK) is a serine protease extracted from a traditional Japanese food called natto. Due to its strong fibrinolytic and thrombolytic activity, NK is regarded as a valuable dietary supplement or nutraceutical for the oral thrombolytic therapy. In addition, NK has been investigated for some other medical applications including treatment of hypertension, Alzheimer's disease, and vitreoretinal disorders. The most widely used clinical anticoagulants are heparin and low molecular weight heparins. The interactions between heparin and proteins modulate diverse patho-physiological processes and heparin modifies the activity of serine proteases. Indeed, heparin plays important roles in almost all of NK's potential therapeutically applications. The current report relies on surface plasmon resonance spectroscopy to examine NK interacting with heparin as well as other glycosaminoglycans (GAGs). These studies showed that NK is a heparin binding protein with an affinity of ~250 nM. Examination with differently sized heparin oligosaccharides indicated that the interaction between NK and heparin is chain-length dependent and the minimum size for heparin binding is a hexasaccharide. Studies using chemically modified heparin showed the 6-O-sulfo as well as the N-sulfo groups but not the 2-O-sulfo groups within heparin, are essential for heparin's interaction with NK. Other GAGs (including HS, DS, and CSE) displayed modest binding affinity to NK. NK also interfered with other heparin-protein interactions, including heparin's interaction with antithrombin and fibroblast growth factors.

Current Trends in Heparin Use During Arterial Vascular Interventional Radiology

International Nuclear Information System (INIS)

Durran, Alexandra C.; Watts, Christopher

2012-01-01

Purpose: This study was designed to assess the current use of heparinized saline and bolus doses of heparin in non-neurological interventional radiology and to determine whether consensus could be reached to produce guidance for heparin use during arterial vascular intervention. Methods: An interactive electronic questionnaire was distributed to members of the British Society of Interventional Radiology regarding their current practice in the use, dosage, and timing of heparin boluses and heparinized flushing solutions.ResultsA total of 108 completed questionnaires were received. More than 80% of respondents used heparinized saline with varying concentrations; the most prevalent was 1,000 IU/l (international units of heparin per liter) and 5,000 IU/l. Fifty-one percent of interventionalists use 3,000 IU as their standard bolus dose; however, the respondents were split regarding the timing of bolus dose with ∼60% administering it after arterial access is obtained and 40% after crossing the lesion. There was no consensus on altering dose according to body weight, and only 4% monitored clotting parameters. Conclusions: There seems to be some coherence among practicing interventionalists regarding heparin administration. We hypothesize that heparinized saline should be used at a recognized standard concentration of 1,000 IU/l as a flushing concentration in all arterial vascular interventions and that 3,000 IU bolus is considered the standard dose for straightforward therapeutic procedures and 5000 IU for complex, crural, and endovascular aneurysm repair work. The bolus should be given after arterial access is obtained to allow time for optimal anticoagulation to be achieved by the time of active intervention and stenting. Further research into clotting abnormalities following such interventional procedures would be an interesting quantifiable follow-up to this initial survey of opinions and practice.

Prevention of after-cataract by application of heparin treatment of capsular tension ring in Marfan syndrome and subluxation of lens

Directory of Open Access Journals (Sweden)

Zhong-Qing Li

2013-08-01

Full Text Available AIM: To investigate the effect of heparin treatment on capsular tension ring(CTRin the prevention of after-cataract postoperative patients with Marfan syndrome and subluxation of lens.METHODS: Totally 34 cases(56 eyeswere divided randomly into experimental and control groups. Preoperative heparin 12500 units was added to 500mL Ringer's infusion, and CTR was dealt with heparin stock solution soak for 20 minutes in experimental group; there was no any drugs in the control group's solution, and CTR was not dealt with heparin. Postoperative IOP, anterior chamber reaction, corneal edema, IOL position, posterior capsular opacification were observed.RESULTS: There was statistically significant difference in the posterior capsular opacification between the heparin group(13.3%and the contral group no-heparin(69.2%(PCONCLUSION: The present results indicate that there is the preventive effect on posterior capsular opacification by CTR soaked in heparin in postoperative patients with Marfan syndrome and subluxation of lens, thus contributing to the recovery of visual function.

Sterilization of heparinized cuprophan hemodialysis membranes

OpenAIRE

ten Hoopen, Hermina W.M.; Hinrichs, W.L.J.; Hinrichs, W.L.J.; Engbers, G.H.M.; Feijen, Jan

1996-01-01

The effects of sterilization of dry heparinized Cuprophan hemodialysis membranes by means of ethylene oxide (EtO) exposure, gamma irradiation, or steam on the anticoagulant activity and chemical characteristics of immobilized heparin and the permeability of the membrane were investigated. Sterilization did not result in a release of heparin or heparin fragments from heparinized Cuprophan. Sterilization of heparinized Cuprophan by means of EtO exposure and gamma irradiation induced a slight, i...

Heparin pharmacovigilance in Brazil.

Science.gov (United States)

Junqueira, Daniela Rezende Garcia; Viana, Thércia Guedes; Peixoto, Eliane R de M; Barros, Fabiana C R de; Carvalho, Maria das Graças; Perini, Edson

2011-01-01

To investigate the biological origin of injectable unfractioned heparin available in Brazilian market by discussing the impact of the profile of commercial products and the changes in heparin monograph on the drug safety. The Anvisa data base for the Registered Products of Pharmaceutical Companies and the Dictionary of Pharmaceutical Specialties (DEF 2008/2009) were searched. A survey with industries having an active permission for marketing the drug in Brazil was conducted. Five companies were granted a permission to market unfractioned heparin in Brazil. Three of them are porcine in origin and two of them are bovine in origin, with only one explicitly showing this information in the package insert. The effectiveness and safety of heparin studied in non-Brazilian populations may not represent the Brazilian reality, since most countries no longer produce bovine heparin. The currently marketed heparin has approximately 10% less anticoagulant activity than that previously produced and this change may have clinical implications. Evidence about the lack of dose interchangeability between bovine and porcine heparins and the unique safety profile of these drugs indicates the need to follow the treatment and the patients' response. Events threatening the patient's safety must be reported to the pharmacovigilance system in each particular country.

Unfractionated heparin versus low molecular weight heparins for avoiding heparin-induced thrombocytopenia in postoperative patients.

Science.gov (United States)

Junqueira, Daniela R; Zorzela, Liliane M; Perini, Edson

2017-04-21

Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction presenting as a prothrombotic disorder related to antibody-mediated platelet activation. It is a paradoxical immune reaction resulting in thrombin generation in vivo, which leads to a hypercoagulable state and the potential to initiate venous or arterial thrombosis. A number of factors are thought to influence the incidence of HIT including the type and preparation of heparin (unfractionated heparin (UFH) or low molecular weight heparin (LMWH)) and the heparin-exposed patient population, with the postoperative patient population at higher risk.Although LMWH has largely replaced UFH as a front-line therapy, there is evidence supporting a lack of superiority of LMWH compared with UFH regarding prevention of deep vein thrombosis and pulmonary embolism following surgery, and similar frequencies of bleeding have been described with LMWH and UFH. The decision as to which of these two preparations of heparin to use may thus be influenced by harmful effects such as HIT. We therefore sought to determine the relative impact of UFH and LMWH on HIT in postoperative patients receiving thromboembolism prophylaxis. This is an update of a review first published in 2012. The objective of this review was to compare the incidence of heparin-induced thrombocytopenia (HIT) and HIT complicated by venous thromboembolism in postoperative patients exposed to unfractionated heparin (UFH) versus low molecular weight heparin (LMWH). For this update, the Cochrane Vascular Information Specialist searched the Specialised Register (May 2016), CENTRAL (2016, Issue 4) and trials registries. The authors searched Lilacs (June 2016) and additional trials were sought from reference lists of relevant publications. We included randomised controlled trials (RCTs) in which participants were postoperative patients allocated to receive prophylaxis with UFH or LMWH, in a blinded or unblinded fashion. Studies were excluded if they did not use

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

International Nuclear Information System (INIS)

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

1986-01-01

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

Heparin: Past, Present, and Future.

Science.gov (United States)

Oduah, Eziafa I; Linhardt, Robert J; Sharfstein, Susan T

2016-07-04

Heparin, the most widely used anticoagulant drug in the world today, remains an animal-derived product with the attendant risks of adulteration and contamination. A contamination crisis in 2007-2008 increased the impetus to provide non-animal-derived sources of heparin, produced under cGMP conditions. In addition, recent studies suggest that heparin may have significant antineoplastic activity, separate and distinct from its anticoagulant activity, while other studies indicate a role for heparin in treating inflammation, infertility, and infectious disease. A variety of strategies have been proposed to produce a bioengineered heparin. In this review, we discuss several of these strategies including microbial production, mammalian cell production, and chemoenzymatic modification. We also propose strategies for creating "designer" heparins and heparan-sulfates with various biochemical and physiological properties.

Endostatin competes with bFGF for binding to heparin-like glycosaminoglycans

International Nuclear Information System (INIS)

Reis, Renata C.M.; Schuppan, Detlef; Barreto, Aline C.; Bauer, Michael; Bork, Jens P.; Hassler, Gerda; Coelho-Sampaio, Tatiana

2005-01-01

Endostatin is a potent inhibitor of angiogenesis and tumor growth. Here, we used human endothelial cells from lung capillaries to investigate if endostatin competes with the proangiogenic growth factors, bFGF and VEGF, for binding to costimulatory heparan sulfate molecules. Endostatin inhibited 79% and 95% of the increase in proliferation induced by bFGF and VEGF 165 , respectively. The stimulatory effect of VEGF 165 was not affected by the presence of exogenous heparin, while that of bFGF was further enhanced in the presence of up to 0.1 μg/ml heparin. The heparin-binding protein protamine completely blocked bFGF-stimulated proliferation, while it did not affect the response to VEGF 165 . Simultaneous addition of endostatin and protamine led to additive effects both in inhibition of proliferation and induction of apoptosis. Although bFGF was found to bind more strongly to heparin-Sepharose than endostatin, the latter, but not the former, displaced protamine from heparin in solution, which supports the notion that endostatin can compete with bFGF for binding to heparan sulfate in vivo. Taken as a whole, our results demonstrate that there is a direct connection between the dependence of endostatin activity on heparin-like glycosaminoglycans and its ability to antagonize bFGF

Low molecular weight heparin versus unfractionated heparin in the initial treatment of venous thromboembolism

NARCIS (Netherlands)

Hettiarachchi, R. J.; Prins, M. H.; Lensing, A. W.; Buller, H. R.

1998-01-01

In this review, we analyze data from randomized trials in which low molecular weight heparin was compared with unfractionated heparin, both to estimate the treatment effect of low molecular weight heparin in the initial treatment of venous thromboembolism and to evaluate the effect of the varied

Collection of heparinized plasma by plasmapheresis

NARCIS (Netherlands)

van der Meer, P. F.; Vrielink, H.; Pietersz, R. N.; Dekker, W. J.; Reesink, H. W.

1999-01-01

BACKGROUND AND OBJECTIVES: Heparinized plasma can be used for exchange transfusions in neonates and is usually collected by drawing whole blood using heparin as anticoagulant. The heparinized red blood cells and buffy coat cannot be used and are therefore discarded. To collect heparinized plasma

Analysis and characterization of heparin impurities.

Science.gov (United States)

Beni, Szabolcs; Limtiaco, John F K; Larive, Cynthia K

2011-01-01

This review discusses recent developments in analytical methods available for the sensitive separation, detection and structural characterization of heparin contaminants. The adulteration of raw heparin with oversulfated chondroitin sulfate (OSCS) in 2007-2008 spawned a global crisis resulting in extensive revisions to the pharmacopeia monographs on heparin and prompting the FDA to recommend the development of additional physicochemical methods for the analysis of heparin purity. The analytical chemistry community quickly responded to this challenge, developing a wide variety of innovative approaches, several of which are reported in this special issue. This review provides an overview of methods of heparin isolation and digestion, discusses known heparin contaminants, including OSCS, and summarizes recent publications on heparin impurity analysis using sensors, near-IR, Raman, and NMR spectroscopy, as well as electrophoretic and chromatographic separations.

Ultrasensitive colorimetric detection of heparin based on self-assembly of gold nanoparticles on graphene oxide.

Science.gov (United States)

Fu, Xiuli; Chen, Lingxin; Li, Jinhua

2012-08-21

A novel colorimetric method was developed for ultrasensitive detection of heparin based on self-assembly of gold nanoparticles (AuNPs) onto the surface of graphene oxide (GO). Polycationic protamine was used as a medium for inducing the self-assembly of citrate-capped AuNPs on GO through electrostatic interaction, resulting in a shift in the surface plasmon resonance (SPR) absorption of AuNPs and exhibiting a blue color. Addition of polyanionic heparin disturbed the self-assemble of AuNPs due to its strong affinity to protamine. With the increase of heparin concentration, the amounts of self-assembly AuNPs decreased and the color changed from blue to red in solution. Therefore, a "blue-to-red" colorimetric sensing strategy based on self-assembly of AuNPs could be established for heparin detection. Compared with the commonly reported aggregation-based methods ("red-to-blue"), the color change from blue to red was more eye-sensitive, especially in low concentration of target. Moreover, stronger interaction between protamine and heparin led to distinguish heparin from its analogues as well as various potentially coexistent physiological species. The strategy was simply achieved by the self-assembly nature of AuNPs and the application of two types of polyionic media, showing it to be label-free, simple, rapid and visual. This method could selectively detect heparin with a detection limit of 3.0 ng mL(-1) in standard aqueous solution and good linearity was obtained over the range 0.06-0.36 μg mL(-1) (R = 0.9936). It was successfully applied to determination of heparin in fetal bovine serum samples as low as 1.7 ng mL(-1) with a linear range of 0-0.8 μg mL(-1).

Heparin-induced thrombocytopenia: real-world issues.

Science.gov (United States)

Linkins, Lori-Ann; Warkentin, Theodore E

2011-09-01

Heparin-induced thrombocytopenia (HIT) is a prothrombotic drug reaction caused by platelet-activating antibodies. HIT sera often activate platelets without needing heparin-such heparin-"independent" platelet activation can be associated with HIT beginning or worsening despite stopping heparin ("delayed-onset HIT"). We address important issues in HIT diagnosis and therapy, using a recent cohort of HIT patients to illustrate influences of heparin type; triggers for HIT investigation; serological features of heparin-independent platelet activation; and treatment. In our cohort of recent HIT cases ( N = 13), low-molecular-weight heparin (dalteparin) was a common causative agent ( N = 8, 62%); most patients were diagnosed after HIT-thrombosis had occurred; and danaparoid was the most frequently selected treatment. Heparin-independent platelet activation was common (7/13 [54%]) and predicted slower platelet count recovery (>1 week) among evaluable patients (5/5 vs 1/6; P = 0.015). In our experience with argatroban-treated patients, HIT-associated consumptive coagulopathy confounds anticoagulant monitoring. Our observations provide guidance on practical aspects of HIT diagnosis and management. Thieme Medical Publishers.

77 FR 7584 - Draft Guidance for Industry on Heparin for Drug and Medical Device Use; Monitoring Crude Heparin...

Science.gov (United States)

2012-02-13

... strategies to ensure that the heparin supply chain is not contaminated with OSCS or any non- porcine origin... device manufacturers of finished products, and others to the potential risk of crude heparin...) among patients injected with heparin sodium in 2008, FDA identified the contaminant OSCS in heparin API...

78 FR 38058 - Guidance for Industry on Heparin for Drug and Medical Device Use: Monitoring Crude Heparin for...

Science.gov (United States)

2013-06-25

... public health. FDA developed this guidance to alert manufacturers to the risks of crude heparin contaminants and to recommend strategies to ensure that the heparin supply chain is not contaminated with OSCS... heparin sodium in 2008, FDA identified the contaminant OSCS in crude heparin sourced from China. FDA is...

Sensitive detection of oversulfated chondroitin sulfate in heparin sodium or crude heparin with a colorimetric microplate based assay.

Science.gov (United States)

Sommers, Cynthia D; Mans, Daniel J; Mecker, Laura C; Keire, David A

2011-05-01

In this work we describe a 96-well microplate assay for oversulfated chondroitin sulfate A (OSCS) in heparin, based on a water-soluble cationic polythiophene polymer (3-(2-(N-(N'-methylimidazole))ethoxy)-4-methylthiophene (LPTP)) and heparinase digestion of heparin. The assay takes advantage of several unique properties of heparin, OSCS, and LPTP, including OSCS inhibition of heparinase I and II activity, the molecular weight dependence of heparin-LPTP spectral shifts, and the distinct association of heparin fragments and OSCS to LPTP. These factors combine to enable detection of the presence of 0.003% w/w spiked OSCS in 10 μg of heparin sodium active pharmaceutical ingredient (API) using a plate reader and with visual detection to 0.1% levels. The same detection limit for OSCS was observed in the presence of 10% levels of dermatan sulfate (DS) or chondroitin sulfate A (CSA) impurities. In addition, we surveyed a selection of crude heparin samples received by the agency in 2008 and 2009 to determine average and extreme DS, CSA, and galactosamine weight percent levels. In the presence of these impurities and the variable heparin content in the crude heparin samples, spiked OSCS was reliably detected to the 0.1% w/w level using a plate reader. Finally, authentically OSCS contaminated heparin sodium API and crude samples were distinguished visually by color from control samples using the LPTP/heparinase test.

Click-coated, heparinized, decellularized vascular grafts.

Science.gov (United States)

Dimitrievska, Sashka; Cai, Chao; Weyers, Amanda; Balestrini, Jenna L; Lin, Tylee; Sundaram, Sumati; Hatachi, Go; Spiegel, David A; Kyriakides, Themis R; Miao, Jianjun; Li, Guoyun; Niklason, Laura E; Linhardt, Robert J

2015-02-01

A novel method enabling the engineering of a dense and appropriately oriented heparin-containing layer on decellularized aortas has been developed. Amino groups of decellularized aortas were first modified to azido groups using 3-azidobenzoic acid. Azide-clickable dendrons were attached onto the azido groups through "alkyne-azide" click chemistry, affording a tenfold amplification of adhesions sites. Dendron end groups were finally decorated with end-on modified heparin chains. Heparin chains were oriented like heparan sulfate groups on native endothelial cells surface. X-ray photoelectron spectroscopy, nuclear magnetic resonance imaging, mass spectrometry and Fourier transform infrared FTIR spectroscopy were used to characterize the synthesis steps, building the final heparin layered coatings. The continuity of the heparin coating was verified using fluorescent microscopy and histological analysis. The efficacy of heparin linkage was demonstrated with factor Xa anti-thrombogenic assay and platelet adhesion studies. The results suggest that oriented heparin immobilization to decellularized aortas may improve the in vivo blood compatibility of decellularized aortas and vessels. Copyright © 2014 Acta Materialia Inc. All rights reserved.

Heparin for assisted reproduction.

Science.gov (United States)

Akhtar, Muhammad A; Sur, Shyamaly; Raine-Fenning, Nick; Jayaprakasan, Kannamannadiar; Thornton, Jim G; Quenby, Siobhan

2013-08-17

Heparin as an adjunct in assisted reproduction (peri-implantation heparin) is given at or after egg collection or at embryo transfer during assisted reproduction. Heparin has been advocated to improve embryo implantation and clinical outcomes.  It has been proposed that heparin enhances the intra-uterine environment by improving decidualisation with an associated activation of growth factors and a cytokine expression profile in the endometrium that is favourable to pregnancy. To investigate whether the administration of heparin around the time of implantation (peri-implantation heparin) improves clinical outcomes in subfertile women undergoing assisted reproduction. A comprehensive and exhaustive search strategy was developed in consultation with the Trials Search Co-ordinator of the Cochrane Menstrual Disorders and Subfertility Group (MDSG). The strategy was used in an attempt to identify all relevant studies regardless of language or publication status (published, unpublished, in press, and in progress). Relevant trials were identified from both electronic databases and other resources (last search 6 May 2013). All randomised controlled trials (RCTs) were included where peri-implantation heparin was given during assisted reproduction. Peri-implantation low molecular weight heparin (LMWH) during IVF/ICSI was given at or after egg collection or at embryo transfer in the included studies. Live birth rate was the primary outcome. Two review authors independently assessed the eligibility and quality of trials and extracted relevant data. The quality of the evidence was evaluated using GRADE methods. Three RCTs (involving 386 women) were included in the review.Peri-implantation LMWH administration during assisted reproduction was associated with a significant improvement in live birth rate compared with placebo or no LMWH (odds ratio (OR) 1.77, 95% confidence interval (CI) 1.07 to 2.90, three studies, 386 women, I(2) = 51%, very low quality evidence with high

Heparin and heparin-induced thrombocytopenia

African Journals Online (AJOL)

2007-06-15

Jun 15, 2007 ... Heparin is one of the most widely used drugs. It is used routinely for treatment and thromboprophylaxis in a broad spectrum of conditions including venous thromboembolism, atrial fibrillation, acute coronary syndromes, peripheral vascular disease and to maintain the patency of indwelling catheters and ...

Analysis of the complex formation of heparin with protamine by light scattering and analytical ultracentrifugation: implications for blood coagulation management.

Science.gov (United States)

Maurer, Jürgen; Haselbach, Stephanie; Klein, Oliver; Baykut, Doan; Vogel, Vitali; Mäntele, Werner

2011-02-02

Heparin, a linear glycosaminoglycan, is used in different forms in anticoagulation treatment. Protamine, a highly positive charged peptide containing about 32 amino acids, acts as an antagonist for heparin to restore normal blood coagulation. The complex formation of protamine with heparin was analyzed by a combination of analytical ultracentrifugation and light scattering. Titration of heparin with protamine in blood plasma preparations results in a drastic increase of turbidity, indicating the formation of nanoscale particles. A similar increase of turbidity was observed in physiological saline solution with or without human serum albumin (HSA). Particle size analysis by analytical ultracentrifugation revealed a particle radius of approximately 30 nm for unfractionated heparin and of approximately 60 nm for low molecular weight heparin upon complexation with excess protamine, in agreement with atomic force microscopy data. In the absence of HSA, larger and more heterogeneous particles were observed. The particles obtained were found to be stable for hours. The particle formation kinetics was analyzed by light scattering at different scattering angles and was found to be complete within several minutes. The time course of particle formation suggests a condensation reaction, with sigmoidal traces for low heparin concentrations and quasi-first-order reaction for high heparin concentrations. Under all conditions, the final scattering intensity reached after several minutes was found to be proportional to the amount of heparin in the blood plasma or buffer solution, provided that excess protamine was available and no multiple scattering occurred. On the basis of a direct relation between particle concentration and the heparin concentration present before protaminization, a light scattering assay was developed which permits the quantitative analysis of the heparin concentration in blood plasma and which could complement or even replace the activated clotting time test

Results of the HepZero study comparing heparin-grafted membrane and standard care show that heparin-grafted dialyzer is safe and easy to use for heparin-free dialysis

NARCIS (Netherlands)

Laville, Maurice; Dorval, Marc; Ros, Joan Fort; Fay, Renaud; Cridlig, Joelle; Nortier, Joelle L.; Juillard, Laurent; Debska-Slizien, Alicja; Lorente, Loreto Fernandez; Thibaudin, Damien; Franssen, Casper; Schulz, Michael; Moureau, Frederique; Loughraieb, Nathalie; Rossignol, Patrick

2014-01-01

Heparin is used to prevent clotting during hemodialysis, but heparin-free hemodialysis is sometimes needed to decrease the risk of bleeding. The HepZero study is a randomized, multicenter international controlled open-label trial comparing no-heparin hemodialysis strategies designed to assess

Layer-by-Layer Heparinization of the Cell Surface by Using Heparin-Binding Peptide Functionalized Human Serum Albumin.

Science.gov (United States)

Song, Guowei; Hu, Yaning; Liu, Yusheng; Jiang, Rui

2018-05-20

Layer-by-layer heparinization of therapeutic cells prior to transplantation is an effective way to inhibit the instant blood-mediated inflammatory reactions (IBMIRs), which are the major cause of early cell graft loss during post-transplantation. Here, a conjugate of heparin-binding peptide (HBP) and human serum albumin (HSA), HBP-HSA, was synthesized by using heterobifunctional crosslinker. After the first heparin layer was coated on human umbilical vein endothelial cells (HUVECs) by means of the HBP-polyethylene glycol-phospholipid conjugate, HBP-HSA and heparin were then applied to the cell surface sequentially to form multiple layers. The immobilization and retention of heparin were analyzed by confocal microscopy and flow cytometry, respectively, and the cytotoxity of HBP-HSA was further evaluated by cell viability assay. Results indicated that heparin was successfully introduced to the cell surface in a layer-by-layer way and retained for at least 24 h, while the cytotoxity of HBP-HSA was negligible at the working concentration. Accordingly, this conjugate provides a promising method for co-immobilization of heparin and HSA to the cell surface under physiological conditions with improved biocompatibility.

Severe heparin osteoporosis in pregnancy.

OpenAIRE

Griffiths, H. T.; Liu, D. T.

1984-01-01

A case of severe osteoporosis following administration of low dose subcutaneous heparin in pregnancy is reported. Possible reasons for the condition are suggested which caution against the indiscriminate use of subcutaneous heparin in pregnancy.

Allergic anaphylaxis due to subcutaneously injected heparin

Directory of Open Access Journals (Sweden)

Anders Diana

2013-01-01

Full Text Available Abstract Heparins are one of the most used class of anticoagulants in daily clinical practice. Despite their widespread application immune-mediated hypersensitivity reactions to heparins are rare. Among these, the delayed-type reactions to s.c. injected heparins are well-known usually presenting as circumscribed eczematous plaques at the injection sites. In contrast, potentially life-threatening systemic immediate-type anaphylactic reactions to heparins are extremely rare. Recently, some cases of non-allergic anaphylaxis could be attributed to undesirable heparin contaminants. A 43-year-old patient developed severe anaphylaxis symptoms within 5–10 minutes after s.c. injection of enoxaparin. Titrated skin prick testing with wheal and flare responses up to an enoxaparin dilution of 1:10.000 indicated a probable allergic mechanism of the enoxaparin-induced anaphylaxis. The basophil activation test as an additional in-vitro test method was negative. Furthermore, skin prick testing showed rather broad cross-reactivity among different heparin preparations tested. In the presented case, history, symptoms, and results of skin testing strongly suggested an IgE-mediated allergic hypersensitivity against different heparins. Therefore, as safe alternative anticoagulants the patient could receive beneath coumarins the hirudins or direct thrombin inhibitors. Because these compounds have a completely different molecular structure compared with the heparin-polysaccharides.

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

Science.gov (United States)

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

2017-09-01

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

Influence of heparin on radioimmunological assay of ACTH

International Nuclear Information System (INIS)

Dupouy, J.P.; Godaut, M.; Chatelain, A.

1986-01-01

1 - Heparin traps plasma ACTH, promoting the formation of aggregates with apparent high molecular weight as shown by chromatography on Sephadex G 50 fine columns. The percentage of 125 I-ACTH which appeared in the void volume of the column, increased linearly with the log. dose of heparin. 2 - Heparin at concentrations of up to 100 IU/ml does not impair ACTH adsorption on either silicic acid or Quso G 32 as well as further elution by acetic acid/acetone/water (I: 40: 59; V/V) or HCl O.I N. Silicic acid traps selectively ACTH but not heparin. 3 - Heparin interferes with direct RIA-ACTH in the plasma by decreasing 125 I-ACTH binding to the antibodies and modifying the slope of the standard curve. Unsuitable artefacts induced by heparin, as overestimation or underestimation of plasma ACTH levels by RIA, can be avoid by previous hormone extraction from heparinized plasmas. Such results emphasized the importance of the sample preparation in order to obtain consistent results [fr

Preparation and characterization of microspheres of albumin-heparin conjugates

NARCIS (Netherlands)

Kwon, Glen S.; Bae, You Han; Kim, Sung Wan; Cremers, Harry; Cremers, H.F.M.; Feijen, Jan

1991-01-01

Albumin-heparin microspheres have been prepared as a new drug carrier. A soluble albumin-heparin conjugate was synthesized by forming amide bonds between human serum albumin and heparin. After purification the albumin-heparin conjugate was crosslinked in a water-in-oil emulsion to form

How to give a heparin shot

Science.gov (United States)

... you put the injection. Storing Your Heparin and Supplies Ask your pharmacist how to store your heparin ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

Phase-locked patterns of the Kuramoto model on 3-regular graphs

Science.gov (United States)

DeVille, Lee; Ermentrout, Bard

2016-09-01

We consider the existence of non-synchronized fixed points to the Kuramoto model defined on sparse networks: specifically, networks where each vertex has degree exactly three. We show that "most" such networks support multiple attracting phase-locked solutions that are not synchronized and study the depth and width of the basins of attraction of these phase-locked solutions. We also show that it is common in "large enough" graphs to find phase-locked solutions where one or more of the links have angle difference greater than π/2.

Endogenous heparin levels in the controlled asthmatic patient ...

African Journals Online (AJOL)

Background. Since heparin possesses anti-inflammatory properties, it is hypothesised that asthmatic patients have decreased levels of circulating heparin compared with healthy individuals. Design. We compared endogenous heparin levels in controlled asthmatic patients (53 adults) from the Asthma Clinic at ...

Heparin increases food intake through AgRP neurons

Science.gov (United States)

Although the widely used anticoagulant drug heparin has been shown to have many other biological functions independent of its anticoagulant role, its effects on energy homeostasis are unknown. Here, we demonstrate that heparin level is negatively associated with nutritional states and that heparin t...

Sterilization of heparinized cuprophan hemodialysis membranes

NARCIS (Netherlands)

ten Hoopen, Hermina W.M.; Hinrichs, W.L.J.; Hinrichs, W.L.J.; Engbers, G.H.M.; Feijen, Jan

1996-01-01

The effects of sterilization of dry heparinized Cuprophan hemodialysis membranes by means of ethylene oxide (EtO) exposure, gamma irradiation, or steam on the anticoagulant activity and chemical characteristics of immobilized heparin and the permeability of the membrane were investigated.

Heparin Assisted Photochemical Synthesis of Gold Nanoparticles and Their Performance as SERS Substrates

Science.gov (United States)

Rodríguez-Torres, Maria del Pilar; Díaz-Torres, Luis Armando; Romero-Servin, Sergio

2014-01-01

Reactive and pharmaceutical-grade heparins were used as biologically compatible reducing and stabilizing agents to photochemically synthesize colloidal gold nanoparticles. Aggregates and anisotropic shapes were obtained photochemically under UV black-light lamp irradiation (λ = 366 nm). Heparin-functionalized gold nanoparticles were characterized by Scanning Electron Microscopy and UV-Vis spectroscopy. The negatively charged colloids were used for the Surface Enhanced Raman Spectroscopy (SERS) analysis of differently charged analytes (dyes). Measurements of pH were taken to inspect how the acidity of the medium affects the colloid-analyte interaction. SERS spectra were taken by mixing the dyes and the colloidal solutions without further functionalization or addition of any aggregating agent. PMID:25342319

Simultaneous estimation of vitamin K1 and heparin with low limit of detection using cascaded channels fiber optic surface plasmon resonance.

Science.gov (United States)

Tabassum, Rana; Gupta, Banshi D

2016-12-15

We report an approach for the simultaneous estimation of vitamin K1 (VK1) and heparin via cascaded channel multianalyte sensing probe employing fiber optic surface plasmon resonance technique. Cladding from two well separated portions of the fiber is removed and are respectively coated with thin films of silver (channel-1) and copper (channel-2). The nanohybrid of multiwalled carbon nanotube in chitosan is fabricated over silver layer for the sensing of VK1 whereas core shell nanostructure of polybrene@ZnO is coated over copper layer for the sensing of heparin. Spectral interrogation method is used for the characterization of the sensor. Analyte selectivity of both the channels is performed by carrying out experiments using independent solutions of VK1 and heparin. Experiments performed on the solution of the mixture of VK1 and heparin show red shifts in both the channels on changing the concentration of both the analytes in the mixture. The operating range of both VK1 and heparin is from 0 to 10(-3)g/l. The limit of detection of the sensor is 2.66×10(-4)µg/l and 2.88×10(-4)µg/l for VK1 and heparin respectively which are lower than the reported ones. The additional advantages of the present sensor are low cost, possibility of online monitoring and remote sensing. Copyright © 2016 Elsevier B.V. All rights reserved.

Structural characterization of pharmaceutical heparins prepared from different animal tissues.

Science.gov (United States)

Fu, Li; Li, Guoyun; Yang, Bo; Onishi, Akihiro; Li, Lingyun; Sun, Peilong; Zhang, Fuming; Linhardt, Robert J

2013-05-01

Although most pharmaceutical heparin used today is obtained from porcine intestine, heparin has historically been prepared from bovine lung and ovine intestine. There is some regulatory concern about establishing the species origin of heparin. This concern began with the outbreak of mad cow disease in the 1990s and was exacerbated during the heparin shortage in the 2000s and the heparin contamination crisis of 2007-2008. Three heparins from porcine, ovine, and bovine were characterized through state-of-the-art carbohydrate analysis methods with a view profiling their physicochemical properties. Differences in molecular weight, monosaccharide and disaccharide composition, oligosaccharide sequence, and antithrombin III-binding affinity were observed. These data provide some insight into the variability of heparins obtained from these three species and suggest some analytical approaches that may be useful in confirming the species origin of a heparin active pharmaceutical ingredient. Copyright © 2013 Wiley Periodicals, Inc.

Does ′heparin-induced thrombocytopenia′ hit our minds?

Directory of Open Access Journals (Sweden)

Arun R Thangavel

2016-01-01

Full Text Available Unfractionated heparin is a widely used drug to prevent deep vein thrombosis and pulmonary emboli in patients at risk. With the advent of newer anticoagulants having lesser side effects, its use has diminished but not out of service. Here, we report a case of deep venous thrombosis, in a patient on prophylactic dose of heparin, which was later found to be a manifestation of heparin-induced thrombocytopenia (HIT. Thrombosis in the presence of heparin prophylaxis should be considered as HIT rather than a failure of anticoagulation.

Automatic locking radioisotope camera lock

International Nuclear Information System (INIS)

Rosauer, P.J.

1978-01-01

The lock of the present invention secures the isotope source in a stored shielded condition in the camera until a positive effort has been made to open the lock and take the source outside of the camera and prevents disconnection of the source pigtail unless the source is locked in a shielded condition in the camera. It also gives a visual indication of the locked or possible exposed condition of the isotope source and prevents the source pigtail from being completely pushed out of the camera, even when the lock is released. (author)

Delay differential equations for mode-locked semiconductor lasers.

Science.gov (United States)

Vladimirov, Andrei G; Turaev, Dmitry; Kozyreff, Gregory

2004-06-01

We propose a new model for passive mode locking that is a set of ordinary delay differential equations. We assume a ring-cavity geometry and Lorentzian spectral filtering of the pulses but do not use small gain and loss and weak saturation approximations. By means of a continuation method, we study mode-locking solutions and their stability. We find that stable mode locking can exist even when the nonlasing state between pulses becomes unstable.

Heparin- induced thrombocytopenia (HIT: a case report of CABG patient

Directory of Open Access Journals (Sweden)

Alireza Jahangirifard

2016-08-01

Full Text Available Heparin- induced thrombocytopenia (HIT is an antibody mediated adverse effect of heparin therapy which is classified into two subtypes, HITI which is non-immune, spontaneously reversible thrombocytopenia and; HITII which is an autoimmune-mediated adverse effect of heparin therapy. In this case report, we described a 65-year old male patient with HITII after coronary artery bypass grafting.Key words: Heparin- induced thrombocytopenia, Heparin- induced thrombosis, coronary artery bypass grafting.

Heparin molecularly imprinted polymer thin flm on gold electrode by plasma-induced graft polymerization for label-free biosensor.

Science.gov (United States)

Orihara, Kouhei; Hikichi, Atsushi; Arita, Tomohiko; Muguruma, Hitoshi; Yoshimi, Yasuo

2018-03-20

Heparin, a highly sulfated glycosaminoglycan, is an important biomaterial having biological and therapeutic functionalities such as anticoagulation, regeneration, and protein stabilization. This study addresses a label-free quartz crystal microbalance (QCM) biosensor for heparin detection based on a macromolecularly imprinted polymer (MIP) as an artificial recognition element. We demonstrate the novel strategy for MIP in the form of thin film on a gold (Au) electrode with the plasma-induced graft polymerization (PIP) technique. The procedure of PIP is as follows: (i) Hexamethyldisiloxane plasma-polymerized thin film (PPF) as a pre-coating scaffold of active species for PIP (post-polymerization) is deposited on an Au electrode. (ii) The PPF/Au electrode is soaked in an water solution containing heparin (template), (2-(methacryloxy)-ethyl)trimethylammonium chloride acrylamide (functional monomer), acrylamide, and N,N-methylenebisacrylamide (crosslinker). Double bonds of monomer and crosslinker attacked by residually active species in pre-coating PPF cause radical chain reaction. Consequently, a growing polymer network of 20 nm thickness of PIP-MIP thin film is formed and grafted on the PPF/Au surface. (iii) The PIP-MIP/PPF/Au is washed by sodium chloride solution so as to remove the template. Non-imprinted polymer (NIP) is carried out like the same procedure without a template. The AFM, XPS, and QCM measurements show that the PIP process facilitates macromolecularly surface imprinting of template heparin where the template is easily removed and is rapidly rebound to PIP-MIP without a diffusional barrier. The heparin-PIP-MIP specifically binds to heparin compared with heparin analog chondroitin sulfate C (selective factor: 4.0) and a detectable range of heparin in the presence of CS (0.1 wt%) was 0.001-0.1 wt%. The PIP-NIP does not show selectivity between them. The evaluated binding kinetics are association (k a  = 350 ± 100 M -1  s -1

Influences of apolipoprotein E on soluble and heparin-immobilized hepatic lipase

International Nuclear Information System (INIS)

Landis, B.A.; Rotolo, F.S.; Meyers, W.C.; Clark, A.B.; Quarfordt, S.H.

1987-01-01

The effect of human apolipoprotein E (apoE), either alone or in combination with apoC, on the lipolysis of a radiolabeled triglyceride emulsion was studied with hepatic lipase in solution and immobilized on heparin-Sepharose. The soluble hepatic lipase was inhibited, whereas the heparin-immobilized lipase was stimulated by apoE. This stimulation was attenuated by combining apoE with either apoC-II or C-III. The heparin-immobilized lipase demonstrated much less lipolysis of the zwitterionic phosphatidylcholine-stabilized triglyceride emulsion than did the soluble enzyme. This difference was less when the emulsion was stabilized by a nonionic detergent. apoE inhibited lipase activity when assayed under conditions (0.4 M NaCl) of bound enzyme and unbound substrate. Increasing the emulsion apoE content beyond optimum inhibited lipolysis by the immobilized enzyme. Kinetic analysis of phosphatidylcholine-stabilized triglyceride emulsions revealed a significant decrease in immobilized enzyme K/sub m/ and an increase in V/sub max/ when the emulsion was supplemented with apoE. Distributing the immobilized lipase in clustered aggregates produced more lipolysis than when the same enzyme content was uniformly bound

Profiling Heparin-Chemokine Interactions Using Synthetic Tools

Science.gov (United States)

de Paz, Jose L.; Moseman, E. Ashley; Noti, Christian; Polito, Laura; von Andrian, Ulrich H.; Seeberger, Peter H.

2009-01-01

Glycosaminoglycans (GAGs), such as heparin or heparan sulfate, are required for the in vivo function of chemokines. Chemokines play a crucial role in the recruitment of leukocyte subsets to sites of inflammation and lymphocytes trafficking. GAG-chemokine interactions mediate cell migration and determine which leukocyte subsets enter tissues. Identifying the exact GAC sequences that bind to particular chemokines is key to understand chemokine function at the molecular level and develop strategies to interfere with chemokine-mediated processes. Here, we characterize the heparin binding profiles of eight chemokines (CCL21, IL-8, CXCL12, CXCL13, CCL19, CCL25, CCL28, and CXCL16) by employing heparin microarrays containing a small library of synthetic heparin oligosaccharides. The chemokines differ significantly in their interactions with heparin oligosaccharides: While some chemokines, (e.g., CCL21) strongly bind to a hexasaccharide containing the GlcNSO3(6-OSO3)-IdoA(2-OSO3) repeating unit, CCL19 does not bind and CXCL12 binds only weakly. The carbohydrate microarray binding results were validated by surface plasmon resonance experiments. In vitro chemotaxis assays revealed that dendrimers coated with the fully sulfated heparin hexasaccharide inhibit lymphocyte migration toward CCL21. Migration toward CXCL12 or CCL19 was not affected. These in vitro homing assays indicate that multivalent synthetic heparin dendrimers inhibit the migration of lymphocytes toward certain chemokine gradients by blocking the formation of a chemokine concentration gradient on GAG endothelial chains. These findings are in agreement with preliminary in vivo measurements of circulating lymphocytes. The results presented here contribute to the understanding of GAG-chemokine interactions, a first step toward the design of novel drugs that modulate chemokine activity. PMID:18030990

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

Science.gov (United States)

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

2015-07-01

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

21 CFR 864.7525 - Heparin assay.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Heparin assay. 864.7525 Section 864.7525 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7525 Heparin assay. (a) Identification. A...

Advanced nanocarriers based on heparin and its derivatives for cancer management.

Science.gov (United States)

Yang, Xiaoye; Du, Hongliang; Liu, Jiyong; Zhai, Guangxi

2015-02-09

To obtain a satisfying anticancer effect, rationally designed nanocarriers are intensively studied. In this field, heparin and its derivatives have been widely attempted recently as potential component of nanocarriers due to their unique biological and physiochemical features, especially the anticancer activity. This review focuses on state-of-the-art nanocarriers with heparin/heparin derivatives as backbone or coating material. At the beginning, the unique advantages of heparin used in cancer nanotechnology are discussed. After that, different strategies of heparin chemical modification are reviewed, laying the foundation of developing various nanocarriers. Then a systematic summary of diverse nanoparticles with heparin as component is exhibited, involving heparin-drug conjugate, polymeric nanoparticles, nanogels, polyelectrolyte complex nanoparticles, and heparin-coated organic and inorganic nanoparticles. The application of these nanoparticles in various novel cancer therapy (containing targeted therapy, magnetic therapy, photodynamic therapy, and gene therapy) will be highlighted. Finally, future challenges and opportunities of heparin-based biomaterials in cancer nanotechnology are discussed.

A sensitive competitive binding assay for exogenous and endogenous heparins

International Nuclear Information System (INIS)

Dawes, J.; Pepper, D.S.

1982-01-01

A new type of assay for heparins has been devised, in which the test material competes with 125 I-labelled heparin for binding to protamine-Sepharose. The assay is very sensitive and will measure heparin concentrations down to 10 ng ml-1. It responds to both the degree of sulphation and the molecular weight of acidic polysaccharides, but is independent of their biological activities. It can be used to quantitate heparins in biological fluids after pretreatment of the samples with protease. In this way endogenous heparins were measured in normal human serum, plasma and urine. The assay is extremely versatile and has great potential for the investigation of endogenous and exogenous heparins

Characterization of heparin aerosols generated in jet and ultrasonic nebulizers

DEFF Research Database (Denmark)

Bendstrup, K.E.; Newhouse, M.T.; Pedersen, Ole Finn

1999-01-01

Inhaled heparin has been used for asthma treatment, but results have been inconsistent, probably due to highly varying lung doses. We determined the output per unit time and the particle size distributions of sodium heparin, calcium heparin, and low molecular weight (LMW) heparin formulations in ...... on the exhalation filter, and 15,000 IU was captured on the inhalation filter (inhaled mass). This corresponds to a respirable mass of 10,000 IU of heparin with a high probability of reaching the lower respiratory tract in normal healthy adults....

Effects of heparin on insulin binding and biological activity

International Nuclear Information System (INIS)

Kriauciunas, K.M.; Grigorescu, F.; Kahn, C.R.

1987-01-01

The effect of heparin, a polyanionic glycosaminoglycan known to alter the function of many proteins, on insulin binding and bioactivity was studied. Cultured human lymphocytes (IM-9) were incubated with varying concentrations of heparin, then extensively washed, and 125 I-labeled insulin binding was measured. Heparin at concentrations used clinically for anticoagulation (1-50 U/ml) inhibited binding in a dose-dependent manner; 50% inhibition of binding occurred with 5-10 U/ml. Scatchard analysis indicated that the decrease in binding was due to a decrease in both the affinity and the apparent number of available insulin receptors. The effect occurred within 10 min at 22 degrees C and persisted even after the cells were extensively washed. Inhibition of insulin binding also occurred when cells were preincubated with heparinized plasma or heparinized serum but not when cells were incubated with normal serum or plasma from blood anticoagulated with EDTA. By contrast, other polyanions and polycations, e.g., poly-L-glutamic acid, poly-L-lysine, succinylated poly-L-lysine, and histone, did not inhibit binding. Heparin also inhibited insulin binding in Epstein-Barr (EB) virus-transformed lymphocytes but had no effect on insulin binding to isolated adipocytes, human erythrocytes, or intact hepatoma cells. When isolated adipocytes were incubated with heparin, there was a dose-dependent inhibition of insulin-stimulated glucose oxidation and, to a lesser extent, of basal glucose oxidation. Although heparin has no effect on insulin binding to intact hepatoma cells, heparin inhibited both insulin binding and insulin-stimulated autophosphorylation in receptors solubilized from these cells

Citrate Anticoagulation for CRRT in Children: Comparison with Heparin

Directory of Open Access Journals (Sweden)

Sara Nicole Fernández

2014-01-01

Full Text Available Regional anticoagulation with citrate is an alternative to heparin in continuous renal replacement therapies, which may prolong circuit lifetime and decrease hemorrhagic complications. A retrospective comparative cohort study based on a prospective observational registry was conducted including critically ill children undergoing CRRT. Efficacy, measured as circuit survival, and secondary effects of heparin and citrate were compared. 12 patients on CRRT with citrate anticoagulation and 24 patients with heparin anticoagulation were analyzed. Median citrate dose was 2.6 mmol/L. Median calcium dose was 0.16 mEq/kg/h. Median heparin dose was 15 UI/kg/h. Median circuit survival was 48 hours with citrate and 31 hours with heparin (P=0.028. 66.6% of patients treated with citrate developed mild metabolic alkalosis, which was directly related to citrate dose. There were no cases of citrate intoxication: median total calcium/ionic calcium index (CaT/I of 2.16 and a maximum CaT/I of 2.33, without metabolic acidosis. In the citrate group, 45.5% of patients developed hypochloremia and 27.3% hypomagnesemia. In the heparin group, 27.8% developed hypophosphatemia. Three patients were moved from heparin to citrate to control postoperatory bleeding. In conclusion citrate is a safe and effective anticoagulation method for CRRT in children and it achieves longer circuit survival than heparin.

Limitations and Extensions of the Lock-and-Key Principle: Differences between Gas State, Solution and Solid State Structures

Directory of Open Access Journals (Sweden)

Hans-Jörg Schneider

2015-03-01

Full Text Available The lock-and-key concept is discussed with respect to necessary extensions. Formation of supramolecular complexes depends not only, and often not even primarily on an optimal geometric fit between host and guest. Induced fit and allosteric interactions have long been known as important modifications. Different binding mechanisms, the medium used and pH effects can exert a major influence on the affinity. Stereoelectronic effects due to lone pair orientation can lead to variation of binding constants by orders of magnitude. Hydrophobic interactions due to high-energy water inside cavities modify the mechanical lock-and-key picture. That optimal affinities are observed if the cavity is only partially filled by the ligand can be in conflict with the lock-and-key principle. In crystals other forces than those between host and guest often dominate, leading to differences between solid state and solution structures. This is exemplified in particular with calixarene complexes, which by X-ray analysis more often than other hosts show guest molecules outside their cavity. In view of this the particular problems with the identification of weak interactions in crystals is discussed.

Electrophoresis for the analysis of heparin purity and quality.

Science.gov (United States)

Volpi, Nicola; Maccari, Francesca; Suwan, Jiraporn; Linhardt, Robert J

2012-06-01

The adulteration of raw heparin with oversulfated chondroitin sulfate (OSCS) in 2007-2008 produced a global crisis resulting in extensive revisions to the pharmacopeia monographs and prompting the FDA to recommend the development of additional methods for the analysis of heparin purity. As a consequence, a wide variety of innovative analytical approaches have been developed for the quality assurance and purity of unfractionated and low-molecular-weight heparins. This review discusses recent developments in electrophoresis techniques available for the sensitive separation, detection, and partial structural characterization of heparin contaminants. In particular, this review summarizes recent publications on heparin quality and related impurity analysis using electrophoretic separations such as capillary electrophoresis (CE) of intact polysaccharides and hexosamines derived from their acidic hydrolysis, and polyacrylamide gel electrophoresis (PAGE) for the separation of heparin samples without and in the presence of its relatively specific depolymerization process with nitrous acid treatment. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biological distribution of 51Cr-heparin

International Nuclear Information System (INIS)

Almeida, M.A.T.M. de.

1979-01-01

The kinetics of heparin in normal Wistar rats using the radioactive tracer 51 Cr, has been studied. The labeled and purified 51 Cr-heparin was injected into rats intravenously and by intraperitoneal injection. In measuring the radioactivity of organs it was possible to conclude that the tissues rich in mast cells, liver and spleen, were found to take up the greater amounts of heparin. The curve that represents the logarithm of the concentration of heparin versus time is biexponential. The half-lives of the two exponential were determined. The volume of distribution, the rate constant and the renal clearance were determined by the values of the plasma levels and urinary excretions. The biological half-time, the turnover rate and the turnover time were determined by measuring the residual radioactivity of the total body and urinary excretions. With the data obtained from the mentioned experiments a compartmental model was performed in which the plasma is the central compartment for the distribution of the drug, exchanging with another extraplasmatic compartment and finally the drug being stored in reticulo endothelial system cells. (Author) [pt

Immunomodulating effects of heparin on human B cell proliferation

International Nuclear Information System (INIS)

Wasik, Maria; Stepien-Sopniewska, Barbara; Gorski, Andrzej

1993-01-01

Recent data indicate that heparin may act as an immunomodulator. In this paper we have analyzed the effect of this agent on human B cell proliferation ''in vitro'' induced by ''S. aureus'' Cowan. The action of heparin is complex, but there was a trend for inhibition of B cell responses obtained from defibrinated but not heparinized blood samples. This suggest that heparin interacts with platelet products (growth factors, cytokines) and the results of such interactions determine the final effect. (author). 6 refs, 4 figs

Heparin and Heparin-Derivatives in Post-Subarachnoid Hemorrhage Brain Injury: A Multimodal Therapy for a Multimodal Disease

Directory of Open Access Journals (Sweden)

Erik G. Hayman

2017-05-01

Full Text Available Pharmacologic efforts to improve outcomes following aneurysmal subarachnoid hemorrhage (aSAH remain disappointing, likely owing to the complex nature of post-hemorrhage brain injury. Previous work suggests that heparin, due to the multimodal nature of its actions, reduces the incidence of clinical vasospasm and delayed cerebral ischemia that accompany the disease. This narrative review examines how heparin may mitigate the non-vasospastic pathological aspects of aSAH, particularly those related to neuroinflammation. Following a brief review of early brain injury in aSAH and heparin’s general pharmacology, we discuss potential mechanistic roles of heparin therapy in treating post-aSAH inflammatory injury. These roles include reducing ischemia-reperfusion injury, preventing leukocyte extravasation, modulating phagocyte activation, countering oxidative stress, and correcting blood-brain barrier dysfunction. Following a discussion of evidence to support these mechanistic roles, we provide a brief discussion of potential complications of heparin usage in aSAH. Our review suggests that heparin’s use in aSAH is not only safe, but effectively addresses a number of pathologies initiated by aSAH.

Heparin-Induced Thrombocytopenia

Science.gov (United States)

... HIT information card. Early identification of HIT and avoidance of inappropriate heparin therapy can help promote a ... Heart Association is a qualified 501(c)(3) tax-exempt organization. *Red Dress™ DHHS, Go Red™ AHA; ...

Detection of growth factor binding to gelatin and heparin using a photonic crystal optical biosensor

International Nuclear Information System (INIS)

Morgan, Abby W.; Chan, Leo L.; Sendemir-Urkmez, Aylin; Cunningham, Brian T.; Jamison, Russell D.

2010-01-01

Drug-carrier interactions are important to protein controlled release systems to protect the protein from denaturation and ensure properly timed release. A novel photonic crystal biosensor was used to investigate a gelatin-protein controlled release system to determine the amount of protein bound to the carrier at physiological conditions. The Biomolecular Interaction Detection (BIND) system reflects a narrow band of wavelengths when white light is shone incident to the grating. As mass is deposited onto the surface, the peak wavelength value is shifted due to changes in the optical density of the biosensor. The BIND system was used to detect the binding of growth factors onto acidic gelatin, basic gelatin, and heparin on the sensor surface. Through a series of experiments, including functionalizing the sensor, adjusting the ionic strength of the solution, adjusting the substrate concentration, and minimizing non-specific signal, the adsorption of the gelatins and heparin on the sensor was enhanced. The binding interaction of recombinant human transforming growth factor (rhTGF)-β1 and bone morphogenetic protein (rhBMP)-2 with the two types of gelatin and heparin were investigated. The strength of the interaction between rhTGF-β1 and the substrates is in the following order: heparin > acidic gelatin > basic gelatin. RhBMP-2 bound to the substrates but with less intensity than TGF-β1: heparin > basic gelatin > acidic gelatin. This work provides support for the controlled release mechanism through degradation of the gelatin carrier.

A spectroscopic study of interaction of cationic dyes with heparin

Directory of Open Access Journals (Sweden)

R. Nandini

2010-01-01

Full Text Available The interaction of two cationic dyes namely, acridine orange and pinacyanol chloride with an anionic polyelectrolyte, heparin, has been investigated by spectrophotometric method.The polymer induced metachromasy in the dyes resulting in the shift of the absorption maxima of the dyes towards shorter wavelengths. The stability of the complexes formed between acridine orange and heparin was found to be lesser than that formed between pinacyanol chloride and heparin. This fact was further confirmed by reversal studies using alcohols, urea and surfactants. The interaction of acridine orange with heparin has also been investigated fluorimetrically.The interaction parameters revealed that binding between acridine orange and heparin arises due to electrostatic interaction while that between pinacyanol chloride and heparin is found to involve both electrostatic and hydrophobic forces. The effect of the structure of the dye in inducing metachromasy has also been discussed.

Identification of a novel structure in heparin generated by potassium permanganate oxidation

Science.gov (United States)

Beccati, Daniela; Roy, Sucharita; Yu, Fei; Gunay, Nur Sibel; Capila, Ishan; Lech, Miroslaw; Linhardt, Robert J.; Venkataraman, Ganesh

2012-01-01

The worldwide heparin contamination crisis in 2008 led health authorities to take fundamental steps to better control heparin manufacture, including implementing appropriate analytical and bio-analytical methods to ensure production and release of high quality heparin sodium product. Consequently, there is an increased interest in the identification and structural elucidation of unusually modified structures that may be present in heparin. Our study focuses on the structural elucidation of species that give rise to a signal observed at 2.10 ppm in the N-acetyl region of the 1H NMR spectrum of some pharmaceutical grade heparin preparations. Structural elucidation experiments were carried out using homonuclear (COSY, TOSCY and NOESY) and heteronuclear (HSQC, HSQC-DEPT, HMQC-COSY, HSQC-TOCSY, and HMBC) 2D NMR spectroscopy on both heparin as well as heparin-like model compounds. Our results identify a novel type of oxidative modification of the heparin chain that results from a specific step in the manufacturing process used to prepare heparin. PMID:25147414

Heparin-associated thrombocytopenia: antibody binding specificity to platelet antigens.

Science.gov (United States)

Lynch, D M; Howe, S E

1985-11-01

Sera from four patients with heparin-associated thrombocytopenia (HAT) were evaluated by a quantitative enzyme-linked immunosorbent assay (ELISA) to detect heparin-dependent serum platelet-bindable immunoglobulin (S-PBIg) and by Western blotting and immunoprecipitation to investigate the specificity of the antibody binding. All HAT sera showed mildly increased S-PBIg (mean, 7.8 fg per platelet; normal, less than 6.0 fg per platelet) to intact target platelets in the ELISA, which was markedly increased in the presence of heparin (mean, 20.9 fg per platelet). This increase was 20-fold greater than normal control sera, which showed a mean differential increase of only 0.5 fg per platelet. Immunoglobulin binding specificity to platelet antigens was investigated using sodium dodecyl sulfate-polyacrylamide gel electrophoresis of platelet lysate with transfer of the platelet fractions onto nitrocellulose strips (Western blotting) and subsequent immunoassay using HAT and normal sera. In the presence of heparin, the four HAT patients demonstrated increased binding of immunoglobulin to platelet antigens of apparent molecular weights of 180, 124, and 82 kd. Radiolabeled heparin when incubated with HAT sera, normal sera, or albumin blanks bound to platelet proteins of the same apparent molecular weights. These observations are consistent with current hypotheses suggesting that HAT antibody is directed to heparin-platelet complexes or, alternatively, that heparin induces conformational change of antigenic sites on the platelet membrane.

Stability of phase locking in a ring of unidirectionally coupled oscillators

International Nuclear Information System (INIS)

Rogge, J A; Aeyels, D

2004-01-01

We discuss the dynamic behaviour of a finite group of phase oscillators unidirectionally coupled in a ring. The dynamics are based on the Kuramoto model. In the case of identical oscillators, all phase locking solutions and their stability properties are obtained. For nonidentical oscillators it is proven that there exist phase locking solutions for sufficiently strong coupling. An algorithm to obtain all phase locking solutions is proposed. These solutions can be classified into classes, each with its own stability properties. The stability properties are obtained by means of a novel extension of Gershgorin's theorem. One class of stable solutions has the property that all phase differences between neighbouring cells are contained in (-π/2, π/2). Contrary to intuition, a second class of stable solutions is established with exactly one of the phase differences contained in (π/2, 3π/2). The stability results are extended from sinusoidal interconnections to a class of odd functions. To conclude, a connection with the field of active antenna arrays is made, generalizing some results earlier obtained in this field

Class-A mode-locked lasers: Fundamental solutions

Science.gov (United States)

Kovalev, Anton V.; Viktorov, Evgeny A.

2017-11-01

We consider a delay differential equation (DDE) model for mode-locked operation in class-A semiconductor lasers containing both gain and absorber sections. The material processes are adiabatically eliminated as these are considered fast in comparison to the delay time for a long cavity device. We determine the steady states and analyze their bifurcations using DDE-BIFTOOL [Engelborghs et al., ACM Trans. Math. Software 28, 1 (2002)]. Multiple forms of coexistence, transformation, and hysteretic behavior of stable steady states and fundamental periodic regimes are discussed in bifurcation diagrams.

