Sample records for plasma deposited heparin-like

  1. Heparin-like activity in uterine fluid.

    PubMed Central

    Foley, M E; Griffin, B D; Zuzel, M; Aparicio, S R; Bradbury, K; Bird, C C; Clayton, J K; Jenkins, D M; Scott, J S; Rajah, S M; McNichol, G P

    1978-01-01

    Uterine fluid was collected from a group of normal patients and a group of patients with menorrhagia. Heparin-like activity was detected in 34 out of 38 samples using an anti-Xa heparin assay. The heparin-like activity in uterine fluid was inhibited by adding the heparin antagonist hexadimethrine bromide to the assay. Concentrations of fibrinogen-fibrin degradation products (FDPs) were measured in five samples of uterine fluid. FDPs in the concentration detected had no effect on the anti-Xa assay. Heparin-like activity was higher in the group with menorrhagia, although the differences were not significant. Heparin-like activity increased throughout the menstrual cycle and decreased during menstruation, suggesting a possible cyclical variation in activity. There was no correlation between mast cell numbers in the endometrium and myometrium and heparin-like activity in uterine fluid and no correlation between the numbers and the stage in the menstrual cycle. In a few patients with intrauterine contraceptive devices (IUCDs) heparin-like activity was increased. PMID:687899

  2. Deposition of diamond-like films by ECR microwave plasma

    NASA Technical Reports Server (NTRS)

    Shing, Yuh-Han (Inventor); Pool, Frederick S. (Inventor)

    1995-01-01

    Hard amorphous hydrogenated carbon, diamond-like films are deposited using an electron cyclotron resonance microwave plasma with a separate radio frequency power bias applied to a substrate stage. The electron cyclotron resonance microwave plasma yields low deposition pressure and creates ion species otherwise unavailable. A magnetic mirror configuration extracts special ion species from a plasma chamber. Different levels of the radio frequency power bias accelerate the ion species of the ECR plasma impinging on a substrate to form different diamond-like films. During the deposition process, a sample stage is maintained at an ambient temperature of less than 100.degree. C. No external heating is applied to the sample stage. The deposition process enables diamond-like films to be deposited on heat-sensitive substrates.

  3. Binding of heparin to plasma proteins and endothelial surfaces is inhibited by covalent linkage to antithrombin.

    PubMed

    Chan, Anthony K C; Paredes, Nethnapha; Thong, Bruce; Chindemi, Paul; Paes, Bosco; Berry, Leslie R; Monagle, Paul

    2004-05-01

    Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are used for prophylaxis and treatment of thrombosis. However, UFH has a short plasma half-life and variable anticoagulant response in vivo due to plasma or vessel wall protein binding and LMWH has a decreased ability to inactivate thrombin, the pivotal enzyme in the coagulation cascade. Covalent linkage of antithrombin to heparin gave a complex (ATH) with superior anticoagulant activity compared to UFH and LMWH, and longer intravenous half-life compared to UFH. We found that plasma proteins bound more to UFH than ATH, and least to LMWH. Also, UFH bound significantly more to endothelial cells than ATH, with 100% of UFH and 94% of ATH binding being on the cell surface and the remainder was endocytosed. Competition studies with UFH confirmed that ATH binding was likely through its heparin moiety. These findings suggest that differences in plasma protein and endothelial cell binding may be due to available heparin chain length. Although ATH is polydisperse, the covalently-linked antithrombin may shield a portion of the heparin chain from association with plasma or endothelial cell surface proteins. This model is consistent with ATH's better bioavailability and more predictable dose response.

  4. Effect of oral administration of unfractionated heparin (UFH) on coagulation parameters in plasma and levels of urine and fecal heparin in dogs

    PubMed Central

    Erickson, Malathi; Hiebert, Linda M.; Carr, Anthony P.; Stickney, Jocelyn D.