Quantitative description of thermodynamic and kinetic properties of the platelet factor 4/heparin bonds

Science.gov (United States)

Nguyen, Thi-Huong; Greinacher, Andreas; Delcea, Mihaela

2015-05-01

Heparin is the most important antithrombotic drug in hospitals. It binds to the endogenous tetrameric protein platelet factor 4 (PF4) forming PF4/heparin complexes which may cause a severe immune-mediated adverse drug reaction, so-called heparin-induced thrombocytopenia (HIT). Although new heparin drugs have been synthesized to reduce such a risk, detailed bond dynamics of the PF4/heparin complexes have not been clearly understood. In this study, single molecule force spectroscopy (SMFS) is utilized to characterize the interaction of PF4 with heparins of defined length (5-, 6-, 8-, 12-, and 16-mers). Analysis of the force-distance curves shows that PF4/heparin binding strength rises with increasing heparin length. In addition, two binding pathways in the PF4/short heparins (=8-mers) are identified. We provide a model for the PF4/heparin complexes in which short heparins bind to one PF4 tetramer, while long heparins bind to two PF4 tetramers. We propose that the interaction between long heparins and PF4s is not only due to charge differences as generally assumed, but also due to hydrophobic interaction between two PF4s which are brought close to each other by long heparin. This complicated interaction induces PF4/heparin complexes more stable than other ligand-receptor interactions. Our results also reveal that the boundary between antigenic and non-antigenic heparins is between 8- and 12-mers. These observations are particularly important to understand processes in which PF4-heparin interactions are involved and to develop new heparin-derived drugs.Heparin is the most important antithrombotic drug in hospitals. It binds to the endogenous tetrameric protein platelet factor 4 (PF4) forming PF4/heparin complexes which may cause a severe immune-mediated adverse drug reaction, so-called heparin-induced thrombocytopenia (HIT). Although new heparin drugs have been synthesized to reduce such a risk, detailed bond dynamics of the PF4/heparin complexes have not been clearly

Analyses of Interactions Between Heparin and the Apical Surface Proteins of Plasmodium falciparum

Science.gov (United States)

Kobayashi, Kyousuke; Takano, Ryo; Takemae, Hitoshi; Sugi, Tatsuki; Ishiwa, Akiko; Gong, Haiyan; Recuenco, Frances C.; Iwanaga, Tatsuya; Horimoto, Taisuke; Akashi, Hiroomi; Kato, Kentaro

2013-11-01

Heparin, a sulfated glycoconjugate, reportedly inhibits the blood-stage growth of the malaria parasite Plasmodium falciparum. Elucidation of the inhibitory mechanism is valuable for developing novel invasion-blocking treatments based on heparin. Merozoite surface protein 1 has been reported as a candidate target of heparin; however, to better understand the molecular mechanisms involved, we characterized the molecules that bind to heparin during merozoite invasion. Here, we show that heparin binds only at the apical tip of the merozoite surface and that multiple heparin-binding proteins localize preferentially in the apical organelles. To identify heparin-binding proteins, parasite proteins were fractionated by means of heparin affinity chromatography and subjected to immunoblot analysis with ligand-specific antibodies. All tested members of the Duffy and reticulocyte binding-like families bound to heparin with diverse affinities. These findings suggest that heparin masks the apical surface of merozoites and blocks interaction with the erythrocyte membrane after initial attachment.

The Advanced Thread-Locking Mechanism

Science.gov (United States)

Weiss, Wolfgang

2005-12-01

Locking of threaded members is accomplished by a wide variety of engineering solutions. Generally, in terms of separate locking devices or by built-in locking features such as friction generating means.In regard of space flight vehicles, threaded joints are subject to severe vibration loads during launch, maneuvering, and reentry. This requires fastening systems which are capable to join structural members and attach accessories or equipment in a secure manner. However, manned spacecraft and especially payload components will be subject to installation activity during orbital or interstellar flight maintenance, repair, or mission modification. This, in turn, requires fast separation and engaging of the concerned fasteners, yet providing performance characteristics for high reliable and safe joints.The further described Advanced Thread Locking Mechanism (ATLM) has been developed to combine the merits of both, safe joining technique and a fast installation process. The ATLM uses a freewheel which is securely installed in one part of the threaded member and releasable coupled with the engaged counterpart. While screwing the threaded members together, once coupled, the freewheel will allow free mating of the threaded members including torquing to the desired value. The moment, the pair of threaded fasteners is forced to unscrew (by intended or unintended occurrence of torque in the undoing direction) the freewheel does lock instantly. Disengaging the coupling between the members of the threaded joint takes a separate release action.Owing to the nature of the ATLM, there are a number of design variants ready for implementation.Threaded fasteners in ATLM design are highly recommended for mechanical joints subject to fastening and unfastening during Extra Vehicular Activity (EVA) in course of space flight operations. This is justified through:1. Threaded members mate free running, thus, torque values preset at the wrenching tool are not influenced by varying prevailing

Use of heparin in the investigation of obscure gastrointestinal bleeding

International Nuclear Information System (INIS)

Mernagh, J.R.; O'Donovan, N.; Somers, S.; Gill, G.; Sridhar, S.

2001-01-01

To determine if the administration of heparin improves the predictive value of angiography in the investigation of obscure gastrointestinal (GI) bleeding. 18 patients with a history of chronic GI bleeding were investigated with angiography. For 6 patients, the cause of GI bleeding was established with angiography; the 12 patients who had negative results were given heparin for 24 h and were reassessed with angiography. After heparin administration, the source of GI bleeding was determined with angiography for 6 of the remaining 12 patients. Thus, heparinization increased diagnostic yield from 33% (6 of 18) to 67% (12 of 18). No significant complications, such as uncontrolled GI bleeding, occurred. Heparinization improves the diagnostic yield of angiography when obscure GI bleeding is being investigated. (author)

Acid-citrate-dextrose compared with heparin in the preparation of in vivo/in vitro technetium-99m red blood cells

International Nuclear Information System (INIS)

Porter, W.C.; Dees, S.M.; Freitas, J.E.; Dworkin, H.J.

1983-01-01

Red blood cells labeled in vivo/in vitro with Tc-99m (Tc-99m RBC) were prepared in a series of 21 patients and two normal volunteers. In each subject both heparin and acid-citrate-dextrose (ACD) solutions were used to label tandem blood samples. The immediate preinjection binding efficiency (BE) was then determined. In each of the 23 studies, the ACD preparation yielded superior BE. The average BE was 93.47% (+/- 3.78) with ACD and 87.23% (+/- 4.29) with heparin. With the ACD method the effect of carrier Tc-99 may be as great as a 24% reduction in BE observed when initial eluates from long-ingrowth-time generators were used. Improved image quality with minimal renal and urinary-bladder activity results with ACD labeling. It is concluded that the use of ACD results in superior RBC labeling with less nontarget activity relative to heparin and is preferred over heparin for preparing in vivo/in vitro Tc-99m RBC

Qualitative and quantitative analysis of heparin and low molecular weight heparins using size exclusion chromatography with multiple angle laser scattering/refractive index and inductively coupled plasma/mass spectrometry detectors.

Science.gov (United States)

Ouyang, Yilan; Zeng, Yangyang; Yi, Lin; Tang, Hong; Li, Duxin; Linhardt, Robert J; Zhang, Zhenqing

2017-11-03

Heparin, a highly sulfated glycosaminoglycan, has been used as a clinical anticoagulant over 80 years. Low molecular weight heparins (LMWHs), heparins partially depolymerized using different processes, are widely used as clinical anticoagulants. Qualitative molecular weight (MW) and quantitative mass content analysis are two important factors that contribute to LMWH quality control. Size exclusion chromatography (SEC), relying on multiple angle laser scattering (MALS)/refractive index (RI) detectors, has been developed for accurate analysis of heparin MW in the absence of standards. However, the cations, which ion-pair with the anionic polysaccharide chains of heparin and LMWHs, had not been considered in previous reports. In this study, SEC with MALS/RI and inductively coupled plasma/mass spectrometry detectors were used in a comprehensive analytical approach taking both anionic polysaccharide and ion-paired cations heparin products. This approach was also applied to quantitative analysis of heparin and LMWHs. Full profiles of MWs and mass recoveries for three commercial heparin/LMWH products, heparin sodium, enoxaparin sodium and nadroparin calcium, were obtained and all showed higher MWs than previously reported. This important improvement more precisely characterized the MW properties of heparin/LMWHs and potentially many other anionic polysaccharides. Copyright © 2017 Elsevier B.V. All rights reserved.

Locking a molecular bond: A case study of CsI

DEFF Research Database (Denmark)

Szakács, Tamás; Amstrup, Bjarne; Gross, Peter

1994-01-01

This paper treats the problem of locking a molecular bond at a length other than the equilibrium distance, with the help of optical electric fields. Locking conditions for single-color fields are examined, and slowly decaying locked wave functions are sought. These were functions are then used...... as target functions in an optimal control procedure. The resultant solution is an optimal field that creates a wave function as close as possible to the target function, followed by the application of a locking single-color field that can keep a large part of this wave function at the given position...

Investigation of the heparin-thrombin interaction by dynamic force spectroscopy.

Science.gov (United States)

Wang, Congzhou; Jin, Yingzi; Desai, Umesh R; Yadavalli, Vamsi K

2015-06-01

The interaction between heparin and thrombin is a vital step in the blood (anti)coagulation process. Unraveling the molecular basis of the interactions is therefore extremely important in understanding the mechanisms of this complex biological process. In this study, we use a combination of an efficient thiolation chemistry of heparin, a self-assembled monolayer-based single molecule platform, and a dynamic force spectroscopy to provide new insights into the heparin-thrombin interaction from an energy viewpoint at the molecular scale. Well-separated single molecules of heparin covalently attached to mixed self-assembled monolayers are demonstrated, whereby interaction forces with thrombin can be measured via atomic force microscopy-based spectroscopy. Further these interactions are studied at different loading rates and salt concentrations to directly obtain kinetic parameters. An increase in the loading rate shows a higher interaction force between the heparin and thrombin, which can be directly linked to the kinetic dissociation rate constant (koff). The stability of the heparin/thrombin complex decreased with increasing NaCl concentration such that the off-rate was found to be driven primarily by non-ionic forces. These results contribute to understanding the role of specific and nonspecific forces that drive heparin-thrombin interactions under applied force or flow conditions. Copyright © 2015 Elsevier B.V. All rights reserved.

The intracellular uptake and protracted release of exogenous heparins by cultured endothelial cells

International Nuclear Information System (INIS)

Hiebert, L.M.; McDuffie, N.M.

1989-01-01

Heparins from bovine or porcine sources were fed in media for 48 hrs to cultured porcine aortic and human umbilical vein endothelial cells. Heparin was found in pericellular and cellular fractions after extraction by chemical methods and 125 I radiolabelled heparins were recovered when radiolabelled heparin was included in the feed. Even after washing and media changes heparin was detected in media and cell fractions up to 6 days post feeding. Metachromatic vacuoles within cells were demonstrated histologically up to 7 days post feeding after staining with toluidine blue. This is the first report of protracted internalization of exogenous heparin by cultured endothelial cells with concurrent prolonged release of the heparin to the media. This clearly demonstrates that the endothelium plays an important role in the distribution and metabolism of heparin

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

Science.gov (United States)

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

2011-01-01

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

Heparin: The Silver Bullet of Aneurysmal Subarachnoid Hemorrhage?

Directory of Open Access Journals (Sweden)

Nicolas K. Khattar

2018-03-01

Full Text Available Various neurological diseases have recently been associated with neuroinflammation and worsening outcomes. Subarachnoid hemorrhage has been shown to generate a potent neuroinflammatory response. Heparin is a potential effective anti-inflammatory agent to prevent initial injury as well as delayed neurological decline. Different mechanisms of action for heparin have been proposed including, but not limited to the binding and neutralization of oxyhemoglobin, decreased transcription and signal transduction of endothelin-1, inhibition of binding to vessel wall selectins and vascular leakage into the subarachnoid space as well as direct binding and neutralization of inflammatory molecules. With a reasonably safe side-effect profile, heparin has shown significant promise in small series in human studies of aneurysmal subarachnoid hemorrhage in decreasing both initial and delayed neurological injury. Further studies are needed to validate various neuroprotective features of heparin in subarachnoid hemorrhage as well as other disease states.

Community nurse resource implications for a change in heparin prophylaxis policy

Directory of Open Access Journals (Sweden)

Parker Martyn J.

2015-01-01

Full Text Available Introduction: A review was undertaken for a consecutive series of hip fracture patients for the year before and then after a change in low dose heparin prophylaxis policy. Patients and methods: For the first year heparin was administered in hospital for a maximum of 14 days only. Patients sent home before this time were not discharged taking heparin. For the second year heparin was administered as recommended by NICE guidelines for 28 days from admission regardless of whether the patient was discharged. Results: For the first year 486 patients were treated with a mean of 10.4 doses of heparin per patient. For the second year 465 patients were treated with a mean of 24.3 doses per patient. In total an extra 6,464 doses of heparin were administered. 33.8% of patients were unable to administer their heparin at home therefore a district nurse administered 2,284 of these doses of subcutaneous heparin at the patient’s home. The increased cost associated with the change in policy was estimated to be £161 per patient, with over 90% of this increase being incurred by the district nurse expense. If applied nationally for the England, using extended heparin prophylaxis for hip fracture patients would cost in excess of 12 million pounds each year. Conclusion: Whilst the necessity for and duration of thromboembolic prophylaxis for these patients remains undetermined, there is a need to re-evaluate the cost effectiveness of the current recommendations for hip fracture patients.

Heparin conjugated quantum dots for in vitro imaging applications.

Science.gov (United States)

Maguire, Ciaran Manus; Mahfoud, Omar Kazem; Rakovich, Tatsiana; Gerard, Valerie Anne; Prina-Mello, Adriele; Gun'ko, Yurii; Volkov, Yuri

2014-11-01

In this work heparin-gelatine multi-layered cadmium telluride quantum dots (QDgel/hep) were synthesised using a novel 'one-pot' method. The QDs produced were characterised using various spectroscopic and physiochemical techniques. Suitable QDs were then selected and compared to thioglycolic acid stabilised quantum dots (QDTGA) and gelatine coated quantum dots (QDgel) for utilisation in in vitro imaging experiments on live and fixed permeabilised THP-1, A549 and Caco-2 cell lines. Exposure of live THP-1 cells to QDgel/hep resulted in localisation of the QDs to the nucleus of the cells. QDgel/hep show affinity for the nuclear compartment of fixed permeabilised THP-1 and A549 cells but remain confined to cytoplasm of fixed permeabilised Caco-2 cells. It is postulated that heparin binding to the CD11b receptor facilitates the internalisation of the QDs into the nucleus of THP-1 cells. In addition, the heparin layer may reduce the unfavourable thrombogenic nature of quantum dots observed in vivo. In this study, heparin conjugated quantum dots were found to have superior imaging properties compared to its native counterparts. The authors postulate that heparin binding to the CD11b receptor facilitates QD internalization to the nucleus, and the heparin layer may reduce the in vivo thrombogenic properties of quantum dots. Copyright © 2014 Elsevier Inc. All rights reserved.

Relaxation towards phase-locked dynamics in long Josephson junctions

DEFF Research Database (Denmark)

Salerno, M.; Grønbech-Jensen, Niels; Samuelsen, Mogens Rugholm

1995-01-01

We study the relaxation phenomenon towards phase-locked dynamics in long Josephson junctions. In particular the dependence of the relaxation frequency for the equal time of flight solution on the junction parameters is derived. The analysis is based on a phase-locked map and is compared with direct...... numerical experiments performed both on the map and on the perturbed sine-Gordon equation. As an interesting result we find that very close to a bifurcation the relaxation frequency is exactly equal to the half of the step frequency, i.e., the frequency characterizing the period-one solution....

Bioinspired Heparin Nanosponge Prepared by Photo-crosslinking for Controlled Release of Growth Factors

DEFF Research Database (Denmark)

Choi, Won Il; Sahu, Abhishek; Vilos, Cristian

2017-01-01

to overcome these limitations. Herein, we have developed a thermosensitive heparin nanosponge (Hep-NS) by a one step photopolymerization reaction between diacrylated pluronic and thiolated heparin molecules. The amount of heparin in Hep-NS was precisely controlled by varying the heparin amount in the reaction...

Preparation and in vitro evaluation of heparin-loaded polymeric nanoparticles.

Science.gov (United States)

Jiao, Y Y; Ubrich, N; Marchand-Arvier, M; Vigneron, C; Hoffman, M; Maincent, P

2001-01-01

Nanoparticles of a highly soluble macromolecular drug, heparin, were formulated with two biodegradable polymers (poly-E-caprolactone [PCL] and poly (D, L-lactic-co-glycolic-acid) 50/50 [PLAGA]) and two nonbiodegradable positively charged polymers (Eudragit RS and RL) by the double emulsion and solvent evaporation method, using a high-pressure homogenization device. The encapsulation efficiency and heparin release profiles were studied as a function of the type of polymers employed (alone or in combination) and the concentration of heparin. Optimal encapsulation efficiency was observed when 5000 IU of heparin were incorporated in the first emulsion. High drug entrapment efficiency was observed in both Eudragit RS and RL nanoparticles (60% and 98%, respectively), compared with PLAGA and PCL nanoparticles (PLAGA increased the encapsulation efficiency compared with these two biodegradable polymers used alone; however, the in vitro drug release was not modified and remained low. On the other hand, the addition of esterase to the dissolution medium resulted in a significant increase in heparin release. The in vitro biological activity of released heparin, evaluated by measuring the anti-Xa activity by a colorimetric assay, was conserved after the encapsulation process.

The regulatory role of heparin on c-Met signaling in hepatocellular carcinoma cells.

Science.gov (United States)

İşcan, Evin; Güneş, Aysim; Korhan, Peyda; Yılmaz, Yeliz; Erdal, Esra; Atabey, Neşe

2017-06-01

The role of heparin as an anticoagulant is well defined; however, its role in tumorigenesis and tumor progression is not clear yet. Some studies have shown that anticoagulant treatment in cancer patients improve overall survival, however, recent clinical trials have not shown a survival benefit in cancer patients receiving heparin treatment. In our previous studies we have shown the inhibitory effects of heparin on Hepatocyte Growth Factor (HGF)-induced invasion and migration in hepatocellular carcinoma (HCC) cells. In this study, we showed the differential effects of heparin on the behaviors of HCC cells based on the presence or absence of HGF. In the absence of HGF, heparin activated HGF/c-Met signaling and promoted motility and invasion in HCC cells. Heparin treatment led to c-Met receptor dimerization and activated c-Met signaling in an HGF independent manner. Heparin-induced c-Met activation increased migration and invasion through ERK1/2, early growth response factor 1 (EGR1) and Matrix Metalloproteinases (MMP) axis. Interestingly, heparin modestly decreased the proliferation of HCC cells by inhibiting activatory phosphorylation of Akt. The inhibition of c-Met signaling reversed heparin-induced increase in motility and invasion and, proliferation inhibition. Our study provides a new perspective into the role of heparin on c-Met signaling in HCC.

DEGRADATION AND INTRAHEPATIC COMPATIBILITY OF ALBUMIN-HEPARIN CONJUGATE MICROSPHERES

NARCIS (Netherlands)

CREMERS, HFM; WOLF, RFE; BLAAUW, EH; SCHAKENRAAD, JM; LAM, KH; NIEUWENHUIS, P; VERRIJK, R; KWON, G; BAE, YH; KIM, SW; FEIJEN, J

The in vitro degradation properties of glutaraldehyde cross-linked albumin and albumin-heparin conjugate microspheres (AMS and AHCMS respectively) were evaluated using light microscopy, turbidity measurements and heparin release determinations, showing that the microspheres are degraded by

In vitro anticoagulation monitoring of low-molecular-weight heparin

Institute of Scientific and Technical Information of China (English)

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

2009-01-01

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

49 CFR 236.330 - Locking dog of switch-and-lock movement.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Locking dog of switch-and-lock movement. 236.330 Section 236.330 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD... Rules and Instructions § 236.330 Locking dog of switch-and-lock movement. Locking dog of switch-and-lock...

Increased accuracy in heparin and protamine administration decreases bleeding

DEFF Research Database (Denmark)

Runge, Marx; Møller, Christian H; Steinbrüchel, Daniel A

2009-01-01

Three to 5 percent of the patients undergoing cardiac surgery are reoperated because of bleeding. When a surgical cause can be excluded, heparin/protamine mismatch may be considered. Insufficient reversal of heparin and overdosing of protamine may cause postoperative bleeding. The purpose......). A reduced number of patients needed blood transfusions in the RxDx group, although this was not statistically significant (19% vs. 38%, respectively; p = .13). Initial heparin dose was significantly reduced in the RxDx group (250 mg; range, 100-375 mg) compared with the control group (300 mg; range, 200...

Prophylaxis of postoperative thromboembolism with low molecular weight heparins

DEFF Research Database (Denmark)

Jørgensen, L N; Wille-Jørgensen, P; Hauch, O

1993-01-01

To evaluate the thromboprophylactic use of low molecular weight heparins (LMWHs), publications from 27 orthopaedic trials and 35 studies of patients undergoing general or gynaecological surgery were scrutinized and subjected to a partial meta-analysis. In orthopaedic surgery, LMWHs were superior...... to placebo or dextran and at least as efficient as unfractionated heparin in the prevention of deep vein thrombosis (DVT). Compared with unfractionated heparin, one of the LMWH preparations significantly reduced the total incidence of DVT. The rate of non-fatal pulmonary embolism was 0.49 per cent...

Heparin induced thrombocytopenia type ii and myocardial infarction: Two case reports

Directory of Open Access Journals (Sweden)

Antonijević Nebojša

2004-01-01

Full Text Available Heparin-induced thrombocytopenia (HIT type II is an acquired thrombophylic state and life-threatening immune complication of a heparin treatment mainly clinically manifested by marked thrombocytopenia, frequently by arterial and venous thrombosis, and sometimes by skin changes. Functional assay as heparin aggregation test and 14C-serotonin release assays are used in diagnostics as well as antigen assays of which detection tests for heparin-platelet factor 4 antibodies are most frequently used. Considering the fact that there is no single reliable assays for HIT II detection available, sometimes it is necessary to combine both of the above-mentioned types of assays. We present the case of a 57-year-old patient with an acute anterior myocardial infarction with cardiac insufficiency of III and IV degree according to Killip, recurrent ventricular fibrillation and diabetes mellitus type II developing thrombocytopenia to 37x10 9/l accompanied with typical skin changes. The diagnosis was confirmed by the heparin aggregation test. The second patient aged 70 undergoing the treatment for anteroseptal myocardial infarction and reinfarction of the inferior wall complicated by a cardiogenic shock and acute right bundle branch block developed thrombocytopenia 59x10 9/I on the third day of the heparin therapy, with the remark that he had received a heparin therapy during the first infarction as well. Antibodies against heparin-platelet factor 4 were detected by particle gel ID-HPF4 immunoassay. In both patients, the disease had a lethal outcome despite all then available therapeutic measures applied. Further on we discuss advantages of certain types of tests, a therapy doctrine, need for urgent therapeutic measures, inclusive of the administration of anitithrombins, avoidance of harmful procedures like low-molecular-weight heparins administration and prophylactic platelet transfusion as well as preventive measures.

Discretely tunable micromachined injection-locked lasers

International Nuclear Information System (INIS)

Cai, H; Yu, M B; Lo, G Q; Kwong, D L; Zhang, X M; Liu, A Q; Liu, B

2010-01-01

This paper reports a micromachined injection-locked laser (ILL) to provide tunable discrete wavelengths. It utilizes a non-continuously tunable laser as the master to lock a Fabry–Pérot semiconductor laser chip. Both lasers are integrated into a deep-etched silicon chip with dimensions of 3 mm × 3 mm × 0.8 mm. Based on the experimental results, significant improvements in the optical power and spectral purity have been achieved in the fully locked state, and optical hysteresis and bistability have also been observed in response to the changes of the output wavelength and optical power of the master laser. As a whole system, the micromachined ILL is able to provide single mode, discrete wavelength tuning, high power and direct modulation with small size and single-chip solution, making it promising for advanced optical communications such as wavelength division multiplexing optical access networks.

Heparin release from thermosensitive polymer coatings: in vivo studies

NARCIS (Netherlands)

Gutowska, Anna; Bae, You Han; Jacobs, Harvey; Mohammad, Fazal; Mix, Donald; Feijen, Jan; Kim, Sung Wan

1995-01-01

Biomer/poly(N-isopropylacrylamide)/[poly(NiPAAm)] thermosensitive polymer blends were prepared and their application as heparin-releasing polymer coatings for the prevention of surface-induced thrombosis was examined. The advantage of using poly(NiPAAm)-based coatings as heparin-releasing polymers

Poly(vinyl alcohol)-heparin hydrogels as sensor catheter membranes

NARCIS (Netherlands)

Brinkman, E.; van der Does, L.; Bantjes, A.

1991-01-01

Poly(vinyl alcohol)-heparin hydrogels with varying water content were synthesized for use as sensor catheter membranes. Films were cast from aqueous mixtures of poly(viny) alcohol) (PVA), a photosensitive cross-linker p-diazonium diphenyl amine polymer (PA), glutaraldehyde (GA) and heparin. After

From Farm to Pharma: An Overview of Industrial Heparin Manufacturing Methods.

Science.gov (United States)

van der Meer, Jan-Ytzen; Kellenbach, Edwin; van den Bos, Leendert J

2017-06-21

The purification of heparin from offal is an old industrial process for which commercial recipes date back to 1922. Although chemical, chemoenzymatic, and biotechnological alternatives for this production method have been published in the academic literature, animal-tissue is still the sole source for commercial heparin production in industry. Heparin purification methods are closely guarded industrial secrets which are not available to the general (scientific) public. However by reviewing the academic and patent literature, we aim to provide a comprehensive overview of the general methods used in industry for the extraction of heparin from animal tissue.

In vivo studies on the binding of heparin and its fractions with platelet factor 4

International Nuclear Information System (INIS)

Walz, D.A.; Hung, G.L.

1985-01-01

PF4 has a half-life in plasma of less than 3 minutes, and its rapid clearance appears to be a function of binding to the vascular endothelium. Once bound to the endothelium, PF4 can be released by heparin in a time-dependent manner; recovery is greater the sooner heparin is administered following PF4 infusion. This heparin-induced release of PF4 can be abolished if the heparin is first complexed with hexadimethrine bromide. Likewise, this heparin-induced release of PF4 is dependent upon the type of heparin used; low molecular weight heparin fractions and fragments do not cause the PF4 rebound seen with intact heparin. Thus, it would appear that low molecular weight forms of heparin are advantageous in that their in vivo administration would not be mediated by such platelet modulators as PF4

P-selectin- and heparanase-dependent antimetastatic activity of non-anticoagulant heparins.

Science.gov (United States)

Hostettler, Nina; Naggi, Annamaria; Torri, Giangiacomo; Ishai-Michaeli, Riva; Casu, Benito; Vlodavsky, Israel; Borsig, Lubor

2007-11-01

Vascular cell adhesion molecules, P- and L-selectins, facilitate metastasis of cancer cells in mice by mediating interactions with platelets, endothelium, and leukocytes. Heparanase is an endoglycosidase that degrades heparan sulfate of extracellular matrix, thereby promoting tumor invasion and metastasis. Heparin is known to efficiently attenuate metastasis in different tumor models. Here we identified modified, nonanticoagulant species of heparin that specifically inhibit selectin-mediated cell-cell interactions, heparanase enzymatic activity, or both. We show that selective inhibition of selectin interactions or heparanase with specific heparin derivatives in mouse models of MC-38 colon carcinoma and B16-BL6 melanoma attenuates metastasis. Selectin-specific heparin derivatives attenuated metastasis of MC-38 carcinoma, but heparanase-specific derivatives had no effect, in accordance with the virtual absence of heparanase activity in these cells. Heparin derivatives had no further effect on metastasis in mice deficient in P- and L-selectin, indicating that selectins are the primary targets of heparin antimetastatic activity. Selectin-specific and heparanase-specific derivatives attenuated metastasis of B16-BL6 melanomas to a similar extent. When mice were injected with a derivative containing both heparanase and selectin inhibitory activity, no additional attenuation of metastasis could be observed. Thus, selectin-specific heparin derivatives efficiently attenuated metastasis of both tumor cell types whereas inhibition of heparanase led to reduction of metastasis only in tumor cells producing heparanase.

Heparin modulates human intestinal smooth muscle (HISM) cell proliferation and matrix production

International Nuclear Information System (INIS)

Graham, M.; Perr, H.; Drucker, D.E.; Diegelmann, R.F.

1986-01-01

(HISM) cell proliferation and collagen production may play a role in the pathogenesis of intestinal stricture in Crohn's disease. The present studies were performed to evaluate the effects of heparin, a known modulator of vascular smooth muscle cells, on HISM cell proliferation and collagen production. Heparin (100 μg/ml) was added daily to HISM cell cultures for cell proliferation studies and for 24 hours at various time points during culture for collagen synthesis studies. Collagen synthesis was determined by the uptake of 3 H proline into collagenase-sensitive protein. Heparin completely inhibited cell proliferation for 7 days, after which cell numbers increased but at a slower rate than controls. Cells released from heparin inhibition demonstrated catch-up growth to control levels. Collagen production was significantly inhibited by 24 hours exposure to heparin but only at those times during culture when collagen synthesis was maximal (8 to 12 days). Non-collagen protein synthesis was inhibited by heparin at all time points during culture. Heparin through its modulation of HISM cells may play an important role in the control of the extracellular matrix of the intestinal wall

Metabolic engineering of Chinese hamster ovary cells: towards a bioengineered heparin.

Science.gov (United States)

Baik, Jong Youn; Gasimli, Leyla; Yang, Bo; Datta, Payel; Zhang, Fuming; Glass, Charles A; Esko, Jeffrey D; Linhardt, Robert J; Sharfstein, Susan T

2012-03-01

Heparin is the most widely used pharmaceutical to control blood coagulation in modern medicine. A health crisis that took place in 2008 led to a demand for production of heparin from non-animal sources. Chinese hamster ovary (CHO) cells, commonly used mammalian host cells for production of foreign pharmaceutical proteins in the biopharmaceutical industry, are capable of producing heparan sulfate (HS), a related polysaccharide naturally. Since heparin and HS share the same biosynthetic pathway, we hypothesized that heparin could be produced in CHO cells by metabolic engineering. Based on the expression of endogenous enzymes in the HS/heparin pathways of CHO-S cells, human N-deacetylase/N-sulfotransferase (NDST2) and mouse heparan sulfate 3-O-sulfotransferase 1 (Hs3st1) genes were transfected sequentially into CHO host cells growing in suspension culture. Transfectants were screened using quantitative RT-PCR and Western blotting. Out of 120 clones expressing NDST2 and Hs3st1, 2 clones, Dual-3 and Dual-29, were selected for further analysis. An antithrombin III (ATIII) binding assay using flow cytometry, designed to recognize a key sugar structure characteristic of heparin, indicated that Hs3st1 transfection was capable of increasing ATIII binding. An anti-factor Xa assay, which affords a measure of anticoagulant activity, showed a significant increase in activity in the dual-expressing cell lines. Disaccharide analysis of the engineered HS showed a substantial increase in N-sulfo groups, but did not show a pattern consistent with pharmacological heparin, suggesting that further balancing the expression of transgenes with the expression levels of endogenous enzymes involved in HS/heparin biosynthesis might be necessary. Copyright © 2012 Elsevier Inc. All rights reserved.

A CMOS delay locked loop and sub-nanosecond time-to-digital converter chip

International Nuclear Information System (INIS)

Santos, D.M.; Dow, S.F.; Levi, M.E.

1995-12-01

Many high energy physics and nuclear science applications require sub-nanosecond time resolution measurements over many thousands of detector channels. Phase-locked loops have been employed in the past to obtain accurate time references for these measurements. An alternative solution, based on a delay-locked loop (DLL) is described. This solution allows for a very high level of integration yet still offers resolution in the sub-nanosecond regime. Two variations on this solution are outlined. A novel phase detector, based on the Muller C element, is used to implement a charge pump where the injected charge approaches zero as the loop approaches lock on the leading edge of an input clock reference. This greatly reduces timing jitter. In the second variation the loop locks to both the leading and trailing clock edges. In this second implementation, software coded layout generators are used to automatically layout a highly integrated, multi-channel, time to digital converter (TDC). Complex clock generation can be, achieved by taking symmetric taps off the delay elements. The two circuits, DLL and TDC, were implemented in a CMOS 1.2μm and 0.8μm technology, respectively. Test results show a timing jitter of less than 35 ps for the DLL circuit and better solution for the TDC circuit

Anticoagulant effect of low molecular weight heparin on central ...

African Journals Online (AJOL)

Purpose: To analyse the effect of low molecular weight heparin on venous catheters in haemodialysis patients. Methods: This study included 140 eligible patients who were randomly and evenly divided into two groups, viz, a study group that received low molecular weight heparin and a control group that received ...

Nerve growth factor loaded heparin/chitosan scaffolds for accelerating peripheral nerve regeneration.

Science.gov (United States)

Li, Guicai; Xiao, Qinzhi; Zhang, Luzhong; Zhao, Yahong; Yang, Yumin

2017-09-01

Artificial chitosan scaffolds have been widely investigated for peripheral nerve regeneration. However, the effect was not as good as that of autologous grafts and therefore could not meet the clinical requirement. In the present study, the nerve growth factor (NGF) loaded heparin/chitosan scaffolds were fabricated via electrostatic interaction for further improving nerve regeneration. The physicochemical properties including morphology, wettability and composition were measured. The heparin immobilization, NGF loading and release were quantitatively and qualitatively characterized, respectively. The effect of NGF loaded heparin/chitosan scaffolds on nerve regeneration was evaluated by Schwann cells culture for different periods. The results showed that the heparin immobilization and NGF loading did not cause the change of bulk properties of chitosan scaffolds except for morphology and wettability. The pre-immobilization of heparin in chitosan scaffolds could enhance the stability of subsequently loaded NGF. The NGF loaded heparin/chitosan scaffolds could obviously improve the attachment and proliferation of Schwann cells in vitro. More importantly, the NGF loaded heparin/chitosan scaffolds could effectively promote the morphology development of Schwann cells. The study may provide a useful experimental basis to design and develop artificial implants for peripheral nerve regeneration and other tissue regeneration. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Thrombocytopenia induced by type II heparin and myocardial infarct: 2 case reports].

Science.gov (United States)

Antonijević, Nabojsa; Stanojević, Milica; Perunicić, Jovan; Djokić, Milan; Miković, Danijla; Kovac, Mirjana; Miljić, Predrag; Milosević, Rajko; Terzić, Branka; Vasiljević, Zorana

2004-01-01

Heparin-induced thrombocytopenia (HIT) type II is an acquired thrombophylic state and life-threatening immune complication of a heparin treatment mainly clinically manifested by marked thrombocytopenia, frequently by arterial and venous thrombosis, and sometimes by skin changes. Functional assay as heparin aggregation test and 14C-serotonin release assays are used in diagnostics as well as antigen assays of which detection tests for heparin-platelet factor 4 antibodies are most frequently used. Considering the fact that there is no single reliable assays for HIT II detection available, sometimes it is necessary to combine both of the above-mentioned types of assays. We present the case of a 57-year-old patient with an acute anterior myocardial infarction with cardiac insufficiency of III and IV degree according to Killip, recurrent ventricular fibrillation and diabetes mellitus type II developing thrombocytopenia to 37 x 10(9)/l accompanied with typical skin changes. The diagnosis was confirmed by the heparin aggregation test. The second patient aged 70 undergoing the treatment for anteroseptal myocardial infarction and reinfarction of the inferior wall complicated by a cardiogenic shock and acute right bundle branch block developed thrombocytopenia 59 x 10(9)/l on the third day of the heparin therapy, with the remark that he had received a heparin therapy during the first infarction as well. Antibodies against heparin-platelet factor 4 were detected by particle gel ID-HPF4 immuno-assay. In both patients, the disease had a lethal outcome despite all then available therapeutic measures applied. Further on we discuss advantages of certain types of tests, a therapy doctrine, need for urgent therapeutic measures, inclusive of the administration of antithrombins, avoidance of harmful procedures like low-molecular-weight heparins administration and prophylactic platelet transfusion as well as preventive measures.

Distribution of heparin-/sup 67/Ga in tumor-bearing rats

Energy Technology Data Exchange (ETDEWEB)

Hiraki, T; Ando, A; Sanada, S [Kanazawa Univ. (Japan). School of Paramedicine; Ando, I; Hisada, K

1976-06-01

Heparin is a kind of acidic mucopolysaccharide. The distribution of heparin-/sup 67/Ga complex in tumor-bearing rats was investigated by administering it to rats into which Yoshida sarcoma had been transplanted subcutaneously. These rats were sacrificed at 10 minutes, 30 minutes, 1 hour and 3 hours after injection. Radioactivity of the tumor, blood, muscle, liver, kidney, spleen and urine were measured with a well-type scintillation counter. Retention values in these organs and excretion rates in the urine were calculated. Excretion rates (%/dose) of heparin-/sup 67/Ga in 10 min., 30 min., 1 hour, and 3 hours were 38.2%, 67.5%, 79.5% and 78.0%, respectively. From these facts, it was thought that heparin-/sup 67/Ga complex was not suitable for tumor scanning, but that this compound might be a suitable agent for the renal function test.

A CMOS delay locked loop and sub-nanosecond time-to-digital converter chip

International Nuclear Information System (INIS)

Santos, D.M.; Dow, S.F.; Flasck, J.M.; Levi, M.E.

1996-01-01

Phase-locked loops have been employed in the past to obtain sub-nanosecond time resolution in high energy physics and nuclear science applications. An alternative solution based on a delay-locked loop (DLL) is described. This solution allows for a very high level of integration yet still offers resolution in the sub-nanosecond regime. Two variations on this solution are outlined. A novel phase detector, based on the Mueller C-element, is used to implement a charge pump where the injected charge approaches zero as the loop approaches lock on the leading edge of an input clock reference. This greatly reduces timing jitter. In the second variation the loop locks to both the leading and trailing clock edges. In this second implementation, software coded layout generators are used to automatically layout a highly integrated, multichannel, time-to-digital converter (TDC) targeted for one specific frequency. The two circuits, DLL and TDC, are implemented in CMOS 1.2 microm and 0.8 microm technologies, respectively. Test results show a timing jitter of less than 30 ps for the DLL circuit and less than 190 ps integral and differential nonlinearity for the TDC circuit

A study on the role of antimicrobial lock solution and radiation in preventing catheter associated infections

International Nuclear Information System (INIS)

Hagras, S.A.A.

2009-01-01

The present study aimed at establishing new techniques for eliminating or preventing microbial colonization of central venous catheters (CVCs) material. Therefore, the microbial contaminants of CVCs used by 100 ICUs patients were isolated . Then the ability of these isolates to produce bio films was in vitro studied.In addition , their susceptibilities to a large number of antibiotics, representing all groups of antibiotics, were examined by determination of their MICs. Gram-negative rods were the major contaminants of tested CVCs, representing about 92% of all isolates. Nevertheless,the percentage of Gram-positive cocci and yeasts did not exceed 4% each.More than 70% of the isolates were positive for slime production and levofloxacin was the most effective antibiotic against bacterial isolates. The effectiveness of different lock solutions of levofloxacin or fluconazole, against bio films of four microbial strains, selected on the basis of their high resistance to tested antibiotics and their ability for slime production, was in vitro studied. Where 1 mg/ml of levofloxacin and 0.5 mg/ml of fluconazole proved to be efficient against bacterial or yeast bio films, respectively, within three days lock period. Upon immobilizing gentamicin molecules on the gamma radiation treated polyurethane catheter material to graft it with spacer or linker chains of poly glycidyl methacrylate (pGMA) molecules, the catheter material acquired antimicrobial and anti adhesive properties.

Quantitation of heparosan with heparin lyase III and spectrophotometry.

Science.gov (United States)

Huang, Haichan; Zhao, Yingying; Lv, Shencong; Zhong, Weihong; Zhang, Fuming; Linhardt, Robert J

2014-02-15

Heparosan is Escherichia coli K5 capsule polysaccharide, which is the key precursor for preparing bioengineered heparin. A rapid and effective quantitative method for detecting heparosan is important in the large-scale production of heparosan. Heparin lyase III (Hep III) effectively catalyzes the heparosan depolymerization, forming unsaturated disaccharides that are measurable using a spectrophotometer at 232 nm. We report a new method for the quantitative detection of heparosan with heparin lyase III and spectrophotometry that is safer and more specific than the traditional carbazole assay. In an optimized detection system, heparosan at a minimum concentration of 0.60 g/L in fermentation broth can be detected. Copyright © 2013 Elsevier Inc. All rights reserved.

Quantitative determination of heparin levels in serum with microtiter plate-format optode

International Nuclear Information System (INIS)

Kim, Sung Bae; Kang, Tae Young; Cha, Geun Sig; Nam, Hakhyun

2006-01-01

A new assay method has been developed for the quantitative determination of heparin in serum using a microtiter plate-format optode (MPO). Heparin and proton in physiological sample are favorably co-extracted into the solvent polymeric optode membrane containing both cationic lipophilic additive, tridodecylmethyl ammonium chloride (TDMAC), and proton-selective ionophore, 3-hydroxy-4-(4-nitrophenylazo)-phenyloctadecanoate (ETH 2412), resulting in the absorbance change of the membrane to varying heparin levels. The optimized MPO composition contains low polymer-to-plasticizer ratio compared to those of conventional ion-selective optodes or electrodes, i.e., poly(vinyl chloride) (20.0)/dioctylsebacate (76.3)/ETH 2412 (1.7)/TDMAC (1.0) (wt.%): it resulted in a quantitative response to heparin from 0 to 15 unit/mL in serum with high sensitivity. The heparin-protamine titration on the MPO could provide rapid and precise determination of heparin. It was shown that the heparin levels in serum sample could be determined from the rate of absorbance change over time (ΔA/Δt); this method was more effective than the direct absorbance measurement in minimizing the interferences from color and turbidity of serum samples. MPO has been developed as a high throughput and convenient disposable sensing device, and may find a wide application in the determination of polyions and charged macromolecules

Cancer Cell Adhesion and Metastasis: Selectins, Integrins, and the Inhibitory Potential of Heparins

Directory of Open Access Journals (Sweden)

Gerd Bendas

2012-01-01

Full Text Available Cell adhesion molecules play a significant role in cancer progression and metastasis. Cell-cell interactions of cancer cells with endothelium determine the metastatic spread. In addition, direct tumor cell interactions with platelets, leukocytes, and soluble components significantly contribute to cancer cell adhesion, extravasation, and the establishment of metastatic lesions. Clinical evidence indicates that heparin, commonly used for treatment of thromboembolic events in cancer patients, is beneficial for their survival. Preclinical studies confirm that heparin possesses antimetastatic activities that lead to attenuation of metastasis in various animal models. Heparin contains several biological activities that may affect several steps in metastatic cascade. Here we focus on the role of cellular adhesion receptors in the metastatic cascade and discuss evidence for heparin as an inhibitor of cell adhesion. While P- and L-selectin facilitation of cellular contacts during hematogenous metastasis is being accepted as a potential target of heparin, here we propose that heparin may also interfere with integrin activity and thereby affect cancer progression. This review summarizes recent findings about potential mechanisms of tumor cell interactions in the vasculature and antimetastatic activities of heparin.

An automatic mode-locked system for passively mode-locked fiber laser

Science.gov (United States)

Li, Sha; Xu, Jun; Chen, Guoliang; Mei, Li; Yi, Bo

2013-12-01

This paper designs and implements one kind of automatic mode-locked system. It can adjust a passively mode-locked fiber laser to keep steady mode-locked states automatically. So the unsteadiness of traditional passively mode-locked fiber laser can be avoided. The system transforms optical signals into electrical pulse signals and sends them into MCU after processing. MCU calculates the frequency of the signals and judges the state of the output based on a quick judgment algorithm. A high-speed comparator is used to check the signals and the comparison voltage can be adjusted to improve the measuring accuracy. Then by controlling two polarization controllers at an angle of 45degrees to each other, MCU extrudes the optical fibers to change the polarization until it gets proper mode-locked output. So the system can continuously monitor the output signal and get it back to mode-locked states quickly and automatically. States of the system can be displayed on the LCD and PC. The parameters of the steady mode-locked states can be stored into an EEPROM so that the system will get into mode-locked states immediately next time. Actual experiments showed that, for a 6.238MHz passively mode-locked fiber lasers, the system can get into steady mode-locked states automatically in less than 90s after starting the system. The expected lock time can be reduced to less than 20s after follow up improvements.

99m Tc-labeled heparin test in orthopaedic surgery

International Nuclear Information System (INIS)

Bouvier, J.F.; Lafon, J.C.; Colin, M.; Chatelut, J.; Beaubatie, F.

1983-01-01

99m Tc-labeled heparin test was performed for early detection of phlebitis or pulmonary embolism after orthopaedic prothesis. Heparinic treatment and surgery per se were demonstrated to have no effect on the results. If this test demonstrates a statistical difference for pathologic patients, it is of greater value to consider ratio between rates before and after intervention [fr

Evidence-based algorithm for heparin dosing before cardiopulmonary bypass. Part 1: Development of the algorithm.

Science.gov (United States)

McKinney, Mark C; Riley, Jeffrey B

2007-12-01

The incidence of heparin resistance during adult cardiac surgery with cardiopulmonary bypass has been reported at 15%-20%. The consistent use of a clinical decision-making algorithm may increase the consistency of patient care and likely reduce the total required heparin dose and other problems associated with heparin dosing. After a directed survey of practicing perfusionists regarding treatment of heparin resistance and a literature search for high-level evidence regarding the diagnosis and treatment of heparin resistance, an evidence-based decision-making algorithm was constructed. The face validity of the algorithm decisive steps and logic was confirmed by a second survey of practicing perfusionists. The algorithm begins with review of the patient history to identify predictors for heparin resistance. The definition for heparin resistance contained in the algorithm is an activated clotting time 450 IU/kg heparin loading dose. Based on the literature, the treatment for heparin resistance used in the algorithm is anti-thrombin III supplement. The algorithm seems to be valid and is supported by high-level evidence and clinician opinion. The next step is a human randomized clinical trial to test the clinical procedure guideline algorithm vs. current standard clinical practice.

Anti-Platelet Factor 4/Heparin Antibody Formation Occurs Endogenously and at Unexpected High Frequency in Polycythemia Vera

Directory of Open Access Journals (Sweden)

Sara C. Meyer

2017-01-01

Full Text Available Background. Myeloproliferative neoplasms (MPN encounter thromboses due to multiple known risk factors. Heparin-induced thrombocytopenia (HIT is a thrombotic syndrome mediated by anti-platelet factor 4 (PF4/heparin antibodies with undetermined significance for thrombosis in MPN. We hypothesized that anti-PF4/heparin Ab might occur in MPN and promote thrombosis. Methods. Anti-PF4/heparin antibodies were analyzed in 127 MPN patients including 76 PV and 51 ET. Screening, validation testing, and isotype testing of anti-PF4/heparin Ab were correlated with disease characteristics. Results. Anti-PF4/heparin antibodies were detected in 21% of PV and 12% of ET versus 0.3–3% in heparin-exposed patients. Validation testing confirmed anti-PF4/heparin immunoglobulins in 15% of PV and 10% of ET. Isotype testing detected 9.2% IgG and 5.3% IgM in PV and exclusively IgM in ET. IgG-positive PV patients encountered thromboses in 57.1% suggesting anti-PF4/heparin IgG may contribute to higher risk for thrombosis in MPN. Overall, 45% of PV patients experienced thromboses with 11.8% positive for anti-PF4/heparin IgG versus 7.1% in PV without thrombosis. Conclusion. Anti-PF4/heparin antibodies occur endogenously and more frequently in MPN than upon heparin exposure. Thrombotic risk increases in anti-PF4/heparin IgG-positive PV reflecting potential implications and calling for larger, confirmatory cohorts. Anti-PF4/heparin IgG should be assessed upon thrombosis in PV to facilitate avoidance of heparin in anti-PF4/heparin IgG-positive PV.

Biomimetic synthesis and biocompatibility evaluation of carbonated apatites template-mediated by heparin

Energy Technology Data Exchange (ETDEWEB)

Deng, Yi [Department of Oral and Maxillofacial Surgery, Laboratory of Interdisciplinary Studies, School and Hospital of Stomatology, Peking University, Beijing 100081 (China); Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871 (China); Sun, Yuhua [Department of Oral and Maxillofacial Surgery, Laboratory of Interdisciplinary Studies, School and Hospital of Stomatology, Peking University, Beijing 100081 (China); Chen, Xiaofang [Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871 (China); Zhu, Peizhi, E-mail: pzzhu@umich.edu [Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871 (China); Department of Chemistry, University of Michigan, Ann Arbor, MI 48109-1055 (United States); Wei, Shicheng, E-mail: sc-wei@pku.edu.cn [Department of Oral and Maxillofacial Surgery, Laboratory of Interdisciplinary Studies, School and Hospital of Stomatology, Peking University, Beijing 100081 (China); Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871 (China)

2013-07-01

Biomimetic synthesis of carbonated apatites with good biocompatibility is a promising strategy for the broadening application of apatites for bone tissue engineering. Most researchers were interested in collagen or gelatin-based templates for synthesis of apatite minerals. Inspired by recent findings about the important role of polysaccharides in bone biomineralization, here we reported that heparin, a mucopolysaccharide, was used to synthesize carbonated apatites in vitro. The results indicated that the Ca/P ratio, carbon content, crystallinity and morphology of the apatites varied depending on the heparin concentration and the initial pH value. The morphology of apatite changed from flake-shaped to needle-shaped, and the degree of crystallinity decreased with the increasing of heparin concentration. Biocompatibility of the apatites was tested by proliferation and alkaline phosphatase activity of MC3T3-E1 cells. The results suggested that carbonated apatites synthesized in the presence of heparin were more favorable to the proliferation and differentiation of MC3T3-E1 cells compared with traditional method. In summary, the heparin concentration and the initial pH value play a key role in the chemical constitution and morphology, as well as biological properties of apatites. These biocompatible nano-apatite crystals hold great potential to be applied as bioactive materials for bone tissue engineering. - Highlights: • Heparin was used as a template to synthesize needle-shaped nano-apatite. • Changing the pH value and concentration led to different properties of apatite. • Apatite prepared by heparin was more favorable to the osteogenic differentiation. • Possible synthesis mechanism of apatite templated by heparin was described.

The impact of preparation parameters on typical attributes of chitosan-heparin nanohydrogels: particle size, loading efficiency, and drug release.

Science.gov (United States)

Shahbazi, Mohammad-Ali; Hamidi, Mehrdad

2013-11-01

Today, developing an optimized nanoparticle (NP) preparation procedure is of paramount importance in all nanoparticulate drug delivery researches, leading to expanding more operative and clinically validated nanomedicines. In this study, a one-at-a-time experimental approach was used for evaluating the effect of various preparation factors on size, loading, and drug release of hydrogel NPs prepared with ionotropic gelation between heparin and chitosan. The size, loading efficiency (LE) and drug release profile of the NPs were evaluated when the chitosan molecular weight, chitosan concentration, heparin addition time to chitosan solution, heparin concentration, pH value of chitosan solution, temperature, and mixing rate were changed separately while other factors were in optimum condition. The results displayed that size and LE are highly influenced by chitosan concentration, getting an optimum of 63 ± 0.57 and 75.19 ± 2.65, respectively, when chitosan concentration was 0.75 mg/ml. Besides, heparin addition time of 3 min leaded to 74.1 ± 0.79 % LE with no sensible effect on size and release profile. In addition, pH 5.5 showed a minimum size of 63 ± 1.87, maximum LE of 73.81 ± 3.13 and the slowest drug release with 63.71 ± 3.84 % during one week. Although LE was not affected by temperature, size and release reduced to 63 ± 0 and 74.21 ± 1.99% when temperature increased from 25°C to 55°C. Also, continuous increase of mixer rate from 500 to 3500 rpm resulted in constant enhancement of LE from 58.3 ± 3.6 to 74.4 ± 2.59 as well as remarkable decrease in size from 148 ± 4.88 to 63 ± 2.64.

Characterization of currently marketed heparin products: key tests for LMWH quality assurance.

Science.gov (United States)

Ye, Hongping; Toby, Timothy K; Sommers, Cynthia D; Ghasriani, Houman; Trehy, Michael L; Ye, Wei; Kolinski, Richard E; Buhse, Lucinda F; Al-Hakim, Ali; Keire, David A

2013-11-01

During the 2007-2008 heparin crisis it was found that the United States Pharmacopeia (USP) testing monograph for heparin sodium or low molecular weight heparins did not detect the presence of the contaminant, oversulfated chondroitin sulfate (OSCS). In response to this concern, new tests and specifications were developed by the Food and Drug Administration (FDA) and USP and put in place to detect not only the contaminant OSCS, but also to improve assurance of quality and purity of these drug products. The USP monographs for the low molecular weight heparins (LMWHs) approved for use in the United States (dalteparin, tinzaparin and enoxaparin) are also undergoing revision to include many of the same tests used for heparin sodium, including; one-dimensional (1D) 500 MHz (1)H NMR, SAX-HPLC, percent galactosamine in total hexosamine and anticoagulation time assays with purified Factor IIa or Factor Xa. These tests represent orthogonal approaches for heparin identification, measurement of bioactivity and for detection of process impurities or contaminants in these drug products. Here we describe results from a survey of multiple lots from three types of LMWHs in the US market which were collected after the 2009 heparin sodium monograph revision. In addition, innovator and generic versions of formulated enoxaparin products purchased in 2011 are compared using these tests and found to be highly similar within the discriminating power of the assays applied. Published by Elsevier B.V.

The US regulatory and pharmacopeia response to the global heparin contamination crisis.

Science.gov (United States)

Szajek, Anita Y; Chess, Edward; Johansen, Kristian; Gratzl, Gyöngyi; Gray, Elaine; Keire, David; Linhardt, Robert J; Liu, Jian; Morris, Tina; Mulloy, Barbara; Nasr, Moheb; Shriver, Zachary; Torralba, Pearle; Viskov, Christian; Williams, Roger; Woodcock, Janet; Workman, Wesley; Al-Hakim, Ali

2016-06-09

The contamination of the widely used lifesaving anticoagulant drug heparin in 2007 has drawn renewed attention to the challenges that are associated with the characterization, quality control and standardization of complex biological medicines from natural sources. Heparin is a linear, highly sulfated polysaccharide consisting of alternating glucosamine and uronic acid monosaccharide residues. Heparin has been used successfully as an injectable antithrombotic medicine since the 1930s, and its isolation from animal sources (primarily porcine intestine) as well as its manufacturing processes have not changed substantially since its introduction. The 2007 heparin contamination crisis resulted in several deaths in the United States and hundreds of adverse reactions worldwide, revealing the vulnerability of a complex global supply chain to sophisticated adulteration. This Perspective discusses how the US Food and Drug Administration (FDA), the United States Pharmacopeial Convention (USP) and international stakeholders collaborated to redefine quality expectations for heparin, thus making an important natural product better controlled and less susceptible to economically motivated adulteration.

Interactions of oversulfated chondroitin sulfate (OSCS) from different sources with unfractionated heparin.

Science.gov (United States)

Gray, Angel; Litinas, Evangelos; Jeske, Walter; Fareed, Jawed; Hoppensteadt, Debra

2012-01-01

In 2008, oversulfated chondroitin sulfate (OSCS) was identified as the main contaminant in recalled heparin. Oversulfated chondroitin sulfate can be prepared from bovine (B), porcine (P), shark (Sh), or skate (S) origin and may produce changes in the antithrombotic, bleeding, and hemodynamic profile of heparins. This study examines the interactions of various OSCSs on heparin in animal models of thrombosis and bleeding, as well as on the anticoagulant and antiprotease effects in in vitro assays. Mixtures of 70% unfractionated heparin (UFH) with 30% OSCS from different sources were tested. In the in vitro activated partial thromboplastin time (aPTT) assay, all contaminant mixtures showed a decrease in clotting times. In addition, a significant increase in bleeding time compared to the control (UFH/saline) was observed. In the thrombosis model, no significant differences were observed. The OSCSs significantly increased anti-Xa activity in ex vivo blood samples. These results indicate that various sources of OSCS affect the hemostatic properties of heparin.

A genome-wide association study of heparin-induced thrombocytopenia using an electronic medical record

DEFF Research Database (Denmark)

Karnes, Jason H; Cronin, Robert M; Rollin, Jerome

2015-01-01

Heparin-induced thrombocytopenia (HIT) is an unpredictable, potentially catastrophic adverse effect of heparin treatment resulting from an immune response to platelet factor 4 (PF4)/heparin complexes. No genome-wide evaluations have been performed to identify potential genetic influences on HIT. ...

Veno-venous bypass without systemic heparinization using a centrifugal pump: a blind comparison of a heparin bonded circuit versus a non heparin bonded circuit

NARCIS (Netherlands)

van der Hulst, V. P.; Henny, C. P.; Moulijn, A. C.; Engbers, G.; ten Cate, H.; Gründeman, P. F.; Klopper, P. J.

1989-01-01

Veno-venous bypass without the use of systemic heparinization has recently become of increasing interest for application during liver transplantation and surgery on the large abdominal veins. However, possible adverse effects on blood components as demonstrated by means of hematologic and hemostatic

Heparin-immobilized hydroxyapatite nanoparticles as a lactoferrin delivery system for improving osteogenic differentiation of adipose-derived stem cells

International Nuclear Information System (INIS)

Kim, Sung Eun; Yun, Young-Pil; Kim, Hak-Jun; Lee, Deok-Won; Shim, Kyu-Sik; Jeon, Daniel I; Rhee, Jin-Kyu; Park, Kyeongsoon

2016-01-01

The aim of this study is to fabricate lactoferrin (LF)-carrying hydroxyapatite nanoparticles (HAp NPs) to enhance osteogenic differentiation of rabbit adipose-derived stem cells (rADSCs). HAp NPs were modified with heparin-dopamine (Hep-DOPA) (Hep-HAp) and further immobilized with LF (LF/Hep-HAp). Heparin immobilization on HAp NPs prevented aggregation of HAp NPs in aqueous solution and prolonged the release of LF from LF/Hep-HAp NPs. In vitro studies of rADSCs have demonstrated that LF-Hep/HAp NPs significantly increase alkaline phosphatase (ALP) activity, calcium deposition, and both mRNA expression of osteocalcin (OCN) and osteopontin (OPN) in comparison with HAp and Hep-HAp NPs. These results suggest that LF/Hep-HAp NPs can effectively induce osteogenic differentiation of rADSCs. (paper)

Interband optical pulse injection locking of quantum dot mode-locked semiconductor laser.

Science.gov (United States)

Kim, Jimyung; Delfyett, Peter J

2008-07-21

We experimentally demonstrate optical clock recovery from quantum dot mode-locked semiconductor lasers by interband optical pulse injection locking. The passively mode-locked slave laser oscillating on the ground state or the first excited state transition is locked through the injection of optical pulses generated via the opposite transition bands, i.e. the first excited state or the ground state transition from the hybridly mode-locked master laser, respectively. When an optical pulse train generated via the first excited state from the master laser is injected to the slave laser oscillating via ground state, the slave laser shows an asymmetric locking bandwidth around the nominal repetition rate of the slave laser. In the reverse injection case of, i.e. the ground state (master laser) to the first excited state (slave laser), the slave laser does not lock even though both lasers oscillate at the same cavity frequency. In this case, the slave laser only locks to higher injection rates as compared to its own nominal repetition rate, and also shows a large locking bandwidth of 6.7 MHz.

Heparin concentration is critical for cell culture with human platelet lysate.

Science.gov (United States)

Hemeda, Hatim; Kalz, Jana; Walenda, Gudrun; Lohmann, Michael; Wagner, Wolfgang

2013-09-01

Culture media for mesenchymal stromal cells (MSCs) are generally supplemented with fetal bovine serum. Human platelet lysate (hPL) has been proven to be a very effective alternative without the risk of xenogeneic infections or immune reactions. In contrast to fetal bovine serum, hPL comprises plasma, and anticoagulants-usually unfractionated heparin (UFH)-need to be added to prevent gel formation. Cultures of MSCs in hPL media with various concentrations of UFH and enoxaparin, a low-molecular-weight heparin (LMWH), were systematically compared with regard to proliferation, fibroblastoid colony-forming unit frequency, immunophenotype and in vitro differentiation. At least 0.61 IU/mL UFH or 0.024 mg/mL LMWH was necessary for reliable prevention of coagulation of hPL pools used in this study. Higher concentrations impaired cellular proliferation in a dose-dependent manner even without benzyl alcohol, which is commonly added to heparins as a bacteriostatic agent. Colony-forming unit frequency was also reduced at higher heparin concentrations, particularly with LMWH, whereas no significant effect was observed on cellular morphology or immunophenotype. High concentrations of heparins reduced the in vitro differentiation toward adipogenic and osteogenic lineages. Heparin concentration is critical for culture of MSCs in hPL media; this is of particular relevance for cellular therapy where cell culture procedures need to be optimized and standardized. Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Low-molecular weight heparin increases circulating sFlt-1 levels and enhances urinary elimination.

Directory of Open Access Journals (Sweden)

Henning Hagmann

Full Text Available RATIONALE: Preeclampsia is a devastating medical complication of pregnancy which leads to maternal and fetal morbidity and mortality. While the etiology of preeclampsia is unclear, human and animal studies suggest that excessive circulating levels of soluble fms-like tyrosine-kinase-1 (sFlt-1, an alternatively spliced variant of VEGF-receptor1, contribute to the signs and symptoms of preeclampsia. Since sFlt-1 binds to heparin and heparan sulfate proteoglycans, we hypothesized that the anticoagulant heparin, which is often used in pregnancy, may interfere with the levels, distribution and elimination of sFlt-1 in vivo. OBJECTIVE: We systematically determined serum and urine levels of angiogenic factors in preeclamptic women before and after administration of low molecular weight heparin and further characterized the interaction with heparin in biochemical studies. METHODS AND RESULTS: Serum and urine samples were used to measure sFlt-1 levels before and after heparin administration. Serum levels of sFlt-1 increased by 25% after heparin administration in pregnant women. The magnitude of the increase in circulating sFlt-1 correlated with initial sFlt-1 serum levels. Urinary sFlt-1 levels were also elevated following heparin administration and levels of elimination were dependent on the underlying integrity of the glomerular filtration barrier. Biochemical binding studies employing cation exchange chromatography revealed that heparin bound sFlt-1 had decreased affinity to negatively charged surfaces when compared to sFlt-1 alone. CONCLUSION: Low molecular weight heparin administration increased circulating sFlt1 levels and enhanced renal elimination. We provide evidence that both effects may be due to heparin binding to sFlt1 and masking the positive charges on sFlt1 protein.

The effect of different forms of heparin on point-of-care blood gas ...

African Journals Online (AJOL)

and heparin vacutainers on blood gas and electrolyte analysis and ... This prospective, cross-sectional study took place in the ED of a ... the effect of two concentrations of liquid heparin and the use of heparin vacutainers on the reliability of blood gas ... Germany) and (iv) a 2 mL plastic syringe (BD) washed with 5 000 IU/.

Prospective multicentre cohort study of heparin-induced thrombocytopenia in acute ischaemic stroke patients

Science.gov (United States)

Kawano, Hiroyuki; Yamamoto, Haruko; Miyata, Shigeki; Izumi, Manabu; Hirano, Teruyuki; Toratani, Naomi; Kakutani, Isami; Sheppard, Jo-Ann I; Warkentin, Theodore E; Kada, Akiko; Sato, Shoichiro; Okamoto, Sadahisa; Nagatsuka, Kazuyuki; Naritomi, Hiroaki; Toyoda, Kazunori; Uchino, Makoto; Minematsu, Kazuo

2011-01-01

Acute ischaemic stroke patients sometimes receive heparin for treatment and/or prophylaxis of thromboembolic complications. This study was designed to elucidate the incidence and clinical features of heparin-induced thrombocytopenia (HIT) in acute stroke patients treated with heparin. We conducted a prospective multicentre cohort study of 267 patients who were admitted to three stroke centres within 7 d after stroke onset. We examined clinical data until discharge and collected blood samples on days 1 and 14 of hospitalization to test anti-platelet factor 4/heparin antibodies (anti-PF4/H Abs) using an enzyme-linked immunosorbent assay (ELISA); platelet-activating antibodies were identified by serotonin-release assay (SRA). Patients with a 4Ts score ≥4 points, positive-ELISA, and positive-SRA were diagnosed as definite HIT. Heparin was administered to 172 patients (64·4%: heparin group). Anti-PF4/H Abs were detected by ELISA in 22 cases (12·8%) in the heparin group. Seven patients had 4Ts ≥ 4 points. Among them, three patients (1·7% overall) were also positive by both ELISA and SRA. National Institutes of Health Stroke Scale score on admission was high (range, 16–23) and in-hospital mortality was very high (66·7%) in definite HIT patients. In this study, the incidence of definite HIT in acute ischaemic stroke patients treated with heparin was 1·7% (95% confidence interval: 0·4–5·0). The clinical severity and outcome of definite HIT were unfavourable. PMID:21671895

Nycthemeral variations of 99Tcsup(m)-labelled heparin pharmacokinetic parameters

International Nuclear Information System (INIS)

Decousus, M.; Gremillet, E.; Decousus, H.; Champailler, A.; Houzard, C.; Perpoint, B.; Jaubert, J.

1985-01-01

Six healthy volunteers received four i.v.boluses of 99 Tcsup(m)-heparin at 8.00, 14.00, 20.00 and 02.00 hours at seven-day intervals. Nine blood samples were taken covering a period of 2 h after administration. Simultaneously urine was collected and diuresis not noted. Plasma and urinary radioactivity were measured and standard pharmacokinetic parameters were calculated. Nycthemeral variations of these kinetic parameters were detected by means of distribution-free tests. Circadian rhythms were analysed by means of the cosinor method and the Gauss-Marquardt method. The mean raw value of the following parameters: apparent volume of distribution, plasmatic clearance and extra-renal metabolic clearance, increased significantly between 8.00 and 14.00 and decreased between 14.00 and 20.00. A circadian rhythm was found for the plasmatic clearance only. On the other hand the elimination half-lives and the renal clearance were unaffected by the time of the injections. These results obtained for low doses of 99 Tcsup(m)-heparin suggest a circadian rhythm of the bio-availability of heparin in man. This fact should be taken into account for the use of 99 Tcsup(m)-heparin in the diagnosis of deep-vein thrombosis and for the safe adjustment of the heparin dosages in the treatment of severe thromboembolism. (author)

Heparin induced alterations in clearance and distribution of blood-borne microparticles following operative trauma.

Science.gov (United States)

Saba, T M; Antikatzides, T G

1979-04-01

The influence of systemic heparin administration on the vascular clearance and tissue distribution of blood-borne microparticles was evaluated in normal rats and rats after operation (laparotomy plus intestinal manipulation) utilizing an (131)I- colloid which is phagocytized by the reticuloendothelial system (RES). Intravenous heparin administration (100 USP/100g body weight) into normal animals three minutes prior to colloid injection (50 mg/lOOg) induced a significant increase in pulmonary localization of the microparticles as compared to nonheparinized control rats, while hepatic and splenic uptake were decreased. Surgical trauma decreased hepatic RE uptake and increased pulmonary localization of the microparticles when injected systemically at 60 minutes postsurgery. Heparin administration 60 minutes after surgery and three minutes prior to colloid injection, magnified the increased pulmonary localization response with an associated further depression of the RES. The ability of heparin to alter both RE clearance function and lung localization of microparticles was dose dependent and a function of the interval between heparin administration and systemic particulate infusion. Thus, low dose heparin administration was capable of stimulating RE activity while heparin in doses of excess of 50 USP units/lOOg body weight decreased RE function. These findings suggest that the functional state of the hepatic RE system can be greatly affected in a dose-dependent manner by systemic heparin administration which may influence distribution of blood-borne microparticles.

12500 E heparin and 12500 E of a semisynthetic heparin analogue (SSHA) in preventing thrombosis during radiotherapy of gynaecological carcinomas

International Nuclear Information System (INIS)

Hilscher, T.M.

1983-01-01

The effects of 12500 E calcium heparin given once daily were contrasted with those seen under daily treatment with 12500 E of a semisynthetic heparin analogue (SSHA) and evaluated using iodine-125-labelled fibrinogen. The study included 80 patients, who were randomly assigned to the two treatment groups on a 1:1 basis. The findings revealed here led to the conclusion that both drugs, administered once daily by the subcutaneous route, were effective in preventing the occurrence of thrombosis during radiation treatment of gynaecological tumours. (orig./MG) [de

Heparin and glutathione II: correlation between decondensation of bull sperm cells and its nucleons.

Science.gov (United States)

Delgado, N M; Flores-Alonso, J C; Rodríguez-Hernández, H M; Merchant-Larios, H; Reyes, R

2001-01-01

The correlation between the kinetics of bull sperm nuclear and nucleon decondensation induced by the action of physiological concentrations of heparin/GSH was studied. Sperm and nucleon suspensions were incubated at 37 degrees C in salt medium, at a constant concentration of either heparin or GSH and increasing concentrations of the other reagent. Even though nucleons are pretreated with DTT/CTAB, when they are incubated alone with GSH for 96 h, they remain intact, no matter which concentration is employed, and it was impossible to observe the slightest sign of nuclei decondensation. Therefore, rupture of disulfide bridges is not the main mechanism to induce nuclei decondensation and perhaps the GSH role resides in potentate the heparin effect by increasing its negative charge. Nevertheless, nucleons reach 95% of chromatin decondensation in the presence of heparin plus GSH or heparin alone. The fact that the correlation between heparin and GSH concentrations needed to induce sperm nuclei decondensation was 3- to 4-fold greater that in nucleons might be due to the complete lack of nucleon membranes. Heparin/GSH seem to induce nuclei decondensation by an ionic chromatin charge neutralization mechanism.

Polyelectrolyte multilayer assembly as a function of pH and ionic strength using the polysaccharides chitosan and heparin.

Science.gov (United States)

Boddohi, Soheil; Killingsworth, Christopher E; Kipper, Matt J

2008-07-01

The goal of this work is to explore the effects of solution ionic strength and pH on polyelectrolyte multilayer (PEM) assembly, using biologically derived polysaccharides as the polyelectrolytes. We used the layer-by-layer (LBL) technique to assemble PEM of the polysaccharides heparin (a strong polyanion) and chitosan (a weak polycation) and characterized the sensitivity of the PEM composition and layer thickness to changes in processing parameters. Fourier-transform surface plasmon resonance (FT-SPR) and spectroscopic ellipsometry provided in situ and ex situ measurements of the PEM thickness, respectively. Vibrational spectroscopy and X-ray photoelectron spectroscopy (XPS) provided details of the chemistry (i.e., composition, electrostatic interactions) of the PEM. We found that when PEM were assembled from 0.2 M buffer, the PEM thickness could be increased from less than 2 nm per bilayer to greater than 4 nm per bilayer by changing the solution pH; higher and lower ionic strength buffer solutions resulted in narrower ranges of accessible thickness. Molar composition of the PEM was not very sensitive to solution pH or ionic strength, but pH did affect the interactions between the sulfonates in heparin and amines in chitosan when PEM were assembled from 0.2 M buffer. Changes in the PEM thickness with pH and ionic strength can be interpreted through descriptions of the charge density and conformation of the polyelectrolyte chains in solution.

Cationization of heparin for film applications

Czech Academy of Sciences Publication Activity Database

Šimkovic, I.; Mendichi, R.; Kelnar, Ivan; Filip, J.; Hricovíni, M.

2015-01-01

Roč. 115, 22 January (2015), s. 551-558 ISSN 0144-8617 Institutional support: RVO:61389013 Keywords : heparin * cationization * NMR Subject RIV: CD - Macromolecular Chemistry Impact factor: 4.219, year: 2015

Double pass locking and spatial mode locking for gravitational wave detectors

CERN Document Server

Cusack, B J; Slagmolen, B; Vine, G D; Gray, M B; McClelland, D E

2002-01-01

We present novel techniques for overcoming problems relating to the use of high-power lasers in mode cleaner cavities for second generation laser interferometric gravitational wave detectors. Rearranging the optical components into a double pass locking regime can help to protect locking detectors from damage. Modulator thermal lensing can be avoided by using a modulation-free technique such as tilt locking, or its recently developed cousin, flip locking.

Structure-Activity Relationships of Bioengineered Heparin/Heparan Sulfates Produced in Different Bioreactors

Directory of Open Access Journals (Sweden)

Ha Na Kim

2017-05-01

Full Text Available Heparin and heparan sulfate are structurally-related carbohydrates with therapeutic applications in anticoagulation, drug delivery, and regenerative medicine. This study explored the effect of different bioreactor conditions on the production of heparin/heparan sulfate chains via the recombinant expression of serglycin in mammalian cells. Tissue culture flasks and continuously-stirred tank reactors promoted the production of serglycin decorated with heparin/heparan sulfate, as well as chondroitin sulfate, while the serglycin secreted by cells in the tissue culture flasks produced more highly-sulfated heparin/heparan sulfate chains. The serglycin produced in tissue culture flasks was effective in binding and signaling fibroblast growth factor 2, indicating the utility of this molecule in drug delivery and regenerative medicine applications in addition to its well-known anticoagulant activity.

SPECIFIC ASPECTS OF INTERACTION OF PLATELETS WITH THE HEPARINIZED MATERIALS

Directory of Open Access Journals (Sweden)

E.A. Nemets

2012-01-01

Full Text Available Comparative analysis of anticoagulant nature on medical materials testing was done. It was found that change of citrate by heparin is accompanied by significant changes in platelet adhesion and activation. This results allowed us to arrive at a conclusion about reasonability of heparin usage as anticoagulant in in vitro testing. 

Safety of low-molecular-weight heparin in pregnancy: a systematic review

NARCIS (Netherlands)

Sanson, B. J.; Lensing, A. W.; Prins, M. H.; Ginsberg, J. S.; Barkagan, Z. S.; Lavenne-Pardonge, E.; Brenner, B.; Dulitzky, M.; Nielsen, J. D.; Boda, Z.; Turi, S.; Mac Gillavry, M. R.; Hamulyák, K.; Theunissen, I. M.; Hunt, B. J.; Büller, H. R.

1999-01-01

Unfractionated heparin (UFH) remains the anticoagulant of choice during pregnancy. Low-molecular-weight heparins (LMWH) are an attractive alternative to UFH due to their logistic advantages and their association with a lower incidence of osteoporosis and HIT. We reviewed all published clinical

Qualitative and Quantitative Analysis of Heparin during Precipitation by Near-Infrared Spectroscopy

OpenAIRE

Lian Li; Jinfeng Wang; Hengchang Zang; Hui Zhang; Wei Jiang; Shang Chen; Fengshan Wang

2016-01-01

Heparin is a glycosaminoglycan (GAG) that plays an important role in the blood coagulation system. Its quality is of great importance, so it is necessary to develop a fast analytical method during the manufacture process to analyse the quality of heparin produced. In this study, the heparin contents of 80 samples collected from five batches during the precipitation process were analysed using nearinfrared (NIR) spectroscopy and a chemometrics approach. This was done in order to improve the ef...

Dansyl (5-dimethylaminonaphthalene-1-sulphonyl)-heparin binds antithrombin III and platelet factor 4 at separate sites

Science.gov (United States)

Piepkorn, Michael W.

1981-01-01

Antithrombin III binds to, and thereby augments the fluorescence of, dansyl-(5-dimethylaminonaphthalene-1-sulphonyl)-heparin; platelet factor 4 binding to the fluorescent heparin has little of this effect. Competition studies in which antithrombin III competes with platelet factor 4 for heparin binding demonstrate that heparin can simultaneously bind both proteins. PMID:7317004

The role of heparin in sepsis: much more than just an anticoagulant.

Science.gov (United States)

Li, Xu; Ma, Xiaochun

2017-11-01

Despite progress in antibiotic treatment, mechanical ventilation, fluid resuscitation and blood glucose maintenance, sepsis remains a cause of high mortality in the intensive care unit to date, there are no proven treatment strategies for the routine management of septic patients. The extensive interaction between inflammation and coagulation contributes to the basic pathophysiology of sepsis. Thus, the agents that attenuate the activation of both inflammation and coagulation may improve the outcome in sepsis. Apart from the well-known anticoagulant effects of heparin, it also possesses various immunomodulatory properties and protects glycocalyx from shedding. Hence, heparin seems to be such an agent. Immunothrombosis plays an important role in early host defence against bacterial dissemination, thus the proper timing for anticoagulant therapy should be determined. We review the available experimental and clinical data supporting the use of heparin in sepsis. At this time the use of heparin in the treatment of sepsis is conflicting. Future trials of heparin therapy for sepsis should concentrate on the very severely ill patients, in whom benefit is most likely to be demonstrated. © 2017 John Wiley & Sons Ltd.

Update on the clinical use of the low-molecular-weight heparin, parnaparin

Directory of Open Access Journals (Sweden)

Giuseppe Camporese

2009-09-01

Full Text Available Giuseppe Camporese1, Enrico Bernardi2, Franco Noventa31Unit of Angiology and 3Department of Clinical and Experimental Medicine, Clinical Epidemiology Group, University Hospital of Padua, Italy; 2Department of Emergency and Accident Medicine, Hospital of Conegliano Veneto, ItalyAbstract: Parnaparin is a low-molecular-weight heparin that has widely shown its efficacy and safety in prevention of venous thromboembolism, in the treatment of chronic venous disorders, and in the treatment of venous and arterial (stable and unstable angina, acute ST-segment elevation myocardial infarction thrombosis. Parnaparin at the respective dosages of 3200, 4250, 6400, or 12800 IUaXa for a period ranging from 3 to 5 days to 6 months, is usually administered subcutaneously by means of once-daily regimen and is better tolerated than unfractionated heparin at the injection site. In the variety of commercially available low-molecular-weight heparins, parnaparin represents a useful therapeutic option, even though little evidence is available comparing the superiority or the equivalent efficacy and safety of parnaparin to that of the unfractionated heparin or placebo. This review summarizes the available literature on the use of parnaparin in different settings of cardiovascular diseases, including papers published during the past year and ongoing studies.Keywords: low-molecular-weight heparin, heparin, parnaparin, acute coronary syndromes, venous thromboembolism

Targeting Heparin to Collagen within Extracellular Matrix Significantly Reduces Thrombogenicity and Improves Endothelialization of Decellularized Tissues.

Science.gov (United States)

Jiang, Bin; Suen, Rachel; Wertheim, Jason A; Ameer, Guillermo A

2016-12-12

Thrombosis within small-diameter vascular grafts limits the development of bioartificial, engineered vascular conduits, especially those derived from extracellular matrix (ECM). Here we describe an easy-to-implement strategy to chemically modify vascular ECM by covalently linking a collagen binding peptide (CBP) to heparin to form a heparin derivative (CBP-heparin) that selectively binds a subset of collagens. Modification of ECM with CBP-heparin leads to increased deposition of functional heparin (by ∼7.2-fold measured by glycosaminoglycan composition) and a corresponding reduction in platelet binding (>70%) and whole blood clotting (>80%) onto the ECM. Furthermore, addition of CBP-heparin to the ECM stabilizes long-term endothelial cell attachment to the lumen of ECM-derived vascular conduits, potentially through recruitment of heparin-binding growth factors that ultimately improve the durability of endothelialization in vitro. Overall, our findings provide a simple yet effective method to increase deposition of functional heparin on the surface of ECM-based vascular grafts and thereby minimize thrombogenicity of decellularized tissue, overcoming a significant challenge in tissue engineering of bioartificial vessels and vascularized organs.

Purification of foot-and-mouth disease virus by heparin as ligand for certain strains.

Science.gov (United States)

Du, Ping; Sun, Shiqi; Dong, Jinjie; Zhi, Xiaoying; Chang, Yanyan; Teng, Zhidong; Guo, Huichen; Liu, Zaixin

2017-04-01

The goal of this project was to develop an easily operable and scalable process for the recovery and purification of foot-and-mouth disease virus (FMDV) from cell culture. Heparin resins HipTrap Heparin HP and AF-Heparin HC-650 were utilized to purify FMDV O/HN/CHA/93. Results showed that the purity of AF-Heparin HC-650 was ideal. Then, the O/HN/CHA/93, O/Tibet/CHA/99, Asia I/HN/06, and A/CHA/HB/2009 strains were purified by AF-Heparin HC-650. Their affinity/virus recoveries were approximately 51.2%/45.8%, 71.5%/70.9%, 96.4%/73.5, and 59.5%/42.1%, respectively. During a stepwise elution strategy, the viral particles were mainly eluted at 300mM ionic strength peaks. The heparin affinity chromatography process removed more than 94% of cellular and medium proteins. Anion exchange resin Capto Q captured four FMD virus particles; 40% of binding proteins and 80%-90% of viral particles were eluted at 450mM NaCl. Moreover, ionic strength varied from 30 to 450mM had no effect on the immunity to FMDV. The results revealed that heparin sulfate may be the main receptor for CHA/99 strain attachment-susceptible cells. Heparin affinity chromatography can reach perfect results, especially when used as a ligand of the virus. Anion exchange is useful only as previous step for further purification. Copyright © 2016. Published by Elsevier B.V.

Covalently bound conjugates of albumin and heparin: Synthesis, fractionation and characterization

NARCIS (Netherlands)

Hennink, Wim E.; Feijen, Jan; Ebert, Charles D.; Kim, Sung Wan

1983-01-01

Covalently bound conjugates of human serum albumin and heparin were prepared as compounds which could improve the blood-compatibility of polymer surfaces either by preadsorption or by covalent coupling of the conjugates onto blood contacting surfaces. The conjugates (10–16 weight % of heparin) were

Characterization of currently marketed heparin products: key tests for quality assurance.

Science.gov (United States)

Keire, David A; Ye, Hongping; Trehy, Michael L; Ye, Wei; Kolinski, Richard E; Westenberger, Benjamin J; Buhse, Lucinda F; Nasr, Moheb; Al-Hakim, Ali

2011-01-01

During the 2007-2008 heparin crisis, it was found that the United States Pharmacopeia (USP) testing monograph for unfractionated heparin sodium (UFH) did not detect the presence of the contaminant, oversulfated chondroitin sulfate (OSCS) in heparin. In response to this concern, new tests and specifications were developed by the Food and Drug Administration (FDA) and USP and put in place to not only detect the contaminant OSCS but also to improve assurance of quality and purity of the drug product. Additional tests were also developed to monitor the heparin supply chain for other possible economically motivated additives or impurities. In 2009, a new USP monograph was put in place that includes 500 MHz (1)H NMR, SAX-HPLC, %galactosamine in total hexosamine, and anticoagulation time assays with purified factor IIa or factor Xa. These tests represent orthogonal approaches for UFH identification, measurement of bioactivity, and for detection of process impurities or contaminants in UFH. The FDA has applied these analytical approaches to the study of UFH active pharmaceutical ingredients in the marketplace. Here, we describe results from a comprehensive survey of UFH collected from seven different sources after the 2009 monograph revision and compare these data with results obtained on other heparin samples collected during the 2007-2008 crisis.

Automatic NMR field-frequency lock-pulsed phase locked loop approach.

Science.gov (United States)

Kan, S; Gonord, P; Fan, M; Sauzade, M; Courtieu, J

1978-06-01

A self-contained deuterium frequency-field lock scheme for a high-resolution NMR spectrometer is described. It is based on phase locked loop techniques in which the free induction decay signal behaves as a voltage-controlled oscillator. By pulsing the spins at an offset frequency of a few hundred hertz and using a digital phase-frequency discriminator this method not only eliminates the usual phase, rf power, offset adjustments needed in conventional lock systems but also possesses the automatic pull-in characteristics that dispense with the use of field sweeps to locate the NMR line prior to closure of the lock loop.

A Heparin Binding Motif Rich in Arginine and Lysine is the Functional Domain of YKL-40

Directory of Open Access Journals (Sweden)

Nipaporn Ngernyuang

2018-02-01

Full Text Available The heparin-binding glycoprotein YKL-40 (CHI3L1 is intimately associated with microvascularization in multiple human diseases including cancer and inflammation. However, the heparin-binding domain(s pertinent to the angiogenic activity have yet been identified. YKL-40 harbors a consensus heparin-binding motif that consists of positively charged arginine (R and lysine (K (RRDK; residues 144–147; but they don't bind to heparin. Intriguingly, we identified a separate KR-rich domain (residues 334–345 that does display strong heparin binding affinity. A short synthetic peptide spanning this KR-rich domain successfully competed with YKL-40 and blocked its ability to bind heparin. Three individual point mutations, where alanine (A substituted for K or R (K337A, K342A, R344A, led to remarkable decreases in heparin-binding ability and angiogenic activity. In addition, a neutralizing anti-YKL-40 antibody that targets these residues and prevents heparin binding impeded angiogenesis in vitro. MDA-MB-231 breast cancer cells engineered to express ectopic K337A, K342A or R344A mutants displayed reduced tumor development and compromised tumor vessel formation in mice relative to control cells expressing wild-type YKL-40. These data reveal that the KR-rich heparin-binding motif is the functional heparin-binding domain of YKL-40. Our findings shed light on novel molecular mechanisms underlying endothelial cell angiogenesis promoted by YKL-40 in a variety of diseases.

Chip-Multiprocessor Hardware Locks for Safety-Critical Java

DEFF Research Database (Denmark)

Strøm, Torur Biskopstø; Puffitsch, Wolfgang; Schoeberl, Martin

2013-01-01

and may void a task set's schedulability. In this paper we present a hardware locking mechanism to reduce the synchronization overhead. The solution is implemented for the chip-multiprocessor version of the Java Optimized Processor in the context of safety-critical Java. The implementation is compared...

Hydrolysis and Sulfation Pattern Effects on Release of Bioactive Bone Morphogenetic Protein-2 from Heparin-Based Microparticles.

Science.gov (United States)

Tellier, Liane E; Miller, Tobias; McDevitt, Todd C; Temenoff, Johnna S

2015-10-28

Glycosaminoglycans (GAGs) such as heparin are promising materials for growth factor delivery due to their ability to efficiently bind positively charged growth factors including bone morphogenetic protein-2 (BMP-2) through their negatively charged sulfate groups. Therefore, the goal of this study was to examine BMP-2 release from heparin-based microparticles (MPs) after first, incorporating a hydrolytically degradable crosslinker and varying heparin content within MPs to alter MP degradation and second, altering the sulfation pattern of heparin within MPs to vary BMP-2 binding and release. Using varied MP formulations, it was found that the time course of MP degradation for 1 wt% heparin MPs was ~4 days slower than 10 wt% heparin MPs, indicating that MP degradation was dependent on heparin content. After incubating 100 ng BMP-2 with 0.1 mg MPs, most MP formulations loaded BMP-2 with ~50% efficiency and significantly more BMP-2 release (60% of loaded BMP-2) was observed from more sulfated heparin MPs (MPs with ~100% and 80% of native sulfation). Similarly, BMP-2 bioactivity in more sulfated heparin MP groups was at least four-fold higher than soluble BMP-2 and less sulfated heparin MP groups, as determined by an established C2C12 cell alkaline phosphatase (ALP) assay. Ultimately, the two most sulfated 10 wt% heparin MP formulations were able to efficiently load and release BMP-2 while enhancing BMP-2 bioactivity, making them promising candidates for future growth factor delivery applications.

Removal of glycosaminoglycans from bovine granulosa cells contributes to increased binding of hydrogen-3 heparin

Energy Technology Data Exchange (ETDEWEB)

Ax, R.L.; Stodd, C.M.; Boehm, S.K.; Bellin, M.E.

1986-02-01

Granulosa cells from small or large bovine follicles were pretreated with enzymes that hydrolyze various glycosaminoglycans, and binding of (/sup 3/H)-heparin to the granulosa was measured. Binding of (/sup 3/H) heparin increased significantly after enzymatic pretreatments with chondroitinase ABC and fungal hyaluronidase, and similar results were obtained with granulosa from small and large follicles. No changes in binding of (/sup 3/H) heparin were detected after hydrolyses with chondroitinase AC and heparinase in either follicle size. Heparitinase, which hydrolyzes heparan sulfate, led to a significant 50% increase in binding of (/sup 3/H) heparin to granulosa from large follicles but was without effect in small follicles. These results suggest that the lower binding of (/sup 3/H) heparin, which has been reported with follicular enlargement, may be due to heparan sulfate occupying or obstructing binding sites for heparin on granulosa from large follicles.

Heparin Interaction with the Primed Polymorphonuclear Leukocyte CD11b Induces Apoptosis and Prevents Cell Activation

Directory of Open Access Journals (Sweden)

Meital Cohen-Mazor

2015-01-01

Full Text Available Heparin is known to have anti-inflammatory effects, yet the mechanisms are not completely understood. In this study, we tested the hypothesis that heparin has a direct effect on activated polymorphonuclear leukocytes (PMNLs, changing their activation state, and can explain its anti-inflammatory effect. To test our hypothesis, we designed both in vitro and ex vivo studies to elucidate the mechanism by which heparin modulates PMNL functions and therefore the inflammatory response. We specifically tested the hypothesis that priming of PMNLs renders them more susceptible to heparin. Amplified levels of CD11b and increased rate of superoxide release manifested PMNL priming. Increase in cell priming resulted in a dose-dependent increase in heparin binding to PMNLs followed by augmented apoptosis. Blocking antibodies to CD11b inhibited heparin binding and abolished the apoptotic response. Moreover, heparin caused a significant dose-dependent decrease in the rate of superoxide release from PMNLs, which was blunted by blocking antibodies to CD11b. Altogether, this study shows that the interaction of heparin with the PMNL CD11b results in cell apoptosis and explains heparin’s anti-inflammatory effects.

Heparin-based hydrogels with tunable sulfation & degradation for anti-inflammatory small molecule delivery.

Science.gov (United States)

Peng, Yifeng; Tellier, Liane E; Temenoff, Johnna S

2016-08-16

Sustained release of anti-inflammatory agents remains challenging for small molecule drugs due to their low molecular weight and hydrophobicity. Therefore, the goal of this study was to control the release of a small molecule anti-inflammatory agent, crystal violet (CV), from hydrogels fabricated with heparin, a highly sulfated glycosaminoglycan capable of binding positively-charged molecules such as CV. In this system, both electrostatic interactions between heparin and CV and hydrogel degradation were tuned simultaneously by varying the level of heparin sulfation and varying the amount of dithiothreitol within hydrogels, respectively. It was found that heparin sulfation significantly affected CV release, whereby more sulfated heparin hydrogels (Hep and Hep(-N)) released CV with near zero-order release kinetics (R-squared values between 0.96-0.99). Furthermore, CV was released more quickly from fast-degrading hydrogels than slow-degrading hydrogels, providing a method to tune total CV release between 5-15 days while maintaining linear release kinetics. In particular, N-desulfated heparin hydrogels exhibited efficient CV loading (∼90% of originally included CV), near zero-order CV release kinetics, and maintenance of CV bioactivity after release, making this hydrogel formulation a promising CV delivery vehicle for a wide range of inflammatory diseases.

Morbidity associated with heparin therapy in spinal surgery patients with cardiovascular diseases

International Nuclear Information System (INIS)

Sawakami, Kimihiko; Ishikawa, Seiichi; Ito, Takui

2011-01-01

The objectives of this study were to investigate morbidity associated with heparin therapy in spinal surgery patients. The management of patients on anticoagulant therapy who undergo spinal surgery is becoming a common clinical problem. Although guidelines for the management of gastrointestinal endoscopy patients on heparin therapy have been published, spinal surgery may lead to specific complications, especially because of heparin therapy. However, only few studies have examined the clinical significance of heparin therapy in spinal surgery patients. The subjects of this study were 116 consecutive patients who were on anticoagulant or antiplatelet therapy. This says that all of the patients were receiving heparin or another anticoagunt. The patients were divided into 2 groups: a group that received heparin therapy before and after surgery (H group, n=25) and a group that did not receive heparin therapy (NH group, n=91). The results of clinical examinations and magnetic resonance imaging (MRI) in the 2 groups were compared. There were no significant differences between the 2 groups in baseline data. Comorbidities in both groups included valvular heart disease, atrial fibrillation, angina pectoris/myocardial infarction, and cerebral infarction. Mean intraoperative and postoperative blood loss in the H group were 324 ml and 536 ml, respectively, and the corresponding values in the NH group were 431 ml and 449 ml, respectively. MRI of all patients was performed within 10 days after surgery and T2-weighted images in the axial plane were examined for evidence of an epidural hematoma. Although the proportion of patients with an epidural hematoma, detected by MRI was higher in the H group than in the NH group (71% vs. 64%), none of the patients in either group required revision surgery because of intolerable pain or muscle weakness. Thrombocytopenia and skin necrosis were observed as complications of the heparin therapy in 1 patient in the H group (4%). The rate of

How much heparin do we really need to go on pump? A rethink of current practices.

LENUS (Irish Health Repository)

Shuhaibar, M N

2012-02-03

OBJECTIVES: Patients undergoing myocardial revascularisation using extracorporeal circulation require heparin anticoagulation. We aimed to evaluate the effect of reducing heparin dosage on target activated clotting time (ACT) and postoperative blood loss. METHODS: In a prospective randomised trial, 195 patients undergoing isolated primary CABG were randomised into four groups A, B, C, and D receiving an initial heparin dosage of 100, 200, 250 and 300 iu\\/kg, respectively. Extra incremental heparin (50 iu\\/kg) was added if required to achieve a target ACT of 480 s before initiating cardiopulmonary bypass. Postoperative blood loss was measured from the time of heparin reversal to drain removal 24h later. RESULTS: Target ACT was achieved in 0, 63, 68.3 and 82.4% of patients in groups A, B, C and D, respectively, after the initial dose of heparin. In group B, of those not achieving target act a single increment of heparin was sufficient to achieve target ACT in further 18.6%. The mean ACT after the initial dose in groups B, C and D was 482.9, 519 and 588 s, respectively (P<0.05). Postoperative blood loss in millilitre per kilogram was directly proportional to preoperative heparin dose. CONCLUSIONS: Patients receiving lower dose of heparin has lower postoperative blood loss. Of those achieving the target ACT, group B was significantly the closest to the target ACT. A starting dose of 200 iu\\/kg of heparin and if necessary one 50 iu\\/kg increment achieved target ACT in 81.5% of patients. The added benefit of significant drop in postoperative blood loss is evident.

The Effect of Low Molecular Weight Heparins on Fracture Healing.

Science.gov (United States)

Kapetanakis, Stylianos; Nastoulis, Evangelos; Demesticha, Theano; Demetriou, Thespis

2015-01-01

Venous Thromboembolism is a serious complication in the trauma patient. The most commonly studied and used anticoagulant treatment in prophylaxis of thrombosis is heparin. The prolonged use of unfractionated heparin has been connected with increased incidence of osteoporotic fractures. Low molecular-weight-heparins (LMWHs) have been the golden rule in antithrombotic therapy during the previous two decades as a way to overcome the major drawbacks of unfractioned heparin. However there are few studies reporting the effects of LMWHs on bone repair after fractures. This review presents the studies about the effects of LMWHs on bone biology (bone cells and bone metabolism) and underlying the mechanisms by which LMWHs may impair fracture healing process. The authors' research based on literature concluded that there are no facts and statistics for the role of LMWHs on fracture healing process in humans and the main body of evidence of their role comes from in vitro and animal studies. Further large clinical studies designed to compare different types of LMWHs, in different dosages and in different patient or animal models are needed for exploring the effects of LMWHs on fracture healing process.

Heparin-Induced Cardiac Tamponade and Life-Threatening Hyperkalemia in a Patient with Chronic Hemodialysis

Directory of Open Access Journals (Sweden)

Ho-Ming Su

2005-03-01

Full Text Available Heparin, a commonly used anticoagulant agent, is frequently used in patients undergoing hemodialysis. As with most medications, heparin has a significant side effect profile. Two of its most important side effects, major bleeding and hyperkalemia, may be devastating without immediate diagnosis and treatment. Major bleeding such as gastrointestinal, genitourinary or intracranial bleeding is occasionally encountered and rarely neglected. However, heparin-induced cardiac tamponade is rarely encountered and may be easily overlooked. Another side effect, heparin-induced hyperkalemia, an unusual but well-described side effect, is frequently forgotten until life-threatening arrhythmia has occurred. We report a case involving a 40-year-old male patient with uremia, who had received heparin for 10 days for deep vein thrombosis in the left lower extremity. Hemopericardium with cardiac tamponade and life-threatening hyperkalemia were both noted in this patient.

Locke and botany.

Science.gov (United States)

Anstey, Peter R; Harris, Stephen A

2006-06-01

This paper argues that the English philosopher John Locke, who has normally been thought to have had only an amateurish interest in botany, was far more involved in the botanical science of his day than has previously been known. Through the presentation of new evidence deriving from Locke's own herbarium, his manuscript notes, journal and correspondence, it is established that Locke made a modest contribution to early modern botany. It is shown that Locke had close and ongoing relations with the Bobarts, keepers of the Oxford Botanic Garden, and that Locke distributed seeds and plant parts to other botanists, seeds of which the progeny almost certainly ended up in the most important herbaria of the period. Furthermore, it is claimed that the depth of Locke's interest in and practice of botany has a direct bearing on our understanding of his views on the correct method of natural philosophy and on the interpretation of his well known discussion of the nature of species in Book III of his Essay concerning human understanding.

Effects of heparin on platelet aggregation and release and thromboxane A2 production

International Nuclear Information System (INIS)

Mohammad, S.F.; Anderson, W.H.; Smith, J.B.; Chuang, H.Y.; Mason, R.G.

1981-01-01

Heparin, when added to citrated platelet-rich plasma (PRP), caused potentiation of platelet aggregation and the release reaction induced by the aggregating agents adenosine diphosphate (ADP), arachidonic acid, collagen, and epinephrine. At low concentrations (4.7 x 10(-5) M) arachidonic acid failed to cause aggregation of platelets in citrated PRP. However, in the presence of heparin, the same concentration of arachidonic acid caused aggregation. Examination of PRP for the presence of thromboxane A2 (TxA2) by use of a bioassay revealed that heparin also stimulated release of TxA2. This finding indicated that platelets released more TxA2 when they were challenged by low concentrations of arachidonic acid in the presence of heparin than in its absence. Platelets were labeled with 3 H-arachidonic acid and 14 C-serotonin, and attempts were made to determine whether heparin stimulated the platelet release reaction first with subsequent increased production of TxA2, or alternatively, whether heparin stimulated TxA2 production first with subsequent enhancement of the release reaction. In view of the demonstrated simultaneous release of 14 C-serotonin and 3 H-arachidonic acid metabolites, it appeared that either release of 14 C and 3 H occurs concurrently or, even if one of these events is dependent on the other, both events take place in rapid succession. Timed sequential studies revealed that in the presence of arachidonic acid, the addition of heparin hastened the apparently simultaneous release of both 14 C and 3 H

Increased accuracy in heparin and protamine administration decreases bleeding: a pilot study

DEFF Research Database (Denmark)

Runge, Marx; Møller, Christian H; Steinbrüchel, Daniel A

2009-01-01

Three to 5 percent of the patients undergoing cardiac surgery are reoperated because of bleeding. When a surgical cause can be excluded, heparin/protamine mismatch may be considered. Insufficient reversal of heparin and overdosing of protamine may cause postoperative bleeding. The purpose......). A reduced number of patients needed blood transfusions in the RxDx group, although this was not statistically significant (19% vs. 38%, respectively; p = .13). Initial heparin dose was significantly reduced in the RxDx group (250 mg; range, 100-375 mg) compared with the control group (300 mg; range, 200...

The locking and unlocking thresholds for tearing modes in a cylindrical tokamak

Energy Technology Data Exchange (ETDEWEB)

Huang, Wenlong [CAS Key Laboratory of Geospace Environment and Department of Modern Physics, University of Science and Technology of China, Hefei, Anhui 230026 (China); Zhu, Ping, E-mail: pzhu@ustc.edu.cn [CAS Key Laboratory of Geospace Environment and Department of Modern Physics, University of Science and Technology of China, Hefei, Anhui 230026 (China); Department of Engineering Physics, University of Wisconsin-Madison, Madison, Wisconsin 53706 (United States)

2016-03-15

The locking and unlocking thresholds for tearing modes are in general different. In this work, the physics origin for this difference is illustrated from theory analysis, and a numerical procedure is developed to find both locking and unlocking thresholds. In particular, a new scaling law for the unlocking threshold that is valid in both weak and strong rotation regimes has been derived from the lowest amplitude of the RMP (resonant magnetic perturbation) allowed for the locked-mode solution. Above the unlocking threshold, the criterion for the phase-flip instability is extended to identify the entire locked-mode states. Two different regimes of the RMP amplitude in terms of the accessibility of the locked-mode states have been found. In the first regime, the locked-mode state may or may not be accessible depending on the initial conditions of an evolving island. In the second regime, the locked-mode state can always be reached regardless of the initial conditions of the tearing mode. The lowest RMP amplitude for the second regime is determined to be the mode-locking threshold. The different characteristics of the two regimes above the unlocking threshold reveal the underlying physics for the gap between the locking and unlocking thresholds and provide an explanation for the closely related and widely observed hysteresis phenomena in island evolution during the sweeping process of the RMP amplitude up and down across that threshold gap.

Elimination of heparin interference during microarray processing of fresh and biobank-archived blood samples.

Science.gov (United States)

Hebels, Dennie G A J; van Herwijnen, Marcel H M; Brauers, Karen J J; de Kok, Theo M C M; Chalkiadaki, Georgia; Kyrtopoulos, Soterios A; Kleinjans, Jos C S

2014-07-01

In the context of environmental health research, biobank blood samples have recently been identified as suitable for high-throughput omics analyses enabling the identification of new biomarkers of exposure and disease. However, blood samples containing the anti-coagulant heparin could complicate transcriptomic analysis because heparin may inhibit RNA polymerase causing inefficient cRNA synthesis and fluorophore labelling. We investigated the inhibitory effect of heparin and the influence of storage conditions (0 or 3 hr bench times, storage at room temperature or -80°C) on fluorophore labelling in heparinized fresh human buffy coat and whole blood biobank samples during the mRNA work-up protocol for microarray analysis. Subsequently, we removed heparin by lithium chloride (LiCl) treatment and performed a quality control analysis of LiCl-treated biobank sample microarrays to prove their suitability for downstream data analysis. Both fresh and biobank samples experienced varying degrees of heparin-induced inhibition of fluorophore labelling, making most samples unusable for microarray analysis. RNA derived from EDTA and citrate blood was not inhibited. No effect of bench time was observed but room temperature storage gave slightly better results. Strong correlations were observed between original blood sample RNA yield and the amount of synthesized cRNA. LiCl treatment restored sample quality to normal standards in both fresh and biobank samples and the previously identified correlations disappeared. Microarrays hybridized with LiCl-treated biobank samples were of excellent quality with no identifiable influence of heparin. We conclude that, to obtain high quality results, in most cases heparin removal is essential in blood-derived RNA samples intended for microarray analysis. Copyright © 2014 Wiley Periodicals, Inc.

Innovation and Lock-in

DEFF Research Database (Denmark)

Cantner, Uwe; Vannuccini, Simone

2016-01-01

This study focuses on a well-known but yet elusive concept: (technological) lock-in. We summarize what is known about the nature of lock-in and offer a critical view on history-dependent processes based on recent contributions to the literature. We discuss if lock-ins are really inescapable......, especially when innovation is concerned. Also, we address the question if lock-in is a well-defined concept at all. To offer a fresh view on lock-in and to tackle the issues just raised, we employ the replicator dynamics model. By making a parallel between monopolization in the replicator dynamics...... and the occurrence of lock-ins, we show that the convergence of a system to a given outcome can be reversed, under certain conditions. We highlight the need for a more precise demarcation of the conceptual boundaries of lock-in and path dependence, both from the formal and the empirical side, and suggest...

Investigation of a Potential Protective Mechanism Against Heparin-Induced Thrombocytopenia in Patients on Chronic Intermittent Hemodialysis

Science.gov (United States)

Tanhehco, Yvette C.; Cuker, Adam; Rudnick, Michael; Sachais, Bruce S.

2015-01-01

BACKGROUND Heparin-induced thrombocytopenia (HIT) develops as a result of platelet (PLT) activation by anti-platelet factor 4 (PF4)/heparin complex antibodies. Despite repeated exposure to heparin, patients undergoing chronic intermittent hemodialysis (HD) rarely develop HIT. We investigated the possibility that HD decreases/removes PF4 from PLT surfaces and/or plasma, thereby disfavoring immune complex formation as a mechanism of protection against HIT. MATERIALS AND METHODS We enrolled 20 patients undergoing chronic HD at the Penn Presbyterian Medical Center. Blood samples were drawn before, during and after treatment in the presence and absence of heparin. PF4, PF4/heparin antibody, heparin, and P-selectin levels were measured. RESULTS No patients demonstrated clinical symptoms of HIT. PLT surface PF4 levels decreased and plasma PF4 levels increased concurrently with increase in plasma heparin concentration. In the absence of heparin, PLT surface and plasma PF4 levels were unchanged. Anti-PF4/heparin antibodies, which were non-functional by the serotonin release assay, were detectable in 8 patients. PLT surface P-selectin levels did not change during treatment. CONCLUSIONS Removal of PLT surface and/or plasma PF4 as a mechanism of protection against HIT in patients undergoing HD is not supported by the results of our study, although the transient decrease in PLT surface PF4 in the presence of large amounts of heparin remains a candidate mechanism. The small sample size, single type of dialyzer membrane, and early sampling time points may have led to the inability to detect changes in PF4 levels. Future studies should explore other potential protective mechanisms. PMID:23305841

Relationship of nonreturn rates of dairy bulls to binding affinity of heparin to sperm

International Nuclear Information System (INIS)

Marks, J.L.; Ax, R.L.

1985-01-01

The binding of the glycosaminoglycan [ 3 H] heparin to bull spermatozoa was compared with nonreturn rates of dairy bulls. Semen samples from five bulls above and five below an average 71% nonreturn rate were used. Samples consisted of first and second ejaculates on a single day collected 1 d/wk for up to 5 consecutive wk. Saturation binding assays using [ 3 H] heparin were performed to quantitate the binding characteristics of each sample. Scatchard plot analyses indicated a significant difference in the binding affinity for [ 3 H] heparin between bulls of high and low fertility. Dissociation constants were 69.0 and 119.3 pmol for bulls of high and low fertility, respectively. In contrast, the number of binding sites for [ 3 H] heparin did not differ significantly among bulls. Differences in binding affinity of [ 3 H] heparin to bull sperm might be used to predict relative fertility of dairy bulls

Simple and Efficient Purification of Recombinant Proteins Using the Heparin-Binding Affinity Tag.

Science.gov (United States)

Jayanthi, Srinivas; Gundampati, Ravi Kumar; Kumar, Thallapuranam Krishnaswamy Suresh

2017-11-01

Heparin, a member of the glycosaminoglycan family, is known to interact with more than 400 different types of proteins. For the past few decades, significant progress has been made to understand the molecular details involved in heparin-protein interactions. Based on the structural knowledge available from the FGF1-heparin interaction studies, we have designed a novel heparin-binding peptide (HBP) affinity tag that can be used for the simple, efficient, and cost-effective purification of recombinant proteins of interest. HBP-tagged fusion proteins can be purified by heparin Sepharose affinity chromatography using a simple sodium chloride gradient to elute the bound fusion protein. In addition, owing to the high density of positive charges on the HBP tag, recombinant target proteins are preferably expressed in their soluble forms. The purification of HBP-fusion proteins can also be achieved in the presence of chemical denaturants, including urea. Additionally, polyclonal antibodies raised against the affinity tag can be used to detect HBP-fused target proteins with high sensitivity. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

Preparation and characterization of chitosan-heparin composite matrices for blood contacting tissue engineering

International Nuclear Information System (INIS)

He Qing; Gong Kai; Gong Yandao; Zhang Xiufang; Ao Qiang; Zhang Lihai; Hu Min

2010-01-01

Chitosan has been widely used for biomaterial scaffolds in tissue engineering because of its good mechanical properties and cytocompatibility. However, the poor blood compatibility of chitosan has greatly limited its biomedical utilization, especially for blood contacting tissue engineering. In this study, we exploited a polymer blending procedure to heparinize the chitosan material under simple and mild conditions to improve its antithrombogenic property. By an optimized procedure, a macroscopically homogeneous chitosan-heparin (Chi-Hep) blended suspension was obtained, with which Chi-Hep composite films and porous scaffolds were fabricated. X-ray photoelectron spectroscopy and sulfur elemental analysis confirmed the successful immobilization of heparin in the composite matrices (i.e. films and porous scaffolds). Toluidine blue staining indicated that heparin was distributed homogeneously in the composite matrices. Only a small amount of heparin was released from the matrices during incubation in normal saline for 10 days. The composite matrices showed improved blood compatibility, as well as good mechanical properties and endothelial cell compatibility. These results suggest that the Chi-Hep composite matrices are promising candidates for blood contacting tissue engineering.

Laboratory tests for identification or exclusion of heparin induced thrombocytopenia: HIT or miss?

Science.gov (United States)

Favaloro, Emmanuel J

2018-02-01

Heparin induced thrombocytopenia (HIT) is a potentially fatal condition that arises subsequent to formation of antibodies against complexes containing heparin, usually platelet-factor 4-heparin ("anti-PF4-heparin"). Assessment for HIT involves both clinical evaluation and, if indicated, laboratory testing for confirmation or exclusion, typically using an initial immunological assay ("screening"), and only if positive, a secondary functional assay for confirmation. Many different immunological and functional assays have been developed. The most common contemporary immunological assays comprise enzyme-linked immunosorbent assay [ELISA], chemiluminescence, lateral flow, and particle gel techniques. The most common functional assays measure platelet aggregation or platelet activation events (e.g., serotonin release assay; heparin-induced platelet activation (HIPA); flow cytometry). All assays have some sensitivity and specificity to HIT antibodies, but differ in terms of relative sensitivity and specificity for pathological HIT, as well as false negative and false positive error rate. This brief article overviews the different available laboratory methods, as well as providing a suggested approach to diagnosis or exclusion of HIT. © 2017 Wiley Periodicals, Inc.

Heparin-Induced Thrombocytopenia in a Patient with Essential Thrombocythemia: A Case Based Update

Directory of Open Access Journals (Sweden)

Edva Noel

2015-01-01

Full Text Available Vascular thrombosis is a common clinical feature of both essential thrombocythemia (ET and heparin-induced thrombocytopenia (HIT. The development of HIT in a patient with ET is rare and underrecognized. We report the case of a 77-year-old woman with preexisting ET, who was admitted with acute coronary syndrome, and IV heparin was started. She was exposed to unfractionated heparin (UFH 5 days prior to this admission. Decrease in platelet count was noted, and HIT panel was sent. Heparin was discontinued. Patient developed atrial fibrillation, and Dabigatran was started. On day three, patient also developed multiple tiny cerebral infarctions and acute right popliteal DVT. On day ten of admission, HIT panel was positive, and Dabigatran was changed to Lepirudin. Two days later, Lepirudin was also discontinued because patient developed pseudoaneurysm on the right common femoral artery at the site of cardiac catheterization access. A progressive increase in the platelet count was noted after discontinuing heparin. Physicians should be aware of the coexistence of HIT and ET, accompanied challenges of the prompt diagnosis, and initiation of appropriate treatment.

Comparing the Overhead of Lock-based and Lock-free Implementations of Priority Queues

DEFF Research Database (Denmark)

Passas, Stavros; Karlsson, Sven

2011-01-01

. In this paper, we compare a lock-free implementation of a priority queue with a lock-based implementation. We perform experiments with processors of different generations and observe large performance differences for lock-free data structures depending on the processor generation. The lock-free implementation...... performs much better on the most recent processor generation. We investigate this performance trend, using a set of micro-benchmarks and show a significant difference in the overhead of atomic operations between processor generations. The lock-free implementation executes approximately three times as many...

Naked eye detection of infertility based on sperm protamine-induced aggregation of heparin gold nanoparticles.

Science.gov (United States)

Vidya, Raj; Saji, Alex

2018-05-01

The development of an easy to use, one-pot, environmentally friendly, non-invasive and label-free colorimetric probe for the determination of semen protamines, the biochemical marker of male fertility, using heparin gold nanoparticles (HAuNPs) is presented. The affinity of HAuNPs for protamines was due to the electrostatic interactions between polycationic protamine and polyanionic heparin. The binding of HAuNPs to protamine was characterized by variation in the plasmon absorption spectra followed by a visibly observable colour change of the solution from red to blue. We observed a red shift in the plasmon peak and the method exhibited linearity in the range of 10-70 ng/mL with a detection limit of 5 ng/mL, which is much lower than that reported for colorimetric sensors of protamine. The colour change and the variation in the absorbance of HAuNPs were highly specific for protamines in the presence of different interfering compounds and the method was successfully applied for determining protamine in real samples of semen and serum. Rather than a quantitative estimation, it seems that the method provides a quick screening between a large array of positive and negative samples and, moreover, it maintains the privacy of the user. The method appears to be simple and would be very useful in third-world countries where high-tech diagnostic aids are inaccessible to the majority of the population. Graphical Abstract Heparin gold nanoparticles aided visual detection of infertility.

Heparin interferes with the radioenzymatic and homogeneous enzyme immunoassays for aminoglycosides

International Nuclear Information System (INIS)

Krogstad, D.J.; Granich, G.G.; Murray, P.R.; Pfaller, M.A.; Valdes, R.

1981-01-01

Heparin interferes with measurement of aminoglycosides in serum by biological, radioenzymatic, and homogeneous enzyme immunoassay techniques, but not with radioimmunoassay. At concentrations greater than or equal to 10 5 and greater than or equal to 3 X 10 6 USP units/L, respectively, it interferes with the radioenzymatic assay by inhibiting the gentamicin 3-acetyltransferase and kanamycin 6'-acetyltransferase enzymes used in the assay. It interferes with the homogeneous enzyme immunoassays for gentamicin and tobramycin (at concentrations greater than or equal to 10 5 and greater than or equal to10 4 USP units/L, respectively), but not with the commercially available homogeneous enzyme immunoassays for other drugs. Heparin interference with the homogeneous enzyme immunoassay for aminoglycosides requires both the heparin polyanion and glucose-6-phosphate dehydrogenase bound to a cationic aminoglycoside. This interference can be reproduced with dextran sulfate (but not dextran), and does not occur with free enzyme (glucose-6-phosphate dehydrogenase) alone. Heparin interference with these two assays and at concentrations that may be present in intravenous infusions or in seriously underfilled blood-collection tubes is described

Prevention of equine herpesvirus myeloencephalopathy - Is heparin a novel option? A case report.

Science.gov (United States)

Walter, Jasmin; Seeh, Christoph; Fey, Kerstin; Bleul, Ulrich; Osterrieder, Nikolaus

2016-10-12

Equine herpesvirus myeloencephalopathy (EHM) is a severe manifestation of equine herpesvirus 1 (EHV-1) infection. Prevention and treatment of EHM during EHV-1 outbreaks is critical, but no reliable and tested specific medication is available. Due to the thromboischemic nature of EHM and due to the fact that EHV-1 entry in cells is blocked by heparin, it was hypothesized that this compound may be useful in reduction of EHM incidence and severity. Therefore, during an acute EHV-1 outbreak with the neuropathogenic G 2254 /D 752 Pol variant, metaphylactic treatment with heparin to prevent EHM was initiated. Clinical signs were present in 61 horses (fever n = 55; EHM n = 8; abortion n = 6). Heparin (25000 IU subcutaneously twice daily for 3 days) was given to 31 febrile horses from day 10 of the outbreak, while the first 30 horses exhibiting fever remained untreated. Treatment outcome was analyzed retrospectively. Heparin-treated horses showed a lower EHM incidence (1/31; 3.2%) than untreated horses (7/30; 23.3%; p = 0.03). Results indicate that heparin may be useful for prevention of EHM during an EHV-1 outbreak. These promising data highlight the need for randomized and possibly blinded studies for the use of heparin in EHV-1 outbreaks.

Preparation of Low Molecular Weight Heparin by Microwave Discharge Electrodeless Lamp/TiO2 Photo-Catalytic Reaction.

Science.gov (United States)

Lee, Do-Jin; Kim, Byung Hoon; Kim, Sun-Jae; Kim, Jung-Sik; Lee, Heon; Jung, Sang-Chul

2015-01-01

An MDEL/TiO2 photo-catalyst hybrid system was applied, for the first time, for the production of low molecular weight heparin. The molecular weight of produed heparin decreased with increasing microwave intensity and treatment time. The abscission of the chemical bonds between the constituents of heparin by photo-catalytic reaction did not alter the characteristics of heparin. Formation of by-products due to side reaction was not observed. It is suggested that heparin was depolymerized by active oxygen radicals produced during the MDEL/TiO2 photo-chemical reaction.

Cost-utility of enoxaparin compared with unfractionated heparin in unstable coronary artery disease

Directory of Open Access Journals (Sweden)

Milne Ruairidh

2001-10-01

Full Text Available Abstract Background Low molecular weight heparins hold several advantages over unfractionated heparin including convenience of administration. Enoxaparin is one such heparin licensed in the UK for use in unstable coronary artery disease (unstable stable angina and non-Q wave myocardial infarction. In these patients, two large randomised controlled trials and their meta-analysis showed small benefits for enoxaparin over unfractionated heparin at 30–43 days and potentially at one year. We found no relevant published full economic evaluations, only cost studies, one of which was conducted in the UK. The other studies, from the US, Canada and France, are difficult to interpret since their resource use and costs may not reflect UK practice. Methods We aimed to compare the benefits and costs of short-term treatment (two to eight days with enoxaparin and unfractionated heparin in unstable coronary artery disease. We used published data sources to estimate the incremental cost per quality adjusted life year (QALY, adopting a NHS perspective and using 1998 prices. Results The base case was a 0.013 QALY gain and net cost saving of £317 per person treated with enoxaparin instead of unfractionated heparin. All but one sensitivity analysis showed net savings and QALY gains, the exception (the worst case being a cost per QALY of £3,305. Best cases were a £495 saving and 0.013 QALY gain, or a £317 saving and 0.014 QALY gain per person. Conclusions Enoxaparin appears cost saving compared with unfractionated heparin in patients with unstable coronary artery disease. However, cost implications depend on local revascularisation practice.