    2014-01-01

    The effects of heparin administration, by the oral route, were evaluated in dogs. In single and multiple dose studies (single 7.5 mg/kg, multiple 3 × 7.5 mg/kg per 48 h), plasma, urine, and fecal samples were collected at various times up to 120 h after oral administration of unfractionated heparin. Changes in plasma and urine anti-Xa activity, plasma and urine anti-IIa activity, plasma activated partial thromboplastin time (APTT) and antithrombin (ATIII), and chemical heparin in urine and feces were examined with time. There was support for heparin absorption, with significant differences in APTT, heparin in plasma as determined by anti-Xa activity (Heptest) in the single dose study and plasma anti-Xa activity, anti-IIa activity and ATIII; and chemical heparin in urine in the multiple dose study. No clinical evidence of bleeding was detected in any dog during the studies. Oral heparin therapy may be applicable for thromboembolic disease in animals. Further studies are warranted to determine the effects of oral heparin at the endothelial level in the dog. PMID:24982550

  5. The Hemolymph of the ascidian Styela plicata (Chordata-Tunicata) contains heparin inside basophil-like cells and a unique sulfated galactoglucan in the plasma.

    PubMed

    de Barros, Cintia M; Andrade, Leonardo R; Allodi, Silvana; Viskov, Christian; Mourier, Pierre A; Cavalcante, Moisés C M; Straus, Anita H; Takahashi, Helio K; Pomin, Vitor H; Carvalho, Vinicius F; Martins, Marco A; Pavão, Mauro S G

    2007-01-19

    The hemolymph of ascidians (Chordata-Tunicata) contains different types of hemocytes embedded in a liquid plasma. In the present study, heparin and a sulfated heteropolysaccharide were purified from the hemolymph of the ascidian Styela plicata. The heteropolysaccharide occurs free in the plasma, is composed of glucose ( approximately 60%) and galactose ( approximately 40%), and is highly sulfated. Heparin, on the other hand, occurs in the hemocytes, and high performance liquid chromatography of the products formed by degradation with specific lyases revealed that it is composed mainly by the disaccharides DeltaUA(2SO(4))-1-->4-beta-d-GlcN(SO(4)) (39.7%) and DeltaUA(2SO(4))-1-->4-beta-d-GlcN(SO(4))(6SO(4)) (38.2%). Small amounts of the 3-O-sulfated disaccharides DeltaUA(2SO(4))-1-->4-beta-d-GlcN(SO(4))(3SO(4)) (9.8%) and DeltaUA(2SO(4))-1-->4-beta-d-GlcN(SO(4))(3SO(4))(6SO(4)) (3.8%) were also detected. These 3-O-sulfated disaccharides were demonstrated to be essential for the binding of the hemocyte heparin to antithrombin III. Electron microscopy techniques were used to characterize the ultrastructure of the hemocytes and to localize heparin and histamine in these cells. At least five cell types were recognized and classified as univacuolated and multivacuolated cells, amebocytes, hemoblasts, and granulocytes. Immunocytochemistry showed that heparin and histamine co-localize in intracellular granules of only one type of hemocyte, the granulocyte. These results show for the first time that in ascidians, a sulfated galactoglucan circulates free in the plasma, and heparin occurs as an intracellular product of a circulating basophil-like cell.

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

    PubMed

    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

  7. Interaction of platelets, fibrinogen and endothelial cells with plasma deposited PEO-like films

    NASA Astrophysics Data System (ADS)

    Yang, Zhilu; Wang, Jin; Li, Xin; Tu, Qiufen; Sun, Hong; Huang, Nan

    2012-02-01

    For blood-contacting biomedical implants like retrievable vena cava filters, surface-based diagnostic devices or in vivo sensors, limiting thrombosis and cell adhesion is paramount, due to a decrease even failure in performance. Plasma deposited PEO-like films were investigated as surface modifications. In this work, mixed gas composed of tetraethylene glycol dimethyl ether (tetraglyme) vapor and oxygen was used as precursor. It was revealed that plasma polymerization under high ratio of oxygen/tetraglyme led to deposition of the films that had high content of ether groups. This kind of PEO-like films had good stability in phosphate buffer solution. In vitro hemocompatibility and endothelial cell (EC) adhesion revealed low platelet adhesion, platelet activation, fibrinogen adhesion, EC adhesion and proliferation on such plasma deposited PEO-like films. This made it a potential candidate for the applications in anti-fouling surfaces of blood-contacting biomedical devices.

  8. The activation of fibroblast growth factors by heparin: synthesis, structure, and biological activity of heparin-like oligosaccharides.