Heparan sulfate C5-epimerase is essential for heparin biosynthesis in mast cells.

Science.gov (United States)

Feyerabend, Thorsten B; Li, Jin-Ping; Lindahl, Ulf; Rodewald, Hans-Reimer

2006-04-01

Biosynthesis of heparin, a mast cell-derived glycosaminoglycan with widespread importance in medicine, has not been fully elucidated. In biosynthesis of heparan sulfate (HS), a structurally related polysaccharide, HS glucuronyl C5-epimerase (Hsepi) converts D-glucuronic acid (GlcA) to L-iduronic acid (IdoA) residues. We have generated Hsepi-null mouse mutant mast cells, and we show that the same enzyme catalyzes the generation of IdoA in heparin and that 'heparin' lacking IdoA shows a distorted O-sulfation pattern.

Heparin-induced increase in serum levels of aminotranferases. A controlled clinical trial.

Science.gov (United States)

Nielsen, H K; Husted, S E; Koopmann, H D; Fasting, H; Simonsen, O; Andersen, K; Husegaard, H C; Petersen, T K

1984-01-01

Sixty-four patients over the age of 40 years, undergoing elective surgery of at least one hour's duration, were randomized to treatment with either a thromboembolic deterrent ( TED ) stocking (Kendall Co.) or subcutaneous low-dose heparin 5 000 IU every 12 hours. Serum levels of alanine aminotransferase (S-ALAT), aspartate aminotransferase (S-ASAT), gamma-glutamyl transpeptidase (S-gamma-GT) and alkaline phosphatase (S-ALP) were measured. S-ALAT increased significantly on the 5th and 10th postoperative day, from 27 +/- 2 (x +/- SE) to 40 +/- 4 (p less than 0.01) and 55 +/- 7 U/l (p less than 0.001), respectively, in the heparin group and was significantly higher in the heparin than in the TED group both on the 5th (p less than 0.01) and 10th (p less than 0.05) postoperative day. S-ASAT and S-gamma-GT increased significantly during heparin treatment, but did not differ significantly from the values of the TED group. No change in S-ALP was registered in either group. It is concluded that prophylactic treatment with low-dose heparin induces a significant increase in S-aminotransferase levels, especially in S-ALAT. The phenomenon has profound differential diagnostic implications in conditions such as pulmonary embolism and acute myocardial infarction.

[Heparin-induced thrombocytopenia developed during the acute phase after left upper lobectomy for lung cancer].

Science.gov (United States)

Mitomo, Hideki; Miyamoto, Akira; Tabata, Toshiharu; Sugawara, Takafumi; Yabuki, Hiroshi; Fujimura, Shigefumi

2014-12-01

Heparin-induced thrombocytopenia (HIT) is a serious adverse effect of heparin administration. This must not be rarely encountered but is not often reported in Japan compared to Western countries. A 68-year-old woman underwent left upper lobectomy for lung cancer. Low-dose unfractionated heparin was administrated to prevent thromboembolism after the operation. Two days later, sudden dyspnea appeared and ultracardiosonography showing an extensive thromboembolus from the main trunk to both main branches of pulmonary artery indicated pulmonary embolization. After the establishment of percutaneous cardiopulmonary support (PCPS) support, the embolus was removed by emergent open heart surgery. However, despite further unfractionated heparin administration following embolization surgery, other thrombus was identified in both the bi-lateral internal jagular veins and inferior vena cava by ultrasonography and contrast computed tomography( CT). Her platelet count was decreased gradually despite platelet transfusion. Plate factor 4( PF4) antibody against heparin in her blood examination was found, and HIT II was diagnosed. Discontinuation of unfractionated heparin and administration of antithrombin agent improved platelet count, and no additional embolization was identified.

Outdraft at Lock Approach, Tom Bevill Lock and Dam, Alabama: Hydraulic Model Investigation

National Research Council Canada - National Science Library

Lynch, Gary

2001-01-01

.... The lock is connected to the dam with a 150-ft abutment wall. A strong crosscurrent or outdraft existing in and around the upstream lock entrance causes difficulty for tow traffic navigating the lock...

Alternative method for determination of contaminated heparin using chiral recognition.

Science.gov (United States)

Szekely, J; Collins, M; Currie, C A

2014-05-15

Since 2008 a significant amount of work has focused on the development of methods to analyze contaminated heparin. This work focuses on utilizing heparin's ability to serve as a chiral selector as a means for determining contamination. Specifically, the effect of contamination on the separation of pheniramine and chloroquine enantiomers was explored. Separations were conducted using heparin contaminated with chondroitin sulfate at varying levels. For each pair of enantiomers, electrophoretic mobility and resolution were calculated. For pheniramine enantiomers, an increase in contamination leads to a decrease in the electrophoretic mobility and resolution. A linear relationship between contamination level and electrophoretic mobility of the pheniramine enantiomers was observed for the entire contamination range. A linear relationship was also found between contamination level and resolution of the enantiomers between 0 and 70 percent contamination. For the separation of chloroquine enantiomers, it was found that at low levels of contamination, the resolution of enantiomers was increased due to the secondary interaction between the chloroquine enantiomers and the chondroitin sulfate. Results of this study illustrate the potential of using chiral recognition as a means to determine heparin contamination as well as the improvement of the chiral resolution of chloroquine with the additional of low levels of chondroitin sulfate A. Copyright © 2014 Elsevier B.V. All rights reserved.

Preparation of tin -heparin complex to be applied for myocardial infarct diagnosis

International Nuclear Information System (INIS)

Badi, J. M.; Al-Azzawi, H. A.; Resen, H. M.; Abed, I. G.; Owiad, H.; Manji, A. N.

2012-12-01

Tin-heparin complex has been prepared (liquid form) to be labeled with technetium-99 can be applied for diagnosis of myocardial infarcts vascular diseases and deep vein thrombosis. The preparation contents are 0.1mg tin chloride dehydrate and 1250 1.U of heparin. The results of the pH effect on the labeling yield indicated that high percentage of labeling yield (96.1%) was obtained in the optimal pH (5.50). The obtained results showed that the quantity of reducing agent (tin chloride dehydrate) and chelating agent (heparin) has no effect on the labeling yield. Results of radio analytical studies by paper chromatography technique wear confirmed by data obtained by Gel chromatography column scanning techniques. These techniques showed the high labeling yield of the tin-heparin complex. The persistence of high labeling yield for 8 hours is a good indication for its stability and efficiency for radio diagnosis examination in nuclear medicine centers. (Author)

Improved assay for measuring heparin binding to bull sperm

International Nuclear Information System (INIS)

Miller, D.J.; Ax, R.L.

1988-01-01

The binding of heparin to sperm has been used to study capacitation and to rank relative fertility of bulls. Previous binding assays were laborious, used 10 7 sperm per assay point, and required large amounts of radiolabeled heparin. A modified heparin-binding assay is described that used only 5 x 10 4 cells per incubation well and required reduced amounts of [ 3 H] heparin. The assay was performed in 96-well Millititer plates, enabling easy incubation and filtering. Dissociation constants and concentrations of binding sites did not differ if analyzed by Scatchard plots, Woolf plots, or by log-logit transformed weighted nonlinear least squares regression, except in the case of outliers. In such cases, Scatchard analysis was more sensitive to outliers. Nonspecific binding was insignificant using nonlinear logistic fit regression and a proportion graph. The effects were tested of multiple free-thawing of sperm in either a commercial egg yolk extender, 40 mM Tris buffer with 8% glycerol, or 40 mM Tris buffer without glycerol. Freeze-thawing in extender did not affect the dissociation constant or the concentration of binding sites. However, freeze-thawing three times in 40 mM Tris reduced the concentration of binding sites and lowered the dissociation constant (raised the affinity). The inclusion of glycerol in the 40 mM Tris did not significantly affect the estimated dissociation constant or the concentration of binding sites as compared to 40 mM Tris without glycerol

Constraint satisfaction problems with isolated solutions are hard

International Nuclear Information System (INIS)

Zdeborová, Lenka; Mézard, Marc

2008-01-01

We study the phase diagram and the algorithmic hardness of the random 'locked' constraint satisfaction problems, and compare them to the commonly studied 'non-locked' problems like satisfiability of Boolean formulae or graph coloring. The special property of the locked problems is that clusters of solutions are isolated points. This simplifies significantly the determination of the phase diagram, which makes the locked problems particularly appealing from the mathematical point of view. On the other hand, we show empirically that the clustered phase of these problems is extremely hard from the algorithmic point of view: the best known algorithms all fail to find solutions. Our results suggest that the easy/hard transition (for currently known algorithms) in the locked problems coincides with the clustering transition. These should thus be regarded as new benchmarks of really hard constraint satisfaction problems

Heparin binding domain of antithrombin III: Characterization using a synthetic peptide directed polyclonal antibody

International Nuclear Information System (INIS)

Smith, J.W.; Dey, B.; Knauer, D.J.

1990-01-01

Antithrombin III (ATIII) is a plasma-borne serine protease inhibitor that apparently forms covalent complexes with thrombin. The interaction between ATIII and thrombin is enhanced several thousandfold by the glycosaminoglycan, heparin. The authors have previously proposed that the heparin binding site of ATIII residues within a region extending from amino acid residues 114-156. Computer-assisted analysis of this region revealed the presence of a 22 amino acid domain (residues 124-145), part of which shows a strong potential for the formation of an amphipathic helix: hydrophobic on one face and highly positively charged on the other. In the presence studies, polyclonal antisera were generated against a synthetic peptide corresponding to residues 124-145 in native human ATIII. Affinity-purified IgG from these antisera, as well as monovalent Fab's derived from them, specifically blocked the binding of heparin to ATIII. Additionally, occupancy of the heparin binding site by these same monovalent and bivalent IgG's at least partially substituted for heparin, accelerating linkage formation between ATIII and thrombin. These results provide the first immunological evidence that region 124-145 is directly involved in the binding of heparin to ATIII and that an antibody-induced conformational change within this region can mediate ATIII activation

49 CFR 236.338 - Mechanical locking required in accordance with locking sheet and dog chart.

Science.gov (United States)

2010-10-01

... locking sheet and dog chart. 236.338 Section 236.338 Transportation Other Regulations Relating to... in accordance with locking sheet and dog chart. Mechanical locking shall be in accordance with locking sheet and dog chart currently in effect. ...

High-throughput differentiation of heparin from other glycosaminoglycans by pyrolysis mass spectrometry.

Science.gov (United States)

Nemes, Peter; Hoover, William J; Keire, David A

2013-08-06

Sensors with high chemical specificity and enhanced sample throughput are vital to screening food products and medical devices for chemical or biochemical contaminants that may pose a threat to public health. For example, the rapid detection of oversulfated chondroitin sulfate (OSCS) in heparin could prevent reoccurrence of heparin adulteration that caused hundreds of severe adverse events including deaths worldwide in 2007-2008. Here, rapid pyrolysis is integrated with direct analysis in real time (DART) mass spectrometry to rapidly screen major glycosaminoglycans, including heparin, chondroitin sulfate A, dermatan sulfate, and OSCS. The results demonstrate that, compared to traditional liquid chromatography-based analyses, pyrolysis mass spectrometry achieved at least 250-fold higher sample throughput and was compatible with samples volume-limited to about 300 nL. Pyrolysis yielded an abundance of fragment ions (e.g., 150 different m/z species), many of which were specific to the parent compound. Using multivariate and statistical data analysis models, these data enabled facile differentiation of the glycosaminoglycans with high throughput. After method development was completed, authentically contaminated samples obtained during the heparin crisis by the FDA were analyzed in a blinded manner for OSCS contamination. The lower limit of differentiation and detection were 0.1% (w/w) OSCS in heparin and 100 ng/μL (20 ng) OSCS in water, respectively. For quantitative purposes the linear dynamic range spanned approximately 3 orders of magnitude. Moreover, this chemical readout was successfully employed to find clues in the manufacturing history of the heparin samples that can be used for surveillance purposes. The presented technology and data analysis protocols are anticipated to be readily adaptable to other chemical and biochemical agents and volume-limited samples.

Isolation of RNA for dot hybridization by heparin-DNase I treatment of whole cell lysate.

Science.gov (United States)

Krawczyk, Z; Wu, C

1987-08-15

We have developed a new procedure for the rapid preparation of undegraded total RNA from cultured cells for specific quantitation by dot blotting analysis. Pelleted cells are resuspended in hypotonic solution containing a ribonuclease inhibitor and heparin and disrupted by freeze-thaw. Heparin is employed as an agent for nuclear lysis, dissociation of chromosomal protein, and release of mRNA from rough endoplasmic reticulum. We eliminate chromosomal DNA by digestion with DNase I and denature the RNA in the lysate with formaldehyde. After centrifugation to remove debris, the supernatant is used directly for dot blotting. All manipulations are performed in the same microfuge tube and recovery of RNA is quantitative. The procedure is especially useful for processing large numbers of samples. We illustrate its versatility by analysis of specific RNAs in Drosophila, rat, and human cell lines. In reconstruction experiments, less than 80 molecules per cell of a small RNA (beta-globin) can be detected under highly stringent hybridization conditions, using only moderately labeled double-stranded plasmid DNA probes and short film exposures.

Coexistence of Antiphospholipid Syndrome and Heparin-Induced Thrombocytopenia in a Patient with Recurrent Venous Thromboembolism

Directory of Open Access Journals (Sweden)

Samuel Adediran

2017-01-01

Full Text Available Heparin-induced thrombocytopenia (HIT is a prothrombotic adverse drug reaction in which heparin forms complexes with platelet factor 4 forming neoantigens that are recognized by autoantibodies. Antiphospholipid syndrome (APS is similar to HIT in that it is mediated by autoantibodies that are also prothrombotic. We present a case of rare coexistence of antiphospholipid antibody syndrome and heparin-induced thrombocytopenia.

In vitro effects of heparin and tissue factor pathway inhibitor on factor VII assays. possible implications for measurements in vivo after heparin therapy

DEFF Research Database (Denmark)

Bladbjerg, E-M; Larsen, L F; Ostergaard, P

2000-01-01

The coagulant activity of blood coagulation factor VII (FVII:C) can be lowered by changes in lifestyle and by therapeutic intervention, e.g. heparin infusion. The question is, however, whether FVII:C determined ex vivo is a valid measure of the FVII activity in vivo. We measured plasma FVII......:C, activated FVII (FVIIa), FVII protein (FVII:Ag), tissue factor pathway inhibitor (TFPI), triglycerides, and free fatty acids (FFA) before and 15 min after infusion of a bolus of unfractionated heparin (50 IU/kg body weight) in 12 healthy subjects. Additionally, we conducted in vitro experiments...

Air lock

International Nuclear Information System (INIS)

Palkovich, P.; Gruber, J.; Madlener, W.

1974-01-01

The patent refers to an air lock system preferably for nuclear stations for the transport of heavy loads by means of a trolley on rails. For opening and closing of the air lock parts of the rails are removed, e.g. by a second rail system perpendicular to the main rails. (P.K.)

N-acetyl-heparin attenuates acute lung injury caused by acid aspiration mainly by antagonizing histones in mice.

Science.gov (United States)

Zhang, Yanlin; Zhao, Zanmei; Guan, Li; Mao, Lijun; Li, Shuqiang; Guan, Xiaoxu; Chen, Ming; Guo, Lixia; Ding, Lihua; Cong, Cuicui; Wen, Tao; Zhao, Jinyuan

2014-01-01

Acute lung injury (ALI) is the leading cause of death in intensive care units. Extracellular histones have recently been recognized to be pivotal inflammatory mediators. Heparin and its derivatives can bind histones through electrostatic interaction. The purpose of this study was to investigate 1) the role of extracellular histones in the pathogenesis of ALI caused by acid aspiration and 2) whether N-acetyl-heparin (NAH) provides more protection than heparin against histones at the high dose. ALI was induced in mice via intratracheal instillation of hydrochloric acid (HCl). Lethality rate, blood gas, myeloperoxidase (MPO) activity, lung edema and pathological changes were used to evaluate the degree of ALI. Heparin/NAH was administered intraperitoneally, twice a day, for 3 days or until death. Acid aspiration caused an obvious increase in extracellular histones. A significant correlation existed between the concentration of HCl aspirated and the circulating histones. Heparin/NAH (10 mg/kg) improved the lethality rate, blood gas, MPO activity, lung edema and pathological score. At a dose of 20 mg/kg, NAH still provided protection, however heparin tended to aggravate the injury due to hemorrhagic complications. The specific interaction between heparin and histones was verified by the binding assay. In summary, high levels of extracellular histones can be pathogenic in ALI caused by acid aspiration. By neutralizing extracellular histones, heparin/NAH can offer similar protection at the moderate doses. At the high dose, NAH provides better protection than heparin.

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

International Nuclear Information System (INIS)

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

1987-01-01

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

Analytical characterization of heparin by capillary zone electrophoresis with conductivity detection and polymeric buffer additives.

Science.gov (United States)

Mikus, Peter; Valásková, Iva; Havránek, Emil

2004-11-15

A capillary zone electrophoresis (CZE) method for the analytical characterization of intact (high-molecular-weight) heparin was developed. For the first time, a hydrodynamically closed CZE separation system with conductivity detector was used for the separation, detection and quantitation of this highly sulfated, linear polysaccharide. Glycine (25mM) adjusted to pH 9.0 by bis-Tris-propane served as the running electrolyte system. Polymeric additives, polyvinylpyrrolidone (PVP), dextran (DEX), were used to improve the separation selectivity as they strongly retarded the heparin macromolecule while they did not practically influence comigrating inorganic anions. The proposed electrophoretic method was successfully validated. It was convenient for the sensitive, simple, rapid and reproducible assay of heparin in raw materials and isotonic saline. Here, the use of the conductivity detector was advantageous as it allowed heparin to be analyzed without a sample pretreatment. The CZE method should be an alternative to the pharmacopoeial conventional gel electrophoresis having used in the quality control of heparin so far. In addition, it should be convenient to quantitative estimation of heparin present in a preparation used, e.g., as the chiral selector in CE separations.

Heparin and insulin in the management of hypertriglyceridemia-associated pancreatitis: case series and literature review.

Science.gov (United States)

Kuchay, Mohammad Shafi; Farooqui, Khalid J; Bano, Tarannum; Khandelwal, Manoj; Gill, Harmandeep; Mithal, Ambrish

2017-01-01

Severe hypertriglyceridemia accounts for up to 7% of all cases of acute pancreatitis. Heparin and insulin activate lipoprotein lipase (LPL), thereby reducing plasma triglyceride levels. However, the safety and efficacy of heparin and insulin in the treatment of hypertriglyceridemia-associated acute pancreatitis have not been well established yet. We successfully used heparin and insulin as first-line therapy in four consecutive patients with acute pancreatitis secondary to hypertriglyceridemia. In a literature search, we revised almost all reports published to date of patients managed successfully with this combination. Heparin and insulin appear to be a safe, effective, and inexpensive first-line therapy for hypertriglyceridemia-associated acute pancreatitis.

Prevention of fatal postoperative pulmonary embolism by low doses of heparin. An international multicentre trial.

Science.gov (United States)

1975-07-12

The efficacy of low-dose heparin in preventing fatal postoperative pulmonary embolism has been investigated in a multicentre prospective randomised trial. 4121 patients over the age of forty years undergoing a variety of elective major surgical procedures were included in the trial; 2076 of these were in the control group and 2045 patients received heparin. The two groups were well matched for age, sex, weight, blood-group, and other factors which could predispose to the development of venous thromboembolism. 180 (4-4 %) patients died during the postoperative period, 100 in the control and 80 in the heparin group: 72% of deaths in the control and 66% in the heparin group had necropsy examination. 16 patients in the control group and 2 in the heparin group were found at necropsy to have died due to acute massive pulmonary embolism (P smaller than 0-005). In addition, emboli found at necropsy in 6 patients in the control group and 3 in the heparin group were considered either contributory to death or an incidental finding since death in these patients was attributed to other causes. Taking all pulmonary emboli together, the findings were again significant (P smaller than 0-005). Of 1292 patients in whom the 125-I-fibrinogen test was performed to detect deep-vein thrombosis (D.V.T.) 667 were in the control group and 625 in the heparin group. The frequency of isotopic D.V.T. was reduced from 24-6% in the control group 7-7% in the heparin group (P smaller 0-005). In 30 patients D.V.T. was detected at necropsy; 24 in the control and 6 in the heparin group (P smaller 0-005). 32 patients in the control group and 11 in the heparin group developed clinically diagnosed D.V.T. which was confirmed by venography (P smaller than 0-005). In addition, 24 patients in the control and 8 in the heparin group were treated for clinically suspected pulmonary emoblism. The difference in the number of patients requiring treatment for D.V.T. and/or pulmonary embolism in the two groups was

Bilateral adrenal haemorrhage associated with heparin-induced thrombocytopaenia during treatment of Fournier gangrene.

Science.gov (United States)

Tattersall, Timothy Lee; Thangasamy, Isaac A; Reynolds, Jamie

2014-10-14

We present a case of bilateral adrenal haemorrhage (BAH) associated with heparin-induced thrombocytopaenia (HIT) in a 61-year-old man admitted to hospital for the treatment of Fournier's gangrene. He presented to hospital with scrotal swelling and fever, and developed spreading erythaema and a gangrenous scrotum. His scrotum was surgically debrided and intravenous broad-spectrum antibiotics were administered. Unfractionated heparin was given postoperatively for venous thromboembolism prophylaxis. The patient deteriorated clinically 8-11 days postoperatively with delirium, chest pain and severe hypertension followed by hypotension and thrombocytopaenia. Abdominal CT scan revealed bilateral adrenal haemorrhage. Antibodies to the heparin-platelet factor 4 complex were present. HIT-associated BAH was diagnosed and heparin was discontinued. Intravenous bivalirudin and hydrocortisone were started, with rapid improvement in clinical status. BAH is a rare complication of HIT and should be considered in the postoperative patient with unexplained clinical deterioration. 2014 BMJ Publishing Group Ltd.

Subtle differences in commercial heparins can have serious consequences for cardiopulmonary bypass patients: A randomized controlled trial.

Science.gov (United States)

Arsenault, Kyle A; Paikin, Jeremy S; Hirsh, Jack; Dale, Brian; Whitlock, Richard P; Teoh, Kevin; Young, Ed; Ginsberg, Jeffrey S; Weitz, Jeffrey I; Eikelboom, John W

2012-10-01

To compare the potency, reversibility, and perioperative bleeding risk of Hepalean with those of PPC heparin. Because in vitro testing failed to detect differences in the potency or protamine reversibility of the 2 heparin preparations, we conducted a parallel group, single-center, double-blind, randomized, controlled trial to compare the anticoagulant effects of Hepalean to those of PPC heparin in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass. From June 1, 2011, to June 30, 2011, we randomly assigned 11 patients to receive PPC heparin and 10 to receive Hepalean. Despite similar initial doses of heparin, the median initial activated clotting time was numerically lower in the PPC heparin group than in the Hepalean group (median, 516.0 seconds; interquartile range, 481.0-633.0; vs median, 584.0 seconds, interquartile range, 520.0-629.0; P = .418). Those given PPC heparin required a greater total heparin dose (median, 46,000.0 U; interquartile range, 39,500.0-60,000.0 vs median, 34,500.0 U; interquartile range, 32,250.0-37,000.0; P = .011) and a greater dose of heparin per kilogram than those given Hepalean (median, 572.9 U/kg; interquartile range, 443.0-659.7 vs median, 401.1 U/kg; interquartile range, 400.0-419.4; P = .003). The key secondary results included an increased median total protamine dose (median, 600.0 mg; interquartile range, 550.0-700.0; vs median, 500.0 mg; interquartile range, 425.0-542.5; P = .026) and a trend toward increased chest tube output within 24 hours (median, 830.0 mL; interquartile range, 425.0-1135.0; vs median, 702.5 mL; interquartile range, 550.0-742.5; P = .324). PPC heparin use was associated with greater heparin and protamine dose requirements than Hepalean. These findings indicate that heparin preparations are not interchangeable and suggest that a direct comparison of the potency with the brand in use is needed if a change is made to ensure that the agents exert similar anticoagulant

Anticoagulation and endothelial cell behaviors of heparin-loaded graphene oxide coating on titanium surface

Energy Technology Data Exchange (ETDEWEB)

Pan, Chang-Jiang, E-mail: panchangjiang@hyit.edu.cn [Jiangsu Provincial Key Laboratory for Interventional Medical Devices, Huaiyin Institute of Technology, Huai' an 223003 (China); Pang, Li-Qun [Department of General Surgery, Huai' an First People' s Hospital, Nanjing Medical University, Huai' an 223300 (China); Gao, Fei [Zhejiang Zylox Medical Devices Co., Ltd., Hangzhou 310000 (China); Wang, Ya-Nan; Liu, Tao; Ye, Wei; Hou, Yan-Hua [Jiangsu Provincial Key Laboratory for Interventional Medical Devices, Huaiyin Institute of Technology, Huai' an 223003 (China)

2016-06-01

Owing to its unique physical and chemical properties, graphene oxide (GO) has attracted tremendous interest in many fields including biomaterials and biomedicine. The purpose of the present study is to investigate the endothelial cell behaviors and anticoagulation of heparin-loaded GO coating on the titanium surface. To this end, the titanium surface was firstly covered by the polydopamine coating followed by the deposition of the GO coating. Heparin was finally loaded on the GO coating to improve the blood compatibility. The results of attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), Raman spectroscopy and X-ray photoelectron spectroscopy (XPS) indicated that the heparin-loaded GO coating was successfully created on the titanium surface. The scanning electron microscopy (SEM) images indicated that a relative uniform GO coating consisting of multilayer GO sheets was formed on the substrate. The hydrophilicity of the titanium surface was enhanced after the deposition of GO and further improved significantly by the loading heparin. The GO coating can enhance the endothelial cell adhesion and proliferation as compared with polydopamine coating and the blank titanium. Loading heparin on the GO coating can significantly reduce the platelet adhesion and prolong the activated partial thromboplastin time (APTT) while not influence the endothelial cell adhesion and proliferation. Therefore, the heparin-loaded GO coating can simultaneously enhance the cytocompatibility to endothelial cells and blood compatibility of biomaterials. Because the polydopamine coating can be easily prepared on most of biomaterials including polymer, ceramics and metal, thus the approach of the present study may open up a new window of promising an effective and efficient way to promote endothelialization and improve the blood compatibility of blood-contact biomedical devices such as intravascular stents. - Highlights: • Heparin-loaded graphene oxide coating was

Quantum noise locking

International Nuclear Information System (INIS)

McKenzie, Kirk; Mikhailov, Eugeniy E; Goda, Keisuke; Lam, Ping Koy; Grosse, Nicolai; Gray, Malcolm B; Mavalvala, Nergis; McClelland, David E

2005-01-01

Quantum optical states which have no coherent amplitude, such as squeezed vacuum states, cannot rely on standard readout techniques to generate error signals for control of the quadrature phase. Here we investigate the use of asymmetry in the quadrature variances to obtain a phase-sensitive readout and to lock the phase of a squeezed vacuum state, a technique which we call noise locking (NL). We carry out a theoretical derivation of the NL error signal and the associated stability of the squeezed and anti-squeezed lock points. Experimental data for the NL technique both in the presence and absence of coherent fields are shown, including a comparison with coherent locking techniques. Finally, we use NL to enable a stable readout of the squeezed vacuum state on a homodyne detector

''Old'' locked inflation

International Nuclear Information System (INIS)

Liu, Yang; Piao, Yun-Song; Si, Zong-Guo

2009-01-01

In this paper, we revisit the idea of locked inflation, which does not require a potential satisfying the normal slow-roll condition, but suffers from the problems associated with ''saddle inflation''. We propose a scenario based on locked inflation, however, with an alternative evolution mechanism of the ''waterfall field'' φ. Instead of rolling down along the potential, the φ field will tunnel to end the inflation stage like in old inflation, by which the saddle inflation could be avoided. Further, we study a cascade of old locked inflation, which can be motivated by the string landscape. Our model is based on the consideration of making locked inflation feasible so as to give a working model without slow roll; It also can be seen as an effort to embed the old inflation in string landscape

Functionalization of chitosan/poly(lactic acid-glycolic acid) sintered microsphere scaffolds via surface heparinization for bone tissue engineering.

Science.gov (United States)

Jiang, Tao; Khan, Yusuf; Nair, Lakshmi S; Abdel-Fattah, Wafa I; Laurencin, Cato T

2010-06-01

Scaffolds exhibiting biological recognition and specificity play an important role in tissue engineering and regenerative medicine. The bioactivity of scaffolds in turn influences, directs, or manipulates cellular responses. In this study, chitosan/poly(lactic acid-co-glycolic acid) (chitosan/PLAGA) sintered microsphere scaffolds were functionalized via heparin immobilization. Heparin was successfully immobilized on chitosan/PLAGA scaffolds with controllable loading efficiency. Mechanical testing showed that heparinization of chitosan/PLAGA scaffolds did not significantly alter the mechanical properties and porous structures. In addition, the heparinized chitosan/PLAGA scaffolds possessed a compressive modulus of 403.98 +/- 19.53 MPa and a compressive strength of 9.83 +/- 0.94 MPa, which are in the range of human trabecular bone. Furthermore, the heparinized chitosan/PLAGA scaffolds had an interconnected porous structure with a total pore volume of 30.93 +/- 0.90% and a median pore size of 172.33 +/- 5.89 mum. The effect of immobilized heparin on osteoblast-like MC3T3-E1 cell growth was investigated. MC3T3-E1 cells proliferated three dimensionally throughout the porous structure of the scaffolds. Heparinized chitosan/PLAGA scaffolds with low heparin loading (1.7 microg/scaffold) were shown to be capable of stimulating MC3T3-E1 cell proliferation by MTS assay and cell differentiation as evidenced by elevated osteocalcin expression when compared with nonheparinized chitosan/PLAGA scaffold and chitosan/PLAGA scaffold with high heparin loading (14.1 microg/scaffold). This study demonstrated the potential of functionalizing chitosan/PLAGA scaffolds via heparinization with improved cell functions for bone tissue engineering applications.

Design of a new type of coating for the controlled release of heparin

NARCIS (Netherlands)

Hinrichs, W.L.J.; Hinrichs, W.L.J.; ten Hoopen, Hermina W.M.; Wissink, M.J.B.; Engbers, G.H.M.; Feijen, Jan

1997-01-01

Thrombus formation at the surface of blood contacting devices can be prevented by local release of heparin. Preferably, the release rate should be constant for prolonged periods of time. The minimum heparin release rate to achieve thromboresistance will be different for various applications and

Mode locking and spatiotemporal chaos in periodically driven Gunn diodes

DEFF Research Database (Denmark)

Mosekilde, Erik; Feldberg, Rasmus; Knudsen, Carsten

1990-01-01

oscillation entrains with the external signal. This produces a devil’s staircase of frequency-locked solutions. At higher microwave amplitudes, period doubling and other forms of mode-converting bifurcations can be seen. In this interval the diode also exhibits spatiotemporal chaos. At still higher microwave...

Frequency locking in auditory hair cells: Distinguishing between additive and parametric forcing

Science.gov (United States)

Edri, Yuval; Bozovic, Dolores; Yochelis, Arik

2016-10-01

The auditory system displays remarkable sensitivity and frequency discrimination, attributes shown to rely on an amplification process that involves a mechanical as well as a biochemical response. Models that display proximity to an oscillatory onset (also known as Hopf bifurcation) exhibit a resonant response to distinct frequencies of incoming sound, and can explain many features of the amplification phenomenology. To understand the dynamics of this resonance, frequency locking is examined in a system near the Hopf bifurcation and subject to two types of driving forces: additive and parametric. Derivation of a universal amplitude equation that contains both forcing terms enables a study of their relative impact on the hair cell response. In the parametric case, although the resonant solutions are 1 : 1 frequency locked, they show the coexistence of solutions obeying a phase shift of π, a feature typical of the 2 : 1 resonance. Different characteristics are predicted for the transition from unlocked to locked solutions, leading to smooth or abrupt dynamics in response to different types of forcing. The theoretical framework provides a more realistic model of the auditory system, which incorporates a direct modulation of the internal control parameter by an applied drive. The results presented here can be generalized to many other media, including Faraday waves, chemical reactions, and elastically driven cardiomyocytes, which are known to exhibit resonant behavior.

Platelet count recovery and seroreversion in immune HIT despite continuation of heparin: further observations and literature review.

Science.gov (United States)

Shih, Andrew W; Sheppard, Jo-Ann I; Warkentin, Theodore E

2017-10-05

One of the standard distinctions between type 1 (non-immune) and type 2 (immune-mediated) heparin-induced thrombocytopenia (HIT) is the transience of thrombocytopenia: type 1 HIT is viewed as early-onset and transient thrombocytopenia, with platelet count recovery despite continuing heparin administration. In contrast, type 2 HIT is viewed as later-onset (i. e., 5 days or later) thrombocytopenia in which it is generally believed that platelet count recovery will not occur unless heparin is discontinued. However, older reports of type 2 HIT sometimes did include the unexpected observation that platelet counts could recover despite continued heparin administration, although without information provided regarding changes in HIT antibody levels in association with platelet count recovery. In recent years, some reports of type 2 HIT have confirmed the observation that platelet count recovery can occur despite continuing heparin administration, with serological evidence of waning levels of HIT antibodies ("seroreversion"). We now report two additional patient cases of type 2 HIT with platelet count recovery despite ongoing therapeutic-dose (1 case) or prophylactic-dose (1 case) heparin administration, in which we demonstrate concomitant waning of HIT antibody levels. We further review the literature describing this phenomenon of HIT antibody seroreversion and platelet count recovery despite continuing heparin administration. Our observations add to the concept that HIT represents a remarkably transient immune response, including sometimes even when heparin is continued.

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

Science.gov (United States)

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

2018-01-31

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

Human IGF-I propeptide A promotes articular chondrocyte biosynthesis and employs glycosylation-dependent heparin binding.

Science.gov (United States)

Shi, Shuiliang; Kelly, Brian J; Wang, Congrong; Klingler, Ken; Chan, Albert; Eckert, George J; Trippel, Stephen B

2018-03-01

Insulin-like growth factor I (IGF-I) is a key regulator of chondrogenesis, but its therapeutic application to articular cartilage damage is limited by rapid elimination from the repair site. The human IGF-I gene gives rise to three IGF-I propeptides (proIGF-IA, proIGF-IB and proIGF-IC) that are cleaved to create mature IGF-I. In this study, we elucidate the processing of IGF-I precursors by articular chondrocytes, and test the hypotheses that proIGF-I isoforms bind to heparin and regulate articular chondrocyte biosynthesis. Human IGF-I propeptides and mutants were overexpressed in bovine articular chondrocytes. IGF-I products were characterized by ELISA, western blot and FPLC using a heparin column. The biosynthetic activity of IGF-I products on articular chondrocytes was assayed for DNA and glycosaminoglycan that the cells produced. Secreted IGF-I propeptides stimulated articular chondrocyte biosynthetic activity to the same degree as mature IGF-I. Of the three IGF-I propeptides, only one, proIGF-IA, strongly bound to heparin. Interestingly, heparin binding of proIGF-IA depended on N-glycosylation at Asn92 in the EA peptide. To our knowledge, this is the first demonstration that N-glycosylation determines the binding of a heparin-binding protein to heparin. The biosynthetic and heparin binding abilities of proIGF-IA, coupled with its generation of IGF-I, suggest that proIGF-IA may have therapeutic value for articular cartilage repair. These data identify human pro-insulin-like growth factor IA as a bifunctional protein. Its combined ability to bind heparin and augment chondrocyte biosynthesis makes it a promising therapeutic agent for cartilage damage due to trauma and osteoarthritis. Copyright © 2017 Elsevier B.V. All rights reserved.

Frequency-Locked Detector Threshold Setting Criteria Based on Mean-Time-To-Lose-Lock (MTLL) for GPS Receivers.

Science.gov (United States)

Jin, Tian; Yuan, Heliang; Zhao, Na; Qin, Honglei; Sun, Kewen; Ji, Yuanfa

2017-12-04

Frequency-locked detector (FLD) has been widely utilized in tracking loops of Global Positioning System (GPS) receivers to indicate their locking status. The relation between FLD and lock status has been seldom discussed. The traditional PLL experience is not suitable for FLL. In this paper, the threshold setting criteria for frequency-locked detector in the GPS receiver has been proposed by analyzing statistical characteristic of FLD output. The approximate probability distribution of frequency-locked detector is theoretically derived by using a statistical approach, which reveals the relationship between probabilities of frequency-locked detector and the carrier-to-noise ratio ( C / N ₀) of the received GPS signal. The relationship among mean-time-to-lose-lock (MTLL), detection threshold and lock probability related to C / N ₀ can be further discovered by utilizing this probability. Therefore, a theoretical basis for threshold setting criteria in frequency locked loops for GPS receivers is provided based on mean-time-to-lose-lock analysis.

Antiproliferative heparin (glycosaminoglycans) isolated from giant ...

African Journals Online (AJOL)

STORAGESEVER

2009-05-18

May 18, 2009 ... source of these sulfated polysaccharides (Nader and. Dietrich, 1989) and it often corresponds up to 90% of the total GAG content of these organisms. Heparin and heap- rin-like substances have a wide range of important biolo- gical activities including inhibition of pulmonary artery smooth muscle cell ...

Furin proteolytically processes the heparin-binding region of extracellular superoxide dismutase

DEFF Research Database (Denmark)

Bowler, Russell P; Nicks, Mike; Olsen, Dorte Aa

2002-01-01

Extracellular superoxide dismutase (EC-SOD) is an antioxidant enzyme that attenuates brain and lung injury from oxidative stress. A polybasic region in the carboxyl terminus distinguishes EC-SOD from other superoxide dismutases and determines EC-SOD's tissue half-life and affinity for heparin....... There are two types of EC-SOD that differ based on the presence or absence of this heparin-binding region. It has recently been shown that proteolytic removal of the heparin-binding region is an intracellular event (Enghild, J. J., Thogersen, I. B., Oury, T. D., Valnickova, Z., Hojrup, P., and Crapo, J. D...... of intracellular proteases implicate furin as a processing protease. In vitro experiments using furin and purified EC-SOD suggest that furin proteolytically cleaves EC-SOD in the middle of the polybasic region and then requires an additional carboxypeptidase to remove the remaining lysines and arginines...

Indium-111-labeled platelets: effect of heparin on uptake by venous thrombi and relationship to the activated partial thromboplastin time

International Nuclear Information System (INIS)

Fedullo, P.F.; Moser, K.M.; Moser, K.S.; Konopka, R.; Hartman, M.T.

1982-01-01

The goal of heparin thepapy in deep vein thrombosis is to prevent thrombus extension. The relationship between thrombus extension and the results of coagulation tests used to monitor heparin thepapy is unclear. To expose this relationship, we studied the effect of several heparin regimens on the accretion of indium-111-labeled platelets on fresh venous thrombi, as detected by gamma imaging, and monitored the activated partial thromboplastin time (APTT). Six dogs were treated with a 300-U/kg bolus of heparin followed by a 90-U/kg/hour heparin infusion, a dose of heparin sufficient to increase the APTT to levels greater than eight times baseline (APTT ratio); platelet accretion (thrombus imaging) occurred only after the heparin effect was reversed with protamine sulfate. Nineteen dogs were treated with a 150-U/kg bolus of heparin followed by a 4-hour, 45-U/kg/hour heparin infusion; a thrombus was demonstrated only after protamine injection in 12 (mean APTT ratio 1.3 +/- 0.19) and before protamine injection in seven. In thirteen of these 19 dogs, 30 minutes separated the platelet injection from heparin therapy, while in six this duration was less than 30 minutes. In four of these six dogs, thrombi were demonstrated before protamine therapy and at APTT ratios greater than 3.0. Finally, 10 dogs were treated with a 100-U/kg bolus followed by a 3-hour, 50-U/kg/hour heparin infusion, after which the APTT was allowed to return to baseline values spontaneously. In all 10 dogs, a thrombus was demonstrated only after cessation of the heparin infusion, and at a mean APTT ratio of 1.4 +/- 0.15 times baseline. These results suggest that, except with very early platelet injection, platelet accretion by thrombi is consistently inhibited by heparin at APTT ratios greater than 2.5

Molecular Weights of Bovine and Porcine Heparin Samples: Comparison of Chromatographic Methods and Results of a Collaborative Survey

Directory of Open Access Journals (Sweden)

Sabrina Bertini

2017-07-01

Full Text Available In a collaborative study involving six laboratories in the USA, Europe, and India the molecular weight distributions of a panel of heparin sodium samples were determined, in order to compare heparin sodium of bovine intestinal origin with that of bovine lung and porcine intestinal origin. Porcine samples met the current criteria as laid out in the USP Heparin Sodium monograph. Bovine lung heparin samples had consistently lower average molecular weights. Bovine intestinal heparin was variable in molecular weight; some samples fell below the USP limits, some fell within these limits and others fell above the upper limits. These data will inform the establishment of pharmacopeial acceptance criteria for heparin sodium derived from bovine intestinal mucosa. The method for MW determination as described in the USP monograph uses a single, broad standard calibrant to characterize the chromatographic profile of heparin sodium on high-resolution silica-based GPC columns. These columns may be short-lived in some laboratories. Using the panel of samples described above, methods based on the use of robust polymer-based columns have been developed. In addition to the use of the USP’s broad standard calibrant for heparin sodium with these columns, a set of conditions have been devised that allow light-scattering detected molecular weight characterization of heparin sodium, giving results that agree well with the monograph method. These findings may facilitate the validation of variant chromatographic methods with some practical advantages over the USP monograph method.

Molecular Weights of Bovine and Porcine Heparin Samples: Comparison of Chromatographic Methods and Results of a Collaborative Survey.

Science.gov (United States)

Bertini, Sabrina; Risi, Giulia; Guerrini, Marco; Carrick, Kevin; Szajek, Anita Y; Mulloy, Barbara

2017-07-19

In a collaborative study involving six laboratories in the USA, Europe, and India the molecular weight distributions of a panel of heparin sodium samples were determined, in order to compare heparin sodium of bovine intestinal origin with that of bovine lung and porcine intestinal origin. Porcine samples met the current criteria as laid out in the USP Heparin Sodium monograph. Bovine lung heparin samples had consistently lower average molecular weights. Bovine intestinal heparin was variable in molecular weight; some samples fell below the USP limits, some fell within these limits and others fell above the upper limits. These data will inform the establishment of pharmacopeial acceptance criteria for heparin sodium derived from bovine intestinal mucosa. The method for MW determination as described in the USP monograph uses a single, broad standard calibrant to characterize the chromatographic profile of heparin sodium on high-resolution silica-based GPC columns. These columns may be short-lived in some laboratories. Using the panel of samples described above, methods based on the use of robust polymer-based columns have been developed. In addition to the use of the USP's broad standard calibrant for heparin sodium with these columns, a set of conditions have been devised that allow light-scattering detected molecular weight characterization of heparin sodium, giving results that agree well with the monograph method. These findings may facilitate the validation of variant chromatographic methods with some practical advantages over the USP monograph method.

49 CFR 236.766 - Locking, movable bridge.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Locking, movable bridge. 236.766 Section 236.766... Locking, movable bridge. The rail locks, bridge locks, bolt locks, circuit controllers, and electric locks used in providing interlocking protection at a movable bridge. ...

Study of the Efficacy, Safety and Tolerability of Low-Molecular-Weight Heparin vs. Unfractionated Heparin as Bridging Therapy in Patients with Embolic Stroke due to Atrial Fibrillation.

Science.gov (United States)

Feiz, Farnia; Sedghi, Reyhane; Salehi, Alireza; Hatam, Nahid; Bahmei, Jamshid; Borhani-Haghighi, Afshin

2016-06-01

Anticoagulation with adjusted dose warfarin is a well-accepted treatment for the prevention of recurrent stroke in patients with atrial fibrillation. Meanwhile, using bridging therapy with heparin or heparinoids before warfarin for initiation of anticoagulation is a matter of debate. We compared safety, efficacy, and tolerability of low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) as a bridging method in patients with recent ischemic stroke due to atrial fibrillation. This study was a randomized single-blind controlled trial in patients with acute ischemic stroke due to atrial fibrillation who were eligible for receiving warfarin and were randomly treated with 60 milligrams (mg) of LMWH (enoxaparin) subcutaneously every 12 h, or 1000 units/h of continuous intravenous heparin. The primary efficacy endpoints were recurrence of new ischemic stroke, myocardial infarction and/or death. The primary safety endpoint was central nervous system and/or systemic bleeding. Seventy-four subjects were recruited. Baseline demographic and clinical characteristics of two groups were matched. Composite endpoint outcome of new ischemic stroke, myocardial infarction, and/or death in follow-up period was seen in 10 subjects (27.03%) in UFH group and in four subjects (10.81%) in LMWH group (p value: 0.136). All hemorrhages and symptomatic central nervous system (CNS) hemorrhages in follow-up period were in 7 (18.9%) and 4 (10.8%) patients in UFH group, in 5 (13.5%), and 3 (8.1%) patients in LMWH group (p values: 0.754 and 0.751), respectively. Drop out and major adverse-effects such as heparin-induced thrombocytopenia and drug hypersensitivity were not seen in any patient. Enoxaparin can be a safe and efficient alternative for UFH as bridging therapy.

111In-labeled platelets: effects of heparin on uptake by venous thrombi and relationship to the activated partial thromboplastin time

International Nuclear Information System (INIS)

Fedullo, P.F.; Moser, K.M.; Moser, K.S.; Konopka, R.; Hartman, M.T.

1982-01-01

The goal of heparin therapy in deep vein thrombosis is to prevent thrombus extension. The relationship between thrombus extension and the results of coagulation tests used to monitor heparin therapy is unclear. To explore this relationship, we studied the effect of several heparin regimens on the accretion of 111 In-labeled platelets on fresh venous thrombi, as detected by gamma imaging, and monitored the activated partial thromboplastin time (APTT). Six dogs were treated with a 300-U/kg bolus of heparin followed by a 90-U/kg/hour heparin infusion, a dose of heparin sufficient to increase the APTT to levels greater than eight times baseline (APTT ratio); platelet accretion (thrombus imaging) occurred only after the heparin effect was reversed with protamine sulfate. Nineteen dogs were treated with a 150-U/kg bolus of heparin followed by a 4-hour, 45-U/kg/hour heparin infusion; a thrombus was demonstrated only after protamine injection in 12 (mean APTT ratio 1.3 +/- 0.19) and before protamine injection in seven. In thirteen of these 19 dogs, 30 minutes separated the platelet injection from heparin therapy, while in six this duration was less than 30 minutes. In four of these six dogs, thrombi were demonstrated before protamine therapy and at APTT ratios greater than 3.0. Finally, 10 dogs were treated with a 100-U/kg bolus followed by a 3-hour, 50-U/kg/hour heparin infusion, after which the APTT was allowed to return to baseline values spontaneously. In all 10 dogs, a thrombus was demonstrated only after cessation of the heparin infusion, and at a mean APTT ratio of 1.4 +/- 0.15 times baseline. These results suggest that, except with very early platelet injection, platelet accretion by thrombi is consistently inhibited by heparin at APTT ratios greater than 2.5. Platelet accretion by venous thrombi occurs within narrow limits of heparin effect as reflected by the APTT

Safety and Efficacy of Argatroban in the Management of Heparin-Induced Thrombocytopenia

Directory of Open Access Journals (Sweden)

Bernd Saugel

2011-01-01

Full Text Available Heparin-induced thrombocytopenia (HIT is a life-threatening adverse reaction to heparin therapy that is characterized by thrombocytopenia and an increased risk of venous and arterial thrombosis. According to guidelines, in patients with strongly suspected or confirmed HIT all sources of heparin have to be discontinued and an alternative, nonheparin anticoagulant for HIT treatment must immediately be started. For both the prophylaxis of thrombembolic events in HIT and the treatment of HIT with thrombosis the direct thrombin inhibitor argatroban is approved in the United States. The objective of this review is to describe the mechanism of action and the pharmacokinetic profile of argatroban, to characterize argatroban regarding its safety and therapeutic efficacy and to discuss its place in therapy in HIT.

Problems in Locke's Theory of Knowledge | Minimah | AFRREV IJAH ...

African Journals Online (AJOL)

As a solution to the epistemological problem of inquiring into what the human mind is capable of knowing, John Locke, founder of British empiricism rejects the rationalist assumption that the human mind does have a privileged access to reality. He is especially critical of the Cartesian notion of innate ideas as an explanation ...

Research of mechanism of density lock

International Nuclear Information System (INIS)

Wang Shengfei; Yan Changqi; Gu Haifeng

2010-01-01

Mechanism of density lock was analyzed according to the work conditions of density lock. The results showed that: the stratification with no disturbance satisfied the work conditions of density lock; fluids between the stratification were not mixed at the condition of connected to each other; the density lock can be open automatically by controlled the pressure balance at the stratification. When disturbance existed, the stratification might be broken and mass would be transferred by convection. The stability of stratification can be enhanced by put the special structure in density lock to ensure the normal work of density lock. At last, the minimum of heat loss in density lock was also analyzed. (authors)

Performance of arm locking in LISA

International Nuclear Information System (INIS)

McKenzie, Kirk; Spero, Robert E.; Shaddock, Daniel A.

2009-01-01

For the Laser Interferometer Space Antenna (LISA) to reach its design sensitivity, the coupling of the free-running laser frequency noise to the signal readout must be reduced by more than 14 orders of magnitude. One technique employed to reduce the laser frequency noise will be arm locking, where the laser frequency is locked to the LISA arm length. In this paper we detail an implementation of arm locking. We investigate orbital effects (changing arm lengths and Doppler frequencies), the impact of errors in the Doppler knowledge that can cause pulling of the laser frequency, and the noise limit of arm locking. Laser frequency pulling is examined in two regimes: at lock acquisition and in steady state. The noise performance of arm locking is calculated with the inclusion of the dominant expected noise sources: ultrastable oscillator (clock) noise, spacecraft motion, and shot noise. We find that clock noise and spacecraft motion limit the performance of dual arm locking in the LISA science band. Studying these issues reveals that although dual arm locking [A. Sutton and D. A. Shaddock, Phys. Rev. D 78, 082001 (2008)] has advantages over single (or common) arm locking in terms of allowing high gain, it has disadvantages in both laser frequency pulling and noise performance. We address this by proposing a modification to the dual arm-locking sensor, a hybrid of common and dual arm-locking sensors. This modified dual arm-locking sensor has the laser frequency pulling characteristics and low-frequency noise coupling of common arm locking, but retains the control system advantages of dual arm locking. We present a detailed design of an arm-locking controller and perform an analysis of the expected performance when used with and without laser prestabilization. We observe that the sensor phase changes beneficially near unity-gain frequencies of the arm-locking controller, allowing a factor of 10 more gain than previously believed, without degrading stability. With a time

Escaping carbon lock-in

International Nuclear Information System (INIS)

Unruh, G.C.

2002-01-01

This article explores the climate policy implications of the arguments made in ''Understanding carbon lock-in'' (Unruh, 2000), which posited that industrial countries have become locked-into fossil fuel-based energy systems through path dependent processes driven by increasing returns to scale. Carbon lock-in arises through technological, organizational, social and institutional co-evolution, ''culminating'' in what was termed as techno-institutional complex (TIC). In order to resolve the climate problem, an escape from the lock-in condition is required. However, due to the self-referential nature of TIC, escape conditions are unlikely to be generated internally and it is argued here that erogenous forces are probably required. (author)

Hemocompatible ɛ-polylysine-heparin microparticles: A platform for detecting triglycerides in whole blood.

Science.gov (United States)

Xu, Tingting; Chi, Bo; Chu, Meilin; Zhang, Qicheng; Zhan, Shuyue; Shi, Rongjia; Xu, Hong; Mao, Chun

2018-01-15

Triglycerides are clinically important marker for atherosclerosis, heart disease and hypertension. Here, a platform for detecting triglycerides in whole blood directly was developed based on hemocompatible ɛ-polylysine-heparin microparticles. The obtained products of ɛ-polylysine-heparin microparticles were characterized by fourier transform infrared (FT-IR) spectra, transmission electron microscopy (TEM) and ζ-potential. Moreover, the blood compatibility of ɛ-polylysine-heparin microparticles was characterized by in vitro coagulation tests, hemolysis assay and whole blood adhesion tests. Considering of uniform particle size, good dispersibility and moderate long-term anticoagulation capability of the microparticles, a Lipase-(ɛ-polylysine-heparin)-glassy carbon electrode (GCE) was constructed to detect triglycerides. The proposed biosensor had good electrocatalytic activity towards triglycerides, in which case the sensitivity was 0.40μAmg -1 dLcm -2 and the detection limit was 4.67mgdL -1 (S/N = 3). Meanwhile, the Lipase-(ɛ-polylysine-heparin)-GCE electrode had strong anti-interference ability as well as a long shelf-life. Moreover, for the detection of triglycerides in whole blood directly, the detection limit was as low as 5.18mgdL -1 . The new constructed platform is suitable for detecting triglycerides in whole blood directly, which provides new analytical systems for clinical illness diagnosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Printed microfluidic filter for heparinized blood.

Science.gov (United States)

Bilatto, Stanley E R; Adly, Nouran Y; Correa, Daniel S; Wolfrum, Bernhard; Offenhäusser, Andreas; Yakushenko, Alexey

2017-05-01

A simple lab-on-a-chip method for blood plasma separation was developed by combining stereolithographic 3D printing with inkjet printing, creating a completely sealed microfluidic device. In some approaches, one dilutes the blood sample before separation, reducing the concentration of a target analyte and increasing a contamination risk. In this work, a single drop (8  μ l) of heparinized whole blood could be efficiently filtered using a capillary effect without any external driving forces and without dilution. The blood storage in heparin tubes during 24 h at 4 °C initiated the formation of small crystals that formed auto-filtration structures in the sample upon entering the 3D-printed device, with pores smaller than the red blood cells, separating plasma from the cellular content. The total filtration process took less than 10 s. The presented printed plasma filtration microfluidics fabricated with a rapid prototyping approach is a miniaturized, fast and easy-to-operate device that can be integrated into healthcare/portable systems for point-of-care diagnostics.

Heparin-independent, PF4-dependent binding of HIT antibodies to platelets: implications for HIT pathogenesis.

Science.gov (United States)

Padmanabhan, Anand; Jones, Curtis G; Bougie, Daniel W; Curtis, Brian R; McFarland, Janice G; Wang, Demin; Aster, Richard H

2015-01-01

Antibodies specific for platelet factor 4 (PF4)/heparin complexes are the hallmark of heparin-induced thrombocytopenia and thrombosis (HIT), but many antibody-positive patients have normal platelet counts. The basis for this is not fully understood, but it is believed that antibodies testing positive in the serotonin release assay (SRA) are the most likely to cause disease. We addressed this issue by characterizing PF4-dependent binding of HIT antibodies to intact platelets and found that most antibodies testing positive in the SRA, but none of those testing negative, bind to and activate platelets when PF4 is present without any requirement for heparin (P HIT antibodies recognize PF4 in a complex with heparin, only a subset of these antibodies recognize more subtle epitopes induced in PF4 when it binds to CS, the major platelet glycosaminoglycan. Antibodies having this property could explain "delayed HIT" seen in some individuals after discontinuation of heparin and the high risk for thrombosis that persists for weeks in patients recovered from HIT. © 2015 by The American Society of Hematology.

Effect of heparin calcium different concentrations on some physical properties and structure in polyacrylamide matrix

International Nuclear Information System (INIS)

Abdelrazek, E.M.; Ibrahim, Hosam S.

2010-01-01

Films of polyacrylamide (PAAm) doped with different concentrations of heparin calcium, from 0.0 to 8 wt%, have been prepared by casting method. Studies were carried out utilizing X-ray, FT-IR, UV/VIS, DSC and DC electrical conduction to characterize the structural, optical and thermal properties of the films. Results revealed that the structural and chemical characterizations of PAAm films are affected by the addition of heparin calcium content. XRD spectra revealed that the amorphous phases increase with increase in filling levels of heparin (FLs). FT-IR analysis revealed that incorporation of heparin calcium leads to a small modification in the spectra of films. The optical absorption spectra in the UV/VIS region revealed structural variation increases with increase in concentration, which is reflected in the form of decrease in the energy band gap E g . Significant changes of DSC curves of the films suggest that strong interaction established between heparin calcium and PAAm molecules. The DC electric conduction data were interpreted on the basis of an intrachain one-dimensional interpolaron hopping model of Kuivalainen.

Homodyne locking of a squeezer.

Science.gov (United States)

Heurs, M; Petersen, I R; James, M R; Huntington, E H

2009-08-15

We report on the successful implementation of an approach to locking the frequencies of an optical parametric oscillator (OPO)-based squeezed-vacuum source and its driving laser. The technique allows the simultaneous measurement of the phase shifts induced by a cavity, which may be used for the purposes of frequency locking, as well as the simultaneous measurement of the sub-quantum-noise-limited (sub-QNL) phase quadrature output of the OPO. The homodyne locking technique is cheap, easy to implement, and has the distinct advantage that subsequent homodyne measurements are automatically phase locked. The homodyne locking technique is also unique in that it is a sub-QNL frequency discriminator.

Selective interaction of heparin with the variable region 3 within surface glycoprotein of laboratory-adapted feline immunodeficiency virus.

Directory of Open Access Journals (Sweden)

Qiong-Ying Hu

Full Text Available Heparan sulfate proteoglycans (HSPG can act as binding receptors for certain laboratory-adapted (TCA strains of feline immunodeficiency virus (FIV and human immunodeficiency virus (HIV. Heparin, a soluble heparin sulfate (HS, can inhibit TCA HIV and FIV entry mediated by HSPG interaction in vitro. In the present study, we further determined the selective interaction of heparin with the V3 loop of TCA of FIV. Our current results indicate that heparin selectively inhibits infection by TCA strains, but not for field isolates (FS. Heparin also specifically interferes with TCA surface glycoprotein (SU binding to CXCR4, by interactions with HSPG binding sites on the V3 loop of the FIV envelope protein. Peptides representing either the N- or C-terminal side of the V3 loop and containing HSPG binding sites were able to compete away the heparin block of TCA SU binding to CXCR4. Heparin does not interfere with the interaction of SU with anti-V3 antibodies that target the CXCR4 binding region or with the interaction between FS FIV and anti-V3 antibodies since FS SU has no HSPG binding sites within the HSPG binding region. Our data show that heparin blocks TCA FIV infection or entry not only through its competition of HSPG on the cell surface interaction with SU, but also by its interference with CXCR4 binding to SU. These studies aid in the design and development of heparin derivatives or analogues that can inhibit steps in virus infection and are informative regarding the HSPG/SU interaction.

A new approach for heparin standardization: combination of scanning UV spectroscopy, nuclear magnetic resonance and principal component analysis.

Directory of Open Access Journals (Sweden)

Marcelo A Lima

Full Text Available The year 2007 was marked by widespread adverse clinical responses to heparin use, leading to a global recall of potentially affected heparin batches in 2008. Several analytical methods have since been developed to detect impurities in heparin preparations; however, many are costly and dependent on instrumentation with only limited accessibility. A method based on a simple UV-scanning assay, combined with principal component analysis (PCA, was developed to detect impurities, such as glycosaminoglycans, other complex polysaccharides and aromatic compounds, in heparin preparations. Results were confirmed by NMR spectroscopy. This approach provides an additional, sensitive tool to determine heparin purity and safety, even when NMR spectroscopy failed, requiring only standard laboratory equipment and computing facilities.

Assessment of HIT Antibody Complex in Hip Fracture Patients Receiving Enoxaparin or Unfractionated Heparin

DEFF Research Database (Denmark)

Griffin, Justin W; Hopkinson, William J; Rud-Lassen, Michael

2011-01-01

of antiheparin-PF4 antibodies and a greater prevalence of immunoglobulin G (IgG) subtype. Heparin and enoxaparin are capable of generating heparin-induced thrombocytopenia (HIT) antibodies in elderly patients undergoing orthopedic surgery but perhaps not to the same extent. When comparing low...

49 CFR 236.765 - Locking, mechanical.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Locking, mechanical. 236.765 Section 236.765 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Locking, mechanical. An arrangement of locking bars, dogs, tappets, cross locking and other apparatus by...

Heparin-Functionalized chitosan/ κ-carrageenan complexes as potential scaffolds for tissue engineering

International Nuclear Information System (INIS)

Dofeliz, Joni L.; Rojas, Nina Rosario L.

2015-01-01

Cell-based approaches to tissue regeneration are playing an increasingly important role in bone and cartilage repair. This is made possible through the use of growth factors, which are signaling molecules that induce a number of effects such as cell proliferation, migration and differentiation. But problems arise as these growth factors tend to be expensive, short-lived and slow moving through the extracellular matrix, making them very inefficient in their current form of introduction. One such growth factor is basic fibroblast growth factor (bFGF). The general objective of this study is to construct heparin-functionalized chitosan/κ-carrageenan scaffolds, which when bound to basic fibroblast growth factor (bFGF), may be used in the culture of mesenchymal stem cells for differentiation into cartilage. In this study, gels of semi-interpenetrating networks (semi-IPN) of chitosan and κ-carrageenan (2:4:1 blend ration) were prepared using calcium chloride as a cross-linker. The gels were then functionalized with heparin, which is known for its growth factor binding ability, using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) as cross-linker. The functionalized gels were then reshaped into scaffold on the wells of 48-well plates through freeze-dry method. The scaffolds were found to be realatively porous with pore sizes larger than 100 μm which satisfies the requirements for cell culture. Subsequent thermogravimetric analysis shows that the scaffolds were relatively stable with a degradation temperature of 277°C. Additionally, there was no observable separation of the individual degradation temperatures of chitosan and κ-carrageenan, confirming that a single miscible phase in the form of a semi-IPN structure was created. Results of scanning electron microscopy also showed that the scaffolds were stable under 2 hours of UV sterilization. The FTIR spectra of the heparinized PEC showed characteristic absorption bands (S=O asymetric stretch) in the area of 1160

Heparin defends against the toxicity of circulating histones in sepsis.

Science.gov (United States)

Wang, Feifei; Zhang, Naipu; Li, Biru; Liu, Lanbo; Ding, Lei; Wang, Ying; Zhu, Yimin; Mo, Xi; Cao, Qing

2015-06-01

Although circulating histones were demonstrated as major mediators of death in septic mice models, their roles in septic patients are not clarified. The present study sought to evaluate the clinical relevance of the circulating histone levels in septic children, and the antagonizing effects of heparin on circulating histones. Histone levels in the plasma of septic children were significantly higher than healthy controls, and positively correlated with disease severity. Histone treatment could activate NF-κB pathway of the endothelial cells and induce the secretion of large amount of cytokines that further amplify inflammation, subsequently leading to organ damage. Co-injection of low dose heparin with lethal dose histones could protect mouse from organ damage and death by antagonizing circulating histones, and similar effects were also observed in other septic models. Collectively, these findings indicated that circulating histones might serve as key factors in the pathogenesis of sepsis and their levels in plasma might be a marker for disease progression and prognosis. Furthermore, low dose heparin might be an effective therapy to hamper sepsis progression and reduce the mortality.

The effect of heparin administration on the FT4-levels and on an unspecific peripheral thyroid parameter

International Nuclear Information System (INIS)

Eber, B.; Borkenstein, J.; Leb, G.

1984-01-01

Heparin produces changes in FT 4 -levels both in vivo and in vitro as determined by commercial kits. Methods utilising the principle of equilibrium dialysis show significant increases whereas methods using T 4 -tracer analogue techniques reveal marked decreases in FT 4 -values. Possible clinical side-effects of heparin administration such as heparin-induced hyperthyroidism and tachyarrhythmias are discussed. The present results confirm the FT 4 -decreasing effect of in vivo and in vitro administration of heparin with FT 4 -RIAs based on the tracer analogue technique; however, the unspecific peripheral thyroid parameter of systolic time-intervals did not reveal any tendency towards hyperthyroidism. Also the discrepant results dependent on the method used, indicate that, following heparin administration FT 4 -levels do not reflect that hormone concentration is relevant to the metabolism of the whole body. (orig.) [de

Kuramoto model with uniformly spaced frequencies: Finite-N asymptotics of the locking threshold.

Science.gov (United States)

Ottino-Löffler, Bertrand; Strogatz, Steven H

2016-06-01

We study phase locking in the Kuramoto model of coupled oscillators in the special case where the number of oscillators, N, is large but finite, and the oscillators' natural frequencies are evenly spaced on a given interval. In this case, stable phase-locked solutions are known to exist if and only if the frequency interval is narrower than a certain critical width, called the locking threshold. For infinite N, the exact value of the locking threshold was calculated 30 years ago; however, the leading corrections to it for finite N have remained unsolved analytically. Here we derive an asymptotic formula for the locking threshold when N≫1. The leading correction to the infinite-N result scales like either N^{-3/2} or N^{-1}, depending on whether the frequencies are evenly spaced according to a midpoint rule or an end-point rule. These scaling laws agree with numerical results obtained by Pazó [D. Pazó, Phys. Rev. E 72, 046211 (2005)PLEEE81539-375510.1103/PhysRevE.72.046211]. Moreover, our analysis yields the exact prefactors in the scaling laws, which also match the numerics.

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

Science.gov (United States)

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

2016-01-01

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

Heparin-binding peptide amphiphile supramolecular architectures as platforms for angiogenesis and drug delivery

Science.gov (United States)

Chow, Lesleyann W.

A fascinating phenomenon in nature is the self-assembly of molecules into a functional, hierarchical structure. In the past decade, the Stupp Laboratory has developed several classes of self-assembling biomaterials, one of which is the synthetic peptide amphiphile (PA). Self-assembling PAs are attractive and versatile biomolecules that can be customized for specific applications in regenerative medicine. In particular, a heparin-binding peptide amphiphile (HBPA) containing a specific heparin-binding peptide sequence was used here to induce angiogenesis and serve as a delivery vehicle for growth factors and small hydrophobic molecules. Throughout this dissertation, the HBPA/heparin system is used in different architectures for a variety of regenerative medicine applications. In one aspect of this work, hybrid scaffolds made from HBPA/heparin gelled on a poly(L-lactic acid) (PLLA) fiber mesh were used to promote angiogenesis to facilitate pancreatic islet transplantation for the treatment of type 1 diabetes. Delivery of growth factors with HBPA/PLLA scafflolds increased vessel density in vivo and correlated with improved transplant outcomes in a streptozotocin-induced diabetic mouse model. Soluble HBPA nanofiber architectures were also useful for islet transplantation applications. These nanofibers were used at concentrations below gelation to deliver growth factors into the dense islet cell aggregate, promoting cell survival and angiogenesis in vitro. The nanostructures infiltrated the islets and promoted the retention of heparin and growth factors within the islet. Another interesting growth factor release system discussed here is the HBPA membrane structure. HBPA was found to self-assemble with hyaluronic acid, a large biopolymer found in the body, into macroscopic, hierarchically-ordered membranes. Heparin was incorporated into these membranes and affected the membrane's mechanical properties and growth factor release. Human mesenchymal stem cells were also shown

Dynamics of temporally localized states in passively mode-locked semiconductor lasers

Science.gov (United States)

Schelte, C.; Javaloyes, J.; Gurevich, S. V.

2018-05-01

We study the emergence and the stability of temporally localized structures in the output of a semiconductor laser passively mode locked by a saturable absorber in the long-cavity regime. For large yet realistic values of the linewidth enhancement factor, we disclose the existence of secondary dynamical instabilities where the pulses develop regular and subsequent irregular temporal oscillations. By a detailed bifurcation analysis we show that additional solution branches that consist of multipulse (molecules) solutions exist. We demonstrate that the various solution curves for the single and multipeak pulses can splice and intersect each other via transcritical bifurcations, leading to a complex web of solutions. Our analysis is based on a generic model of mode locking that consists of a time-delayed dynamical system, but also on a much more numerically efficient, yet approximate, partial differential equation. We compare the results of the bifurcation analysis of both models in order to assess up to which point the two approaches are equivalent. We conclude our analysis by the study of the influence of group velocity dispersion, which is only possible in the framework of the partial differential equation model, and we show that it may have a profound impact on the dynamics of the localized states.

Heparin for prolonging peripheral intravenous catheter use in neonates: a randomized controlled trial.

Science.gov (United States)

Upadhyay, A; Verma, K K; Lal, P; Chawla, D; Sreenivas, V

2015-04-01

To determine the efficacy of heparinized saline administered as intermittent flush on functional duration of the peripheral intravenous catheter (PIVC) in neonates. Randomized, double-blind and placebo-controlled trial. Neonatal intensive care unit of a teaching hospital. Term and preterm neonates born at >32 weeks of gestation who required PIVC only for intermittent administration of antibiotics. Eligible neonates were randomized to receive 1 ml of either heparinized saline (10 U ml(-1)) (n=60) or normal saline (n=60) every 12 h before and after intravenous antibiotics. Functional duration of first peripheral intravenous catheter. A total of 120 neonates were randomized to two groups of 60 neonates each. The mean (s.d.) of age of babies in case and control group was 5.7 (2.5) days and 4.6 (3.1) days, respectively. The average weight of babies in both the groups was 2.1 kg. Mean functional duration of first catheter was more in heparinized saline group, mean (s.d.) of 71.68 h  (27.3) as compared with 57.7 h (23.6) in normal saline group (P<0.005). The mean (95% confidence interval) difference in functional duration in the two groups was 13.9 h (4.7-23.15). Mean duration of patency for any catheter was also significantly more in heparinized saline group than control group. Heparinized saline flush increases the functional duration of peripheral intravenous catheter.

Protective air lock

International Nuclear Information System (INIS)

Evans, H.W.

1976-01-01

A device suitable for preventing escape and subsequent circulation of toxic gases is described. An enclosure is sealed by a surrounding air lock, and an automatic mechanism partially evacuates the enclosure and air lock. The enclosure ventilating mechanism can be disconnected so that a relatively undisturbed atmosphere is created in the enclosure

Vascular access site complication in transfemoral coronary angiography between uninterrupted warfarin and heparin bridging.

Science.gov (United States)

Wongcharoen, Wanwarang; Pinyosamosorn, Kittipong; Gunaparn, Siriluck; Boonnayhun, Suchada; Thonghong, Tasalak; Suwannasom, Pannipa; Phrommintikul, Arintaya

2017-08-01

Warfarin discontinuation with heparin bridging is a common practice in patients receiving warfarin prior to elective coronary angiography (CAG). The uninterrupted warfarin strategy has been suggested to be alternative option for patients with high thromboembolic risk. Therefore, we aimed to assess the safety of elective transfemoral CAG during uninterrupted warfarin therapy compared to heparin bridging. This study was a randomized open-label design with blinded event evaluation. The 110 consecutive patients (age ≥ 18 years) receiving warfarin before the planned transfemoral CAG were randomly assigned to either heparin bridging or uninterrupted warfarin with targeted INR (2.0-3.0). The primary outcome was the incidence of major vascular access site complications. The baseline characteristics were comparable between two groups (mean age was 60.1 ± 7.8 years, 49 males). The mean INR on the day of CAG of heparin bridging and uninterrupted warfarin groups was 1.2 ± 0.3 and 2.2 ± 0.5 (P warfarin patients (P = 0.243). The total vascular access site complications occurred in 6 (10.9%) heparin-bridging and one (1.8%) uninterrupted warfarin patients (P = 0.113). No patient developed either other bleeding or thromboembolic events during 7 days after CAG. We demonstrated that an uninterrupted warfarin strategy did not increase vascular access site complications in patients undergoing transfemoral CAG compared to heparin bridging therapy. Due to the safety and the ease of uninterrupted warfarin strategy, this approach should be encouraged in patients receiving long-term warfarin who undergo elective transfemoral CAG. © 2017, Wiley Periodicals, Inc.

21 CFR 864.5680 - Automated heparin analyzer.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Automated heparin analyzer. 864.5680 Section 864.5680 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Automated and Semi-Automated Hematology Devices § 864...

Pressure locking test results

Energy Technology Data Exchange (ETDEWEB)

DeWall, K.G.; Watkins, J.C.; McKellar, M.G.; Bramwell, D. [Idaho National Engineering Lab., Idaho Falls, ID (United States)] [and others

1996-12-01

The U.S. Nuclear Regulatory Commission (NRC), Office of Nuclear Regulatory Research, is funding the Idaho National Engineering Laboratory (INEL) in performing research to provide technical input for their use in evaluating responses to Generic Letter 95-07, {open_quotes}Pressure Locking and Thermal Binding of Safety-Related Power-Operated Gate Valves.{close_quotes} Pressure locking and thermal binding are phenomena that make a closed gate valve difficult to open. This paper discusses only the pressure locking phenomenon in a flexible-wedge gate valve; the authors will publish the results of their thermal binding research at a later date. Pressure locking can occur when operating sequences or temperature changes cause the pressure of the fluid in the bonnet (and, in most valves, between the discs) to be higher than the pressure on the upstream and downstream sides of the disc assembly. This high fluid pressure presses the discs against both seats, making the disc assembly harder to unseat than anticipated by the typical design calculations, which generally consider friction at only one of the two disc/seat interfaces. The high pressure of the bonnet fluid also changes the pressure distribution around the disc in a way that can further contribute to the unseating load. If the combined loads associated with pressure locking are very high, the actuator might not have the capacity to open the valve. The results of the NRC/INEL research discussed in this paper show that the relationship between bonnet pressure and pressure locking stem loads appears linear. The results also show that for this valve, seat leakage affects the bonnet pressurization rate when the valve is subjected to thermally induced pressure locking conditions.

Pressure locking test results

International Nuclear Information System (INIS)

DeWall, K.G.; Watkins, J.C.; McKellar, M.G.; Bramwell, D.

1996-01-01

The U.S. Nuclear Regulatory Commission (NRC), Office of Nuclear Regulatory Research, is funding the Idaho National Engineering Laboratory (INEL) in performing research to provide technical input for their use in evaluating responses to Generic Letter 95-07, open-quotes Pressure Locking and Thermal Binding of Safety-Related Power-Operated Gate Valves.close quotes Pressure locking and thermal binding are phenomena that make a closed gate valve difficult to open. This paper discusses only the pressure locking phenomenon in a flexible-wedge gate valve; we will publish the results of our thermal binding research at a later date. Pressure locking can occur when operating sequences or temperature changes cause the pressure of the fluid in the bonnet (and, in most valves, between the discs) to be higher than the pressure on the upstream and downstream sides of the disc assembly. This high fluid pressure presses the discs against both seats, making the disc assembly harder to unseat than anticipated by the typical design calculations, which generally consider friction at only one of the two disc/seat interfaces. The high pressure of the bonnet fluid also changes the pressure distribution around the disc in a way that can further contribute to the unseating load. If the combined loads associated with pressure locking are very high, the actuator might not have the capacity to open the valve. The results of the NRC/INEL research discussed in this paper show that the relationship between bonnet pressure and pressure locking stem loads appears linear. The results also show that for this valve, seat leakage affects the bonnet pressurization rate when the valve is subjected to thermally induced pressure locking conditions

Biosynthesis of heparin. Effects of n-butyrate on cultured mast cells

International Nuclear Information System (INIS)

Jacobsson, K.G.; Riesenfeld, J.; Lindahl, U.

1985-01-01

Murine mastocytoma cells were incubated in vitro with inorganic [ 35 S]sulfate, in the absence or presence of 2.5 mM n-butyrate, and labeled heparin was isolated. The polysaccharide produced in the presence of butyrate showed a lower charge density on anion exchange chromatography than did the control material and a 3-fold increased proportion of components with high affinity for antithrombin. Structural analysis of heparin labeled with [ 3 H] glucosamine in the presence of butyrate showed that approximately 35% of the glucosamine units were N-acetylated, as compared to approximately 10% in the control material; the nonacetylated glucosamine residues were N-sulfated. The presence of butyrate thus leads to an inhibition of the N-deacetylation/N-sulfation process in heparin biosynthesis, along with an augmented formation of molecules with high affinity for antithrombin. Preincubation of the mastocytoma cells with butyrate was required for manifestation of either effect; when the preincubation period was reduced from 24 to 10 h the effects of butyrate were no longer observed. A polysaccharide formed on incubating mastocytoma microsomal fraction with UDP-[ 3 H]glucuronic acid, UDP-N-acetylglucosamine, and 3'-phosphoadenylylsulfate in the presence of 5 mM butyrate showed the same N-acetyl/N-sulfate ratio as did the corresponding control polysaccharide, produced in the absence of butyrate. These findings suggest that the effect of butyrate on heparin biosynthesis depends on the integrity of the cell

Association between Activated Partial Thromboplastin Time and the Amount of Infused Heparin at Bone Marrow Transplantation.

Science.gov (United States)

Kusuda, Machiko; Kimura, Shun-Ichi; Misaki, Yukiko; Yoshimura, Kazuki; Gomyo, Ayumi; Hayakawa, Jin; Tamaki, Masaharu; Akahoshi, Yu; Ugai, Tomotaka; Kameda, Kazuaki; Wada, Hidenori; Ishihara, Yuko; Kawamura, Koji; Sakamoto, Kana; Sato, Miki; Terasako-Saito, Kiriko; Kikuchi, Misato; Nakasone, Hideki; Kako, Shinichi; Tanihara, Aki; Kanda, Yoshinobu

2018-03-27

The actual heparin concentration of harvested allogeneic bone marrow varies among harvest centers. We monitor the activated partial thromboplastin time (APTT) of the patient during bone marrow infusion and administer prophylactic protamine according to the APTT. We retrospectively reviewed the charts of consecutive patients who underwent bone marrow transplantation without bone marrow processing at our center between April 2007 and March 2016 (n = 94). APTT was monitored during marrow transfusion in 52 patients. We analyzed the relationship between the APTT ratio and several parameters related to heparin administration. As a result, the weight-based heparin administration rate (U/kg/hour) seemed to be more closely related to the APTT ratio (r = .38, P = .005) than to the total amount of heparin. There was no significant correlation between the APTT ratio and renal or liver function. Bleeding complications during and early after infusion were seen in 3 of 52 patients, and included intracranial, nasal, and punctured-skin bleeding. The APTT ratio during transfusion was over 5.88 in the former 2 patients and 2.14 in the latter. All of these patients recovered without sequelae. In conclusion, slow bone marrow infusion is recommended to decrease the weight-based heparin administration rate when the heparin concentration per patient body weight is high. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

An Analytical Model for Rotation Stiffness and Deformation of an Antiloosening Nut under Locking Force

Directory of Open Access Journals (Sweden)

X. J. Jiang

2014-01-01

Full Text Available Screw fasteners are undoubtedly one of the most important machine elements due to their outstanding characteristic to provide a high clamping force just with a simplified design. However, the loosen vibration is their inherent and inevitable fault. The friction locking approach is one of the basic locking fastener categories by enhancing the bearing load on the contact surface of thread by applying a locking force on an antiloosening nut. This locking force may cause more severe deformation in the nut. The contact stress distribution on the nut would be changed and that can cause the variation of the friction torque for the bolt joint. However, there exists no established design calculation procedure that accounts for the rotation deformation and its stiffness of the antiloosening nut under the locking force. The main objective of the work is to develop an analytical solution to the rotation deformation problem encountered in the antiloosening nut. The proposed model is supported by comparison with numerical finite element analysis of different sizes of joint elements and different applied forces.

PWR integral tie plate and locking mechanism

International Nuclear Information System (INIS)

Flora, B.S.; Osborne, J.L.

1980-01-01

A locking mechanism for securing an upper tie plate to the tie rods of a nuclear fuel bundle is described. The mechanism includes an upper tie plate assembly and locking sleeves fixed to the ends of the tie rods. The tie plate is part of the upper tie plate assembly and is secured to the fuel bundle by securing the entire upper tie plate assembly to the locking sleeves fixed to the tie rods. The assembly includes, in addition to the tie plate, locking nuts for engaging the locking sleeves, retaining sleeves to operably connect the locking nuts to the assembly, a spring biased reaction plate to restrain the locking nuts in the locked position and a means to facilitate the removal of the entire assembly as a unit from the fuel bundle

Heparin modulates the endopeptidase activity of Leishmania mexicana cysteine protease cathepsin L-Like rCPB2.8.

Directory of Open Access Journals (Sweden)

Wagner A S Judice

Full Text Available Cysteine protease B is considered crucial for the survival and infectivity of the Leishmania in its human host. Several microorganism pathogens bind to the heparin-like glycosaminoglycans chains of proteoglycans at host-cell surface to promote their attachment and internalization. Here, we have investigated the influence of heparin upon Leishmania mexicana cysteine protease rCPB2.8 activity.THE DATA ANALYSIS REVEALED THAT THE PRESENCE OF HEPARIN AFFECTS ALL STEPS OF THE ENZYME REACTION: (i it decreases 3.5-fold the k 1 and 4.0-fold the k -1, (ii it affects the acyl-enzyme accumulation with pronounced decrease in k 2 (2.7-fold, and also decrease in k 3 (3.5-fold. The large values of ΔG  =  12 kJ/mol for the association and dissociation steps indicate substantial structural strains linked to the formation/dissociation of the ES complex in the presence of heparin, which underscore a conformational change that prevents the diffusion of substrate in the rCPB2.8 active site. Binding to heparin also significantly decreases the α-helix content of the rCPB2.8 and perturbs the intrinsic fluorescence emission of the enzyme. The data strongly suggest that heparin is altering the ionization of catalytic (Cys(25-S(-/(His(163-Im(+ H ion pair of the rCPB2.8. Moreover, the interaction of heparin with the N-terminal pro-region of rCPB2.8 significantly decreased its inhibitory activity against the mature enzyme.Taken together, depending on their concentration, heparin-like glycosaminoglycans can either stimulate or antagonize the activity of cysteine protease B enzymes during parasite infection, suggesting that this glycoconjugate can anchor parasite cysteine protease at host cell surface.

Safety lock for radiography exposure device

International Nuclear Information System (INIS)

Gaines, T.M.

1982-01-01

A safety lock for securing a radiation source in a radiography exposure device is disclosed. The safety lock prevents the inadvertent extension of the radiation source from the exposure device. The exposure devices are used extensively in industry for nondestructive testing of metal materials for defect. Unnecessary exposure of the radiographer or operator occurs not infrequently due to operator's error in believing that the radiation source is secured in the exposure device when, in fact, it is not. The present invention solves this problem of unnecessary exposure by releasingly trapping the radiation source in the shield of the radiography exposure device each time the source is retracted therein so that it is not inadvertently extended therefrom without the operator resetting the safety lock, thereby releasing the radiation source. Further, the safety lock includes an indicator which indicates when the source is trapped in the exposure device and also when it is untrapped. The safety lock is so designed that it does not prevent the return of the source to the trapped, shielded position in the exposure device. Further the safety lock includes a key means for locking the radiation source in the trapped position. The key means cannot be actuated until said radiation source is in said trapped position to further insure the safety lock cannot be inadvertently locked with the source untrapped and thus still extendable from the exposure device

Clinical effects of low-molecular-weight heparin combined with ...

African Journals Online (AJOL)

Tropical Journal of Pharmaceutical Research August 2016; 15 (8): 1787-1792 ... Keywords: Acute pancreatitis, Low-molecular-weight heparin, Multiple organ function syndrome,. APACHE II score ... mediators by lowering the expression of.

[Morphology research of the rat sciatic nerve bridged by collage-heparin sulfate scaffold].

Science.gov (United States)

Wang, Shu-sen; Hu, Yun-yu; Luo, Zhuo-jing; Chen, Liang-wei; Liu, Hui-ling; Meng, Guo-lin; Lü, Rong; Xu, Xin-zhi

2005-04-15

To observe the treating effect of collage-heparin sulfate after the 10 mm rat sciatic nerve defect was bridged by it. A new kind of nervous tissue engineering scaffold was produced by freeze-drying technique from collagen-heparin sulfate. Thirty-two SD rats were randomly divided into A, B, C and D groups. Sciatic nerve defect in group A was bridged by collagen-heparin sulfate. In group B, sciatic nerve was bridged by auto-nerve transplantation. Group C was the blank control group. Animals in group D were normal. And 10 mm sciatic nerve defect was bridged in the experiment. Thirty-six weeks after the operation, the experimental animals were detected by HRP labeled retrograde trace, HE staining, toluidine staining, silvering staining, S100, GAP-43 and NF immunohistological staining, MBP immunofluorescence staining and transmission electron microscope to observe the nerve regeneration inducing effect of this new scaffold. Nine months after operation, the collage-heparin sulfate scaffold was replaced by newly regenerated nerve. The number of HRP labeled spinal cord anterior horn cells and the area of sensation nerve fiber at the posterior horn were similar with that was repaired by auto-nerve. GAP-43, NF and S100 labeled regenerated nerve fiber had passed the total scaffold and entered the distal terminal. The regenerated nerve fibers were paralleled, lineage arranged, coincide with the prearranged regenerating "channel" in the collagen-heparin sulfate scaffold. MBP immunofluorescence staining also proved that the newly regenerated nerve fiber could be ensheathed. In the experimental group, the area of myelinated nerve fiber and the thickness of the myelin sheath had no obvious difference with that of the group repaired by auto-nerve, except that the density of the regenerated myelinated sheath fiber was lower than that of the control group. Nervous tissue engineering scaffold produced by collagen-heparin sulfate can guide the regeneration of nerve fibers. The nerve

Minimizing Hemodialysis Catheter Dysfunction: An Ounce of Prevention

Directory of Open Access Journals (Sweden)

Timmy Lee

2012-01-01

Full Text Available The maintenance of tunneled catheter (TC patency is critical for the provision of adequate hemodialysis in patients who are TC-dependent. TC dysfunction results in the need for costly and inconvenient interventions, and reduced quality of life. Since the introduction of TCs in the late 1980s, heparin catheter lock has been the standard prophylactic regimen for the prevention of TC dysfunction. More recently, alternative catheter locking agents have emerged, and in some cases have shown to be superior to heparin lock with respect to improving TC patency and reducing TC-associated infections. These include citrate, tissue plasminogen activator, and a novel agent containing sodium citrate, methylene blue, methylparaben, and propylparaben. In addition, prophylaxis using oral anticoagulants/antiplatelet agents, including warfarin, aspirin, ticlodipine, as well as the use of modified heparin-coated catheters have also been studied for the prevention of TC dysfunction with variable results. The use of oral anticoagulants and/or antiplatelet agents as primary or secondary prevention of TC dysfunction must be weighed against their potential adverse effects, and should be individualized for each patient.

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

Science.gov (United States)

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

2015-08-01

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

Farmacovigilância da heparina no Brasil Heparin pharmacovigilance in Brazil

Directory of Open Access Journals (Sweden)

Daniela Rezende Garcia Junqueira

2011-06-01

Full Text Available OBJETIVO: Investigar a origem das preparações de heparina, na forma farmacêutica injetável, disponíveis no mercado brasileiro, discutindo o impacto do perfil dos produtos comercializados e das alterações na monografia da heparina na segurança do fármaco. MÉTODOS: Pesquisou-se o banco de dados de Produtos Registrados das Empresas de Medicamentos da Anvisa e o Dicionário de Especialidades Farmacêuticas (DEF 2008/2009. Foi realizado inquérito com as indústrias com autorização ativa para o comércio do fármaco no Brasil. RESULTADOS: Cinco indústrias possuem autorização para o comércio de heparina não fracionada no Brasil. Três são de origem suína e duas de origem bovina, sendo que apenas uma possui essa informação explicitada na bula. A efetividade e a segurança da heparina, estudadas em populações estrangeiras, podem não representar a nossa realidade, já que a maioria dos países não produz a heparina bovina. A heparina atualmente comercializada tem, ainda, aproximadamente 10% menos atividade anticoagulante que a anteriormente produzida, e essa alteração pode ter implicações clínicas. CONCLUSÃO: Evidências acerca da ausência de intercambialidade de doses entre as heparinas de origem bovina e suína e o diferenciado perfil de segurança entre esses fármacos indicam necessidade de acompanhamento do tratamento e da resposta dos pacientes. Eventos que ameacem a segurança do paciente devem ser comunicados ao sistema da farmacovigilância do país.OBJECTIVE: To investigate the biological origin of injectable unfractioned heparin available in Brazilian market by discussing the impact of the profile of commercial products and the changes in heparin monograph on the drug safety. METHODS: The Anvisa data base for the Registered Products of Pharmaceutical Companies and the Dictionary of Pharmaceutical Specialties (DEF 2008/2009 were searched. A survey with industries having an active permission for marketing the drug

Dynamic analysis of the locking automatic rotor-balancing device of the multistage centrifugal pump for a turbulent fluid motion

OpenAIRE

Павленко, Іван

2013-01-01

The solution of the problem of the stress-strain state of the lock joint of a number of the operating blades of the steam turbine in an elastic formulation is presented. Also, the results of research in the form of the field of the stress, strain and contact pressure at the reference sites of the lock joint are presented.

Inversion of lithium heparin gel tubes after centrifugation is a significant source of bias in clinical chemistry testing.

Science.gov (United States)

Lippi, Giuseppe; Salvagno, Gian Luca; Danese, Elisa; Lima-Oliveira, Gabriel; Brocco, Giorgio; Guidi, Gian Cesare

2014-09-25

This study was planned to establish whether random orientation of gel tubes after centrifugation may impair sample quality. Eight gel tubes were collected from 17 volunteers: 2 Becton Dickinson (BD) serum tubes, 2 Terumo serum tubes, 2 BD lithium heparin tubes and 2 Terumo lithium heparin tubes. One patient's tube for each category was kept in a vertical, closure-up position for 90 min ("upright"), whereas paired tubes underwent bottom-up inversion every 15 min, for 90 min ("inverted"). Immediately after this period of time, 14 clinical chemistry analytes, serum indices and complete blood count were then assessed in all tubes. Significant increases were found for phosphate and lipaemic index in all inverted tubes, along with AST, calcium, cholesterol, LDH, potassium, hemolysis index, leukocytes, erythrocytes and platelets limited to lithium heparin tubes. The desirable quality specifications were exceeded for AST, LDH, and potassium in inverted lithium heparin tubes. Residual leukocytes, erythrocytes, platelets and cellular debris were also significantly increased in inverted lithium heparin tubes. Lithium heparin gel tubes should be maintained in a vertical, closure-up position after centrifugation. Copyright © 2014 Elsevier B.V. All rights reserved.

A study of lock-free based concurrent garbage collectors for multicore platform.

Science.gov (United States)

Wu, Hao; Ji, Zhen-Zhou

2014-01-01

Concurrent garbage collectors (CGC) have recently obtained extensive concern on multicore platform. Excellent designed CGC can improve the efficiency of runtime systems by exploring the full potential processing resources of multicore computers. Two major performance critical components for designing CGC are studied in this paper, stack scanning and heap compaction. Since the lock-based algorithms do not scale well, we present a lock-free solution for constructing a highly concurrent garbage collector. We adopt CAS/MCAS synchronization primitives to guarantee that the programs will never be blocked by the collector thread while the garbage collection process is ongoing. The evaluation results of this study demonstrate that our approach achieves competitive performance.

Globalizing carbon lock-in

International Nuclear Information System (INIS)

Unruh, Gregory C.; Carrillo-Hermosilla, Javier

2006-01-01

This paper extends the arguments surrounding carbon lock-in elaborated in Unruh (Energy Policy 28 (2000) 817; 30 (2002) 317) to countries currently undergoing industrialization. It argues that, for numerous reasons, industrializing countries are unlikely to leapfrog carbon intensive energy development. On the contrary, carbon lock-in may be globalizing and could further constrain climate change mitigation options. It is then argued that many policy recommendations ignore carbon lock-in, possibly limiting their potential for successful implementation. The paper then discusses four policy approaches that appear to have advantages given lock-in conditions. It is recognized, however, that relative ease of implementation does not necessarily equate with superiority. Instead, it is merely a path dependent outcome of past development decisions. Pursuing policies on the basis of relative implementation ease may help address the issue of climate change, but could also result in sub-optimal outcomes along other dimensions of sustainable development

LOCKS AND KEYS SERVICE

CERN Multimedia

Locks and Keys Service

2002-01-01

The Locks and Keys service (ST/FM) will move from building 55 to building 570 from the 2nd August to the 9th August 2002 included. During this period the service will be closed. Only in case of extreme urgency please call the 164550. Starting from Monday, 12th August, the Locks and Keys Service will continue to follow the activities related to office keys (keys and locks) and will provide the keys for furniture. The service is open from 8h30 to 12h00 and from 13h00 to 17h30. We remind you that your divisional correspondents can help you in the execution of the procedures. We thank you for your comprehension and we remain at your service to help you in solving all the matters related to keys for offices and furniture. Locks and Keys Service - ST Division - FM Group

Immobilized enzymes to convert N-sulfo, N-acetyl heparosan to a critical intermediate in the production of bioengineered heparin.

Science.gov (United States)

Xiong, Jian; Bhaskar, Ujjwal; Li, Guoyun; Fu, Li; Li, Lingyun; Zhang, Fuming; Dordick, Jonathan S; Linhardt, Robert J

2013-09-10

Heparin is a critically important anticoagulant drug that is prepared from pig intestine. In 2007-2008, there was a crisis in the heparin market when the raw material was adulterated with the toxic polysaccharide, oversulfated chondroitin sulfate, which was associated with 100 deaths in the U.S. alone. As the result of this crisis, our laboratory and others have been actively pursuing alternative sources for this critical drug, including synthetic heparins and bioengineered heparin. In assessing the bioengineering processing costs it has become clear that the use of both enzyme-catalyzed cofactor recycling and enzyme immobilization will be needed for commercialization. In the current study, we examine the use of immobilization of C₅-epimerase and 2-O-sulfotransferase involved in the first enzymatic step in the bioengineered heparin process, as well as arylsulfotransferase-IV involved in cofactor recycling in all three enzymatic steps. We report the successful immobilization of all three enzymes and their use in converting N-sulfo, N-acetyl heparosan into N-sulfo, N-acetyl 2-O-sulfo heparin. Copyright © 2013 Elsevier B.V. All rights reserved.

A new biocompatible delivery scaffold containing heparin and bone morphogenetic protein 2

Directory of Open Access Journals (Sweden)

Thanyaphoo Suphannee

2016-09-01

Full Text Available Silicon-substituted calcium phosphate (Si-CaP was developed in our laboratory as a biomaterial for delivery in bone tissue engineering. It was fabricated as a 3D-construct of scaffolds using chitosan-trisodium polyphosphate (TPP cross-linked networks. In this study, heparin was covalently bonded to the residual -NH2 groups of chitosan on the scaffold applying carbodiimide chemistry. Bonded heparin was not leached away from scaffold surfaces upon vigorous washing or extended storage. Recombinant human bone morphogenetic protein 2 (rhBMP-2 was bound to conjugated scaffolds by ionic interactions between the negatively charged SO42- clusters of heparin and positively charged amino acids of rhBMP-2. The resulting scaffolds were inspected for bone regenerative capacity by subcutaneous implanting in rats. Histological observation and mineralization assay were performed after 4 weeks of implantation. Results from both in vitro and in vivo experiments suggest the potential of the developed scaffolds for bone tissue engineering applications in the future.

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

Science.gov (United States)

O'Connell, Casey L; Liebman, Howard A

2008-12-01

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

Obstacles in the diagnostics and therapy of heparin-induced thrombocytopenia.

Science.gov (United States)

Antonijević, Nebojsa M; Radovanović, Nebojsa; Obradović, Slobodan; Vucelić, Dragica; Stojanović, Bojan; Miković, Danijela; Kovac, Mirjana; Kocica, Tina; Tadić, Svetlana; Antonijević, Irina; Drasković, Snezana; Djordjević, Valentina; Calija, Branko; Perunicić, Jovan; Vasiljević, Zorana

2010-01-01

An immune-mediated, severe, acquired prothrombotic disorder, heparin-induced thrombocytopenia type II (HIT II) occurs in 0.5-5% of patients exposed to unfractionated heparin longer than 5-7 days. Arterial and venous thromboses are induced by HIT II in about 35-50% of patients. Typical death rate for HIT is about 29%, while 21% of HIT patients result in amputation of a limb. The trend towards the occurrence of HIT due to the administration of low molecular weight heparins (LMWH) taking ever conspicuous place in the standard venous thromboembolism (VTE) prophylaxis has been more frequently observed recently. It is considered that LMWH may cause HIT II in about 0.25-1%. The need for further modification of HIPA assays with LMWH has been imposed in the HIT laboratory diagnostics, heretofore overburdened with complexity. There are several constantly opposing problems arising in HIT laboratory diagnostics, one of which is that in a certain number of patients immunologic assays detect nonpathogenic antibodies (mainly IgM or IgA heparin-PF4 antibodies) while, on the other hand, the occurrence of HIT pathogenetically mediated by minor antigens (neutrophil-activating peptide 2 or interleukin 8) may be neglected in certain cases. The following factors play an important role in the interpretation of each laboratory HIT assays performed: 1. correlation with HIT clinical probability test, the best known of which is 4T'score, 2. the interpretation of the laboratory findings dependent on the time of the thrombocytopenia onset, as well as 3. the sensitivity and specificity of each test respectively. The HIT diagnostics in the presence of other comorbid states which may also induce thrombocytopenia, more precisely known as pseudo HIT (cancer, sepsis, disseminated intravascular coagulation, pulmonary embolism, antiphospholipid syndrome, etc), represents a specific clinical problem.

49 CFR 236.761 - Locking, electric.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Locking, electric. 236.761 Section 236.761 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Locking, electric. The combination of one or more electric locks and controlling circuits by means of...

49 CFR 236.105 - Electric lock.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Electric lock. 236.105 Section 236.105 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION...: All Systems Inspections and Tests; All Systems § 236.105 Electric lock. Electric lock, except forced...

The physiologic and therapeutic role of heparin in implantation and placentation

Directory of Open Access Journals (Sweden)

Michela Quaranta

2015-01-01

Full Text Available Implantation, trophoblast development and placentation are crucial processes in the establishment and development of normal pregnancy. Abnormalities of these processes can lead to pregnancy complications known as the great obstetrical syndromes: preeclampsia, intrauterine growth restriction, fetal demise, premature prelabor rupture of membranes, preterm labor, and recurrent pregnancy loss. There is mounting evidence regarding the physiological and therapeutic role of heparins in the establishment of normal gestation and as a modality for treatment and prevention of pregnancy complications. In this review, we will summarize the properties and the physiological contributions of heparins to the success of implantation, placentation and normal pregnancy.

Protein interactions with quaternized chitosan/heparin multilayers

Czech Academy of Sciences Publication Activity Database

Kumorek, Marta M.; Kubies, Dana; Riedel, Tomáš

2016-01-01

Roč. 65, Suppl. 2 (2016), S253-S261 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) LQ1604 Institutional support: RVO:61389013 Keywords : heparin * chitosan * protein Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.461, year: 2016 http://www.biomed.cas.cz/physiolres/pdf/65%20Suppl%202/65_S253.pdf

Assessing carbon lock-in

International Nuclear Information System (INIS)

Erickson, Peter; Kartha, Sivan; Lazarus, Michael; Tempest, Kevin

2015-01-01

The term ‘carbon lock-in’ refers to the tendency for certain carbon-intensive technological systems to persist over time, ‘locking out’ lower-carbon alternatives, and owing to a combination of linked technical, economic, and institutional factors. These technologies may be costly to build, but relatively inexpensive to operate and, over time, they reinforce political, market, and social factors that make it difficult to move away from, or ‘unlock’ them. As a result, by investing in assets prone to lock-in, planners and investors restrict future flexibility and increase the costs of achieving agreed climate protection goals. Here, we develop a straight-forward approach to assess the speed, strength, and scale of carbon lock-in for major energy-consuming assets in the power, buildings, industry, and transport sectors. We pilot the approach at the global level, finding that carbon lock-in is greatest, globally, for coal power plants, gas power plants, and oil-based vehicles. The approach can be readily applied at the national or regional scale, and may be of particular relevance to policymakers interested in enhancing flexibility in their jurisdictions for deeper emissions cuts in the future, and therefore in limiting the future costs associated with ‘stranded assets’. (letter)

Phase-locked Josephson soliton oscillators

DEFF Research Database (Denmark)

Holst, T.; Hansen, Jørn Bindslev; Grønbech-Jensen, N.

1991-01-01

Detailed experimental characterization of the phase-locking at both DC and at microwave frequencies is presented for two closely spaced Josephson soliton (fluxon) oscillators. In the phase-locked state, the radiated microwave power exhibited an effective gain. With one common bias source......, a frequency tunability of the phase-locked oscillators up to 7% at 10 GHz was observed. The interacting soliton oscillators were modeled by two inductively coupled nonlinear transmission lines...

Basic fibroblast growth factor binds to subendothelial extracellular matrix and is released by heparitinase and heparin-like molecules

International Nuclear Information System (INIS)

Bashkin, P.; Doctrow, S.; Klagsbrun, M.; Svahn, C.M.; Folkman, J.; Vlodavsky, I.

1989-01-01

Basic fibroblast growth factor (bFGF) exhibits specific binding to the extracellular matrix (ECM) produced by cultured endothelial cells. Binding was saturable as a function both of time and of concentration of 125 I-bFGF. Scatchard analysis of FGF binding revealed the presence of about 1.5 x 10 12 binding sites/mm 2 ECM with an apparent k D of 610 nM. FGF binds to heparan sulfate (HS) in ECM as evidenced by (i) inhibition of binding in the presence of heparin or HS at 0.1-1 μg/mL, but not by chondroitin sulfate, keratan sulfate, or hyaluronic acid at 10 μg/mL, (ii) lack of binding to ECM pretreated with heparitinase, but not with chondroitinase ABC, and (iii) rapid release of up to 90% of ECM-bound FGF by exposure to heparin, HS, or heparitinase, but not to chondroitin sulfate, keratan sulfate, hyaluronic acid, or chondroitinase ABC. Oligosaccharides derived from depolymerized heparin, and as small as the tetrasaccharide, released the ECM-bound FGF, but there was little or no release of FGF by modified nonanticoagulant heparins such as totally desulfated heparin, N-desulfated heparin, and N-acetylated heparin. FGF released from ECM was biologically active, as indicated by its stimulation of cell proliferation and DNA synthesis in vascular endothelial cells and 3T3 fibroblasts. Similar results were obtained in studies on release of endogenous FGF-like mitogenic activity from Descement's membranes of bovine corneas. It is suggested that ECM storage and release of bFGF provide a novel mechanism for regulation of capillary blood vessel growth. Whereas ECM-bound FGF may be prevented from acting on endothelial cells, its displacement by heparin-like molecules and/or HS-degrading enzymes may elicit a neovascular response

Breaking Carbon Lock-in

DEFF Research Database (Denmark)

Driscoll, Patrick Arthur

2014-01-01

This central focus of this paper is to highlight the ways in which path dependencies and increasing returns (network effects) serve to reinforce carbon lock-in in large-scale road transportation infrastructure projects. Breaking carbon lock-in requires drastic changes in the way we plan future...

Phase-locking and bistability in neuronal networks with synaptic depression

Science.gov (United States)

Akcay, Zeynep; Huang, Xinxian; Nadim, Farzan; Bose, Amitabha

2018-02-01

We consider a recurrent network of two oscillatory neurons that are coupled with inhibitory synapses. We use the phase response curves of the neurons and the properties of short-term synaptic depression to define Poincaré maps for the activity of the network. The fixed points of these maps correspond to phase-locked modes of the network. Using these maps, we analyze the conditions that allow short-term synaptic depression to lead to the existence of bistable phase-locked, periodic solutions. We show that bistability arises when either the phase response curve of the neuron or the short-term depression profile changes steeply enough. The results apply to any Type I oscillator and we illustrate our findings using the Quadratic Integrate-and-Fire and Morris-Lecar neuron models.

A photovoltaic module diagnostic setup for lock-in-thermography and lock-in electroluminescence imaging

DEFF Research Database (Denmark)

Parikh, Harsh; Spataru, Sergiu; Sera, Dezso

2018-01-01

Electroluminescence (EL) imaging and infrared (IRT) thermography techniques have become indispensable tools in recent years for health diagnostic of PV modules in solar industry application. Complementary to these imaging methods, lock-in techniques can effectively remove noise by periodically...... modulating the input signal and averaging it over a desired number of periods. We propose a combined lock-in EL and lock-in IRT diagnostic setup for accurate analysis of different types of faults occurring in a solar module. The setup is built around a Goldeye CL-033 high-speed SWIR camera, which can acquire...... experimental work on a (36/72) cell solar module using combined (EL) or (IRT) lock-in-thermography. The setup allows one to investigate the different technological problems that can occur when performing PV diagnostics in drone-based inspections....

The N-terminal of a heparin-binding sperm membrane mitogen possess lectin-like sequence

International Nuclear Information System (INIS)

Mor, Visesato; Chatterjee, Tapati

2007-01-01

Glycosaminoglycans like heparin and heparin sulfate in follicular fluid induce changes in the intracellular environment during the spermatozoal functional maturation. We previously reported the isolation, purification and partial characterization of a heparin binding sperm membrane protein (HBSM). In the present study, the amino acids analysis provided evidence of a single sequence, which suggest the homogeneity of the purified HBSM. Fourteen amino acids- 1 A D T I V A V E L D T Y P N 14 -correspond to the amino terminal sequence of Concanavalin A (Con A) and contain 45.2% carbohydrate by weight. HBSM possess mitogenic property on lymphocytes with comparable magnitude to the well-known mitogen; Con A, inducing 83% radiolabel thymidine incorporation in growing lymphocytes. Unlike Con A, there was no agglutination of cell by HBSM upto 5 ng/ml concentration. Interestingly, we found that heparin and chondroitin sulfate-conjugated HBSM inhibit the proliferative activity. Similar effect was also found with an in-house isolate sulfated glycans; G-I (28% sulfate). In contrast, there was no inhibition by the desulfated form; G-ID. Altogether, our data suggest that the mechanism of cell proliferative pathway may be different for HBSM and Con A

49 CFR 236.705 - Bar, locking.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Bar, locking. 236.705 Section 236.705..., MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Definitions § 236.705 Bar, locking. A bar in an interlocking machine to which the locking dogs are attached. ...

49 CFR 236.768 - Locking, time.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Locking, time. 236.768 Section 236.768... Locking, time. A method of locking, either mechanical or electrical, which, after a signal has been caused to display an aspect to proceed, prevents, until after the expiration of a predetermined time...

Phase locking between Josephson soliton oscillators

DEFF Research Database (Denmark)

Holst, T.; Hansen, Jørn Bindslev; Grønbech-Jensen, N.

1990-01-01

We report observations of phase-locking phenomena between two Josephson soliton (fluxon) oscillators biased in self-resonant modes. The locking strength was measured as a function of bias conditions. A frequency tunability of the phase-locked oscillators up to 7% at 10 GHz was observed. Two coupled...... perturbed sine-Gordon equations were derived from an equivalent circuit consisting of inductively coupled, nonlinear, lossy transmission lines. These equations were solved numerically to find the locking regions. Good qualitative agreement was found between the experimental results and the calculations...

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

International Nuclear Information System (INIS)

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

1987-01-01

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

Low-power wide-locking-range injection-locked frequency divider for OFDM UWB systems

Energy Technology Data Exchange (ETDEWEB)

Yin Jiangwei; Li Ning; Zheng Renliang; Li Wei; Ren Junyan, E-mail: lining@fudan.edu.c [State Key Laboratory of ASIC and System, Fudan University, Shanghai 201203 (China)

2009-05-01

This paper describes a divide-by-two injection-locked frequency divider (ILFD) for frequency synthesizers as used in multiband orthogonal frequency division multiplexing (OFDM) ultra-wideband (UWB) systems. By means of dual-injection technique and other conventional tuning techniques, such as DCCA and varactor tuning, the divider demonstrates a wide locking range while consuming much less power. The chip was fabricated in the Jazz 0.18 mum RF CMOS process. The measurement results show that the divider achieves a locking range of 4.85 GHz (6.23 to 11.08 GHz) at an input power of 8 dBm. The core circuit without the test buffer consumes only 3.7 mA from a 1.8 V power supply and has a die area of 0.38 x 0.28 mm{sup 2}. The wide locking range combined with low power consumption makes the ILFD suitable for its application in UWB systems.

Low-power wide-locking-range injection-locked frequency divider for OFDM UWB systems

International Nuclear Information System (INIS)

Yin Jiangwei; Li Ning; Zheng Renliang; Li Wei; Ren Junyan

2009-01-01

This paper describes a divide-by-two injection-locked frequency divider (ILFD) for frequency synthesizers as used in multiband orthogonal frequency division multiplexing (OFDM) ultra-wideband (UWB) systems. By means of dual-injection technique and other conventional tuning techniques, such as DCCA and varactor tuning, the divider demonstrates a wide locking range while consuming much less power. The chip was fabricated in the Jazz 0.18 μm RF CMOS process. The measurement results show that the divider achieves a locking range of 4.85 GHz (6.23 to 11.08 GHz) at an input power of 8 dBm. The core circuit without the test buffer consumes only 3.7 mA from a 1.8 V power supply and has a die area of 0.38 x 0.28 mm 2 . The wide locking range combined with low power consumption makes the ILFD suitable for its application in UWB systems.

The clinical significance and risk factors of anti-platelet factor 4/heparin antibody on maintenance hemodialysis patients: a two-year prospective follow-up.

Directory of Open Access Journals (Sweden)

Delong Zhao

Full Text Available BACKGROUND: Heparin-induced thrombocytopenia is an immune response mediated by anti-PF4/heparin antibody, which is clinically characterized by thrombocytopenia and thromboembolic events. In this study, a prospective and multi-center clinical investigation 1 determined the positive rate of anti-PF4/heparin antibody in maintenance hemodialysis patients in China, 2 identified the related risk factors, and 3 further explored the effect of the anti-PF4/heparin antibody on bleeding, thromboembolic events, and risk of death in the patients. METHODS: The serum anti-PF4/heparin antibody was measured in 661 patients from nine hemodialysis centers, detected by IgG-specific ELISA and followed by confirmation with excess heparin. Risk factors of these patients were analyzed. Based on a two-year follow-up, the association between the anti-PF4/heparin antibody and bleeding, thromboembolic events, and risk of death in the patients was investigated. RESULTS: 1 The positivity rate of the anti-PF4/heparin antibody in maintenance hemodialysis patients was 5.6%. With diabetes as an independent risk factor, the positivity rate of the anti-PF4/heparin antibody decreased in the patients undergoing weekly dialyses ≥3 times. 2 The positivity rate of the anti-PF4/heparin antibody was not related to the occurrence of clinical thromboembolic events and was not a risk factor for death within two years in maintenance hemodialysis patients. 3 Negativity for the anti-PF4/heparin antibody combined with a reduction of the platelet count or combined with the administration of antiplatelet drugs yielded a significant increase in bleeding events. However, the composite determination of the anti-PF4/heparin antibody and thrombocytopenia, as well as the administration of antiplatelet drugs, was not predictive for the risk of thromboembolic events in the maintenance hemodialysis patients. CONCLUSIONS: A single detection of the anti-PF4/heparin antibody did not predict the occurrence

Self-locking degree-4 vertex origami structures.

Science.gov (United States)

Fang, Hongbin; Li, Suyi; Wang, K W

2016-11-01

A generic degree-4 vertex (4-vertex) origami possesses one continuous degree-of-freedom for rigid folding, and this folding process can be stopped when two of its facets bind together. Such facet-binding will induce self-locking so that the overall structure stays at a pre-specified configuration without additional locking elements or actuators. Self-locking offers many promising properties, such as programmable deformation ranges and piecewise stiffness jumps, that could significantly advance many adaptive structural systems. However, despite its excellent potential, the origami self-locking features have not been well studied, understood, and used. To advance the state of the art, this research conducts a comprehensive investigation on the principles of achieving and harnessing self-locking in 4-vertex origami structures. Especially, for the first time, this study expands the 4-vertex structure construction from single-component to dual-component designs and investigates their self-locking behaviours. By exploiting various tessellation designs, this research discovers that the dual-component designs offer the origami structures with extraordinary attributes that the single-component structures do not have, which include the existence of flat-folded locking planes, programmable locking points and deformability. Finally, proof-of-concept experiments investigate how self-locking can effectively induce piecewise stiffness jumps. The results of this research provide new scientific knowledge and a systematic framework for the design, analysis and utilization of self-locking origami structures for many potential engineering applications.

Optical double-locked semiconductor lasers

Science.gov (United States)

AlMulla, Mohammad

2018-06-01

Self-sustained period-one (P1) nonlinear dynamics of a semiconductor laser are investigated when both optical injection and modulation are applied for stable microwave frequency generation. Locking the P1 oscillation through modulation on the bias current, injection strength, or detuning frequency stabilizes the P1 oscillation. Through the phase noise variance, the different modulation types are compared. It is demonstrated that locking the P1 oscillation through optical modulation on the output of the master laser outperforms bias-current modulation of the slave laser. Master laser modulation shows wider P1-oscillation locking range and lower phase noise variance. The locking characteristics of the P1 oscillation also depend on the operating conditions of the optical injection system

First Metatarsophalangeal Joint Arthrodesis: A Retrospective Comparison of Crossed-screws, Locking and Non-Locking Plate Fixation with Lag Screw

Directory of Open Access Journals (Sweden)

Leif Claassen

2017-07-01

Full Text Available Background:Locking plate fixation is increasingly used for first metatarsophalangeal joint (MTP-I arthrodesis. Still there is few comparable clinical data regarding this procedure. Methods:We retrospectively evaluated 60 patients who received an arthrodesis of the MTP-I between January 2008 and June 2010. With 20 patients each we performed a locking plate fixation with lag screw, arthrodesis with crossed-screwsor with a nonlocking plate with lag screw. Results: There were four non-unions in crossed-screws patients and one nonunion in non-locked plate group. All the patients in locking plate group achieved union. 90% of the patients were completely or mildly satisfied in locking plate group, whereas this rate was 80% for patients in both crossed screws and non-locking plate groups. Conclusions: Use of dorsal plating for arthrodesis of MTP1 joint either locking or non-locking were associated with high union rate and acceptable and comparable functional outcome. Although nonunion rate was high using two crossed screws but functional outcome was not significantly different compare to dorsal plating. Level of evidence:Ш, retrospective comparative study

Bicycle Parking and Locking

DEFF Research Database (Denmark)

Larsen, Jonas

2017-01-01

. This article contributes with new insights into parking and locking - ‘moorings’ - to cycling literature. It presents an ethnography of ‘design moorings’ and practices associated with parking and locking bikes. The main case study is the very pro-cycling city of Copenhagen. Yet to explore what is unique about...

Platelet-derived growth factor inhibits platelet activation in heparinized whole blood.

Science.gov (United States)

Selheim, F; Holmsen, H; Vassbotn, F S

1999-08-15

We previously have demonstrated that human platelets have functionally active platelet-derived growth factor alpha-receptors. Studies with gel-filtered platelets showed that an autocrine inhibition pathway is transduced through this tyrosine kinase receptor during platelet activation. The physiological significance of this inhibitory effect of platelet-derived growth factor on gel-filtered platelets activation is, however, not known. In the present study, we investigated whether platelet-derived growth factor inhibits platelet activation under more physiological conditions in heparinized whole blood, which represents a more physiological condition than gel-filtered platelets. Using flow cytometric assays, we demonstrate here that platelet-derived growth factor inhibits thrombin-, thrombin receptor agonist peptide SFLLRN-, and collagen-induced platelet aggregation and shedding of platelet-derived microparticles from the platelet plasma membrane during platelet aggregation in stirred heparinized whole blood. The inhibitory effect of platelet-derived growth factor was dose dependent. However, under nonaggregating conditions (no stirring), we could not demonstrate any significant effect of platelet-derived growth factor on thrombin- and thrombin receptor agonist peptide-induced platelet surface expression of P-selectin. Our results demonstrate that platelet-derived growth factor appears to be a true antithrombotic agent only under aggregating conditions in heparinized whole blood.

The effect of heparin on pregnancy associated plasma protein-A concentration in healthy, non-pregnant individuals

DEFF Research Database (Denmark)

Jespersen, Camilla H B; Vestergaard, Kirstine R.; Schou, Morten

2015-01-01

Objectives: The objective of this study was to determine the differences in pregnancy associated plasma protein-A (PAPP-A) concentrations in heparin naive and heparin treated healthy men and non-pregnant women, to find a possible difference in different age groups, and to determine the response...

49 CFR 236.757 - Lock, electric.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Lock, electric. 236.757 Section 236.757... Lock, electric. A device to prevent or restrict the movement of a lever, a switch or a movable bridge, unless the locking member is withdrawn by an electrical device, such as an electromagnet, solenoid or...

Proteomic analysis of heparin-binding proteins from human seminal ...

Indian Academy of Sciences (India)

Prakash

(MALDI TOF/MS) for protein analysis of human HBPs. We resolved 70 ... Thus, the combined effects of seminal plasma components support the survival of ...... The BBXB motif of RANTES is the principal site for heparin binding and controls ...

Vitamin K antagonists or low-molecular-weight heparin for the long term treatment of symptomatic venous thromboembolism

NARCIS (Netherlands)

van der Heijden, J. F.; Hutten, B. A.; Büller, H. R.; Prins, M. H.

2002-01-01

BACKGROUND: People with venous thromboembolism are generally treated for five days with intravenous unfractionated heparin or subcutaneous low-molecular-weight heparin followed by three months of vitamin K antagonists treatment. Treatment with vitamin K antagonists requires regular laboratory

Influence of spacer length on heparin coupling efficiency and fibrinogen adsorption of modified titanium surfaces

Directory of Open Access Journals (Sweden)

Gbureck Uwe

2007-07-01

Full Text Available Abstract Background Chemical bonding of the drug onto surfaces by means of spacer molecules is accompanied with a reduction of the biological activity of the drug due to a constricted mobility since normally only short spacer molecule like aminopropyltrimethoxysilane (APMS are used for drug coupling. This work aimed to study covalent attachment of heparin to titanium(oxide surfaces by varying the length of the silane coupling agent, which should affect the biological potency of the drug due to a higher mobility with longer spacer chains. Methods Covalent attachment of heparin to titanium metal and TiO2 powder was carried out using the coupling agents 3-(Trimethoxysilyl-propylamine (APMS, N- [3-(Trimethoxysilylpropyl]ethylenediamine (Diamino-APMS and N1- [3-(Trimethoxy-silyl-propyl]diethylenetriamine (Triamino-APMS. The amount of bound coupling agent and heparin was quantified photometrically by the ninhydrin reaction and the tolidine-blue test. The biological potency of heparin was determined photometrically by the chromogenic substrate Chromozym TH and fibrinogen adsorption to the modified surfaces was researched using the QCM-D (Quartz Crystal Microbalance with Dissipation Monitoring technique. Results Zeta-potential measurements confirmed the successful coupling reaction; the potential of the unmodified anatase surface (approx. -26 mV shifted into the positive range (> + 40 mV after silanisation. Binding of heparin results in a strongly negatively charged surface with zeta-potentials of approx. -39 mV. The retaining biological activity of heparin was highest for the spacer molecule Triamino-APMS. QCM-D measurements showed a lower viscosity for adsorbed fibrinogen films on heparinised surfaces by means of Triamino-APMS. Conclusion The remaining activity of heparin was found to be highest for the covalent attachment with Triamino-APMS as coupling agent due to the long chain of this spacer molecule and therefore the highest mobility of the drug

A Study of Lock-Free Based Concurrent Garbage Collectors for Multicore Platform

Directory of Open Access Journals (Sweden)

Hao Wu

2014-01-01

Full Text Available Concurrent garbage collectors (CGC have recently obtained extensive concern on multicore platform. Excellent designed CGC can improve the efficiency of runtime systems by exploring the full potential processing resources of multicore computers. Two major performance critical components for designing CGC are studied in this paper, stack scanning and heap compaction. Since the lock-based algorithms do not scale well, we present a lock-free solution for constructing a highly concurrent garbage collector. We adopt CAS/MCAS synchronization primitives to guarantee that the programs will never be blocked by the collector thread while the garbage collection process is ongoing. The evaluation results of this study demonstrate that our approach achieves competitive performance.

Safety and potential anticoagulant effects of nebulised heparin in burns patients with inhalational injury at Singapore General Hospital Burns Centre.

Science.gov (United States)

Yip, Lian Yee; Lim, Yen Fang; Chan, Hong Ngee

2011-11-01

Nebulised heparin, N-acetylcysteine (NAC) and salbutamol were shown to decrease reintubation rates, incidence of atelectasis and mortality in paediatric patients and reduce lung injury scores in adult burns patients with inhalational lung injury (ILI). Nebulised heparin, NAC and salbutamol treatment protocol was introduced in Singapore General Hospital (SGH) Burns Centre in 2006. However, safety data on the use of nebulised heparin and NAC for burns patients with ILI is not well established. In this study, we investigated the safety and potential anticoagulant effects of nebulised heparin in burns patients with ILI. A retrospective study with historical control was conducted. The treatment group consisted of 52 mechanically ventilated adult patients, with a diagnosis of ILI as confirmed by bronchoscopy, admitted to burn intensive care unit (BICU) from the year 2006 to 2009. The group was treated with nebulised heparin, NAC and salbutamol. The control group consists of 11 mechanically ventilated BICU ILI patients treated from year 2001 to 2005 before protocol initiation. Blood coagulation indices (prothrombin time (PT), activated partial thromboplastin time (APTT) and platelet count) were monitored and bleeding incidences were assessed. Blood coagulation indices did not suggest an increase risk of bleeding with nebulised heparin. The APTT, PT and platelet count followed a similar trend for both groups over 7 days. No clinically significant increase in bleeding risk was found to be associated with nebulised heparin. Nebulised heparin was not found to potentiate the risk of bleeding in burns patients with ILI. Copyright © 2011 Elsevier Ltd and ISBI. All rights reserved.

ADRIAMYCIN-LOADED ALBUMIN-HEPARIN CONJUGATE MICROSPHERES FOR INTRAPERITONEAL CHEMOTHERAPY

NARCIS (Netherlands)

CREMERS, HFM; SEYMOUR, LW; LAM, K; LOS, G; KWON, G; BAE, YH; KIM, SW; FEIJEN, J

1994-01-01

Adriamycin-loaded albumin-heparin conjugate microspheres (ADR-AHCMS) were evaluated as possible intraperitoneal (i.p.) delivery systems for site-specific cytotoxic action. The biocompatibility of the microspheres after intraperitoneal injection was tested first. 1 day after i.p. administration of

Robust tilt and lock mechanism for hopping actuator

Energy Technology Data Exchange (ETDEWEB)

Salton, Jonathan R.; Buerger, Stephen; Dullea, Kevin J.; Marron, Lisa C.; Salisbury, Curt Michael; Spletzer, Barry Louis

2017-02-07

A tilt and lock apparatus that includes a tilt servomechanism, a spiral torsion spring, a lock wheel, and a lock hook is described herein. The spiral torsion spring is mechanically coupled to the tilt servomechanism and the lock wheel (which includes an opening). When a shaft is positioned through the opening, rotation of the lock wheel is in unison with rotation of the shaft. An external surface of the lock wheel includes one or more grooves. The lock hook includes a head that engages and disengages the grooves. The lock wheel is stationary when the head engages one of the grooves and is rotatable when the head disengages the grooves. The head and the grooves are geometrically aligned when engaged to prevent creation of a force that acts to disengage the head responsive to an applied force acting on the shaft.

Cooperative control of blood compatibility and re-endothelialization by immobilized heparin and substrate topography.

Science.gov (United States)

Ding, Yonghui; Yang, Meng; Yang, Zhilu; Luo, Rifang; Lu, Xiong; Huang, Nan; Huang, Pingbo; Leng, Yang

2015-03-01

A wide variety of environmental cues provided by the extracellular matrix, including biophysical and biochemical cues, are responsible for vascular cell behavior and function. In particular, substrate topography and surface chemistry have been shown to regulate blood and vascular compatibility individually. The combined impact of chemical and topographic cues on blood and vascular compatibility, and the interplay between these two types of cues, are subjects that are currently being explored. In the present study, a facile polydopamine-mediated approach is introduced for immobilization of heparin on topographically patterned substrates, and the combined effects of these cues on blood compatibility and re-endothelialization are systematically investigated. The results show that immobilized heparin and substrate topography cooperatively modulate anti-coagulation activity, endothelial cell (EC) attachment, proliferation, focal adhesion formation and endothelial marker expression. Meanwhile, the substrate topography is the primary determinant of cell alignment and elongation, driving in vivo-like endothelial organization. Importantly, combining immobilized heparin with substrate topography empowers substantially greater competitive ability of ECs over smooth muscle cells than each cue individually. Moreover, a model is proposed to elucidate the cooperative interplay between immobilized heparin and substrate topography in regulating cell behavior. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Heparin binding chitosan derivatives for production of pro-angiogenic hydrogels for promoting tissue healing

Energy Technology Data Exchange (ETDEWEB)

Yar, Muhammad, E-mail: drmyar@ciitlahore.edu.pk [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000 (Pakistan); Shahzad, Sohail [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000 (Pakistan); Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100 (Pakistan); Shahzadi, Lubna [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000 (Pakistan); Shahzad, Sohail Anjum [Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad 22060 (Pakistan); Mahmood, Nasir [Department of Allied Health Sciences and Chemical Pathology, University of Health Sciences, Lahore (Pakistan); Department of Human Genetics and Molecular Biology, University of Health Sciences, Lahore (Pakistan); Chaudhry, Aqif Anwar [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000 (Pakistan); Rehman, Ihtesham ur [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000 (Pakistan); Materials Science and Engineering, North Campus, University of Sheffield, Broad Lane, Sheffield S3 7HQ (United Kingdom); MacNeil, Sheila, E-mail: s.macneil@sheffield.ac.uk [Materials Science and Engineering, North Campus, University of Sheffield, Broad Lane, Sheffield S3 7HQ (United Kingdom)

2017-05-01

Our aim was to develop a biocompatible hydrogel that could be soaked in heparin and placed on wound beds to improve the vasculature of poorly vascularized wound beds. In the current study, a methodology was developed for the synthesis of a new chitosan derivative (CSD-1). Hydrogels were synthesized by blending CSD-1 for either 4 or 24 h with polyvinyl alcohol (PVA). The physical/chemical interactions and the presence of specific functional groups were confirmed by Fourier transform infrared (FT-IR) spectroscopy and proton nuclear magnetic resonance ({sup 1}H NMR). The porous nature of the hydrogels was confirmed by scanning electron microscopy (SEM). Thermal gravimetric analysis (TGA) showed that these hydrogels have good thermal stability which was slightly increased as the blending time was increased. Hydrogels produced with 24 h of blending supported cell attachment more and could be loaded with heparin to induce new blood vessel formation in a chick chorionic allantoic membrane assay. - Highlights: • Chitosan based hydrogels were designed to stimulate angiogenesis. • Two new derivatives of chitosan were produced using a Mannich type reaction. • Blending a chitosan derivative with PVA gave a porous biocompatible hydrogel. • Heparin bound to the hydrogel on immersion changing its morphology. • Heparin loaded hydrogel stimulated blood vessel formation in a chick model.

Heparin sodium compliance to USP monograph: structural elucidation of an atypical 2.18 ppm NMR signal.

Science.gov (United States)

Mourier, Pierre A J; Guichard, Olivier Y; Herman, Fréderic; Viskov, Christian

2012-01-01

The ¹H nuclear magnetic resonance (NMR) acceptance criteria in the new heparin US Pharmacopeia (USP) monograph do not take into account potential structural modifications responsible for any extra signals observed in ¹H NMR spectra, some purified heparins may be non-compliant under the proposed new USP guidelines and incorrectly classified as unsuitable for pharmaceutical use. Heparins from the "ES" source, containing an extra signal at 2.18 ppm, were depolymerized under controlled conditions using heparinases I, II, and III. The oligosaccharides responsible for the 2.18 ppm signal were enriched using orthogonal chromatographic techniques. After multiple purification steps, we obtained an oligosaccharide mixture containing a highly enriched octasaccharide bearing the structural modification responsible for the extra signal. Following heparinase I depolymerization, a pure tetrasaccharide containing the fingerprint structural modification was isolated for full structural determination. Using 1D and 2D ¹H NMR spectroscopy, the structural moiety responsible for the extra signal at 2.18 ppm was identified as an acetyl group on the heparin backbone, most likely resulting from a very minor manufacturing process side reaction that esterifies the uronic acid at position 3. Such analytical peculiarity has always been present in this heparin source and it was used safety over the years. Copyright © 2012 Elsevier B.V. All rights reserved.

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

Science.gov (United States)

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

2016-02-01

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

Spurious hypocalcemia in hemodialysis patients after heparinization. In-vitro formation of calcium soaps.

Science.gov (United States)

Godolphin, W; Cameron, E C; Frohlich, J; Price, J D

1979-02-01

Patients on long-term hemodialysis via arteriovenous fistula received heparin when the fistula needle was inserted, before a sample of blood was obtained for chemical analysis. The resultant release of lipoprotein lipase activity in vivo and continued lipolytic activity in vitro sometimes produced sufficient free fatty acid to precipitate calcium soaps. The consequent spurious hypocalcemia was most frequently observed when the patients had chylomicronemia. This cause of apparent hypocalcemia was eliminated either by immediate analyses of the blood samples or by obtaining samples before systemic heparinization.

Vitamin K antagonists or low-molecular-weight heparin for the long term treatment of symptomatic venous thromboembolism

NARCIS (Netherlands)

van der Heijden, J. F.; Hutten, B. A.; Büller, H. R.; Prins, M. H.

2000-01-01

Patients who have had an episode of symptomatic venous thromboembolism are usually treated for at least five days with intravenous unfractionated heparin or subcutaneous low-molecular-weight heparin. Thereafter, they received a three month course of a vitamin K antagonist, with a dose adjusted to

Accelerating the peroxidase-like activity of gold nanoclusters at neutral pH for colorimetric detection of heparin and heparinase activity.

Science.gov (United States)

Hu, Lianzhe; Liao, Hong; Feng, Lingyan; Wang, Min; Fu, Wensheng

2018-04-26

The peroxidase-like catalytic activity of gold nanoclusters (NCs) is quite low around physiological pH, which greatly limits their biological applications. Herein, we found heparin can greatly accelerate the peroxidase-like activity of Au-NCs at neutral pH. The catalytic activity of Au-NCs toward the peroxidase substrate 3,3',5,5'-tetramethylbenzidine (TMB) oxidation by H2O2 was 25-fold increased in the presence of heparin at pH 7. The addition of heparin not only accelerated the initial catalytic rate of Au-NCs, but also prevented the Au-NCs from catalyst deactivation. This allows the sensitive colorimetric detection of heparin at neutral pH. In the presence of heparinase, heparin was hydrolyzed into small fragments, weakening the enhancement effect of catalytic activity. Based on this phenomenon, the sensitive colorimetric determination of heparinase in biological samples was also developed.

Microcontroller-based locking in optics experiments

International Nuclear Information System (INIS)

Huang, K.; Le Jeannic, H.; Ruaudel, J.; Morin, O.; Laurat, J.

2014-01-01

Optics experiments critically require the stable and accurate locking of relative phases between light beams or the stabilization of Fabry-Perot cavity lengths. Here, we present a simple and inexpensive technique based on a stand-alone microcontroller unit to perform such tasks. Easily programmed in C language, this reconfigurable digital locking system also enables automatic relocking and sequential functioning. Different algorithms are detailed and applied to fringe locking and to low- and high-finesse optical cavity stabilization, without the need of external modulations or error signals. This technique can readily replace a number of analog locking systems advantageously in a variety of optical experiments

Microcontroller-based locking in optics experiments.

Science.gov (United States)

Huang, K; Le Jeannic, H; Ruaudel, J; Morin, O; Laurat, J

2014-12-01

Optics experiments critically require the stable and accurate locking of relative phases between light beams or the stabilization of Fabry-Perot cavity lengths. Here, we present a simple and inexpensive technique based on a stand-alone microcontroller unit to perform such tasks. Easily programmed in C language, this reconfigurable digital locking system also enables automatic relocking and sequential functioning. Different algorithms are detailed and applied to fringe locking and to low- and high-finesse optical cavity stabilization, without the need of external modulations or error signals. This technique can readily replace a number of analog locking systems advantageously in a variety of optical experiments.

Microcontroller-based locking in optics experiments

Energy Technology Data Exchange (ETDEWEB)

Huang, K. [Laboratoire Kastler Brossel, UPMC-Sorbonne Universités, CNRS, ENS-PSL Research University, Collège de France, 4 place Jussieu, 75005 Paris (France); State Key Laboratory of Precision Spectroscopy, East China Normal University, Shanghai 200062 (China); Le Jeannic, H.; Ruaudel, J.; Morin, O.; Laurat, J., E-mail: julien.laurat@upmc.fr [Laboratoire Kastler Brossel, UPMC-Sorbonne Universités, CNRS, ENS-PSL Research University, Collège de France, 4 place Jussieu, 75005 Paris (France)

2014-12-15

Optics experiments critically require the stable and accurate locking of relative phases between light beams or the stabilization of Fabry-Perot cavity lengths. Here, we present a simple and inexpensive technique based on a stand-alone microcontroller unit to perform such tasks. Easily programmed in C language, this reconfigurable digital locking system also enables automatic relocking and sequential functioning. Different algorithms are detailed and applied to fringe locking and to low- and high-finesse optical cavity stabilization, without the need of external modulations or error signals. This technique can readily replace a number of analog locking systems advantageously in a variety of optical experiments.

Biofilm formation in long-term central venous catheters in children with cancer

DEFF Research Database (Denmark)

Handrup, Mette Møller; Fuursted, Kurt; Funch, Peter

2012-01-01

Taurolidine has demonstrated inhibition of biofilm formation in vitro. The aim of this study was to compare the effect of catheter locking with taurolidine vs heparin in biofilm formation in central venous catheters. Forty-eight children with cancer were randomized to catheter locking by heparin (n...... = 22) or taurolidine (n = 26), respectively. After removal, catheters were examined by standardized scanning electron microscopy to assess quantitative biofilm formation. Biofilm was present if morphologically typical structures and bacterial cells were identified. Quantitative and semi...... in the intraluminal biofilm formation and the rate of bacterial colonization detected by scanning electron microscopy in the two groups....

Heparin-binding epidermal growth factor-like growth factor promotes neuroblastoma differentiation.

Science.gov (United States)

Gaviglio, Angela L; Knelson, Erik H; Blobe, Gerard C

2017-05-01

High-risk neuroblastoma is characterized by undifferentiated neuroblasts and low schwannian stroma content. The tumor stroma contributes to the suppression of tumor growth by releasing soluble factors that promote neuroblast differentiation. Here we identify heparin-binding epidermal growth factor-like growth factor (HBEGF) as a potent prodifferentiating factor in neuroblastoma. HBEGF mRNA expression is decreased in human neuroblastoma tumors compared with benign tumors, with loss correlating with decreased survival. HBEGF protein is expressed only in stromal compartments of human neuroblastoma specimens, with tissue from high-stage disease containing very little stroma or HBEGF expression. In 3 human neuroblastoma cell lines (SK-N-AS, SK-N-BE2, and SH-SY5Y), soluble HBEGF is sufficient to promote neuroblast differentiation and decrease proliferation. Heparan sulfate proteoglycans and heparin derivatives further enhance HBEGF-induced differentiation by forming a complex with the epidermal growth factor receptor, leading to activation of the ERK1/2 and STAT3 pathways and up-regulation of the inhibitor of DNA binding transcription factor. These data support a role for loss of HBEGF in the neuroblastoma tumor microenvironment in neuroblastoma pathogenesis.-Gaviglio, A. L., Knelson, E. H., Blobe, G. C. Heparin-binding epidermal growth factor-like growth factor promotes neuroblastoma differentiation. © FASEB.

Heparin-Induced Thrombocytopenia Associated with Massive Intracardiac Thrombosis: A Case Report

Directory of Open Access Journals (Sweden)

Atheer Ahmed

2012-01-01

Full Text Available A 60-years old patient was admitted to a community hospital with septic arthritis. He was treated with antibiotics and subcutaneous unfractionated heparin (UH was used for venous thromboprophylaxis. After three days, he developed leg deep venous thrombosis and was treated with IV heparin. One day later, the patient developed pulmonary emboli, which was found using ventilation/perfusion scan. He was transferred to the University Hospital for further management. Upon arrival, antibiotic and intravenous UH were continued. Trans-Esophageal Echocardiogram showed a thrombus in the right atrium, a small portion of which extended to the left atrium through a patent foramen ovale. Another large thrombus was noted in the right ventricle, which extended to the pulmonary artery. Review of the patient’s medical records revealed a halving of his platelet count three days following the heparin administration. Therefore, HIT seemed very likely. Intravenous UH was stopped and an emergency thrombectomy was performed. ELISA testing of HIT antibodies came negative. This made HIT diagnosis unlikely and the patient received dalteparin. A week later, as the platelet count declined again, HIT antibodies’ testing using ELISA and C-14 serotonin release was repeated, and both assays were positive. Argatroban was restarted and the platelet count normalized.

Heterogeneous Silicon III-V Mode-Locked Lasers

Science.gov (United States)

Davenport, Michael Loehrlein

Mode-locked lasers are useful for a variety of applications, such as sensing, telecommunication, and surgical instruments. This work focuses on integrated-circuit mode-locked lasers: those that combine multiple optical and electronic functions and are manufactured together on a single chip. While this allows production at high volume and lower cost, the true potential of integration is to open applications for mode-locked laser diodes where solid state lasers cannot fit, either due to size and power consumption constraints, or where small optical or electrical paths are needed for high bandwidth. Unfortunately, most high power and highly stable mode-locked laser diode demonstrations in scientific literature are based on the Fabry-Perot resonator design, with cleaved mirrors, and are unsuitable for use in integrated circuits because of the difficulty of producing integrated Fabry-Perot cavities. We use silicon photonics and heterogeneous integration with III-V gain material to produce the most powerful and lowest noise fully integrated mode-locked laser diode in the 20 GHz frequency range. If low noise and high peak power are required, it is arguably the best performing fully integrated mode-locked laser ever demonstrated. We present the design methodology and experimental pathway to realize a fully integrated mode-locked laser diode. The construction of the device, beginning with the selection of an integration platform, and proceeding through the fabrication process to final optimization, is presented in detail. The dependence of mode-locked laser performance on a wide variety of design parameters is presented. Applications for integrated circuit mode-locked lasers are also discussed, as well as proposed methods for using integration to improve mode-locking performance to beyond the current state of the art.

Chronic intravascular coagulation associated with chronic myelocytic leukemia. Use of heparin in connection with a surgical procedure.

Science.gov (United States)

German, H J; Smith, J A; Lindenbaum, J

1976-10-01

A women with Philadelphia chromosome-positive chronic myelocytic leukemia lived nearly 12 years from the time of diagnosis. During most of this period she received no therapy, and marked cyclic oscillations in the white blood cell count were documented. The last two years of her illness were marked by a hemorrhagic disorder associated with hypofibrinogenemia, thrombocytopenia, increased plasma fibrinopeptide A concentration and markedly elevated serum levels of fibrin degradation products. The coagulation disorder was rapidly reversible on several occasions with heparin therapy. After treatment with heparin and platelet transfusions, the patient underwent successful resection of a large ovarian cyst with excellent hemostasis during the procedure. Postoperatively, the administration of heparin and platelets was discontinued and a large wound hematoma developed. After resumption of therapy with heparin and platelets, the remainder of her postoperative course was uneventful. The literature on the subject is reviewed and tentative guidelines are offered concerning the management of patients with intravascular coagulation who require diagnostic or therapeutic surgical procedures.

30 CFR 56.12068 - Locking transformer enclosures.

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Locking transformer enclosures. 56.12068 Section 56.12068 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND... § 56.12068 Locking transformer enclosures. Transformer enclosures shall be kept locked against...

Bilateral locked facets in the thoracic spine

NARCIS (Netherlands)

M.H.A. Willems; Braakman, R. (Reinder); B. van Linge (Bert)

1984-01-01

textabstractTwo cases of traumatic bilateral locked facets in the thoracic spine are reported. Both patients had only minor neurological signs. They both made a full neurological recovery after surgical reduction of the locked facets. Bilateral locked facets are very uncommon in the thoracic spine.

Computation of the lock-in ranges of phase-locked loops with PI filter

OpenAIRE

Aleksandrov, Konstantin D.; Kuznetsov, Nikolay; Leonov, Gennady A.; Neittaanmäki, Pekka; Yuldashev, Marat V.; Yuldashev, Renat V.

2016-01-01

In the present work the lock-in range of PLL-based circuits with proportionallyintegrating filter and sinusoidal phase-detector characteristics are studied. Considered circuits have sinusoidal phase detector characteristics. Analytical approach based on the methods of phase plane analysis is applied to estimate the lock-in ranges of the circuits under consideration. Obtained analytical results are compared with simulation results.

Biomechanics of far cortical locking.

Science.gov (United States)

Bottlang, Michael; Feist, Florian

2011-02-01

The development of far cortical locking (FCL) was motivated by a conundrum: locked plating constructs provide inherently rigid stabilization, yet they should facilitate biologic fixation and secondary bone healing that relies on flexible fixation to stimulate callus formation. Recent studies have confirmed that the high stiffness of standard locked plating constructs can suppress interfragmentary motion to a level that is insufficient to reliably promote secondary fracture healing by callus formation. Furthermore, rigid locking screws cause an uneven stress distribution that may lead to stress fracture at the end screw and stress shielding under the plate. This review summarizes four key features of FCL constructs that have been shown to enhance fixation and healing of fractures: flexible fixation, load distribution, progressive stiffening, and parallel interfragmentary motion. Specifically, flexible fixation provided by FCL reduces the stiffness of a locked plating construct by 80% to 88% to actively promote callus proliferation similar to an external fixator. Load is evenly distributed between FCL screws to mitigate stress risers at the end screw. Progressive stiffening occurs by near cortex support of FCL screws and provides additional support under elevated loading. Finally, parallel interfragmentary motion by the S-shaped flexion of FCL screws promotes symmetric callus formation. In combination, these features of FCL constructs have been shown to induce more callus and to yield significantly stronger and more consistent healing compared with standard locked plating constructs. As such, FCL constructs function as true internal fixators by replicating the biomechanical behavior and biologic healing response of external fixators.

Comparison of hematologic values in blood samples with lithium heparin or dipotassium ethylenediaminetetraacetic acid anticoagulants in Hispaniolan Amazon parrots (Amazona ventralis).

Science.gov (United States)

Guzman, David Sanchez-Migallon; Mitchell, Mark A; Gaunt, Stephen D; Beaufrère, Hugues; Tully, Thomas N

2008-06-01

Blood samples were collected from 20 Hispaniolan Amazon parrots (Amazona ventralis) and were divided into tubes that contained dipotassium ethylenediaminetetraacetic acid (K2EDTA) and lithium heparin. Complete blood cell counts were determined in each sample within 2 hours of collection. The level of agreement in results was moderate for plasma protein, packed cell volume (PCV), and leukocyte, monocyte, and lymphocyte counts between the anticoagulants. Plasma protein and PCV values were significantly lower in samples with lithium heparin than in those with K2EDTA, whereas lymphocyte numbers were significantly higher in lithium heparin samples than in K2EDTA samples. The level of agreement was good for the other cell types (heterophils, eosinophils, and basophils) when comparing the different anticoagulants. The poor level of agreement between anticoagulants with the increase in thrombocyte clumping in lithium heparin samples indicates that the use of lithium heparin as anticoagulant may affect thrombocyte count. No negative effects on morphology and staining of blood cells were apparent in smears from heparin samples compared with K2EDTA samples. Within the different values compared, the limits of agreement are small enough to be confident that lithium heparin can be used for routine CBC counts in a clinical setting. The use of the same anticoagulant should be recommended to follow trends within the same patient, especially when considering plasma protein concentration, PCV, and lymphocyte count.

A novel mode-locking technique

International Nuclear Information System (INIS)

Chen Shaoh; Chen Youming; Chen Taolue; Si Xiangdong; Yang Yi; Deng Ximing

1993-01-01

A novel mode-locked Nd:YAG oscillator has been developed by using an ultrafast photoconductive feedback controlled loop, and mode-locked pulses with a duration of 100ps have been obtained. The energy instability of the pulse trains is ±5%. In this type of mode-locking technology, a type of deep-level doped GaAs (Cr-doped) photoconductive switch, which has a fast response in time and is free of avalance process, is used to drive a Pockels' cell to realize mode-locking. The dark resistance of this type of photoconductive switch is 6 orders of magnitude higher than that of the intrinsic single-crystal silicon, and it can reach a level as high as 10 9 ohms. Consequently, it is able to withstand longterm operation at several thousand DC volts. By means of the photoconductive ohmic switch characteristics, the authors have designed a positive feedback control network which has a very fast response time, and can couple a voltage of up to a thousand volts. Using this unit in a Nd:YAG laser, they have successfully realized a very stable mode-locked pulse train with pulse width shorter than 100 ps. The operation principle, and the results of the preliminary experiments are presented here. 1 ref., 3 figs

Effect of combined topical heparin and steroid on corneal neovascularization in children.

Science.gov (United States)

Michels, Rike; Michels, Stephan; Kaminski, Stephan

2012-01-01

To demonstrate the effect of topical heparin combined with topical steroid on corneal neovascularization (CN) in children. Four children (5 eyes) with new-onset progressive CN in at least one eye received topical rimexolone or dexamethasone in combination with heparin until complete regression of CN was obtained. The regression of CN was documented by slit-lamp or anterior segment photography. All 5 eyes showed complete regression of CN within 5 months. An anti-angiogenic effect was found as early as 1 week after starting topical combination treatment. No ocular and systemic side effects were detected and treatment was well tolerated by all children. In the 3 eyes with involvement of the optical axis, symmetrical visual acuity was obtained by amblyopia treatment. Recurrence of the CN was detectable in 2 eyes at 1 and 6 months, respectively, after ending combination therapy. Both eyes responded favorably to re-treatment. Combination of topical heparin and steroid leads to rapid regression and complete inactivity of CN. This therapeutic approach is promising, especially in children with limited therapeutic alternatives and a high risk for amblyopia. Copyright 2012, SLACK Incorporated.

Power spectrum of an injection-locked Josephson oscillator

International Nuclear Information System (INIS)

Stancampiano, C.V.; Shapiro, S.

1975-01-01

Experiments have shown that a Josephson oscillator, exposed to a weak narrow-band input signal, exhibits behavior characteristic of an injection-locked oscillator. When in lock, Adler's theory of injection locking describes the experimental observations reasonably well. The range of applicability of the theory is extended to the out-of-lock regime where a spectrum of output frequencies is observed. Obtaining the theoretical output power spectrum requires solving a differential equation having the same form as the equation describing the resistively shunted junction model of Stewart and of McCumber. Experimental measurements of the output spectrum of a nearly locked Josephson oscillator are shown to be in reasonable agreement with the theory. Additional results discussed briefly include the observation of a frequency dependence of the locked Josephson oscillator output and experiments in which a Josephson oscillator-mixer was injection locked by a weak signal at the rf

The variable finesse locking technique

International Nuclear Information System (INIS)

Acernese, F; Al-Shourbagy, M

2006-01-01

Virgo is a power recycled Michelson interferometer, with 3 km long Fabry-Perot cavities in the arms. The locking of the interferometer has been obtained with an original lock acquisition technique. The main idea is to lock the instrument away from its working point. Lock is obtained by misaligning the power recycling mirror and detuning the Michelson from the dark fringe. In this way, a good fraction of light escapes through the antisymmetric port and the power build-up inside the recycling cavity is extremely low. The benefit is that all the degrees of freedom are controlled when they are almost decoupled, and the linewidth of the recycling cavity is large. The interferometer is then adiabatically brought on to the dark fringe. This technique is referred to as variable finesse, since the recycling cavity is considered as a variable finesse Fabry-Perot. This technique has been widely tested and allows us to reach the dark fringe in few minutes, in an essentially deterministic way

Clinical effects of low-molecular-weight heparin combined with ...

African Journals Online (AJOL)

Purpose: To explore the clinical effects of low-molecular-weight heparin (LMWH) combined with ulinastatin (UTI) in children with acute pancreatitis. Methods: In total, 560 patients with severe acute pancreatitis treated at Binzhou People's Hospital, Shandong, China, from April 2012 to June 2014 were enrolled in this study.

Mapping the heparin-binding site of the BMP antagonist gremlin by site-directed mutagenesis based on predictive modelling.

Science.gov (United States)

Tatsinkam, Arnold Junior; Mulloy, Barbara; Rider, Christopher C

2015-08-15

Gremlin is a member of the CAN (cerberus and DAN) family of secreted BMP (bone morphogenetic protein) antagonists and also an agonist of VEGF (vascular endothelial growth factor) receptor-2. It is critical in limb skeleton and kidney development and is re-expressed during tissue fibrosis. Gremlin binds strongly to heparin and heparan sulfate and, in the present study, we sought to investigate its heparin-binding site. In order to explore a putative non-contiguous binding site predicted by computational molecular modelling, we substituted a total of 11 key arginines and lysines located in three basic residue sequence clusters with homologous sequences from cerberus and DAN (differential screening selected gene abberative in neuroblastoma), CAN proteins which lack basic residues in these positions. A panel of six Myc-tagged gremlin mutants, MGR-1-MGR-6 (MGR, mutant gremlin), each containing different combinations of targeted substitutions, all showed markedly reduced affinity for heparin as demonstrated by their NaCl elution on heparin affinity chromatography, thus verifying our predictions. Both MGR-5 and MGR-6 retained BMP-4-binding activity comparable to that of wild-type gremlin. Low-molecular-mass heparin neither promoted nor inhibited BMP-4 binding. Finally, glutaraldehyde cross-linking demonstrated that gremlin forms non-covalent dimers, similar behaviour to that of DAN and also PRDC (protein related to cerberus and DAN), another CAN protein. The resulting dimer would possess two heparin-binding sites, each running along an exposed surface on the second β-strand finger loop of one of the monomers. © 2015 Authors; published by Portland Press Limited.

Early Heparin Administration Reduces Risk for Left Atrial Thrombus Formation during Atrial Fibrillation Ablation Procedures

Directory of Open Access Journals (Sweden)

Stefan Asbach

2011-01-01

Full Text Available Objective. Despite the use of anticoagulation during left atrial (LA ablation procedures, ischemic cerebrovascular accidents (CVAs are recognized as a serious complication. Heparin is usually given after safe transseptal access has been obtained, resulting in a short unprotected dwell time of catheters within the LA, which may account for CVAs. We investigated the frequency of CVAs and LA thrombus formation as detected by intracardiac ultrasound (ICE depending on the timing of heparin administration. Methods and Results. Sixty LA ablation procedures with the use of ICE were performed in 55 patients. Patients were grouped by heparin administration after (Group I, =13 and before (Group II, =47 transseptal access. Group I patients were younger (56.6±13.7 versus 65.9±9.9 years, =.01; other clinical and echocardiographic characteristics did not differ between groups. Early thrombus formation was observed in 2 (15.4% of group I patients as compared to 0% of group II patients (=.04. One CVA (2.1% occurred in one group II patient without prior thrombus detection, and none occurred in group I patients (=ns. Conclusion. Early administration of heparin reduces the risk of early intracardiac thrombus formation during LA ablation procedures. This did not result in reduced rate of CVAs.

Hersendood. Mackies leibniziaanse herinterpretatie van Lockes theorie van persoonsidentiteit

OpenAIRE

De Vleeschouwer, Gregory

2009-01-01

In his book, 'Problems from Locke', John Leslie Mackie presents a theory of personal identity (pi) that is meant to be a supplement and correction of Locke's pi-theory. In a first part I introduce the criterion of pi that was standard before Locke's pi-theory. By showing in a second part how Locke reacted against this traditional criterion, I show wherein the singularity of Locke's pi-theory exists. In a third part I explain how Leibniz is moved by the same solicitude as Locke, but also how h...

Brain communication in the locked-in state.

Science.gov (United States)

De Massari, Daniele; Ruf, Carolin A; Furdea, Adrian; Matuz, Tamara; van der Heiden, Linda; Halder, Sebastian; Silvoni, Stefano; Birbaumer, Niels

2013-06-01

Patients in the completely locked-in state have no means of communication and they represent the target population for brain-computer interface research in the last 15 years. Although different paradigms have been tested and different physiological signals used, to date no sufficiently documented completely locked-in state patient was able to control a brain-computer interface over an extended time period. We introduce Pavlovian semantic conditioning to enable basic communication in completely locked-in state. This novel paradigm is based on semantic conditioning for online classification of neuroelectric or any other physiological signals to discriminate between covert (cognitive) 'yes' and 'no' responses. The paradigm comprised the presentation of affirmative and negative statements used as conditioned stimuli, while the unconditioned stimulus consisted of electrical stimulation of the skin paired with affirmative statements. Three patients with advanced amyotrophic lateral sclerosis participated over an extended time period, one of which was in a completely locked-in state, the other two in the locked-in state. The patients' level of vigilance was assessed through auditory oddball procedures to study the correlation between vigilance level and the classifier's performance. The average online classification accuracies of slow cortical components of electroencephalographic signals were around chance level for all the patients. The use of a non-linear classifier in the offline classification procedure resulted in a substantial improvement of the accuracy in one locked-in state patient achieving 70% correct classification. A reliable level of performance in the completely locked-in state patient was not achieved uniformly throughout the 37 sessions despite intact cognitive processing capacity, but in some sessions communication accuracies up to 70% were achieved. Paradigm modifications are proposed. Rapid drop of vigilance was detected suggesting attentional

Locked modes and magnetic field errors in MST

International Nuclear Information System (INIS)

Almagri, A.F.; Assadi, S.; Prager, S.C.; Sarff, J.S.; Kerst, D.W.

1992-06-01

In the MST reversed field pinch magnetic oscillations become stationary (locked) in the lab frame as a result of a process involving interactions between the modes, sawteeth, and field errors. Several helical modes become phase locked to each other to form a rotating localized disturbance, the disturbance locks to an impulsive field error generated at a sawtooth crash, the error fields grow monotonically after locking (perhaps due to an unstable interaction between the modes and field error), and over the tens of milliseconds of growth confinement degrades and the discharge eventually terminates. Field error control has been partially successful in eliminating locking

Gender-based outcomes of bivalirudin versus heparin in patients undergoing percutaneous coronary interventions: Meta-analysis of randomized controlled trials.

Science.gov (United States)

Mina, George S; Firouzbakht, Tina; Modi, Kalgi; Dominic, Paari

2017-11-01

We aimed to perform a gender-based meta-analysis of the outcome of bivalirudin versus heparin in patients undergoing percutaneous coronary interventions (PCI). Bivalirudin has been shown to decrease major bleeding when compared to heparin ± glycoprotein IIb/IIIa inhibitors (GPI) in patients undergoing PCI. It is unclear, however, if those differences in outcomes are the same for men and women. We included randomized controlled trials (RCTs) that compared bivalirudin to heparin with or without GPI in patients undergoing PCI and reported outcome data that were stratified by gender. Random effect model was used to pool odds ratio (OR) and 95% confidence intervals (CI). We included 9 trials with 33,224 patients. Bivalirudin decreased major bleeding when compared to heparin plus routine GPI in both men (OR: 0.51, P < 0.001) and women (OR: 0.55, P < 0.001). However, when GPI were used selectively with heparin, the bleeding lowering effect of bivalirudin was statistically significant in men (OR: 0.69, P = 0.02) but not in women (OR: 0.71, P = 0.21). When compared to heparin ± GPI, there was a nonstatistically significant trend toward lower all-cause mortality with bivalirudin in both men (OR: 0.76, P = 0.055) and women (OR: 0.79, P = 0.21). There were no significant differences in major adverse cardiovascular events between heparin and bivalirudin in both men and women. Bivalirudin decreases major bleeding in both men and women when compared to heparin plus routine GPI. However, when compared to heparin alone, the bleeding lowering benefit of bivalirudin is less evident in women. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Shareholder Lock-In Contracts : Share Price and Trading Volume Effects at the Lock-In Expiry

NARCIS (Netherlands)

Angenandt, P.P.; Goergen, M.; Renneboog, L.D.R.

2005-01-01

This paper unveils the diversity in lock-in agreements of firms listed on the Nouveau Marche stock exchange in France.We give the main economic reasons why shareholders adopt lock-in agreements that are more stringent than legally required.We relate the abnormal returns and the abnormal volume at

Biochemical and microscopic evidence for the internalization and degradation of heparin-containing mast cell granules by bovine endothelial cells

International Nuclear Information System (INIS)

Atkins, F.M.; Friedman, M.M.; Metcalfe, D.D.

1985-01-01

Incubation of [ 35 S]heparin-containing mast cell granules with cultured bovine endothelial cells was followed by the appearance of 35 S-granule-associated radioactivity within the endothelial cells and a decrease in radioactivity in the extracellular fluid. These changes occurred during the first 24 hours of incubation and suggested ingestion of the mast cell granules by the endothelial cells. Periodic electron microscopic examination of the monolayers confirmed this hypothesis by demonstrating apposition of the granules to the plasmalemma of endothelial cells, which was followed by the engulfment of the granules by cytoplasmic projections. Under light microscopic examination, mast cell granules within endothelial cells then appeared to undergo degradation. The degradation of [ 35 S]heparin in mast cell granules was demonstrated by a decrease in the amount of intracellular [ 35 S]heparin proteoglycan after 24 hours and the appearance of free [ 35 S]sulfate in the extracellular compartment. Intact endothelial cells were more efficient at degrading [ 35 S]heparin than were cell lysates or cell supernatants. These data provide evidence of the ability of endothelial cells to ingest mast cell granules and degrade native heparin that is presented as a part of the mast cell granule

Heparin as a pharmacologic intervention to induce positive scintiscan in occult gastrointestinal bleeding

International Nuclear Information System (INIS)

Chaudhuri, T.K.; Brantly, M.

1984-01-01

The value of using heparin as a pharmacologic intervention to induce a positive scintiscan was studied in a patient with chronic occult gastrointestinal bleeding. When all standard diagnostic tests (upper and lower gastrointestinal series, upper and lower endoscopy, and conventional noninterventional Tc-99m RBC imaging) fail to detect and localize gastrointestinal bleeding in a patient who has definite clinical evidence (guaiac positive stool and dropping hemoglobin, hematocrit) of chronic occult gastrointestinal oozing, heparin may be used (with proper precaution) as a last resort to aid in the scintigraphic detection and localization of chronic occult gastrointestinal bleeding

Successful Implantation of a Left Ventricular Assist Device in a Patient with Heparin-Induced Thrombocytopenia and Thrombosis

Science.gov (United States)

Garland, Cassandra; Somogyi, David

2014-01-01

Abstract: We report the case of a 27-year-old woman with signs of heparin-induced thrombocytopenia and thrombosis (HITT) and left heart failure presenting for urgent implantation of a left ventricular assist device (LVAD). HITT can occur in 4.2–6.1% of patients with LVADs. If the patient remains hemodynamically stable, implantation can be delayed for several months until the heparin/PF-4 antibodies decline allowing the use of heparin on cardiopulmonary bypass, However, in most cases related to cardiogenic shock, surgery cannot be delayed. We present the case of a patient who underwent implantation of a HeartMate II LVAD and discuss management strategy using bivalirudin during cardiopulmonary bypass. PMID:25208434

Intravitreal low molecular weight heparin in PVR surgery.

Directory of Open Access Journals (Sweden)

Kumar Atul

2003-01-01

Full Text Available Purpose: To evaluate the efficacy of low molecular weight heparin (LMWH in prevention of postoperative fibrin formation following vitreoretinal surgery with proliferative vitreoretinopathy (PVR. Material and Methods: Thirty consecutive patients of retinal detachment with advanced PVR were enrolled in the study. They were randomised to study and control groups (n = 15 each. Study group patients received vitreoretinal surgery with 5 IU/cc of LMWH in vitrectomy infusion fluid. The control group patients received vitroretinal surgery without heparin in the infusion fluid. Patients were followed up at 1 week, 1 month and 3 months after surgery. Postoperative bleeding, media clarity, best-corrected visual acuity and success of the surgery at the end of 3 months were compared between the two groups. Results: At each follow-up visit, the study group showed a better media clarity, which was statistically significant ( P = 0.0042. The study group had a 50% better chance of retinal reattachment compared to the control group. Five patients had intraoperative bleeding in the study group (33% compared to 3 patients in the control group (20%. Conclusion: Use of intravitreal LMWH prevents postoperative fibrin formation and is beneficial in repair of retinal detachments with PVR.

Deciphering the Role of Sulfonated Unit in Heparin-Mimicking Polymer to Promote Neural Differentiation of Embryonic Stem Cells.

Science.gov (United States)

Lei, Jiehua; Yuan, Yuqi; Lyu, Zhonglin; Wang, Mengmeng; Liu, Qi; Wang, Hongwei; Yuan, Lin; Chen, Hong

2017-08-30

Glycosaminoglycans (GAGs), especially heparin and heparan sulfate (HS), hold great potential for inducing the neural differentiation of embryonic stem cells (ESCs) and have brought new hope for the treatment of neurological diseases. However, the disadvantages of natural heparin/HS, such as difficulty in isolating them with a sufficient amount, highly heterogeneous structure, and the risk of immune responses, have limited their further therapeutic applications. Thus, there is a great demand for stable, controllable, and well-defined synthetic alternatives of heparin/HS with more effective biological functions. In this study, based upon a previously proposed unit-recombination strategy, several heparin-mimicking polymers were synthesized by integrating glucosamine-like 2-methacrylamido glucopyranose monomers (MAG) with three sulfonated units in different structural forms, and their effects on cell proliferation, the pluripotency, and the differentiation of ESCs were carefully studied. The results showed that all the copolymers had good cytocompatibility and displayed much better bioactivity in promoting the neural differentiation of ESCs as compared to natural heparin; copolymers with different sulfonated units exhibited different levels of promoting ability; among them, copolymer with 3-sulfopropyl acrylate (SPA) as a sulfonated unit was the most potent in promoting the neural differentiation of ESCs; the promoting effect is dependent on the molecular weight and concentration of P(MAG-co-SPA), with the highest levels occurring at the intermediate molecular weight and concentration. These results clearly demonstrated that the sulfonated unit in the copolymers played an important role in determining the promoting effect on ESCs' neural differentiation; SPA was identified as the most potent sulfonated unit for copolymer with the strongest promoting ability. The possible reason for sulfonated unit structure as a vital factor influencing the ability of the copolymers

Release of proteins via ion exchange from albumin-heparin microspheres

NARCIS (Netherlands)

Kwon, Glen S.; Bae, You Han; Cremers, H.F.M.; Cremers, Harry; Feijen, Jan; Kim, Sung Wan

1992-01-01

Albumin-heparin and albumin microspheres were prepared as ion exchange gels for the controlled release of positively charged polypeptides and proteins. The adsorption isotherms of chicken egg and human lysozyme, as model proteins, on microspheres were obtained. An adsorption isotherm of chicken egg

Thermodynamic parameters associated with the binding of adrenaline and norephedrine to heparin

International Nuclear Information System (INIS)

Ali-Ali, A.K.; Buchanan, J.D.; Power, D.M.; Butler, J.

1983-01-01

Pulse radiolysis was used to determine the thermodynamic parameters (ΔG', ΔH' and ΔS') governing the binding of adrenalin and norephedrine to heparin. The complexes were completely dissociated by increasing concentrations of inorganic salts. Lower concentrations of divalent cations (e.g. Ca 2+ ) were more necessary to affect dissociation than those of monovalent cations (e.g. Na + ). For each interaction, an increase in drug binding occurred as the temperature was increased from ambient. However, a transition temperature was observed (48 degC) above which the drug was progressively released as temperature was increased. These observations probably reflect conformational changes induced in the heparin below and above its melting temperature. (author)

Photochemically synthesized heparin-based silver nanoparticles: an antimicrobial activity study

Science.gov (United States)

Rodriguez-Torres, Maria del Pilar; Acosta-Torres, Laura Susana; Díaz-Torres, Luis Armando

2017-08-01

The antimicrobial activity of silver nanoparticles has been extensively studied in the last years. Such nanoparticles constitute a potential and promising approach for the development of new antimicrobial systems especially due to the fact that several microorganisms are developing resistance to some already existing antimicrobial agents, therefore making antibacterial and antimicrobial studies on alternative materials necessary to overcome this issue. Silver nanoparticle concentration and size are determining factors on the antimicrobial activity of these nano systems. Heparin is a polysaccharide that belongs to the glycosaminoglycans (GAGs) family, molecules formed by a base disaccharide whose components are joined by a glycosidic linkage that is a repeating unit along their structure. It is highly sulfated making it a negatively charged material that is also widely used as an anticoagulant in Medicine because its biocompatibility besides it is also produced within the human body, specifically in the mast cells. Heparin alone possesses antimicrobial activity although it has not been studied very much in detail, it only has been demonstrated that it inhibits E. coli, P. aeruginosa, S. aureus and S. epidermidis, so taking this into account, this study is dedicated to assess UV photochemically-synthesized (λ=254 nm) heparin-based silver nanoparticles antimicrobial activity using the agar disk diffusion method complemented by the broth microdilution method to estimate de minimum inhibitory concentration (MIC), that is the lowest concentration at which an antimicrobial will inhibit visible growth of a microorganism. The strains used were the ones aforementioned to assess the antimicrobial activity degree these heparinbased nanoparticles exhibit.

Heparin-mimicking multilayer coating on polymeric membrane via LbL assembly of cyclodextrin-based supramolecules.

Science.gov (United States)

Deng, Jie; Liu, Xinyue; Ma, Lang; Cheng, Chong; Shi, Wenbin; Nie, Chuanxiong; Zhao, Changsheng

2014-12-10

In this study, multifunctional and heparin-mimicking star-shaped supramolecules-deposited 3D porous multilayer films with improved biocompatibility were fabricated via a layer-by-layer (LbL) self-assembly method on polymeric membrane substrates. Star-shaped heparin-mimicking polyanions (including poly(styrenesulfonate-co-sodium acrylate; Star-PSS-AANa) and poly(styrenesulfonate-co-poly(ethylene glycol)methyl ether methacrylate; Star-PSS-EGMA)) and polycations (poly(methyl chloride-quaternized 2-(dimethylamino)ethyl methacrylate; Star-PMeDMA) were first synthesized by atom transfer radical polymerization (ATRP) from β-cyclodextrin (β-CD) based cores. Then assembly of 3D porous multilayers onto polymeric membrane surfaces was carried out by alternating deposition of the polyanions and polycations via electrostatic interaction. The surface morphology and composition, water contact angle, blood activation, and thrombotic potential as well as cell viability for the coated heparin-mimicking films were systematically investigated. The results of surface ATR-FTIR spectra and XPS spectra verified successful deposition of the star-shaped supramolecules onto the biomedical membrane surfaces; scanning electron microscopy (SEM) and atomic force microscopy (AFM) observations revealed that the modified substrate had 3D porous surface morphology, which might have a great biological influence on the biointerface. Furthermore, systematic in vitro investigation of protein adsorption, platelet adhesion, human platelet factor 4 (PF4, indicates platelet activation), activate partial thromboplastin time (APTT), thrombin time (TT), coagulation activation (thrombin-antithrombin III complex (TAT, indicates blood coagulant)), and blood-related complement activation (C3a and C5a, indicates inflammation potential) confirmed that the heparin-mimicking multilayer coated membranes exhibited ultralow blood component activations and excellent hemocompatibility. Meanwhile, after surface coating

Pulse-forming and line-broadening in AM mode locking of the TEA-CO2laser

NARCIS (Netherlands)

Witteman, W.J.; Olbertz, A.H.M.

1977-01-01

The present paper describes AM mode locking for homogeneously broadened systems, a procedure for measuring linewidths under laser conditions, and finally, experimental results for a 1-atm CO2laser. Working in the frequency domain, analytic solutions are given for the pulse bandwidth and pulse shape

Identification of heparin samples that contain impurities or contaminants by chemometric pattern recognition analysis of proton NMR spectral data

Energy Technology Data Exchange (ETDEWEB)

Zang, Qingda [University of Medicine and Dentistry of New Jersey, Department of Pharmacology, Robert Wood Johnson Medical School, Piscataway, NJ (United States); Snowdon, Inc., Monmouth Junction, NJ (United States); University of Medicine and Dentistry of New Jersey, Department of Health Informatics, School of Health Related Professions, Newark, NJ (United States); Keire, David A.; Buhse, Lucinda F.; Trehy, Michael L. [Food and Drug Administration, CDER, Division of Pharmaceutical Analysis, St. Louis, MO (United States); Wood, Richard D. [Snowdon, Inc., Monmouth Junction, NJ (United States); Mital, Dinesh P.; Haque, Syed; Srinivasan, Shankar [University of Medicine and Dentistry of New Jersey, Department of Health Informatics, School of Health Related Professions, Newark, NJ (United States); Moore, Christine M.V.; Nasr, Moheb; Al-Hakim, Ali [Food and Drug Administration, CDER, Office of New Drug Quality Assessment, Silver Spring, MD (United States); Welsh, William J. [University of Medicine and Dentistry of New Jersey, Department of Pharmacology, Robert Wood Johnson Medical School, Piscataway, NJ (United States)

2011-08-15

Chemometric analysis of a set of one-dimensional (1D) {sup 1}H nuclear magnetic resonance (NMR) spectral data for heparin sodium active pharmaceutical ingredient (API) samples was employed to distinguish USP-grade heparin samples from those containing oversulfated chondroitin sulfate (OSCS) contaminant and/or unacceptable levels of dermatan sulfate (DS) impurity. Three chemometric pattern recognition approaches were implemented: classification and regression tree (CART), artificial neural network (ANN), and support vector machine (SVM). Heparin sodium samples from various manufacturers were analyzed in 2008 and 2009 by 1D {sup 1}H NMR, strong anion-exchange high-performance liquid chromatography, and percent galactosamine in total hexosamine tests. Based on these data, the samples were divided into three groups: Heparin, DS {<=} 1.0% and OSCS = 0%; DS, DS > 1.0% and OSCS = 0%; and OSCS, OSCS > 0% with any content of DS. Three data sets corresponding to different chemical shift regions (1.95-2.20, 3.10-5.70, and 1.95-5.70 ppm) were evaluated. While all three chemometric approaches were able to effectively model the data in the 1.95-2.20 ppm region, SVM was found to substantially outperform CART and ANN for data in the 3.10-5.70 ppm region in terms of classification success rate. A 100% prediction rate was frequently achieved for discrimination between heparin and OSCS samples. The majority of classification errors between heparin and DS involved cases where the DS content was close to the 1.0% DS borderline between the two classes. When these borderline samples were removed, nearly perfect classification results were attained. Satisfactory results were achieved when the resulting models were challenged by test samples containing blends of heparin APIs spiked with non-, partially, or fully oversulfated chondroitin sulfate A, heparan sulfate, or DS at the 1.0%, 5.0%, and 10.0% (w/w) levels. This study demonstrated that the combination of 1D {sup 1}H NMR spectroscopy

A superconducting phase-locked local oscillator for a submillimetre integrated receiver

International Nuclear Information System (INIS)

Koshelets, V P; Shitov, S V; Filippenko, L V; Dmitriev, P N; Ermakov, A B; Sobolev, A S; Torgashin, M Yu; Pankratov, A L; Kurin, V V; Yagoubov, P; Hoogeveen, R

2004-01-01

Comprehensive measurements of the flux flow oscillator (FFO) radiation linewidth are performed using an integrated harmonic SIS mixer; the FFO linewidth and spectral line profile are compared to a theory. An essential dependence of the FFO linewidth on frequency is found; a possible explanation is proposed. The results of the numerical solution of the perturbed sine-Gordon equation qualitatively confirm this assumption. To optimize the FFO design, the influence of the FFO parameters on the radiation linewidth is studied. A novel FFO design at a moderate current density has resulted in a free-running FFO linewidth of about 10 MHz in the flux flow regime up to 712 GHz, limited only by the gap frequency of Nb. This relatively narrow free-running linewidth (along with implementation of a wide-band phase locking loop system) allows continuous phase locking of the FFO in the wide frequency range of 500-710 GHz. These results are the basis for the development of a 550-650 GHz integrated receiver for the terahertz limb sounder (TELIS) intended for atmosphere study and scheduled to fly on a balloon in 2005. We report here also on the design of the second generation of the phase-locked superconducting integrated receiver chip for TELIS

Tidal locking of habitable exoplanets

Science.gov (United States)

Barnes, Rory

2017-12-01

Potentially habitable planets can orbit close enough to their host star that the differential gravity across their diameters can produce an elongated shape. Frictional forces inside the planet prevent the bulges from aligning perfectly with the host star and result in torques that alter the planet's rotational angular momentum. Eventually the tidal torques fix the rotation rate at a specific frequency, a process called tidal locking. Tidally locked planets on circular orbits will rotate synchronously, but those on eccentric orbits will either librate or rotate super-synchronously. Although these features of tidal theory are well known, a systematic survey of the rotational evolution of potentially habitable exoplanets using classic equilibrium tide theories has not been undertaken. I calculate how habitable planets evolve under two commonly used models and find, for example, that one model predicts that the Earth's rotation rate would have synchronized after 4.5 Gyr if its initial rotation period was 3 days, it had no satellites, and it always maintained the modern Earth's tidal properties. Lower mass stellar hosts will induce stronger tidal effects on potentially habitable planets, and tidal locking is possible for most planets in the habitable zones of GKM dwarf stars. For fast-rotating planets, both models predict eccentricity growth and that circularization can only occur once the rotational frequency is similar to the orbital frequency. The orbits of potentially habitable planets of very late M dwarfs ([InlineEquation not available: see fulltext.]) are very likely to be circularized within 1 Gyr, and hence, those planets will be synchronous rotators. Proxima b is almost assuredly tidally locked, but its orbit may not have circularized yet, so the planet could be rotating super-synchronously today. The evolution of the isolated and potentially habitable Kepler planet candidates is computed and about half could be tidally locked. Finally, projected TESS planets

Improved synthesis of polystyrene-poly(ethylene oxide)-heparin block copolymers

NARCIS (Netherlands)

Vulic, I.; Loman, A.J.B.; Feijen, Jan; Okano, T.; Kim, S.W.

1990-01-01

A novel procedure for the synthesis of block copolymers composed of a hydrophobic block of polystyrene, a hydrophilic block of poly(ethylene oxide) and a bioactive block of nitrous acid-degraded heparin was developed. Amino-semitelechelic polystyrene was prepared by anionic polymerization of styrene

Universal spin-momentum locked optical forces

Energy Technology Data Exchange (ETDEWEB)

Kalhor, Farid [Department of Electrical and Computer Engineering, University of Alberta, Edmonton, Alberta T6G 1H9 (Canada); Thundat, Thomas [Department of Chemical and Materials Engineering, University of Alberta, Edmonton, Alberta T6G 1H9 (Canada); Jacob, Zubin, E-mail: zjacob@purdue.edu [Department of Electrical and Computer Engineering, University of Alberta, Edmonton, Alberta T6G 1H9 (Canada); Birck Nanotechnology Center, Department of Electrical and Computer Engineering, Purdue University, West Lafayette, Indiana 47906 (United States)

2016-02-08

Evanescent electromagnetic waves possess spin-momentum locking, where the direction of propagation (momentum) is locked to the inherent polarization of the wave (transverse spin). We study the optical forces arising from this universal phenomenon and show that the fundamental origin of recently reported non-trivial optical chiral forces is spin-momentum locking. For evanescent waves, we show that the direction of energy flow, the direction of decay, and the direction of spin follow a right hand rule for three different cases of total internal reflection, surface plasmon polaritons, and HE{sub 11} mode of an optical fiber. Furthermore, we explain how the recently reported phenomena of lateral optical force on chiral and achiral particles are caused by the transverse spin of the evanescent field and the spin-momentum locking phenomenon. Finally, we propose an experiment to identify the unique lateral forces arising from the transverse spin in the optical fiber and point to fundamental differences of the spin density from the well-known orbital angular momentum of light. Our work presents a unified view on spin-momentum locking and how it affects optical forces on chiral and achiral particles.

Multiprocessor Real-Time Locking Protocols for Replicated Resources

Science.gov (United States)

2016-07-01

assignment problem, the ac- tual identities of the allocated replicas must be known. When locking protocols are used, tasks may experience delays due to both...Multiprocessor Real-Time Locking Protocols for Replicated Resources ∗ Catherine E. Jarrett1, Kecheng Yang1, Ming Yang1, Pontus Ekberg2, and James H...replicas to execute. In prior work on replicated resources, k-exclusion locks have been used, but this restricts tasks to lock only one replica at a time. To

Locking of intrinsic angular momentum in collision complexes

International Nuclear Information System (INIS)

Berengolts, Alexander.

1995-04-01

A concept of locking of the intrinsic angular momentum of a fragment of a collision complex to a body-fixed axis is widely used in the description of heavy-particle dynamics. The aim of this work is to provide a semiclassical description of the locking phenomenon which occur in diatomic and three atomic collision complexes. The first part of this work is devoted to the semiclassical study of the locking of the electronic angular momentum that occurs in slow collisions of two atoms, one in the spherically symmetric state and the other in state with j= 1. Here we calculate explicitly the complete locking matrix for different types of interatomic interactions. The elements of this matrix directly enter into the semiclassical expression for the different cross sections of polarized atoms. Limitations to the notion of the the locking radius and slipping probability are discussed in connection with the steepness of the interaction. Numerical calculations confirm analytical result: the optimal criterion for determination of the locking radius is a condition for the accumulated phase difference between two molecular states. Analytical expressions are suggested for the locking angle and the slipping probability. Implication of the locking approximation for calculation of the quasiclassical scattering matrix is discussed. The second part considers the locking of the rotational angular momentum of a diatom in the decomposition of a triatomic complexes. We discuss here cases J = 1,2,3 and 4, but restrict ourselves to calculation of the so-called dynamic orientation of the diatomic fragment. The letter represents one of the characteristics of the locking matrix which in principle can be measured experimentally. The orientation is created as a result of the interplay between the adiabatic interaction in the atom- diatom exit channel and the rotationally non adiabatic coupling in the perturbed rotor region

Intra-articular TSG-6 delivery from heparin-based microparticles reduces cartilage damage in a rat model of osteoarthritis.

Science.gov (United States)

Tellier, Liane E; Treviño, Elda A; Brimeyer, Alexandra L; Reece, David S; Willett, Nick J; Guldberg, Robert E; Temenoff, Johnna S

2018-05-01

As a potential treatment for osteoarthritis (OA), we have developed injectable and hydrolytically degradable heparin-based biomaterials with tunable sulfation for the intra-articular delivery of tumor necrosis factor-alpha stimulated gene-6 (TSG-6), a protein known to inhibit plasmin which may degrade extracellular matrix within OA joints. We first assessed the effect of heparin sulfation on TSG-6 anti-plasmin activity and found that while fully sulfated (Hep) and heparin desulfated at only the N position (Hep-N) significantly enhanced TSG-6 bioactivity in vitro, fully desulfated heparin (Hep-) had no effect, indicating that heparin sulfation plays a significant role in modulating TSG-6 bioactivity. Next, TSG-6 loaded, degradable 10 wt% Hep-N microparticles (MPs) were delivered via intra-articular injection into the knee at 1, 7, and 15 days following medial meniscal transection (MMT) injury in a rat model. After 21 days, cartilage thickness, volume, and attenuation were significantly increased with soluble TSG-6, indicating degenerative changes. In contrast, no significant differences were observed with TSG-6 loaded MP treatment, demonstrating that TSG-6 loaded MPs reduced cartilage damage following MMT injury. Ultimately, our results indicate that Hep-N can enhance TSG-6 anti-plasmin activity and that Hep-N-based biomaterials may be an effective method for TSG-6 delivery to treat OA.

Effects of the repeated administration of adenosine and heparin on myocardial perfusion in patients with chronic stable angina pectoris.

Science.gov (United States)

Barron, H V; Sciammarella, M G; Lenihan, K; Michaels, A D; Botvinick, E H

2000-01-01

The mechanism by which ischemia stimulates angiogenesis is unknown. Adenosine is released during myocardial ischemia and may be a mediator of this process. Experimental data suggest that heparin may enhance this effect. The purpose of this open-labeled, placebo-controlled trial was to determine whether repeated intravenous administration of adenosine and heparin could mimic physiologic angiogenesis and reduce the amount of exercise-induced myocardial ischemia in patients with coronary artery disease. Subjects with chronic stable angina refractory to conventional medical therapy and not suitable for revascularization received either adenosine (140 microg/kg/min for 6 minutes) and heparin (10,000 U bolus), (n = 14), or placebo, (n = 7) daily for 10 days. All patients underwent baseline and follow-up exercise testing with thallium-201 single-photon emission computed tomography myocardial perfusion imaging. A semiquantitative assessment of the extent and severity of the perfusion abnormalities was calculated by 2 blinded investigators. There was no significant change in exercise duration or in the peak heart rate systolic blood pressure product associated with adenosine and heparin compared with placebo treatment. There was, however, a 9% reduction in the extent (60.6 +/- 4.0 vs 54.9 +/- 4.1, p = 0.03) and a 14% improvement in severity (41.5 +/- 3.2 vs 35.7 +/- 2.9, p = 0.01) of the myocardial perfusion abnormalities seen in patients who received adenosine and heparin compared with placebo. Thus, in this pilot study, repeated administration of adenosine and heparin reduced the amount of exercise-induced ischemia in patients with chronic stable angina refractory to conventional treatment.

Injection locking of optomechanical oscillators via acoustic waves.

Science.gov (United States)

Huang, Ke; Hossein-Zadeh, Mani

2018-04-02

Injection locking is an effective technique for synchronization of oscillator networks and controlling the phase and frequency of individual oscillators. As such, exploring new mechanisms for injection locking of emerging oscillators is important for their usage in various systems. Here, we present the first demonstration of injection locking of a radiation pressure driven optomechanical oscillator (OMO) via acoustic waves. As opposed to previously reported techniques (based on pump modulation or direct application of a modulated electrostatic force), injection locking of OMO via acoustic waves does not require optical power modulation or physical contact with the OMO and it can be easily implemented on various platforms to lock different types of OMOs independent of their size and structure. Using this approach we have locked the phase and frequency of two distinct modes of a microtoroidal silica OMO to a piezoelectric transducer (PZT). We have characterized the behavior of the injection locked OMO with three acoustic excitation configurations and showed that even without proper acoustic impedance, matching the OMO can be locked to the PZT and tuned over 17 kHz with only -30 dBm of RF power fed to the PZT. The high efficiency, simplicity, and scalability of the proposed approach paves the road toward a new class of photonic systems that rely on synchronization of several OMOs to a single or multiple RF oscillators with applications in optical communication, metrology, and sensing. Beyond its practical applications, injection locking via acoustic waves can be used in fundamental studies in quantum optomechanics where thermal and optical isolation of the OMO are critical.

No Snowball on Habitable Tidally Locked Planets

Science.gov (United States)

Checlair, Jade; Menou, Kristen; Abbot, Dorian S.

2017-08-01

The TRAPPIST-1, Proxima Centauri, and LHS 1140 systems are the most exciting prospects for future follow-up observations of potentially inhabited planets. All of the planets orbit nearby M-stars and are likely tidally locked in 1:1 spin–orbit states, which motivates the consideration of the effects that tidal locking might have on planetary habitability. On Earth, periods of global glaciation (snowballs) may have been essential for habitability and remote signs of life (biosignatures) because they are correlated with increases in the complexity of life and in the atmospheric oxygen concentration. In this paper, we investigate the snowball bifurcation (sudden onset of global glaciation) on tidally locked planets using both an energy balance model and an intermediate-complexity global climate model. We show that tidally locked planets are unlikely to exhibit a snowball bifurcation as a direct result of the spatial pattern of insolation they receive. Instead, they will smoothly transition from partial to complete ice coverage and back. A major implication of this work is that tidally locked planets with an active carbon cycle should not be found in a snowball state. Moreover, this work implies that tidally locked planets near the outer edge of the habitable zone with low CO2 outgassing fluxes will equilibrate with a small unglaciated substellar region rather than cycling between warm and snowball states. More work is needed to determine how the lack of a snowball bifurcation might affect the development of life on a tidally locked planet.

No Snowball on Habitable Tidally Locked Planets

International Nuclear Information System (INIS)

Checlair, Jade; Abbot, Dorian S.; Menou, Kristen

2017-01-01

The TRAPPIST-1, Proxima Centauri, and LHS 1140 systems are the most exciting prospects for future follow-up observations of potentially inhabited planets. All of the planets orbit nearby M-stars and are likely tidally locked in 1:1 spin–orbit states, which motivates the consideration of the effects that tidal locking might have on planetary habitability. On Earth, periods of global glaciation (snowballs) may have been essential for habitability and remote signs of life (biosignatures) because they are correlated with increases in the complexity of life and in the atmospheric oxygen concentration. In this paper, we investigate the snowball bifurcation (sudden onset of global glaciation) on tidally locked planets using both an energy balance model and an intermediate-complexity global climate model. We show that tidally locked planets are unlikely to exhibit a snowball bifurcation as a direct result of the spatial pattern of insolation they receive. Instead, they will smoothly transition from partial to complete ice coverage and back. A major implication of this work is that tidally locked planets with an active carbon cycle should not be found in a snowball state. Moreover, this work implies that tidally locked planets near the outer edge of the habitable zone with low CO 2 outgassing fluxes will equilibrate with a small unglaciated substellar region rather than cycling between warm and snowball states. More work is needed to determine how the lack of a snowball bifurcation might affect the development of life on a tidally locked planet.

Heparin induces an accumulation of atherogenic lipoproteins during hemodialysis in normolipidemic end-stage renal disease patients.

Science.gov (United States)

Barbagallo, Carlo M; Noto, Davide; Cefalù, Angelo B; Ganci, Antonia; Giammarresi, Carlo; Panno, Donata; Cusumano, Gaspare; Greco, Massimiliano; Di Gaudio, Francesca; Averna, Maurizio R

2015-07-01

Dyslipidemias may account for the excess of cardiovascular mortality in end-stage renal disease (ESRD). Lipoprotein studies in ESRD patients are usually relative to prehemodialysis samples even if significative changes may occur after dialysis. In this study, we aimed to investigate the effects of ESRD on triglyceride-rich lipoproteins (TRL) subpopulations distribution and acute change following hemodialytic procedures, including the relative contribution of heparin administration. We selected a group of normolipidemic male middle-aged ESRD patients free of any concomitant disease affecting lipoprotein remnant metabolism compared with controls. We separated TRL subfractions according to density and apoE content and evaluated the changes of these particles after hemodialytic procedures with or without heparin. ESRD subjects had higher TRL subfractions, with the exception of apoE-rich particles, lower high-density lipoprotein (HDL) largest subclasses, and a smaller low-density lipoprotein peak particle size than controls. After a hemodialytic standard procedure with heparin, we demonstrated a significant reduction of triglyceride, an increase of HDL-cholesterol levels, and a raise of small very-low-density lipoprotein, intermediate-density lipoproteins (IDL), apoE-rich particles, and non-HDL-cholesterol levels. When hemodialysis was performed without heparin, no significant changes were observed. In the absence of concomitant hyperlipidemic triggers, ESRD patients show significant lipoprotein abnormalities before dialysis, but without any increased remnant particles concentrations. We speculate that hemodialysis, in particular heparin administration during this procedure, leads to a massive atherogenic TRLs production because of the acute stimulation of the dysfunctional lipolytic system not followed by an efficient removal, determining a recurrent lipoprotein remnant accumulation. © 2014 International Society for Hemodialysis.

Cyclic Voltammetry of Biopolymer Heparin at PVC Plasticized Liquid Membrane

Czech Academy of Sciences Publication Activity Database

Samec, Zdeněk; Trojánek, Antonín; Langmaier, Jan; Samcová, E.

2003-01-01

Roč. 5, - (2003), s. 867-870 ISSN 1388-2481 R&D Projects: GA ČR GA203/04/0424 Institutional research plan: CEZ:AV0Z4040901 Keywords : cyclic voltammetry * PVC plasticized liquit membrane * heparin Subject RIV: CG - Electrochemistry Impact factor: 2.300, year: 2003

Heparin crisis 2008: a tipping point for increased FDA enforcement in the pharma sector?

Science.gov (United States)

Rosania, Larry

2010-01-01

Against a backdrop of steady deregulation, the pharmaceutical industry is increasingly outsourcing manufacturing, resulting in decentralized control of the global supply chain. Established products such as heparin have been held to outdated analytical standards. Ten million Americans receive heparin every year; Baxter International accounts for half of this market. In 2008, contamination of Baxter's heparin--sourced in China--resulted in about 350 adverse events and 150 deaths in the United States. In future, increasingly stringent FDA inspections and enforcement are expected for imported drugs and ingredients. More regional FDA offices will be set up overseas. FDA funding will likely be supplemented in future by user fees charged to importers. For newer products, companies will face pressure to adopt Quality by Design, with solid control of the global supply chain and a proactive focus on GMP. Older products will be held to modern standards. Long-term, imports of drugs and ingredients from developing markets will continue. This makes sense to companies from an economic standpoint, but protections will be essential to ensure that it is also justifiable from a public health perspective.

Commonwealth Edison Company pressure locking test report

Energy Technology Data Exchange (ETDEWEB)

Bunte, B.D.; Kelly, J.F.

1996-12-01

Pressure Locking is a phenomena which can cause the unseating thrust for a gate valve to increase dramatically from its typical static unseating thrust. This can result in the valve actuator having insufficient capability to open the valve. In addition, this can result in valve damage in cases where the actuator capability exceeds the valve structural limits. For these reasons, a proper understanding of the conditions which may cause pressure locking and thermal binding, as well as a methodology for predicting the unseating thrust for a pressure locked or thermally bound valve, are necessary. This report discusses the primary mechanisms which cause pressure locking. These include sudden depressurization of piping adjacent to the valve and pressurization of fluid trapped in the valve bonnet due to heat transfer. This report provides a methodology for calculating the unseating thrust for a valve which is pressure locked. This report provides test data which demonstrates the accuracy of the calculation methodology.

Commonwealth Edison Company pressure locking test report

International Nuclear Information System (INIS)

Bunte, B.D.; Kelly, J.F.

1996-01-01

Pressure Locking is a phenomena which can cause the unseating thrust for a gate valve to increase dramatically from its typical static unseating thrust. This can result in the valve actuator having insufficient capability to open the valve. In addition, this can result in valve damage in cases where the actuator capability exceeds the valve structural limits. For these reasons, a proper understanding of the conditions which may cause pressure locking and thermal binding, as well as a methodology for predicting the unseating thrust for a pressure locked or thermally bound valve, are necessary. This report discusses the primary mechanisms which cause pressure locking. These include sudden depressurization of piping adjacent to the valve and pressurization of fluid trapped in the valve bonnet due to heat transfer. This report provides a methodology for calculating the unseating thrust for a valve which is pressure locked. This report provides test data which demonstrates the accuracy of the calculation methodology

A Turn-on Fluorescence Sensor for Heparin Detection Based on a Release of Taiwan Cobra Cardiotoxin from a DNA Aptamer or Adenosine-Based Molecular Beacon.

Science.gov (United States)

Shi, Yi-Jun; Wang, Liang-Jun; Lee, Yuan-Chin; Huang, Chia-Hui; Hu, Wan-Ping; Chang, Long-Sen

2018-02-19

This study presents two sensitive fluorescent assays for sensing heparin on the basis of the electrostatic interaction between heparin and Naja naja atra cardiotoxin 3 (CTX3). Owing to CTX3-induced folded structure of an adenosine-based molecular beacon (MB) or a DNA aptamer against CTX3, a reduction in the fluorescent signal of the aptamer or MB 5'-end labeled with carboxyfluorescein (FAM) and 3'-end labeled with 4-([4-(dimethylamino)phenyl]azo)-benzoic acid (DABCYL) was observed upon the addition of CTX3. The presence of heparin and formation of the CTX3-heparin complex caused CTX3 detachment from the MB or aptamer, and restoration of FAM fluorescence of the 5'-FAM-and-3'-DABCYL-labeled MB and aptamer was subsequently noted. Moreover, the detection of heparin with these CTX3-aptamer and CTX3-MB sensors showed high sensitivity and selectivity toward heparin over chondroitin sulfate and hyaluronic acid regardless of the presence of plasma. The limit of detection for heparin in plasma was determined to be 16 ng/mL and 15 ng/mL, respectively, at a signal-to-noise ratio of 3. This study validates the practical utility of the CTX3-aptamer and CTX3-MB systems for determining the concentration of heparin in a biological matrix.

Concept design of the DEMO divertor cassette-to-vacuum vessel locking system adopting a systems engineering approach

International Nuclear Information System (INIS)

Di Gironimo, G.; Carfora, D.; Esposito, G.; Lanzotti, A.; Marzullo, D.; Siuko, M.

2015-01-01

Highlights: • An iterative and incremental design process for cassette-to-VV locking system of DEMO divertor is presented. • Three different concepts have been developed with a systematic design approach. • The final concept has been selected with Fuzzy-Analytic Hierarchy Process in virtual reality. - Abstract: This paper deals with pre-concept studies of DEMO divertor cassette-to-vacuum vessel locking system under the work program WP13-DAS-07-T06: Divertor Remote Maintenance System pre-concept study. An iterative design process, consistent with Systems Engineering guidelines and named Iterative and Participative Axiomatic Design Process (IPADeP), is used in this paper to propose new innovative solutions for divertor locking system, which can overcome the difficulties in applying the ITER principles to DEMO. The solutions conceived have been analysed from the structural point of view using the software Ansys and, eventually, evaluated using the methodology known as Fuzzy-Analytic Hierarchy Process. Due to the lack and the uncertainty of the requirements in this early conceptual design stage, the aim is to cover a first iteration of an iterative and incremental process to propose an innovative design concept to be developed in more details as the information will be completed

Concept design of the DEMO divertor cassette-to-vacuum vessel locking system adopting a systems engineering approach

Energy Technology Data Exchange (ETDEWEB)

Di Gironimo, G., E-mail: giuseppe.digironimo@unina.it [Università degli Studi di Napoli “Federico II”, Dipartimento di Ingegneria Industriale, Piazzale Tecchio 80, 80135 Napoli (Italy); Carfora, D. [Tampere University of Technology, Korkeakoulunkatu 6, 33720 Tampere (Finland); VTT Technical Research Centre of Finland, Tekniikankatu 1, PO Box 1300, FI-33101 Tampere (Finland); Università degli Studi di Napoli “Federico II”, Dipartimento di Ingegneria Industriale, Piazzale Tecchio 80, 80135 Napoli (Italy); Esposito, G.; Lanzotti, A.; Marzullo, D. [Università degli Studi di Napoli “Federico II”, Dipartimento di Ingegneria Industriale, Piazzale Tecchio 80, 80135 Napoli (Italy); Siuko, M. [VTT Technical Research Centre of Finland, Tekniikankatu 1, PO Box 1300, FI-33101 Tampere (Finland)

2015-05-15

Highlights: • An iterative and incremental design process for cassette-to-VV locking system of DEMO divertor is presented. • Three different concepts have been developed with a systematic design approach. • The final concept has been selected with Fuzzy-Analytic Hierarchy Process in virtual reality. - Abstract: This paper deals with pre-concept studies of DEMO divertor cassette-to-vacuum vessel locking system under the work program WP13-DAS-07-T06: Divertor Remote Maintenance System pre-concept study. An iterative design process, consistent with Systems Engineering guidelines and named Iterative and Participative Axiomatic Design Process (IPADeP), is used in this paper to propose new innovative solutions for divertor locking system, which can overcome the difficulties in applying the ITER principles to DEMO. The solutions conceived have been analysed from the structural point of view using the software Ansys and, eventually, evaluated using the methodology known as Fuzzy-Analytic Hierarchy Process. Due to the lack and the uncertainty of the requirements in this early conceptual design stage, the aim is to cover a first iteration of an iterative and incremental process to propose an innovative design concept to be developed in more details as the information will be completed.

Wall locking and multiple nonlinear states of magnetic islands

International Nuclear Information System (INIS)

Persson, Mikael; Australian National Univ., Canberra, ACT

1994-01-01

The nonlinear evolution of magnetic islands is analysed in configurations with multiple resonant magnetic surfaces. The existence of multiple nonlinear steady states, is discussed. These are shown to be associated with states where the dynamics around the different rational surfaces are coupled or decoupled and in the presence of a wall of finite resistivity may correspond wall-locked or non-wall-locked magnetic islands. For the case of strong wall stabilization the locking is shown to consist of two different phases. During the first phase the locking of the plasma at the different rational surfaces occurs. Only when the outermost resonant magnetic surface has locked to the inner surfaces can the actual wall locking process take place. Consequently, wall locking, of a global mode, involving more than one rational surface, can be prevented by the decoupling of the resonant magnetic surfaces by plasma rotation. Possible implications on tokamak experiments are discussed. (author)

Impact of the Tactical Picture Quality on the Fire Control Radar Search-Lock-On Time

Science.gov (United States)

2006-09-01

theory terminology). It is required to grade the benefits from the different possible actions so that an optimal solution can be chosen. For instance, in...the fire control radar search-lock-on time (U) 4. AUTEURS (Nom de famille, prénom et initiales. Indiquer les grades militaires, ex.: Bleau, Maj

No Snowball on Habitable Tidally Locked Planets

Energy Technology Data Exchange (ETDEWEB)

Checlair, Jade; Abbot, Dorian S. [Department of the Geophysical Sciences, University of Chicago, 5734 South Ellis Avenue, Chicago, IL 60637 (United States); Menou, Kristen, E-mail: jadecheclair@uchicago.edu [Centre for Planetary Sciences, Department of Physical and Environmental Sciences, University of Toronto at Scarborough, Toronto, ON M1C 1A4 (Canada)

2017-08-20

The TRAPPIST-1, Proxima Centauri, and LHS 1140 systems are the most exciting prospects for future follow-up observations of potentially inhabited planets. All of the planets orbit nearby M-stars and are likely tidally locked in 1:1 spin–orbit states, which motivates the consideration of the effects that tidal locking might have on planetary habitability. On Earth, periods of global glaciation (snowballs) may have been essential for habitability and remote signs of life (biosignatures) because they are correlated with increases in the complexity of life and in the atmospheric oxygen concentration. In this paper, we investigate the snowball bifurcation (sudden onset of global glaciation) on tidally locked planets using both an energy balance model and an intermediate-complexity global climate model. We show that tidally locked planets are unlikely to exhibit a snowball bifurcation as a direct result of the spatial pattern of insolation they receive. Instead, they will smoothly transition from partial to complete ice coverage and back. A major implication of this work is that tidally locked planets with an active carbon cycle should not be found in a snowball state. Moreover, this work implies that tidally locked planets near the outer edge of the habitable zone with low CO{sub 2} outgassing fluxes will equilibrate with a small unglaciated substellar region rather than cycling between warm and snowball states. More work is needed to determine how the lack of a snowball bifurcation might affect the development of life on a tidally locked planet.

Short locking time and low jitter phase-locked loop based on slope charge pump control

International Nuclear Information System (INIS)

Guo Zhongjie; Liu Youbao; Wu Longsheng; Wang Xihu; Tang Wei

2010-01-01

A novel structure of a phase-locked loop (PLL) characterized by a short locking time and low jitter is presented, which is realized by generating a linear slope charge pump current dependent on monitoring the output of the phase frequency detector (PFD) to implement adaptive bandwidth control. This improved PLL is created by utilizing a fast start-up circuit and a slope current control on a conventional charge pump PLL. First, the fast start-up circuit is enabled to achieve fast pre-charging to the loop filter. Then, when the output pulse of the PFD is larger than a minimum value, the charge pump current is increased linearly by the slope current control to ensure a shorter locking time and a lower jitter. Additionally, temperature variation is attenuated with the temperature compensation in the charge pump current design. The proposed PLL has been fabricated in a kind of DSP chip based on a 0.35 μm CMOS process. Comparing the characteristics with the classical PLL, the proposed PLL shows that it can reduce the locking time by 60% with a low peak-to-peak jitter of 0.3% at a wide operation temperature range. (semiconductor integrated circuits)

Arm locking with Doppler estimation errors

Energy Technology Data Exchange (ETDEWEB)

Yu Yinan; Wand, Vinzenz; Mitryk, Shawn; Mueller, Guido, E-mail: yinan@phys.ufl.ed [Department of Physics, University of Florida, Gainesville, FL 32611 (United States)

2010-05-01

At the University of Florida we developed the University of Florida LISA Interferometer Simulator (UFLIS) in order to study LISA interferometry with hardware in the loop at a system level. One of the proposed laser frequency stabilization techniques in LISA is arm locking. Arm locking uses an adequately filtered linear combination of the LISA arm signals as a frequency reference. We will report about experiments in which we demonstrated arm locking using UFLIS. During these experiments we also discovered a problem associated with the Doppler shift of the return beam. The initial arm locking publications assumed that this Doppler shift can perfectly be subtracted inside the phasemeter or adds an insignificant offset to the sensor signal. However, the remaining Doppler knowledge error will cause a constant change in the laser frequency if unaccounted for. Several ways to circumvent this problem have been identified. We performed detailed simulations and started preliminary experiments to verify the performance of the proposed new controller designs.

Surface biomimetic modification with laminin-loaded heparin/poly-L-lysine nanoparticles for improving the biocompatibility

Energy Technology Data Exchange (ETDEWEB)

Liu, Tao, E-mail: 11140021@hyit.edu.cn [Jiangsu Provincial Key Laboratory for Interventional Medical Devices, Huaiyin Institute of Technology, Huai' an (China); Hu, Youdong [Department of Geriatrics, The Affiliated Huai' an Hospital of Xuzhou Medical College, Huai' an (China); Tan, Jianying [Key Lab. of Advanced Technology for Materials of Chinese Education Ministry, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu (China); Liu, Shihui [Jiangsu Provincial Key Laboratory for Interventional Medical Devices, Huaiyin Institute of Technology, Huai' an (China); Chen, Junying [Key Lab. of Advanced Technology for Materials of Chinese Education Ministry, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu (China); Guo, Xin; Pan, Changjiang [Jiangsu Provincial Key Laboratory for Interventional Medical Devices, Huaiyin Institute of Technology, Huai' an (China); Li, Xia, E-mail: xial_li@qq.com [Department of Geriatrics, The Affiliated Huai' an Hospital of Xuzhou Medical College, Huai' an (China)

2017-02-01

Late thrombus and restenosis caused by delayed endothelialization and insufficient biocompatibility of polymer coating continue to be the greatest limitations of drug-eluting stents. In this study, based on the specific structure of vascular basement membrane, a novel biomimetic nano-coating was constructed by incorporating laminin into electrostatic-assembled heparin/poly-L-lysine nanoparticles. Alteration of heparin and poly-L-lysine concentration ratio in a certain range has no significantly influence nanoparticle size, uniformity and stability, but may affect the chemical property and subsequently the binding efficiency to dopamine-coated titanium surface. By use of this feature, four different nanoparticles were synthesized and immobilized on titanium surface for creating gradient nanoparticle binding density. According to in vitro biocompatibility evaluation, the nanoparticle modified surfaces were found to effectively block coagulation pathway and reduce thrombosis formation. Moreover, NP10L and NP15L modified surface with relatively low heparin exposing density (4.9 to 7.1 μg/cm2) showed beneficial effect in selective promoting EPCs and ECs proliferation, as well as stimulating cell migration and NO synthesis. - Highlights: • A novel laminin-loaded anticoagulant nanoparticle was prepared and used for titanium surface modification. • The nanoparticle binding density was adjustable by alteration the concentration ratio of heparin and poly-L-lysine. • In a certain range of NPs density, the surface was found to selectively direct platelet and vascular cells behavior.

Surface biomimetic modification with laminin-loaded heparin/poly-L-lysine nanoparticles for improving the biocompatibility

International Nuclear Information System (INIS)

Liu, Tao; Hu, Youdong; Tan, Jianying; Liu, Shihui; Chen, Junying; Guo, Xin; Pan, Changjiang; Li, Xia

2017-01-01

Late thrombus and restenosis caused by delayed endothelialization and insufficient biocompatibility of polymer coating continue to be the greatest limitations of drug-eluting stents. In this study, based on the specific structure of vascular basement membrane, a novel biomimetic nano-coating was constructed by incorporating laminin into electrostatic-assembled heparin/poly-L-lysine nanoparticles. Alteration of heparin and poly-L-lysine concentration ratio in a certain range has no significantly influence nanoparticle size, uniformity and stability, but may affect the chemical property and subsequently the binding efficiency to dopamine-coated titanium surface. By use of this feature, four different nanoparticles were synthesized and immobilized on titanium surface for creating gradient nanoparticle binding density. According to in vitro biocompatibility evaluation, the nanoparticle modified surfaces were found to effectively block coagulation pathway and reduce thrombosis formation. Moreover, NP10L and NP15L modified surface with relatively low heparin exposing density (4.9 to 7.1 μg/cm2) showed beneficial effect in selective promoting EPCs and ECs proliferation, as well as stimulating cell migration and NO synthesis. - Highlights: • A novel laminin-loaded anticoagulant nanoparticle was prepared and used for titanium surface modification. • The nanoparticle binding density was adjustable by alteration the concentration ratio of heparin and poly-L-lysine. • In a certain range of NPs density, the surface was found to selectively direct platelet and vascular cells behavior.

Voltammetric determination of heparin based on its interaction with ...

African Journals Online (AJOL)

... with the linear regression equation as ∆ip″ (nA) = 360.19 C (mg/L) + 178.88 (n = 15, γ = 0.998) and the detection limit as 0.28 mg/L (3σ). The effects of coexisting substances such as metal ions, amino acids on the determination of heparin were investigated and the results showed that this method had good selectivity.

The differences in heparin binding for the C-terminal basic-sequence-rich peptides of HPV-16 and HPV-18 capsid protein L1

International Nuclear Information System (INIS)

Sun Jian; Yu Jisheng; Yu Zhiwu; Zha Xiao; Wu Yuqing

2012-01-01

Graphial abstract: The differences in heparin binding for the C-terminal basic-sequence-rich peptides of HPV-16 and HPV-18 capsid protein L1. Highlights: ► Several driving forces contribute to the interaction between heparin and peptides. ► C-terminal of HPV L1 is a potential candidate for the attachment to host cells. ► The C-terminal peptides of HPV-16 and -18 L1 have different heparin-binding. ► The different heparin-binding provides an explanation for the distinct prevalences. - Abstract: The high-risk types of human papillomaviruses (HPV) HPV-16 and -18 are the predominant types associated with cervical cancer. HPV-16 and -18 account for about 50% and 20%, respectively, of cervical cancers worldwide. While the reason and molecular mechanism of the distinct prevalence and distributions between them remain poorly understood, the binding affinity of cell surface receptor with capsid proteins, especially L1, may be involved. We examined heparin binding with two synthetic peptides corresponding to the 14 amino acid C-terminal peptides of HPV-16 and -18 L1 with the goal of comparing the equivalent residues in different HPV types. Using isothermal titration calorimetry (ITC) and static right-angle light scattering (SLS), we determined the binding constant K, reaction enthalpy ΔH, and other thermodynamic parameters in the interaction. Especially, we assessed the role of specific residues in binding with heparin by comparing the NMR spectra of free and heparin-bound peptides.

Multipulse dynamics of a passively mode-locked semiconductor laser with delayed optical feedback

Science.gov (United States)

Jaurigue, Lina; Krauskopf, Bernd; Lüdge, Kathy

2017-11-01

Passively mode-locked semiconductor lasers are compact, inexpensive sources of short light pulses of high repetition rates. In this work, we investigate the dynamics and bifurcations arising in such a device under the influence of time delayed optical feedback. This laser system is modelled by a system of delay differential equations, which includes delay terms associated with the laser cavity and feedback loop. We make use of specialised path continuation software for delay differential equations to analyse the regime of short feedback delays. Specifically, we consider how the dynamics and bifurcations depend on the pump current of the laser, the feedback strength, and the feedback delay time. We show that an important role is played by resonances between the mode-locking frequencies and the feedback delay time. We find feedback-induced harmonic mode locking and show that a mismatch between the fundamental frequency of the laser and that of the feedback cavity can lead to multi-pulse or quasiperiodic dynamics. The quasiperiodic dynamics exhibit a slow modulation, on the time scale of the gain recovery rate, which results from a beating with the frequency introduced in the associated torus bifurcations and leads to gain competition between multiple pulse trains within the laser cavity. Our results also have implications for the case of large feedback delay times, where a complete bifurcation analysis is not practical. Namely, for increasing delay, there is an ever-increasing degree of multistability between mode-locked solutions due to the frequency pulling effect.

Investigation on Locking and Pulling Modes in Analog Frequency Dividers

Directory of Open Access Journals (Sweden)

Antonio Buonomo

2013-01-01

Full Text Available We compare the main analytical results available to estimate the locking range, which is the key figure-of-merit of LC frequency dividers based on the injection locking phenomenon. Starting from the classical result by Adler concerning injection-locked oscillators, we elucidate the merits and the shortcomings of the different approaches to study injection-locked frequency dividers, with particular emphasis on divider-by-2. In particular, we show the potential of a perturbation approach which enables a more complete analysis of frequency dividers, making it possible to calculate not only the amplitude and the phase of the locked oscillation, but also the region where it exists and is stable, which defines the locking region. Finally, we analyze the dynamical behaviour of the dividers in the vicinity of the boundary of the locking region, showing that there exists a border region where the occurrence of the locking or the pulling operation mode is possible, depending on the initial conditions of the system.

Forced phase-locked response of a nonlinear system with time delay after Hopf bifurcation

International Nuclear Information System (INIS)

Ji, J.C.; Hansen, Colin H.

2005-01-01

The trivial equilibrium of a nonlinear autonomous system with time delay may become unstable via a Hopf bifurcation of multiplicity two, as the time delay reaches a critical value. This loss of stability of the equilibrium is associated with two coincident pairs of complex conjugate eigenvalues crossing the imaginary axis. The resultant dynamic behaviour of the corresponding nonlinear non-autonomous system in the neighbourhood of the Hopf bifurcation is investigated based on the reduction of the infinite-dimensional problem to a four-dimensional centre manifold. As a result of the interaction between the Hopf bifurcating periodic solutions and the external periodic excitation, a primary resonance can occur in the forced response of the system when the forcing frequency is close to the Hopf bifurcating periodic frequency. The method of multiple scales is used to obtain four first-order ordinary differential equations that determine the amplitudes and phases of the phase-locked periodic solutions. The first-order approximations of the periodic solutions are found to be in excellent agreement with those obtained by direct numerical integration of the delay-differential equation. It is also found that the steady state solutions of the nonlinear non-autonomous system may lose their stability via either a pitchfork or Hopf bifurcation. It is shown that the primary resonance response may exhibit symmetric and asymmetric phase-locked periodic motions, quasi-periodic motions, chaotic motions, and coexistence of two stable motions

Determination of Oversulphated Chondroitin Sulphate and Dermatan Sulphate in unfractionated heparin by (1)H-NMR - Collaborative study for quantification and analytical determination of LoD.

Science.gov (United States)

McEwen, I; Mulloy, B; Hellwig, E; Kozerski, L; Beyer, T; Holzgrabe, U; Wanko, R; Spieser, J-M; Rodomonte, A

2008-12-01

Oversulphated Chondroitin Sulphate (OSCS) and Dermatan Sulphate (DS) in unfractionated heparins can be identified by nuclear magnetic resonance spectrometry (NMR). The limit of detection (LoD) of OSCS is 0.1% relative to the heparin content. This LoD is obtained at a signal-to-noise ratio (S/N) of 2000:1 of the heparin methyl signal. Quantification is best obtained by comparing peak heights of the OSCS and heparin methyl signals. Reproducibility of less than 10% relative standard deviation (RSD) has been obtained. The accuracy of quantification was good.

Disparate effects of heparin on free thyroxine measured by two different radioimmunoassays

International Nuclear Information System (INIS)

McDougall, I.R.; Bayer, M.F.; Nierenberg, D.; Lewis, S.J.

1983-01-01

Heparin causes a rise in free thyroxine (FT4) measured by equilibrium dialysis (E.D.). With the introduction of at least 4 commercial radioimmunoassays (RIA) for FT4, FT4 measurements have become accepted as one of the best routine thyroid function tests. Investigators have indicated that FT4 levels determined by RIA may be of particular value in patients hospitalized for various severe nonthyroidal illnesses in whom conventional thyroid function tests tend to be abnormal. However, very little information is as yet available on possible effects of various drugs on FT4 levels measured by these new methods. A study was undertaken to evaluate the effect of heparin on FT4 measured by 2 different RIA procedures: RIA-I, GammaCoat FT4 by clinical Assays and RIA-II, Amerlex FT4 by Amersham

The strength of polyaxial locking interfaces of distal radius plates.

Science.gov (United States)

Hoffmeier, Konrad L; Hofmann, Gunther O; Mückley, Thomas

2009-10-01

Currently available polyaxial locking plates represent the consequent enhancement of fixed-angle, first-generation locking plates. In contrast to fixed-angle locking plates which are sufficiently investigated, the strength of the new polyaxial locking options has not yet been evaluated biomechanically. This study investigates the mechanical strength of single polyaxial interfaces of different volar radius plates. Single screw-plate interfaces of the implants Palmar 2.7 (Königsee Implantate und Instrumente zur Osteosynthese GmbH, Allendorf, Germany), VariAx (Stryker Leibinger GmbH & Co. KG, Freiburg, Germany) und Viper (Integra LifeSciences Corporation, Plainsboro, NJ, USA) were tested by cantilever bending. The strength of 0 degrees, 10 degrees and 20 degrees screw locking angle was obtained during static and dynamic loading. The Palmar 2.7 interfaces showed greater ultimate strength and fatigue strength than the interfaces of the other implants. The strength of the VariAx interfaces was about 60% of Palmar 2.7 in both, static and dynamic loading. No dynamic testing was applied to the Viper plate because of its low ultimate strength. By static loading, an increase in screw locking angle caused a reduction of strength for the Palmar 2.7 and Viper locking interfaces. No influence was observed for the VariAx locking interfaces. During dynamic loading; angulation had no influence on the locking strength of Palmar 2.7. However, reduction of locking strength with increasing screw angulation was observed for VariAx. The strength of the polyaxial locking interfaces differs remarkably between the examined implants. Depending on the implant an increase of the screw locking angle causes a reduction of ultimate or fatigue strength, but not in all cases a significant impact was observed.

Multifunctional silk-heparin biomaterials for vascular tissue engineering applications

Science.gov (United States)

Seib, F. Philipp; Herklotz, Manuela; Burke, Kelly A.; Maitz, Manfred F.; Werner, Carsten; Kaplan, David L.

2013-01-01

Over the past 30 years, silk has been proposed for numerous biomedical applications that go beyond its traditional use as a suture material. Silk sutures are well tolerated in humans, but the use of silk for vascular engineering applications still requires extensive biocompatibility testing. Some studies have indicated a need to modify silk to yield a hemocompatible surface. This study examined the potential of low molecular weight heparin as a material for refining silk properties by acting as a carrier for vascular endothelial growth factor (VEGF) and improving silk hemocompatibility. Heparinized silk showed a controlled VEGF release over 6 days; the released VEGF was bioactive and supported the growth of human endothelial cells. Silk samples were then assessed using a humanized hemocompatibility system that employs whole blood and endothelial cells. The overall thrombogenic response for silk was very low and similar to the clinical reference material polytetrafluoroethylene. Despite an initial inflammatory response to silk, apparent as complement and leukocyte activation, the endothelium was maintained in a resting, anticoagulant state. The low thrombogenic response and the ability to control VEGF release support the further development of silk for vascular applications. PMID:24099708

Performance Monitoring System: Summary of Lock Statistics. Revision 1.

Science.gov (United States)

1985-12-01

2751 84 4057 4141 526 798 18 1342 5727 19 5523 3996 4587 8583 1056 1630 35 2721 6536LOCK A DAMI 2 AUXILIARY I Ins NO DATA RECORDD FOR THIS LOCK- " LOCK I...TOTAL (KTOMS) ’ - (AVt OPNP ETC) ’’ ,q [ " ARKANSAS RIVER "" FORRELL LOCK IP 7A/3TRC 9/N83 UPBOUID STATISTICS ISO 53 42 M6 553 356 909 221 41 21 M8

Key-lock colloids in a nematic liquid crystal.

Science.gov (United States)

Silvestre, Nuno M; Tasinkevych, M

2017-01-01

The Landau-de Gennes free energy is used to study theoretically the effective interaction of spherical "key" and anisotropic "lock" colloidal particles. We assume identical anchoring properties of the surfaces of the key and of the lock particles, and we consider planar degenerate and perpendicular anchoring conditions separately. The lock particle is modeled as a spherical particle with a spherical dimple. When such a particle is introduced into a nematic liquid crystal, it orients its dimple at an oblique angle θ_{eq} with respect to the far field director n_{∞}. This angle depends on the depth of the dimple. Minimization results show that the free energy of a pair of key and lock particles exhibits a global minimum for the configuration when the key particle is facing the dimple of the lock colloidal particle. The preferred orientation ϕ_{eq} of the key-lock composite doublet relative to n_{∞} is robust against thermal fluctuations. The preferred orientation θ_{eq}^{(2)} of the dimple particle in the doublet is different from the isolated situation. This is related to the "direct" interaction of defects accompanying the key particle with the edge of the dimple. We propose that this nematic-amplified key-lock interaction can play an important role in self-organization and clustering of mixtures of colloidal particles with dimple colloids present.

THE IMPACT OF HEPARIN IMPLEMENTER (GAG IN THE RABBIT INSEMINATION DOSE

Directory of Open Access Journals (Sweden)

Martin Fik

2013-10-01

Full Text Available The aim of this work was to evaluate the impact of implementer heparin in insemination dose in rabbits selected on reproductive parameters.The experiment was monitored reproductive parameters (conceptual relationship, the number of live-born pups per litter, the number of dead-born pups per litter, the number of live-born pups per inseminated does 156 does in the experimental group and 165 does in the control group. We used the ejaculate of synthetic broiler rabbit population with concentration of sperm 25-50 mil. / 0.5 ml / 1 ID. Heparin was added at a dose - 0.06 ml = 10 mg per 0.5 ml semen / 1 ID. Assessing selected reproductive parameters in does inseminated with insemination dose with the addition of heparin, we observed a higher conceptual proportion of 14.12 % in the experimental group compared to the control group. These differences did not show a statistically significant difference (χ 2 3.56-. The number of live-born pups per litter was 8.69 ± 4.10 pc in the experimental group and 8.41 ± 3.62 pc in the control group (P> 0.05. The number of dead-born pups was recorded 0.74 pc in the experimental group and 0.76 pc in the control group (P> 0.05. The number of live-born pups per litter per inseminated does we have seen improvement in favor of experimental group by 1.39 pc. This parameter was within each of experiments ranged from 0.91 to 1.66 pc live-born pups to inseminated does.

Prediction of the oversulphated chondroitin sulphate contamination of unfractionated heparin by ATR-IR spectrophotometry.

Science.gov (United States)

Norwig, J; Beyer, T; Brinz, D; Holzgrabe, U; Diller, M; Manns, D

2009-03-01

The detection of a contamination of heparin with oversulphated chondroitin sulphate (OSCS) was first analysed in an unfractionated heparin batch supplied to the US API-market in April 2006. OSCS is a semi-synthetic derivative of the natural occuring glycosaminoglycan chondroitin sulphate. Moreover some spectroscopic characteristics of the substance overlap with those of heparin, so that the infrared (IR) spectra are visually difficult to distinguish whereas (1)H-NMR (Nuclear Magnetic Resonance) spectroscopy or capillary electrophoresis (CE) provides identification by a simple visual inspection of either the spectrum or the electropherogram respectively. However, applying special tools of Multivariate Data Analysis (MVA) to the IR spectra an identification of the contaminated samples is possible. In detail a rapid Attenuation Total Reflectance-Infrared (ATR-IR) measurement was selected, which does not require any sample preparation. The result (contaminated or not contaminated) is predicted within a few minutes. A method transfer to mobile ATR-IR spectrometers seems to be possible. The analysis is based on the fact that the fingerprint of the OSCS IR spectrum (1st derivative) complies with a theoretically calculated principal component in the MVA.

Monolithic Hybrid and Passive Mode-Locked 40GHz Quantum Dot Laser Diodes

DEFF Research Database (Denmark)

Thompson, M. G.; Larsson, David; Rae, A. R.

2006-01-01

For the first time hybrid and passive mode-locking jitter performance is investigated in 40GHz quantum-dot mode-locked lasers. Record low passive mode-locking jitter of 219fs is presented, along with promising hybrid mode-locking results of 124fs.......For the first time hybrid and passive mode-locking jitter performance is investigated in 40GHz quantum-dot mode-locked lasers. Record low passive mode-locking jitter of 219fs is presented, along with promising hybrid mode-locking results of 124fs....

Improved patency and reduced intimal hyperplasia in PTFE grafts with luminal immobilized heparin compared with standard PTFE grafts at six months in a sheep model.

Science.gov (United States)

Pedersen, G; Laxdal, E; Ellensen, V; Jonung, T; Mattsson, E

2010-06-01

The aim of this study was to compare the performance of polytetrafluoroethylene (PTFE) grafts with luminal coating of immobilized heparin to that of standard PTFE grafts at six months. Twenty-eight common carotid arteries in fourteen sheep were bypassed with heparin-coated PTFE grafts (6 mm diameter, 6 cm length) on one side and standard PTFE grafts on the other. The grafts were explanted after six months. The thickness of intimal hyperplasia (IH) in open grafts was measured with histomorphometrical methods. Two of 14 heparinized PTFE grafts and nine of 14 grafts in the control PTFE-group were occluded at explantation (P=0.006). Six-month patency rates for heparinized PTFE grafts and for standard PTFE grafts were 86% and 36%, respectively. Mean graft anastomotic IH thickness in open grafts were 0.074 mm for heparinized PTFE grafts and 0.259 mm for PTFE-grafts (P=0.006). PTFE grafts with luminal coating containing immobilized heparin had significantly better patency and recruited less intimal hyperplasia than standard PTFE grafts at six months.

A triad of lys12, lys41, arg78 spatial domain, a novel identified heparin binding site on tat protein, facilitates tat-driven cell adhesion.

Directory of Open Access Journals (Sweden)

Jing Ai

Full Text Available Tat protein, released by HIV-infected cells, has a battery of important biological effects leading to distinct AIDS-associated pathologies. Cell surface heparan sulfate protoglycans (HSPGs have been accepted as endogenous Tat receptors, and the Tat basic domain has been identified as the heparin binding site. However, findings that deletion or substitution of the basic domain inhibits but does not completely eliminate Tat-heparin interactions suggest that the basic domain is not the sole Tat heparin binding site. In the current study, an approach integrating computational modeling, mutagenesis, biophysical and cell-based assays was used to elucidate a novel, high affinity heparin-binding site: a Lys12, Lys41, Arg78 (KKR spatial domain. This domain was also found to facilitate Tat-driven β1 integrin activation, producing subsequent SLK cell adhesion in an HSPG-dependent manner, but was not involved in Tat internalization. The identification of this new heparin binding site may foster further insight into the nature of Tat-heparin interactions and subsequent biological functions, facilitating the rational design of new therapeutics against Tat-mediated pathological events.

Mapping of low molecular weight heparins using reversed phase ion pair liquid chromatography-mass spectrometry.

Science.gov (United States)

Li, Daoyuan; Chi, Lequan; Jin, Lan; Xu, Xiaohui; Du, Xuzhao; Ji, Shengli; Chi, Lianli

2014-01-01

Low molecular weight heparins (LMWHs) are structurally complex, highly sulfated and negatively charged, linear carbohydrate polymers prepared by chemical or enzymatic depolymerization of heparin. They are widely used as anticoagulant drugs possessing better bioavailability, longer half-life, and lower side effects than heparin. Comprehensive structure characterization of LMWHs is important for drug quality assurance, generic drug application, and new drug research and development. However, fully characterization of all oligosaccharide chains in LMWHs is not feasible for current available analytical technologies due to their structure complexity and heterogeneity. Fingerprinting profiling is an efficient way for LMWHs' characterization and comparison. In this work, we present a simple, sensitive, and powerful analytical approach for structural characterization of LMWHs. Two different LMWHs, enoxaparin and nadroparin, were analyzed using reversed phase ion pair electrospray ionization mass spectrometry (RPIP-ESI-MS). More than 200 components were identified, including major structures, minor structures, and process related impurities. This approach is robust for high resolution and complementary fingerprinting analysis of LMWHs. Copyright © 2013 Elsevier Ltd. All rights reserved.

The lock-in effect and the greening of automotive cooling systems in the European Union.

Science.gov (United States)

Bjørnåvold, Amalie; Van Passel, Steven

2017-12-01

As of 2017, the sale and use of the refrigerants most commonly used in automotive cooling systems - hydrofluorocarbons - are entirely banned in all new vehicles placed on the market in the European Union. These refrigerants have been recognised as potent greenhouse gases and, therefore, direct contributors to climate change. It is within this regulation-driven market that the technologies for a sustainable solution have been developed. However, this paper argues that the market for automotive cooling systems has been 'locked-in', which means that competing technologies, operating under dynamic increasing returns, will allow for one - potentially inferior technology - to dominate the market. Whilst such a situation is not uncommon, this paper discusses the way that regulation has reinforced a patented monopoly in 'picking winners': to the advantage of a synthetic chemical, R-1234yf, as opposed to the natural solution, which is CO 2 . By developing a generic conceptual framework of path dependence and lock-in, the presented evidence seeks to show how a snowballing effect has led to the intensification of differences in market share. We also argue that the automotive industry is potentially promoting short-term fixes, rather than long-term, sustainable and economically viable solutions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Locks at reactor safety containments of nuclear power plants

International Nuclear Information System (INIS)

1978-12-01

The rule is to be applied for material access locks. A material access lock as defined by this rule is a pressure resistant and technically gas-tight hollow body that is connected with the containment and has got two doors, the inner door of which connects the lock chamber with the interior of the containment and the outer door connects the lock chamber with the outside. It serves exclusively for transferring material or objects. (orig./HP) [de

Endothelial cell capture of heparin-binding growth factors under flow.

Directory of Open Access Journals (Sweden)

Bing Zhao

2010-10-01

Full Text Available Circulation is an important delivery method for both natural and synthetic molecules, but microenvironment interactions, regulated by endothelial cells and critical to the molecule's fate, are difficult to interpret using traditional approaches. In this work, we analyzed and predicted growth factor capture under flow using computer modeling and a three-dimensional experimental approach that includes pertinent circulation characteristics such as pulsatile flow, competing binding interactions, and limited bioavailability. An understanding of the controlling features of this process was desired. The experimental module consisted of a bioreactor with synthetic endothelial-lined hollow fibers under flow. The physical design of the system was incorporated into the model parameters. The heparin-binding growth factor fibroblast growth factor-2 (FGF-2 was used for both the experiments and simulations. Our computational model was composed of three parts: (1 media flow equations, (2 mass transport equations and (3 cell surface reaction equations. The model is based on the flow and reactions within a single hollow fiber and was scaled linearly by the total number of fibers for comparison with experimental results. Our model predicted, and experiments confirmed, that removal of heparan sulfate (HS from the system would result in a dramatic loss of binding by heparin-binding proteins, but not by proteins that do not bind heparin. The model further predicted a significant loss of bound protein at flow rates only slightly higher than average capillary flow rates, corroborated experimentally, suggesting that the probability of capture in a single pass at high flow rates is extremely low. Several other key parameters were investigated with the coupling between receptors and proteoglycans shown to have a critical impact on successful capture. The combined system offers opportunities to examine circulation capture in a straightforward quantitative manner that

Simplified Analytical Methods to Analyze Lock Gates Submitted to Ship Collisions and Earthquakes

Directory of Open Access Journals (Sweden)

Buldgen Loic

2015-09-01

Full Text Available This paper presents two simplified analytical methods to analyze lock gates submitted to two different accidental loads. The case of an impact involving a vessel is first investigated. In this situation, the resistance of the struck gate is evaluated by assuming a local and a global deforming mode. The super-element method is used in the first case, while an equivalent beam model is simultaneously introduced to capture the overall bending motion of the structure. The second accidental load considered in this paper is the seismic action, for which an analytical method is presented to evaluate the total hydrodynamic pressure applied on a lock gate during an earthquake, due account being taken of the fluid-structure interaction. For each of these two actions, numerical validations are presented and the analytical results are compared to finite-element solutions.

Comparison of two doses of heparin on outcome in off-pump coronary artery bypass surgery patients: A prospective randomized control study

Directory of Open Access Journals (Sweden)

Murali Chakravarthy

2017-01-01

Full Text Available Introduction: While off pump coronary artery bypass surgery is practiced with an intention to reduce the morbidity associated with cardiopulmonary bypass, the resultant ′hypercoagulability′ needs to be addressed. Complications such as cavitary thrombus possibly due to the hyper coagulability after off pump coronary artery bypass surgery have been described. Many clinicians use higher doses of heparin - up to 5 mg/kg in order to thwart this fear. Overall, there appears to be no consensus on the dose of heparin in off pump coronary artery bypass surgeries. Aim of the Study: The aim of the study was understand the differences in outcome of such as transfusion requirement, myocardial ischemia, and morbidity when two different doses were used for systemic heparinization. Methods: Elective patients scheduled for off pump coronary artery bypass surgery were included. Ongoing anti platelet medication was not an exclusion criteria, however, anti platelet medications were ceased about a week prior to surgery when possible. Thoracic epidural anesthesia was administered as an adjunct in patients who qualified for it. By computer generated randomization chart, patients were chosen to receive either 2 or 3 mg/kg of intravenous unfractioned heparin to achieve systemic heparinization with activated clotting time targeted at >240 secs. Intraoperative blood loss, postoperative blood loss, myocardial ischemic episodes, requirement of intraaortic balloon counter pulsation and transfusion requirement were analyzed. Results: Sixty two patients participated in the study. There was one conversion to cardiopulmonary bypass. The groups had comparable ACT at baseline (138.8 vs. 146.64 seconds, P = 0.12; 3 mg/kg group had significantly higher values after heparin, as expected. But after reversal with protamine, ACT and need for additional protamine was similar among the groups. Intraoperative (685.56 ± 241.42 ml vs. 675.15 ± 251.86 ml, P = 0.82 and postoperative

Subcutis calcinosis caused by injection of calcium-containing heparin in a chronic kidney injury patient

Directory of Open Access Journals (Sweden)

Lilia Ben Fatma

2014-01-01

Full Text Available Subcutis calcinosis, characterized by abnormal calcium deposits in the skin, is a rare complication of using calcium-containing heparin occurring in patients with advanced renal failure. We report the case of an 83-year-old female, a known case of chronic kidney disease (CKD for four years with recent worsening of renal failure requiring hospitalization and hemodialysis. She developed subcutis calcinosis following injection of calcium-containing heparin. Biochemical tests showed serum parathormone level at 400 pg/dL, hypercalcemia, elevated calcium-phosphate product and monoclonal gammopathy related to multiple myeloma. She developed firm subcu-taneous nodules in the abdomen and the thighs, the injection sites of Calciparin ® (calcium nadroparin that was given as a preventive measure against deep vein thrombosis. The diagnosis of subcutis calcinosis was confirmed by the histological examination showing calcium deposit in the dermis and hypodermis. These lesions completely disappeared after discontinuing calcium nadro-parin injections. Subcutis calcinosis caused by injections of calcium-containing heparin is rare, and, to the best our knowledge, not more than 12 cases have been reported in the literature. Pathogenesis is not well established but is attributed to the calcium disorders usually seen in advanced renal failure. Diagnosis is confirmed by histological tests. Outcome is mostly favorable. The main differential diagnosis is calciphylaxis, which has a poor prognosis. Even though rarely reported, we should be aware that CKD patients with elevated calcium-phosphorus product can develop subcutis calcinosis induced by calcium-containing heparin. When it occurs, fortunately and unlike calci-phylaxis, outcome is favorable.

Polyguluronate sulfate and its oligosaccharides but not heparin promotes FGF19/FGFR1c signaling

Science.gov (United States)

Lan, Ying; Zeng, Xuan; Guo, Zhihua; Zeng, Pengjiao; Hao, Cui; Zhao, Xia; Yu, Guangli; Zhang, Lijuan

2017-06-01

Fibroblast growth factor 19(FGF19) functions as a hormone by affecting glucose metabolism. FGF19 improves glucose tolerance when overexpressed in mice with impaired glucose tolerance or diabetes. A functional cellular FGF19 receptor consists of FGF receptor (FGFR) and glycosaminoglycan complexed with either α Klotho or β Klotho. Interestingly, in mice with diet-induced diabetes, a single injection of FGF1 is enough to restore blood sugar levels to a healthy range. FGF1 binds heparin with high affinity whereas FGF19 does not, indicating that polysaccharides other than heparin might enhance FGF19/FGFR signaling. Using a FGFs/FGFR1c signaling-dependent BaF3 cell proliferation assay, we discovered that polyguluronate sulfate (PGS) and its oligosaccharides, PGS12 and PGS25, but not polyguluronate (PG), a natural marine polysaccharide, enhanced FGF19/FGFR1c signaling better than that of heparin based on 3H-thymidine incorporation. Interestingly, PGS6, PGS8, PGS10, PGS12, PGS25, and PGS, but not PG, had comparable FGF1/FGFR1c signal-stimulating activity compared to that of heparin. These results indicated that PGS and its oligosaccharides were excellent FGF1/FGFR1c and FGF19/FGFR1c signaling enhancers at cellular level. Since the inexpensive PGS and PGS oligosaccharides can be absorbed through oral route, these seaweed-derived compounds merit further investigation as novel agents for the treatment of type 2 diabetes through enhancing FGF1/FGFR1c and FGF19/FGFR1c signaling in future.

''Old'' locked inflation

Energy Technology Data Exchange (ETDEWEB)

Liu, Yang; Piao, Yun-Song [College of Physical Sciences, Graduate University of Chinese Academy of Sciences, Beijing 100049 (China); Si, Zong-Guo, E-mail: liuyangbyf@mail.sdu.edu.cn, E-mail: yspiao@gucas.ac.cn, E-mail: zgsi@sdu.edu.cn [Department of Physics, Shandong University, Jinan 250100 (China)

2009-05-15

In this paper, we revisit the idea of locked inflation, which does not require a potential satisfying the normal slow-roll condition, but suffers from the problems associated with ''saddle inflation''. We propose a scenario based on locked inflation, however, with an alternative evolution mechanism of the ''waterfall field'' {phi}. Instead of rolling down along the potential, the {phi} field will tunnel to end the inflation stage like in old inflation, by which the saddle inflation could be avoided. Further, we study a cascade of old locked inflation, which can be motivated by the string landscape. Our model is based on the consideration of making locked inflation feasible so as to give a working model without slow roll; It also can be seen as an effort to embed the old inflation in string landscape.

Improving generalized inverted index lock wait times

Science.gov (United States)

Borodin, A.; Mirvoda, S.; Porshnev, S.; Ponomareva, O.

2018-01-01

Concurrent operations on tree like data structures is a cornerstone of any database system. Concurrent operations intended for improving read\\write performance and usually implemented via some way of locking. Deadlock-free methods of concurrency control are known as tree locking protocols. These protocols provide basic operations(verbs) and algorithm (ways of operation invocations) for applying it to any tree-like data structure. These algorithms operate on data, managed by storage engine which are very different among RDBMS implementations. In this paper, we discuss tree locking protocol implementation for General inverted index (Gin) applied to multiversion concurrency control (MVCC) storage engine inside PostgreSQL RDBMS. After that we introduce improvements to locking protocol and provide usage statistics about evaluation of our improvement in very high load environment in one of the world’s largest IT company.

Development and in vivo evaluation of an oral delivery system for low molecular weight heparin based on thiolated polycarbophil.

Science.gov (United States)

Kast, Constantia E; Guggi, Davide; Langoth, Nina; Bernkop-Schnürch, Andreas

2003-06-01

It was the purpose of this study to develop a new oral drug delivery system for low molecular weight heparin (LMWH) providing an improved bioavailability and a prolonged therapeutic effect. The permeation enhancing polycarbophil-cysteine conjugate (PCP-Cys) used in this study displayed 111.4 +/- 6.4 microM thiol groups per gram polymer. Permeation studies on freshly excised intestinal mucosa were performed in Ussing chambers demonstrating a 2-fold improved uptake of heparin as a result of the addition of 0.5% (w/v) PCP-Cys and the permeation mediator glutathione (GSH). Tablets containing PCP-Cys, GSH, and 279 IU of LMWH showed a sustained drug release over 4 h. To guarantee the swelling of the polymeric carrier matrix in the small intestine tablets were enteric coated. They were orally given to rats. For tablets being based on the thiomer/GSH system an absolute bioavailability of 19.9 +/- 9.3% (means +/- SD; n = 5) vs. intravenous injection could be achieved. whereas tablets comprising unmodified PCP did not lead to a significant (p < 0.01) heparin concentration in plasma. The permeation enhancing effect and subsequently a therapeutic heparin level was maintained for 24 h after a single dose. Because of the strong and prolonged lasting permeation enhancing effect of the thiomer/GSH system, the oral bioavailability of LMWH could be significantly improved. This new delivery system represents therefore a promising tool for the oral administration of heparin.

Comparison on Anticoagulation and Antiplatelet Aggregation Effects of Puerarin with Heparin Sodium and Tirofiban Hydrochloride: An In Vitro Study.

Science.gov (United States)

Li, Si-Wei; Feng, Xue; Xu, Hao; Chen, Ke-Ji

2018-02-01

To detect the anticoagulation and antiplatelet effects of different concentrations of puerarin, heparin sodium and tirofiban hydrochloride on the blood samples of healthy volunteers by Sonoclot coagulation and platelet function analyzer. Peripheral blood samples were extracted from 20 healthy volunteers, followed by adding different concentrations of puerarin, heparin sodium and tirofiban hydrochloride. Samples were detected for activated clotting time (ACT), clot rate (CR) and platelet function (PF) by Sonoclot coagulation and platelet function analyzer instrument. For puerarin and heparin sodium, the values of ACT gradually increased, and the values of CR and PF gradually decreased with increasing in drug concentration. There was a linear (or log linear) relationship between ACT, CR, PF value and drug concentration (Phydrochloride, the values of ACT and CR had no significant changes, while PF values gradually decreased with concentration increasing. There was also a linear relationship between PF values and concentrations of tirofiban hydrochloride (Psodium. For high concentrations of puerarin (e.g. 3.8 mg/600 μL) and tirofiban hydrochloride (e.g. 0.8 μg/600 μL), PF values had no significant difference. However, PF values for high puerarin concentration had a larger variance. Puerarin has similar anticoagulant and antiplatelet effects with the heparin sodium, and may have a lower hemorrhage risk than heparin sodium when obtained the same anticoagulation effect in the concentration range of this experiment. In addition, for high concentration, puerarin had the same antiplatelet function as tirofiban hydrochloride but with a larger individual variability.

Synthesis and characterization of polystyrene-poly(ethylene oxide)-heparin block copolymers

NARCIS (Netherlands)

Vulić, I.; Okano, T.; Kim, S.W.; Feijen, Jan

1988-01-01

A procedure for the preparation of new block copolymers composed of a hydrophobic block of polystyrene, a hydrophilic spacer-block of poly(ethylene oxide) and a bioactive block of heparin was investigated. Polystyrene with one amino group per chain was synthesized by free radical oligomerization of

John locke on personal identity.

Science.gov (United States)

Nimbalkar, Namita

2011-01-01

John Locke speaks of personal identity and survival of consciousness after death. A criterion of personal identity through time is given. Such a criterion specifies, insofar as that is possible, the necessary and sufficient conditions for the survival of persons. John Locke holds that personal identity is a matter of psychological continuity. He considered personal identity (or the self) to be founded on consciousness (viz. memory), and not on the substance of either the soul or the body.

John Locke on Personal Identity**

OpenAIRE

Nimbalkar, Namita

2011-01-01

John Locke speaks of personal identity and survival of consciousness after death. A criterion of personal identity through time is given. Such a criterion specifies, insofar as that is possible, the necessary and sufficient conditions for the survival of persons. John Locke holds that personal identity is a matter of psychological continuity. He considered personal identity (or the self) to be founded on consciousness (viz. memory), and not on the substance of either the soul or the body.

Capillary electrophoresis of heparin and other glycosaminoglycans using a polyamine running electrolyte

Energy Technology Data Exchange (ETDEWEB)

Loegel, Thomas N.; Trombley, John D.; Taylor, Richard T. [Department of Chemistry and Biochemistry, Miami University, Oxford, OH 45056 (United States); Danielson, Neil D., E-mail: danielnd@muohio.edu [Department of Chemistry and Biochemistry, Miami University, Oxford, OH 45056 (United States)

2012-11-13

Highlights: Black-Right-Pointing-Pointer Ethylenediamine is likely acting as an ion-pairing agent. Black-Right-Pointing-Pointer Oversulfated chondroitin sulfate is last peak instead of first peak. Black-Right-Pointing-Pointer There is about a factor of five improved detectability with a 12.5 min analysis time. Black-Right-Pointing-Pointer Use of a 50 {mu}m ID capillary is possible. - Abstract: This study involves the use of polyamines as potential resolving agents for the capillary electrophoresis (CE) of glycosaminoglycans (GAGs), specifically heparin, dermatan sulfate, chondroitin sulfate, over-sulfated chondroitin sulfate (OSCS), and hyaluronan. All of the compounds can be separated from each other with the exception of chondroitin sulfate and hyaluronan. Using optimization software, the final run conditions are found to be 200 mM ethylenediamine and 45.5 mM phosphate as the electrolyte with -14 V applied across a 50 {mu}m ID Multiplication-Sign 24.5 cm fused silica capillary at 15 Degree-Sign C. The ion migration order, with OSCS as the last instead of the first peak, is in contrast to previous reports using either a high molarity TRIS or lithium phosphate run buffer with narrower bore capillaries. Total analysis time is 12. 5 min and the relative standard deviation of the heparin migration time is about 2.5% (n = 5). The interaction mechanism between selected polyamines and heparin is explored using conductivity measurements in addition to CE experiments to show that an ion-pairing mechanism is likely.

Capillary electrophoresis of heparin and other glycosaminoglycans using a polyamine running electrolyte

International Nuclear Information System (INIS)

Loegel, Thomas N.; Trombley, John D.; Taylor, Richard T.; Danielson, Neil D.

2012-01-01

Highlights: ► Ethylenediamine is likely acting as an ion-pairing agent. ► Oversulfated chondroitin sulfate is last peak instead of first peak. ► There is about a factor of five improved detectability with a 12.5 min analysis time. ► Use of a 50 μm ID capillary is possible. - Abstract: This study involves the use of polyamines as potential resolving agents for the capillary electrophoresis (CE) of glycosaminoglycans (GAGs), specifically heparin, dermatan sulfate, chondroitin sulfate, over-sulfated chondroitin sulfate (OSCS), and hyaluronan. All of the compounds can be separated from each other with the exception of chondroitin sulfate and hyaluronan. Using optimization software, the final run conditions are found to be 200 mM ethylenediamine and 45.5 mM phosphate as the electrolyte with −14 V applied across a 50 μm ID × 24.5 cm fused silica capillary at 15 °C. The ion migration order, with OSCS as the last instead of the first peak, is in contrast to previous reports using either a high molarity TRIS or lithium phosphate run buffer with narrower bore capillaries. Total analysis time is 12. 5 min and the relative standard deviation of the heparin migration time is about 2.5% (n = 5). The interaction mechanism between selected polyamines and heparin is explored using conductivity measurements in addition to CE experiments to show that an ion-pairing mechanism is likely.

Injection locking of optomechanical oscillators via acoustic waves

Science.gov (United States)

Huang, Ke; Hossein-Zadeh, Mani

2018-04-01

Injection locking is a powerful technique for synchronization of oscillator networks and controlling the phase and frequency of individual oscillators using similar or other types of oscillators. Here, we present the first demonstration of injection locking of a radiation-pressure driven optomechanical oscillator (OMO) via acoustic waves. As opposed to previously reported techniques (based on pump modulation or direct application of a modulated electrostatic force), injection locking of OMO via acoustic waves does not require optical power modulation or physical contact with the OMO and it can easily be implemented on various platforms. Using this approach we have locked the phase and frequency of two distinct modes of a microtoroidal silica OMO to a piezoelectric transducer (PZT). We have characterized the behavior of the injection locked OMO with three acoustic excitation configurations and showed that even without proper acoustic impedance matching the OMO can be locked to the PZT and tuned over 17 kHz with only -30 dBm of RF power fed to the PZT. The high efficiency, simplicity and scalability of the proposed approach paves the road toward a new class of photonic systems that rely on synchronization of several OMOs to a single or multiple RF oscillators with applications in optical communication, metrology and sensing. Beyond its practical applications, injection locking via acoustic waves can be used in fundamental studies in quantum optomechanics where thermal and optical isolation of the OMO are critical.

Coupled optical resonance laser locking.

Science.gov (United States)

Burd, S C; du Toit, P J W; Uys, H

2014-10-20

We have demonstrated simultaneous laser frequency stabilization of a UV and IR laser, to coupled transitions of ions in the same spectroscopic sample, by detecting only the absorption of the UV laser. Separate signals for locking the different lasers are obtained by modulating each laser at a different frequency and using lock-in detection of a single photodiode signal. Experimentally, we simultaneously lock a 369 nm and a 935 nm laser to the (2)S(1/2) → (2)(P(1/2) and (2)D(3/2) → (3)D([3/2]1/2) transitions, respectively, of Yb(+) ions generated in a hollow cathode discharge lamp. Stabilized lasers at these frequencies are required for cooling and trapping Yb(+) ions, used in quantum information and in high precision metrology experiments. This technique should be readily applicable to other ion and neutral atom systems requiring multiple stabilized lasers.

Heparin surface stent-graft for the treatment of a carotid pseudoaneurysm.

Science.gov (United States)

Tsolaki, Elpiniki; Elpiniki, Tsolaki; Salviato, Elisabetta; Rocca, Tiberio; Braccini, Lucia; Galeotti, Roberto; Mascoli, Francesco

2010-10-01

Carotid pseudoaneurysms are a rare consequence of carotid surgery, trauma, and infection. Historically, carotid aneurysms and pseudoaneurysms were treated surgically. However, endovascular techniques have recently become a valid alternative for the treatment of carotid pseudoaneurysms. The case of a 57-year-old male patient with a pseudoaneurysm of the right internal carotid artery is described. The patient came to our unit with a painless and pulsatile mass in the neck, which was growing slowly. Five years earlier, he had undergone surgery on a saccular aneurysm located on the distal extracranial segment of the right internal carotid artery. The pseudoaneurysm was successfully treated with a heparin surface Viabahn stent-graft system (Gore AL, Flagstaff, AZ). Heparin surface stent-grafts can be used for the treatment of carotid lesions and may offer protection against intimal hyperplasia and thrombosis. Further studies are needed to evaluate the long-term results. Copyright © 2010 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.

Genomic and Functional Characterization of the Unusual pLOCK 0919 Plasmid Harboring the spaCBA Pili Cluster in Lactobacillus casei LOCK 0919

Science.gov (United States)

Aleksandrzak-Piekarczyk, Tamara; Koryszewska-Bagińska, Anna; Grynberg, Marcin; Nowak, Adriana; Cukrowska, Bożena; Kozakova, Hana; Bardowski, Jacek

2016-01-01

Here, we report the extensive bioinformatic and functional analyses of the unusual pLOCK 0919, a plasmid originating from the probiotic Lactobacillus casei LOCK 0919 strain. This plasmid is atypical because it harbors the spaCBA-srtC gene cluster encoding SpaCBA pili. We show that all other spaCBA-srtC sequences of the Lactobacillus genus that have been previously described and deposited in GenBank are present in the chromosomal DNA. Another important observation for pLOCK 0919 is that the spaCBA-srtC gene cluster and its surrounding genes are highly similar to the respective DNA region that is present in the most well-known and active SpaCBA pili producer, the probiotic Lactobacillus rhamnosus GG strain. Our results demonstrate that the spaCBA-srtC clusters of pLOCK 0919 and L. rhamnosus GG are genealogically similar, located in DNA regions that are rich in transposase genes and are poorly conserved among the publicly available sequences of Lactobacillus sp. In contrast to chromosomally localized pilus gene clusters from L. casei and Lactobacillus paracasei, the plasmidic spaC of L. casei LOCK 0919 is expressed and undergoes a slight glucose-induced repression. Moreover, results of series of in vitro tests demonstrate that L. casei LOCK 0919 has an adhesion potential, which is largely determined by the presence of the pLOCK 0919 plasmid. In particular, the plasmid occurrence positively influenced the hydrophobicity and aggregation abilities of L. casei LOCK 0919. Moreover, in vivo studies indicate that among the three Lactobacillus strains used to colonize the gastrointestinal tract of germ-free mice, already after 2 days of colonization, L. casei LOCK 0919 became the dominant strain and persisted there for at least 48 days. PMID:26637469

Heparin binding sites on Ross River virus revealed by electron cryo-microscopy

International Nuclear Information System (INIS)

Zhang Wei; Heil, Marintha; Kuhn, Richard J.; Baker, Timothy S.

2005-01-01

Cell surface glycosaminoglycans play important roles in cell adhesion and viral entry. Laboratory strains of two alphaviruses, Sindbis and Semliki Forest virus, have been shown to utilize heparan sulfate as an attachment receptor, whereas Ross River virus (RRV) does not significantly interact with it. However, a single amino acid substitution at residue 218 in the RRV E2 glycoprotein adapts the virus to heparan sulfate binding and expands the host range of the virus into chicken embryo fibroblasts. Structures of the RRV mutant, E2 N218R, and its complex with heparin were determined through the use of electron cryo-microscopy and image reconstruction methods. Heparin was found to bind at the distal end of the RRV spikes, in a region of the E2 glycoprotein that has been previously implicated in cell-receptor recognition and antibody binding

Biomechanical comparison of double-row locking plates versus single- and double-row non-locking plates in a comminuted metacarpal fracture model.

Science.gov (United States)

Gajendran, Varun K; Szabo, Robert M; Myo, George K; Curtiss, Shane B

2009-12-01

Open or unstable metacarpal fractures frequently require open reduction and internal fixation. Locking plate technology has improved fixation of unstable fractures in certain settings. In this study, we hypothesized that there would be a difference in strength of fixation using double-row locking plates compared with single- and double-row non-locking plates in comminuted metacarpal fractures. We tested our hypothesis in a gap metacarpal fracture model simulating comminution using fourth-generation, biomechanical testing-grade composite sawbones. The metacarpals were divided into 6 groups of 15 bones each. Groups 1 and 4 were plated with a standard 6-hole, 2.3-mm plate in AO fashion. Groups 2 and 5 were plated with a 6-hole double-row 3-dimensional non-locking plate with bicortical screws aimed for convergence. Groups 3 and 6 were plated with a 6-hole double-row 3-dimensional locking plate with unicortical screws. The plated metacarpals were then tested to failure against cantilever apex dorsal bending (groups 1-3) and torsion (groups 4-6). The loads to failure in groups 1 to 3 were 198 +/- 18, 223 +/- 29, and 203 +/- 19 N, respectively. The torques to failure in groups 4 to 6 were 2,033 +/- 155, 3,190 +/- 235, and 3,161 +/- 268 N mm, respectively. Group 2 had the highest load to failure, whereas groups 5 and 6 shared the highest torques to failure (p row plates had equivalent bending and torsional stiffness, significantly higher than observed for the single-row non-locking plate. No other statistical differences were noted between groups. When subjected to the physiologically relevant forces of apex dorsal bending and torsion in a comminuted metacarpal fracture model, double-row 3-dimensional non-locking plates provided superior stability in bending and equivalent stability in torsion compared with double-row 3-dimensional locking plates, whereas single-row non-locking plates provided the least stability.

Analysis of peer-to-peer locking of magnetrons

International Nuclear Information System (INIS)

Pengvanich, P.; Lau, Y. Y.; Cruz, E.; Gilgenbach, R. M.; Hoff, B.; Luginsland, J. W.

2008-01-01

The condition for mutual, or peer-to-peer, locking of two magnetrons is derived. This condition reduces to Adler's classical phase-locking condition in the limit where one magnetron becomes the ''master'' and the other becomes the ''slave.'' The formulation is extended to the peer-to-peer locking of N magnetrons, under the assumption that the electromagnetic coupling among the N magnetrons is modeled by an N-port network.

Comparison of heparinized saline and 0.9% sodium chloride for maintaining peripheral intravenous catheter patency in dogs.

Science.gov (United States)

Ueda, Yu; Odunayo, Adesola; Mann, F A

2013-01-01

To determine whether heparinized saline would be more effective in maintaining the patency of peripheral IV catheters in dogs compared to 0.9% sodium chloride. Prospective blinded randomized study. University Veterinary Teaching Hospital. Thirty healthy purpose bred dogs, intended for use in the junior surgery laboratory, were utilized. The dogs were randomized into 1 of 3 groups, 2 treatment groups and a control group. An 18-Ga cephalic catheter was placed in the cephalic vein of each dog. Each dog in the treatment group had their catheter flushed with either 10 IU/mL heparinized saline or 0.9% sodium chloride every 6 hours for 42 hours. The dogs in the control group did not have their catheters flushed until the end of the study period. Immediately prior to flushing catheters, each catheter was evaluated for patency by aspiration of blood and the catheter site was evaluated for phlebitis. All dogs in the heparinized saline and 0.9% sodium chloride group had catheters that flushed easily at each evaluation point. More dogs in the saline group had catheters from which blood could not be aspirated, but there was no significant difference between these groups. All dogs in the control group had catheters that flushed easily at the end of the assigned 6 hour interval except in 1 dog. Phlebitis was not detected in any dog. Flushes of 0.9% sodium chloride were found to be as effective as 10 IU/mL heparinized saline flushes in maintaining patency of 18-Ga peripheral venous catheters in dogs for up to 42 hours. For peripheral catheters placed with the intention of performing serial blood draws, heparinized flushes may be warranted. © Veterinary Emergency and Critical Care Society 2013.

Nuclear androgen receptors in human prostatic tissue. Extraction with heparin and estimation of the number of binding sites with different methods

International Nuclear Information System (INIS)

Foekens, J.A.; Bolt-de Vries, J.; Mulder, E.; Blankenstein, M.A.; Schroeder, F.H.; Molen, H.J. van der

1981-01-01

A procedure for the estimation of nuclear androgen receptors in benign prostatic hyperplastic tissue is described, which employs extraction of receptors from nuclei with buffers containing heparin. Extraction of a nuclear pellet with a heparin-containing (1 g/l) buffer appeared to have definite advantages over 0.4 mol/l KCl extraction. Heparin appeared to be twice as efficient in extracting androgen receptors. In addition aggregated receptor proteins, formed after storage at -80 0 C, were partly deaggregated by heparin. Specific isolation of the androgen receptor was performed using either agar gel electrophoresis, protamine sulphate precipitation or LH-20 gel filtration. A comparison was made between the amounts of estimated receptors with these different techniques. Protamine sulphate precipitation resulted in the highest estimates of receptor-bound 5α-[ 3 H]dihydrotestosterone ( 3 H-DHT). Treatment of the labelled nuclear extracts with a charcoal suspension prior to the receptor assay resulted in lower amounts of estimated androgen receptors. A method for routine evaluation of nuclear androgen receptors in prostatic tissue has been evaluated, which involves extraction of nuclear pellets with a heparin-containing (1 g/l) buffer, exchange labelling of the nuclear extracts for 20 h at 10 0 C and quantification of the receptors with protamine sulphate precipitation. (Auth.)

Low-thrombogenic fibrin-heparin coating promotes in vitro endothelialization

Czech Academy of Sciences Publication Activity Database

Kaplan, Ondřej; Hierlemann, T.; Krajewski, S.; Kurz, J.; Nevoralová, Martina; Houska, Milan; Riedel, Tomáš; Riedelová, Zuzana; Zárubová, Jana; Wendel, H. P.; Brynda, Eduard

2017-01-01

Roč. 105, č. 11 (2017), s. 2995-3005 ISSN 1549-3296 R&D Projects: GA MZd(CZ) NV15-29153A Institutional support: RVO:61389013 ; RVO:67985823 Keywords : fibrin-heparin coating * hemocompatibility * endothelialization Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery; FA - Cardiovascular Diseases incl. Cardiotharic Surgery (FGU-C) OBOR OECD: Cardiac and Cardiovascular systems; Cardiac and Cardiovascular systems (FGU-C) Impact factor: 3.076, year: 2016

ELB-trees - Efficient Lock-free B+trees

DEFF Research Database (Denmark)

Bonnichsen, Lars Frydendal; Karlsson, Sven; Probst, Christian W.

2014-01-01

As computer systems scale in the number of processors, data structures with good parallel performance become increasingly important. Lock-free data structures promise improved parallel performance at the expense of higher complexity and sequential execution time.We present ELBtrees, a new lock-fr...

In vitro Heparin Precipitation in the Plasma of Euthyroid women with ...

African Journals Online (AJOL)

OBJECTIVE: Women with elevated Lp(a), who are susceptible to atherosclerosis, get to reduce, their cardiovascular disease by in-vivo administration of low dose heparin. And history of recurrent miscarriage associated with auto antibodies have had a high rate of life births in subsequent pregnancies when they were ...

Hew Locke: House of Cards

OpenAIRE

Reckitt, Helena; Joyce, Julie; Locke, Hew

2004-01-01

‘Hew Locke: House of Cards’ featured a selection of the artist's portraits of British royalty in various media, and his response to other trappings of the monarchy and empire. The show included works previously exhibited at the Luckman Gallery, Los Angeles, in tandem with a newly commissioned coat of arms, and other recent works. \\ud \\ud Locke draws from everyday sources, ranging from items found in London's Brixton Market to discount fabric shops and thrift stores. Other sources of inspirati...

Graft patency after off-pump coronary artery bypass surgery is inferior even with identical heparinization protocols

DEFF Research Database (Denmark)

Houlind, Kim; Fenger-Grøn, Morten; Holme, Susanne J

2014-01-01

OBJECTIVE: To determine whether graft patency after on-pump and off-pump coronary artery bypass surgery is similar when performed using the same heparinization protocol. METHODS: In a randomized, controlled, multicenter trial, 900 patients more than 70 years of age received either on-pump or off......-pump coronary artery bypass surgery. Heparin was given to achieve an activated clotting time of 400 seconds before arteriotomy in both groups. After the procedure, protamine sulfate was given to revert the activated clotting time to less than 120 seconds. Coronary angiography was performed 6 months after...

Venous thromboembolism in pregnancy: prophylaxis and treatment with low molecular weight heparin

DEFF Research Database (Denmark)

Andersen, Anita Sylvest; Berthelsen, Jørgen G; Bergholt, Thomas

2010-01-01

OBJECTIVE: To evaluate the safety of individually dosed low molecular weight heparin (LMWH) for prophylaxis and treatment of thromboembolic complications in pregnancy. DESIGN: Cohort study with a chronologic register-based control group. SETTING: Department of Obstetrics and Gynecology, Hillerød ...

Role of the A+ helix in heparin binding to protein C inhibitor

NARCIS (Netherlands)

Elisen, M. G.; Maseland, M. H.; Church, F. C.; Bouma, B. N.; Meijers, J. C.

1996-01-01

Interactions between proteins and heparin(-like) structures involve electrostatic forces and structural features. Based on charge distributions in the linear sequence of protein C inhibitor (PCI), two positively charged regions of PCI were proposed as possible candidates for this interaction. The

Comparison of a priori versus provisional heparin therapy on radial artery occlusion after transradial coronary angiography and patent hemostasis (from the PHARAOH Study).

Science.gov (United States)

Pancholy, Samir B; Bertrand, Olivier F; Patel, Tejas

2012-07-15

Systemic anticoagulation decreases the risk of radial artery occlusion (RAO) after transradial catheterization and standard occlusive hemostasis. We compared the efficacy and safety of provisional heparin use only when the technique of patent hemostasis was not achievable to standard a priori heparin administration after radial sheath introduction. Patients referred for coronary angiography were randomized in 2 groups. In the a priori group, 200 patients received intravenous heparin (50 IU/kg) immediately after sheath insertion. In the provisional group, 200 patients did not receive heparin during the procedure. After sheath removal, hemostasis was obtained using a TR band (Terumo corporation, Tokyo, Japan) with a plethysmography-guided patent hemostasis technique. In the provisional group, no heparin was given if radial artery patency could be obtained and maintained. If radial patency was not achieved, a bolus of heparin (50 IU/kg) was given. Radial artery patency was evaluated at 24 hours (early RAO) and 30 days after the procedure (late RAO) by plethysmography. Patent hemostasis was obtained in 67% in the a priori group and 74% in the provisional group (p = 0.10). Incidence of RAO remained similar in the 2 groups at the early (7.5% vs 7.0%, p = 0.84) and late (4.5% vs 5.0%, p = 0.83) evaluations. Women, patients with diabetes, patients having not received heparin, and patients without radial artery patency during hemostasis had more RAO. By multivariate analysis, patent radial artery during hemostasis (odds ratio [OR] 0.03, 95% confidence interval [CI] 0.004 to 0.28, p = 0.002) and diabetes (OR 11, 95% CI 3 to 38,p patent hemostasis is maintained. Copyright © 2012 Elsevier Inc. All rights reserved.

Construction of mussel-inspired coating via the direct reaction of catechol and polyethyleneimine for efficient heparin immobilization

Energy Technology Data Exchange (ETDEWEB)

Liu, Yujie [School of Material Science and Engineering, Southwest Jiaotong University, Chengdu 610031 (China); The Institute of Biomaterials and Surface Engineering, Southwest Jiaotong University, Chengdu 610031 (China); Luo, Rifang, E-mail: lrifang@126.com [School of Material Science and Engineering, Southwest Jiaotong University, Chengdu 610031 (China); The Institute of Biomaterials and Surface Engineering, Southwest Jiaotong University, Chengdu 610031 (China); Shen, Fangyu; Tang, Linlin [School of Material Science and Engineering, Southwest Jiaotong University, Chengdu 610031 (China); The Institute of Biomaterials and Surface Engineering, Southwest Jiaotong University, Chengdu 610031 (China); Wang, Jin, E-mail: jinxxwang@263.net [School of Material Science and Engineering, Southwest Jiaotong University, Chengdu 610031 (China); The Institute of Biomaterials and Surface Engineering, Southwest Jiaotong University, Chengdu 610031 (China); Huang, Nan [School of Material Science and Engineering, Southwest Jiaotong University, Chengdu 610031 (China); The Institute of Biomaterials and Surface Engineering, Southwest Jiaotong University, Chengdu 610031 (China)

2015-02-15

Highlights: • Catechol (CA) and PEI copolymerization was a mimetic and dopamine-like coating method. • CA/PEI film provided amine groups and was effective in heparin immobilization. • CA/PEI coating could inhibit smooth muscle cell proliferation. • CA/PEI coating did not show any significant cytotoxicity to endothelial cell. - Abstract: Dopamine could self-polymerize to form the coating on various substrates and the co-existence of catechols and amines was crucial in performing such polymerization process. In this work, a mimetic approach of coating formation was carried out based on the co-polymerization of catechol (CA) and polyethyleneimine (PEI). Mussel-inspired CA/PEI coating was deposited on 316L stainless steel (SS). Fourier transform infrared spectra (FTIR) and X-ray photoelectron spectroscopy (XPS) demonstrated the successful coating formation. QCM measurement showed good affinity of heparin immobilization on CA/PEI coating surface ascribed to the amine groups. Herein, vascular cell-material interactions like endothelial cells (ECs) and smooth muscle cells (SMCs) were also investigated. Interestingly, CA/PEI and heparin modified coatings presented no cytotoxicity to ECs, however to a certain extent, decreased SMCs proliferation. Moreover, heparin-binding surface presented significant anti-platelet adhesion and activation properties. These results effectively suggested that the mussel-inspired CA/PEI coating might be promising when served as a platform for biomolecule immobilization.

Activation of M1 macrophages in sepsis-induced acute kidney injury in response to heparin-binding protein.

Directory of Open Access Journals (Sweden)

Li Xing

Full Text Available In the early stage of sepsis, M1 macrophages result in the production of inflammatory mediators and AKI. Heparin-binding protein (HBP have been shown to play important roles in sepsis-induced AKI. In this study, we investigate the association of HBP with M1 macrophages in sepsis-induced AKI.Male C57BL6 mice were subjected to cecal ligation and puncture (CLP or sham surgery. Biochemical and histological renal damage was assessed. Macrophage infiltration was assessed by immunohistochemistry. RT-PCR was used to investigate the expression of heparin-binding protein (HBP, the inducible nitric oxide synthase (iNOS and arginase 1 (Arg-1 mRNAs. Western blots were performed to assay the tissue levels of HBP, tumor necrosis factor alpha (TNF-α and interleukin-6 (IL-6.High levels of HBP were obviously detected 24 h after sepsis-induced AKI. Heparin inhibited HBP expression during sepsis-induced AKI. The suppression of HBP expression by heparin injection after the establishment of sepsis-induced AKI resulted in a reduction in renal injury severity accompanied with a significant repression of M1 macrophage activation and expression of TNF-α and IL-6.HBP plays an important role in the initial inflammatory reaction associated with sepsis-induced AKI, presumably by activating M1 macrophages and suppressing TNF-α and IL-6 secretion.

Modeling of mode-locked coupled-resonator optical waveguide lasers

DEFF Research Database (Denmark)

Agger, Christian; Skovgård, Troels Suhr; Gregersen, Niels

2010-01-01

Coupled-resonator optical waveguides made from coupled high-Q photonic crystal nanocavities are investigated for use as cavities in mode-locked lasers. Such devices show great potential in slowing down light and can serve to reduce the cavity length of a mode-locked laser. An explicit expression...... of the emerging pulse train. A range of tuning around this frequency allows for effective mode locking. Finally, noise is added to the generalized single-cavity eigenfrequencies in order to evaluate the effects of fabrication imperfections on the cold-cavity transmission properties and consequently on the locking...

Comparative evaluation of 2.3 mm locking plate system vs conventional 2.0 mm non locking plate system for mandibular condyle fracture fixation: a seven year retrospective study.

Science.gov (United States)

Zhang, J; Wang, X; Wu, R-H; Zhuang, Q-W; Gu, Q P; Meng, J

2015-01-01

This retrospective study evaluated the efficacy of a 2.3 mm locking plate/screw system compared with a 2.0-mm non-locking plate/screw system in fixation of isolated non comminuted mandibular condyle fractures. Surgical records of 101 patients who received either a 2.3 mm locking plate (group A, n = 51) or 2.0 mm non locking plate (group B, n = 50) were analyzed. All patients were followed up to a minimum of 6 months postoperatively and evaluated for hardware related complications, occlusal stability, need for and duration of MMF and mandibular functional results. Four complications occurred in the locking group and eighteen in the non locking group with complication rates equalling 8% and 36% respectively. When comparing the overall results according to plates used, the χ2 test showed a statistically significant difference between the locking and non locking plates (p Mandibular condyle fractures treated with a 2.3 mm locking plate exhibited stable osteosynthesis, were associated with minimal complications and resulted in acceptable mandibular range of motion compared with a 2.0 mm non locking plate.

30 CFR 57.12068 - Locking transformer enclosures.

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Locking transformer enclosures. 57.12068 Section 57.12068 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND... Electricity Surface Only § 57.12068 Locking transformer enclosures. Transformer enclosures shall be kept...

Identification of chondroitin sulfate E proteoglycans and heparin proteoglycans in the secretory granules of human lung mast cells

International Nuclear Information System (INIS)

Stevens, R.L.; Austen, K.F.; Fox, C.C.; Lichtenstein, L.M.

1988-01-01

The predominant subclasses of mast cells in both the rat and the mouse can be distinguished from one another by their preferential synthesis of 35 S-labeled proteoglycans that contain either heparin or oversulfated chondroitin sulfate glycosaminoglycans. Although [ 35 S]heparin proteoglycans have been isolated from human lung mast cells of 40-70% purity and from a skin biopsy specimen of a patient with urticaria pigmentosa, no highly sulfated chondroitin sulfate proteoglycan has been isolated from any enriched or highly purified population of human mast cells. The authors demonstrate that human lung mast cells of 96% purity incorporate [ 35 S]sulfate into separate heparin and chondroitin sulfate proteoglycans in an ∼2:1 ratio. As assessed by HPLC of the chondroitinase ABC digests, the chondroitin [ 35 S]sulfate proteoglycans isolated from these human lung mast cells contain the same unusual chondroitin sulfate E disaccharide that is present in proteoglycans produced by interleukin 3-dependent mucosal-like mouse mast cells. Both the chondroitin [ 35 S]sulfate E proteoglycans and the [ 35 S]heparin proteoglycans were exocytosed from the [ 35 S]sulfate-labeled cells via perturbation of the IgE receptor, indicating that both types of 35 S-labeled proteoglycans reside in the secretory granules of these human lung mast cells

Correlations between locked modes and impurity influxes

Energy Technology Data Exchange (ETDEWEB)

Fishpool, G M [Commission of the European Communities, Abingdon (United Kingdom). JET Joint Undertaking; Lawson, K D [UKAEA Culham Lab., Abingdon (United Kingdom)

1994-07-01

An analysis of pulses that were disturbed by medium Z impurity influxes (Cl, Cr, Fe and Ni) recorded during the 91/92 JET operations, has demonstrated that such influxes can result in MHD modes which subsequently ``lock``. A correlation is found between the power radiated by the influx and the time difference between the start of the influx and the beginning of the locked mode. The growth in the amplitude of the locked mode itself can lead to further impurity influxes. A correlation is noted between intense influxes (superior to 10 MW) and the mode ``unlocking``. (authors). 4 refs., 4 figs.

Squeezing in an injection-locked semiconductor laser

Science.gov (United States)

Inoue, S.; Machida, S.; Yamamoto, Y.; Ohzu, H.

1993-09-01

The intensity-noise properties of an injection-locked semiconductor laser were studied experimentally. The constant-current-driven semiconductor laser producing the amplitude-squeezed state whose intensity noise was reduced below the standard quantum limit (SQL) by 0.72 dB was injection-locked by an external master laser. The measured intensity-noise level of the injection-locked semiconductor laser was 0.91 dB below the SQL. This experimental result indicates that a phase-coherent amplitude-squeezed state or squeezed vacuum state together with a reference local oscillator wave can be generated directly by semiconductor laser systems.

Deep vein thrombosis, ecythyma gangrenosum and heparin-induced thrombocytopenia occurring in a man with a heterozygous Factor V Leiden mutation

Directory of Open Access Journals (Sweden)

Mariya Apostolova

2012-11-01

Full Text Available Skin necrosis and limb gangrene are occasional thrombotic manifestations of anticoagulation therapy. We report a man heterozygous for the Factor V Leiden (FVL mutation, and with a history of recurrent deep venous thrombosis, who initially presented with a necrotic skin lesion of the right flank while on warfarin therapy with a therapeutic international normalized ratio. Warfarin was discontinued and he received intravenous heparin. Thereafter he developed thrombocytopenia and pedal erythema and was diagnosed with heparin-induced thrombocytopenia (HIT. Heparin was replaced with argatroban. He ultimately underwent bilateral below-knee amputations for the thrombotic complications of the HIT. The initial necrotic lesion healed with antibiotics and wound care. Pathologic examination of multiple biopsy specimens revealed two separate lesions. One was necrotic tissue infiltrated with methicillin resistant Staphylococcus aureus having features of ecthyma gangrenosum. The second showed thrombotic changes consistent with HIT. The case illustrates the differential diagnosis of skin necrosis and limb gangrene in patients on warfarin and heparin, and also the clinical complexities that can occur in a FVL heterozygote.

Mutual phase-locking of planar nano-oscillators

Directory of Open Access Journals (Sweden)

K. Y. Xu

2014-06-01

Full Text Available Characteristics of phase-locking between Gunn effect-based planar nano-oscillators are studied using an ensemble Monte Carlo (EMC method. Directly connecting two oscillators in close proximity, e.g. with a channel distance of 200 nm, only results in incoherent oscillations. In order to achieve in-phase oscillations, additional considerations must be taken into account. Two coupling paths are shown to exist between oscillators. One coupling path results in synchronization and the other results in anti-phase locking. The coupling strength through these two paths can be adjusted by changing the connections between oscillators. When two identical oscillators are in the anti-phase locking regime, fundamental components of oscillations are cancelled. The resulting output consists of purely second harmonic oscillations with a frequency of about 0.66 THz. This type of second harmonic generation is desired for higher frequency applications since no additional filter system is required. This transient phase-locking process is further analyzed using Adler's theory. The locking range is extracted, and a criterion for the channel length difference required for realizing phased arrays is obtained. This work should aid in designing nano-oscillator arrays for high power applications and developing directional transmitters for wireless communications.

Experimental implementation of phase locking in a nonlinear interferometer

Energy Technology Data Exchange (ETDEWEB)

Wang, Hailong; Jing, Jietai, E-mail: jtjing@phy.ecnu.edu.cn [State Key Laboratory of Precision Spectroscopy, Department of Physics, East China Normal University, Shanghai 200062 (China); Marino, A. M. [Homer L. Dodge Department of Physics and Astronomy, The University of Oklahoma, 440 West Brooks Street, Norman, Oklahoma 73019 (United States)

2015-09-21

Based upon two cascade four-wave mixing processes in two identical hot rubidium vapor cells, a nonlinear interferometer has been experimentally realized [Jing et al., Appl. Phys. Lett. 99, 011110 (2011); Hudelist et al., Nat. Commun. 5, 3049 (2014)]. It has a higher degree of phase sensitivity than a traditional linear interferometer and has many potential applications in quantum metrology. Phase locking of the nonlinear interferometer is needed before it can find its way into applications. In this letter, we investigate the experimental implementation of phase locking of the relative phase between the three beams at different frequencies involved in such a nonlinear interferometer. We have utilized two different methods, namely, beat note locking and coherent modulation locking. We find that coherent modulation locking can achieve much better phase stability than beat note locking in our system. Our results pave the way for real applications of a nonlinear interferometer in precision measurement and quantum manipulation, for example, phase control in phase-sensitive N-wave mixing process, N-port nonlinear interferometer and quantum-enhanced real-time phase tracking.

Locked doors in acute inpatient psychiatry: a literature review.

Science.gov (United States)

van der Merwe, M; Bowers, L; Jones, J; Simpson, A; Haglund, K

2009-04-01

Many acute inpatient psychiatric wards in the UK are permanently locked, although this is contrary to the current Mental Health Act Code of Practice. To conduct a literature review of empirical articles concerning locked doors in acute psychiatric inpatient wards, an extensive literature search was performed in SAGE Journals Online, EBM Reviews, British Nursing Index, CINAHL, EMBASE Psychiatry, International Bibliography of the Social Sciences, Ovid MEDLINE, PsycINFO and Google, using the search terms 'open$', 'close$', '$lock$', 'door', 'ward', 'hospital', 'psychiatr', 'mental health', 'inpatient' and 'asylum'. A total of 11 empirical papers were included in the review. Both staff and patients reported advantages (e.g. preventing illegal substances from entering the ward and preventing patients from absconding and harming themselves or others) and disadvantages (e.g. making patients feel depressed, confined and creating extra work for staff) regarding locked doors. Locked wards were associated with increased patient aggression, poorer satisfaction with treatment and more severe symptoms. The limited literature available showed the urgent need for research to determine the real effects of locked doors in inpatient psychiatry.

Potentiation of C1-esterase inhibitor by heparin and interactions with C1s protease as assessed by surface plasmon resonance.

Science.gov (United States)

Rajabi, Mohsen; Struble, Evi; Zhou, Zhaohua; Karnaukhova, Elena

2012-01-01

Human C1-esterase inhibitor (C1-INH) is a multifunctional plasma protein with a wide range of inhibitory and non-inhibitory properties, mainly recognized as a key down-regulator of the complement and contact cascades. The potentiation of C1-INH by heparin and other glycosaminoglycans (GAGs) regulates a broad spectrum of C1-INH activities in vivo both in normal and disease states. SCOPE OF RESEARCH: We have studied the potentiation of human C1-INH by heparin using Surface Plasmon Resonance (SPR), circular dichroism (CD) and a functional assay. To advance a SPR for multiple-unit interaction studies of C1-INH we have developed a novel (consecutive double capture) approach exploring different immobilization and layout. Our SPR experiments conducted in three different design versions showed marked acceleration in C1-INH interactions with complement protease C1s as a result of potentiation of C1-INH by heparin (from 5- to 11-fold increase of the association rate). Far-UV CD studies suggested that heparin binding did not alter C1-INH secondary structure. Functional assay using chromogenic substrate confirmed that heparin does not affect the amidolytic activity of C1s, but does accelerate its consumption due to C1-INH potentiation. This is the first report that directly demonstrates a significant acceleration of the C1-INH interactions with C1s due to heparin by using a consecutive double capture SPR approach. The results of this study may be useful for further C-INH therapeutic development, ultimately for the enhancement of current C1-INH replacement therapies. Published by Elsevier B.V.

Venous thromboembolism in pregnancy: prophylaxis and treatment with low molecular weight heparin

DEFF Research Database (Denmark)

Andersen, Anita Sylvest; Berthelsen, Jørgen G.; Bergholt, Thomas

2010-01-01

OBJECTIVE: To evaluate the safety of individually dosed low molecular weight heparin (LMWH) for prophylaxis and treatment of thromboembolic complications in pregnancy. DESIGN: Cohort study with a chronologic register-based control group. SETTING: Department of Obstetrics and Gynecology, Hillerød...

Effects of inhaled nitric oxide on hemostasis in healthy adults treated with heparin: a randomized, controlled, blinded crossover study

Directory of Open Access Journals (Sweden)

Goldstein Brahm

2012-01-01

Full Text Available Abstract Background Effects of nitric oxide (NO on hemostasis have been studied in various investigational settings, but data regarding inhaled NO on bleeding and platelet function are conflicting. It is not known if inhaled NO has an effect when administered with drugs that influence hemostasis. This trial evaluated effects of inhaled NO on hemostasis in the presence of heparin using aspirin as a positive control. Patients/Methods Twelve healthy adult males were enrolled in a single-center, randomized, single-blind, four-way crossover trial. Subjects received 80 ppm NO or medical air (placebo inhalation for 30 min with simultaneous injection of placebo or heparin. Aspirin capsules were used as a positive control. Parameters of hemostasis were measured before treatment and at post-treatment intervals. Results Activated clotting time (ACT, prothrombin time (PT and activated partial thromboplastin time (aPTT increased only in groups that received heparin. Areas under the curve for ACT in heparin groups receiving inhaled NO were judged to be equivalent to those receiving medical air for both 0- to 4-h (ratio: 1.00; 90% CI, 0.90-1.11 and 0- to 24-h time intervals (ratio: 1.01; 90% CI, 0.92-1.12. Changes in bleeding time and platelet aggregation were observed only in aspirin groups. No clinically significant changes in hemoglobin, red blood cell counts or haematocrit were observed in any group. Conclusions Inhaled NO, when administered with heparin, exhibited no significant additive effects on ACT, PT, aPTT, bleeding time or platelet aggregation.

QPSK regeneration without active phase-locking

DEFF Research Database (Denmark)

Kjøller, Niels-Kristian; Da Ros, Francesco; Røge, Kasper Meldgaard

2016-01-01

QPSK regeneration without active phase stabilization is investigated in numerical simulations. We propose an improved scheme for phase-locking free QPSK regeneration showing significant improvements in the error vector magnitude of the signal.......QPSK regeneration without active phase stabilization is investigated in numerical simulations. We propose an improved scheme for phase-locking free QPSK regeneration showing significant improvements in the error vector magnitude of the signal....

A Digital Phase Lock Loop for an External Cavity Diode Laser

Science.gov (United States)

Wang, Xiao-Long; Tao, Tian-Jiong; Cheng, Bing; Wu, Bin; Xu, Yun-Fei; Wang, Zhao-Ying; Lin, Qiang

2011-08-01

A digital optical phase lock loop (OPLL) is implemented to synchronize the frequency and phase between two external cavity diode lasers (ECDL), generating Raman pulses for atom interferometry. The setup involves all-digital phase detection and a programmable digital proportional-integral-derivative (PID) loop in locking. The lock generates a narrow beat-note linewidth below 1 Hz and low phase-noise of 0.03rad2 between the master and slave ECDLs. The lock proves to be stable and robust, and all the locking parameters can be set and optimized on a computer interface with convenience, making the lock adaptable to various setups of laser systems.

Phase-locked loops. [in analog and digital circuits communication system

Science.gov (United States)

Gupta, S. C.

1975-01-01

An attempt to systematically outline the work done in the area of phase-locked loops which are now used in modern communication system design is presented. The analog phase-locked loops are well documented in several books but discrete, analog-digital, and digital phase-locked loop work is scattered. Apart from discussing the various analysis, design, and application aspects of phase-locked loops, a number of references are given in the bibliography.

Design of intelligent locks based on the triple KeeLoq algorithm

Directory of Open Access Journals (Sweden)

Huibin Chen

2016-04-01

Full Text Available KeeLoq algorithm with high security was usually used in wireless codec. Its security lack is indicated in this article according to the detailed rationale and the introduction of previous attack researches. Taking examples from Triple Data Encryption Standard algorithm, the triple KeeLoq codec algorithm was first proposed. Experimental results showed that the algorithm would not reduce powerful rolling effect and in consideration of limited computing power of embedded microcontroller three 64-bit keys were suitable to increase the crack difficulties and further improved its security. The method was applied to intelligent door access system for experimental verification. 16F690 extended Bluetooth or WiFi interface was employed to design the lock system on door. Key application was constructed on Android platform. The wireless communication between the lock on door and Android key application employed triple KeeLoq algorithm to ensure the higher security. Due to flexibility and multiformity (an Android key application with various keys of software-based keys, the solution owned overwhelmed advantages of low cost, high security, humanity, and green environmental protection.

Pressure locking and thermal binding of gate valves

Energy Technology Data Exchange (ETDEWEB)

Kelly, E.M.

1996-12-01

Pressure locking and thermal binding represent potential common mode failure mechanisms that can cause safety-related power-operated gate valves to fail in the closed position, thus rendering redundant safety-related systems incapable of performing their safety functions. Supplement 6 to Generic Letter 89-10, {open_quotes}Safety-Related Motor-Operated Gate Valve Testing and Surveillance,{close_quotes} provided an acceptable approach to addressing pressure locking and thermal binding of gate valves. More recently, the NRC has issued Generic Letter 95-07, {open_quotes}Pressure Locking and Thermal Binding of Safety-Related Power-Operated Gate Valves,{close_quotes} to request that licensees take certain actions to ensure that safety-related power-operated gate valves that are susceptible to pressure locking or thermal binding are capable of performing their safety functions within the current licensing bases. Over the past two years, several plants in Region I determined that valves in certain systems were potentially susceptible to pressure locking and thermal binding, and have taken various corrective actions. The NRC Region I Systems Engineering Branch has been actively involved in the inspection of licensee actions in response to the pressure locking and thermal binding issue. Region I continues to maintain an active involvement in this area, including participation with the Office of Nuclear Reactor Regulation in reviewing licensee responses to Generic Letter 95-07.

Heparin removal by ecteola-cellulose pre-treatment enables the use of plasma samples for accurate measurement of anti-Yellow fever virus neutralizing antibodies.

Science.gov (United States)

Campi-Azevedo, Ana Carolina; Peruhype-Magalhães, Vanessa; Coelho-Dos-Reis, Jordana Grazziela; Costa-Pereira, Christiane; Yamamura, Anna Yoshida; Lima, Sheila Maria Barbosa de; Simões, Marisol; Campos, Fernanda Magalhães Freire; de Castro Zacche Tonini, Aline; Lemos, Elenice Moreira; Brum, Ricardo Cristiano; de Noronha, Tatiana Guimarães; Freire, Marcos Silva; Maia, Maria de Lourdes Sousa; Camacho, Luiz Antônio Bastos; Rios, Maria; Chancey, Caren; Romano, Alessandro; Domingues, Carla Magda; Teixeira-Carvalho, Andréa; Martins-Filho, Olindo Assis

2017-09-01

Technological innovations in vaccinology have recently contributed to bring about novel insights for the vaccine-induced immune response. While the current protocols that use peripheral blood samples may provide abundant data, a range of distinct components of whole blood samples are required and the different anticoagulant systems employed may impair some properties of the biological sample and interfere with functional assays. Although the interference of heparin in functional assays for viral neutralizing antibodies such as the functional plaque-reduction neutralization test (PRNT), considered the gold-standard method to assess and monitor the protective immunity induced by the Yellow fever virus (YFV) vaccine, has been well characterized, the development of pre-analytical treatments is still required for the establishment of optimized protocols. The present study intended to optimize and evaluate the performance of pre-analytical treatment of heparin-collected blood samples with ecteola-cellulose (ECT) to provide accurate measurement of anti-YFV neutralizing antibodies, by PRNT. The study was designed in three steps, including: I. Problem statement; II. Pre-analytical steps; III. Analytical steps. Data confirmed the interference of heparin on PRNT reactivity in a dose-responsive fashion. Distinct sets of conditions for ECT pre-treatment were tested to optimize the heparin removal. The optimized protocol was pre-validated to determine the effectiveness of heparin plasma:ECT treatment to restore the PRNT titers as compared to serum samples. The validation and comparative performance was carried out by using a large range of serum vs heparin plasma:ECT 1:2 paired samples obtained from unvaccinated and 17DD-YFV primary vaccinated subjects. Altogether, the findings support the use of heparin plasma:ECT samples for accurate measurement of anti-YFV neutralizing antibodies. Copyright © 2017 Elsevier B.V. All rights reserved.

Sustained Thromboresistant Bioactivity with Reduced Intimal Hyperplasia of Heparin-Bonded Polytetrafluoroethylene Propaten Graft in a Chronic Canine Femoral Artery Bypass Model.

Science.gov (United States)

Freeman, John; Chen, Aaron; Weinberg, Roy J; Okada, Tamuru; Chen, Changyi; Lin, Peter H

2018-05-01

Bypass graft thrombosis remains a significant mode of failure in prosthetic graft revascularization. The purpose of this investigation was to evaluate the long-term thromboresistant effect of heparin-bonded expanded polytetrafluoroethylene (ePTFE) graft using Carmeda BioActive Surface technology in a canine model. Bilateral femorofemoral artery bypass grafts with ePTFE grafts were performed in 25 adult grayhound dogs. In each animal, a heparin-bonded ePTFE graft (Propaten, WL Gore) was placed on one side, whereas a control nonheparin graft was placed on the contralateral side. The graft patency was assessed at 1, 6, 12, 18, and 24 months (n = 5 per group) following the bypass. Heparin bioactivity of the graft material was analyzed. The effect of intimal hyperplasia was also assessed. All bypass grafts were patent at 1 month. Significantly greater patency rates were noted in the Propaten group compared to the control group at 12, 18, and 24 months, which were 84%, 80%, and 80% vs. 55%, 35%, and 20%, respectively (P  0.05). Heparin-bonded ePTFE graft provides a thromboresistant surface and reduced anastomotic intimal hyperplasia at 2 years. The stable heparin bioactivity of the Propaten graft confers an advantage in long-term graft patency. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

High-Order Frequency-Locked Loops

DEFF Research Database (Denmark)

Golestan, Saeed; Guerrero, Josep M.; Quintero, Juan Carlos Vasquez

2017-01-01

In very recent years, some attempts for designing high-order frequency-locked loops (FLLs) have been made. Nevertheless, the advantages and disadvantages of these structures, particularly in comparison with a standard FLL and high-order phase-locked loops (PLLs), are rather unclear. This lack...... study, and its small-signal modeling, stability analysis, and parameter tuning are presented. Finally, to gain insight about advantages and disadvantages of high-order FLLs, a theoretical and experimental performance comparison between the designed second-order FLL and a standard FLL (first-order FLL...

Mode-locked silicon evanescent lasers.

Science.gov (United States)

Koch, Brian R; Fang, Alexander W; Cohen, Oded; Bowers, John E

2007-09-03

We demonstrate electrically pumped lasers on silicon that produce pulses at repetition rates up to 40 GHz. The mode locked lasers generate 4 ps pulses with low jitter and extinction ratios above 18 dB, making them suitable for data and telecommunication transmitters and for clock generation and distribution. Results of both passive and hybrid mode locking are discussed. This type of device could enable new silicon based integrated technologies, such as optical time division multiplexing (OTDM), wavelength division multiplexing (WDM), and optical code division multiple access (OCDMA).

Transfer of heparin polyion across a polarized water/ionic liquid membrane interface

Czech Academy of Sciences Publication Activity Database

Langmaier, Jan; Samec, Zdeněk; Samcová, E.; Tůma, P.

2012-01-01

Roč. 24, OCT 2012 (2012), s. 25-27 ISSN 1388-2481 R&D Projects: GA ČR GAP206/11/0707 Institutional support: RVO:61388955 Keywords : heparin polyion * ionic liquid membrane * amperometric detection Subject RIV: CG - Electrochemistry Impact factor: 4.425, year: 2012

Low-molecular-weight heparin in the treatment of patients with venous thromboembolism

NARCIS (Netherlands)

tenCate, JW; Buller, HR; Gent, M; Hirsh, J; Prins, MH; Baildon, R; Lensing, AWA; Anderson, DR; vanBeek, EJR; Fiesinger, JN; Tijssen, JGP; vanBarneveld, A; Eimers, LT; Graafsma, YP; Hettiarachchi, R; Hutten, B; Redekop, K; Haley, S; LIberale, L; Finch, T; Whittaker, S; Wilkinson, L; Prandoni, P; Villalta, S; Girolami, B; Bagatella, P; Rossi, L; Girolami, A; Piovella, F; Barone, M; Beltrametti, C; Serafini, S; Siragusa, S; Ascari, E; Kovacs, MJ; Morrow, B; Kovacs, J; Kuijer, PMM; Koopman, MMW; Jagt, H; Weitz, J; Kearon, C; Biagioni, L; Haas, S; Lossner, F; Spengel, FA; Berger, M; Demers, C; Poulin, J; vanderMeer, J; Que, GTH; Smid, WM; Robinson, KS; Boyle, E; Leclerc, [No Value; StJacques, B; Finkenbine, S; Gallus, AS; Cohlan, D; Rich, C; Brandjes, DPM; Hoefnagel, CA; deRijk, M; Turkstra, F; Desjardins, L; CoteDesjardins, J; Couture, L; Ruel, M; Villenueve, J; Geerts, WH; Jay, RM; Code, EKI; Turpie, AGG; Johnson, J; Nguyen, P; Cusson, [No Value; Roy, S; Wells, PS; Bormanis, J; Goudie, D; Cruickshank, M; vonLewinski, M; Monreal, M; Sahuquillo, JC; Lafoz, E; Simonneau, G; Parent, F; Jagot, J; Douketis, JD; Kinnon, K; Ginsberg, JS; BrillEdwards, P; Donovan, D; Ockelford, PA; Kassis, J; Bornais, S; Planchon, B; ElKouri, D; Pistorius, MA; Escribano, M; Garrido, G; Chesterman, CN; Chong, BH; Pritchard, S; Cade, JF; Bynon, T; Stanford, J; Brien, WM; Palmer, B; Faivre, R; Petiteau, B; Manucci, PM; Moia, M; Bucciarelli, P

1997-01-01

Background Low-molecular-weight heparin is known to be safe and effective for the initial Treatment of patients with proximal deep-vein thrombosis. However, its application to patients with pulmonary embolism or previous episodes of thromboembolism has not been studied. Methods We randomly assigned

Experimental study on working characteristics of density lock

International Nuclear Information System (INIS)

Sun Furong; Yan Changqi; Gu Haifeng

2011-01-01

The working principle of density lock was introduced in this paper, and the experimental loop was built so that researches on working performance of density lock in the system were done at steady-state operation and pump trip conditions. The results show that at steady-state operation conditions, density lock can keep close in a long run, which will separate passive residual heat removal circuit from primary circuit. As a result, passive residual heat removal circuit is in the non-operating conditions, which dose not influence normal operation of reactors. At the pump trip conditions, density lock can be automatically opened quickly, which will make primary and passive residual heat removal system communicated. The natural circulation is well established in the two systems, and is enough to ensure removal of residual heat. (authors)

Development of thermal actuators with multi-locking positions

Science.gov (United States)

Luo, J. K.; Zhu, Y.; Fu, Y. Q.; Flewitt, A. J.; Spearing, S. M.; Miao, J. M.; Milne, W. I.

2006-04-01

To reduce power consumption and operation temperature for micro-thermal actuators, metal-based micro-mechanical locks with multi-locking positions were analyzed and fabricated. The micro-locks consist of two or three U-shaped thermal actuators. The devices were made by a single mask process using electroplated Ni as the active material. Tests showed that the metal based thermal actuators deliver a maximum displacement of ~20µm at a much lower temperature than that of Si-based actuators. However Ni-actuators showed a severe back bending, which increases with increasing applied power. The temperature to initiate the back bending is as low as ~240°C. Back bending increases the distance between the two actuators, and leads to locking function failure. For practical application, Ni-based thermal actuators must be operated below 200°C.

Active stabilization of a diode laser injection lock.

Science.gov (United States)

Saxberg, Brendan; Plotkin-Swing, Benjamin; Gupta, Subhadeep

2016-06-01

We report on a device to electronically stabilize the optical injection lock of a semiconductor diode laser. Our technique uses as discriminator the peak height of the laser's transmission signal on a scanning Fabry-Perot cavity and feeds back to the diode current, thereby maintaining maximum optical power in the injected mode. A two-component feedback algorithm provides constant optimization of the injection lock, keeping it robust to slow thermal drifts and allowing fast recovery from sudden failures such as temporary occlusion of the injection beam. We demonstrate the successful performance of our stabilization method in a diode laser setup at 399 nm used for laser cooling of Yb atoms. The device eases the requirements on passive stabilization and can benefit any diode laser injection lock application, particularly those where several such locks are employed.

A Digital Phase Lock Loop for an External Cavity Diode Laser

International Nuclear Information System (INIS)

Wang Xiao-Long; Tao Tian-Jiong; Cheng Bing; Wu Bin; Xu Yun-Fei; Wang Zhao-Ying; Lin Qiang

2011-01-01

A digital optical phase lock loop (OPLL) is implemented to synchronize the frequency and phase between two external cavity diode lasers (ECDL), generating Raman pulses for atom interferometry. The setup involves all-digital phase detection and a programmable digital proportional-integral-derivative (PID) loop in locking. The lock generates a narrow beat-note linewidth below 1 Hz and low phase-noise of 0.03rad 2 between the master and slave ECDLs. The lock proves to be stable and robust, and all the locking parameters can be set and optimized on a computer interface with convenience, making the lock adaptable to various setups of laser systems. (fundamental areas of phenomenology(including applications))