    PubMed

    de Paz, J L; Angulo, J; Lassaletta, J M; Nieto, P M; Redondo-Horcajo, M; Lozano, R M; Giménez-Gallego, G; Martín-Lomas, M

    2001-09-03

    An effective strategy has been designed for the synthesis of oligosaccharides of different sizes structurally related to the regular region of heparin; this is illustrated by the preparation of hexasaccharide 1 and octasaccharide 2. This synthetic strategy provides the oligosaccharide sequence containing a D-glucosamine unit at the nonreducing end that is not available either by enzymatic or chemical degradation of heparin. It may permit, after slight modifications, the preparation of oligosaccharide fragments with different charge distribution as well. NMR spectroscopy and molecular dynamics simulations have shown that the overall structure of 1 in solution is a stable right-hand helix with four residues per turn. Hexasaccharide 1 and, most likely, octasaccharide 2 are, therefore, chemically well-defined structural models of naturally occurring heparin-like oligosaccharides for use in binding and biological activity studies. Both compounds 1 and 2 induce the mitogenic activity of acid fibroblast growth factor (FGF1), with the half-maximum activating concentration of 2 being equivalent to that of heparin. Sedimentation equilibrium analysis with compound 2 suggests that heparin-induced FGF1 dimerization is not an absolute requirement for biological activity.

  9. Dynamic properties of biologically active synthetic heparin-like hexasaccharides.

    PubMed

    Angulo, Jesús; Hricovíni, Milos; Gairi, Margarida; Guerrini, Marco; de Paz, José Luis; Ojeda, Rafael; Martín-Lomas, Manuel; Nieto, Pedro M

    2005-10-01

    A complete study of the dynamics of two synthetic heparin-like hexasaccharides, D-GlcNHSO3-6-SO4-alpha-(1-->4)-L-IdoA-2-SO4-alpha-(1-->4)-D-GlcNHSO3-6-SO4-alpha-(1-->4)-L-IdoA-2-SO4-alpha-(1-->4)-D-GlcNHSO3-6-SO4-alpha-(1-->4)-L-IdoA-2-SO4-alpha-1-->iPr (1) and -->4)-L-IdoA-2-SO4-alpha-(1-->4)-D-GlcNHAc-6-SO4-alpha-(1-->4)-L-IdoA-alpha-(1-->4)-D-GlcNHSO3-alpha-(1-->4)-L-IdoA-2-SO4-alpha-1-->iPr (2), has been performed using 13C-nuclear magnetic resonance (NMR) relaxation parameters, T1, T2, and heteronuclear nuclear Overhauser effect (NOEs). Compound 1 is constituted from sequences corresponding to the major polysaccharide heparin region, while compound 2 contains a sequence never found in natural heparin. They differ from each other only in sulphation patterns, and are capable of stimulating fibroblast growth factors (FGFs)-1 induced mitogenesis. Both oligosaccharides exhibit a remarkable anisotropic overall motion in solution as revealed by their anisotropic ratios (tau /tau||), 4.0 and 3.0 respectively. This is a characteristic behaviour of natural glycosaminoglycans (GAG) which has also been observed for the antithrombin (AT) binding pentasaccharide D-GlcNHSO3-6-SO4-alpha-(1-->4)-D-GlcA-beta-(1-->4)-D-GlcNHSO3-(3,6-SO4)-alpha-(1-->4)-L-IdoA-2-SO4-alpha-(1-->4)-D-GlcNHSO3-6-SO4-alpha-1-->Me (3) (Hricovíni, M., Guerrini, M., Torri, G., Piani, S., and Ungarelli, F. (1995) Conformational analysis of heparin epoxide in aqueous solution. An NMR relaxation study. Carbohydr. Res., 277, 11-23). The motional properties observed for 1 and 2 provide additional support to the suitability of these compounds as heparin models in agreement with previous structural (de Paz, J.L., Angulo, J., Lassaletta, J.M., Nieto, P.M., Redondo-Horcajo, M., Lozano, R.M., Jiménez-Gallego, G., and Martín-Lomas, M. (2001) The activation of fibroblast growth factors by heparin: synthesis, structure and biological activity of heparin-like oligosaccharides. Chembiochem, 2, 673-685; Ojeda, R

  10. Colorimetric assay of heparin in plasma based on the inhibition of oxidase-like activity of citrate-capped platinum nanoparticles.

    PubMed

    You, Jyun-Guo; Liu, Yao-Wen; Lu, Chi-Yu; Tseng, Wei-Lung; Yu, Cheng-Ju

    2017-06-15

    We report citrate-capped platinum nanoparticles (Pt NPs) as oxidase mimetics for effectively catalyzing the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB), 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid), dopamine, and methylene blue in the presence of O 2 . To confirm oxidase-like activity of citrate-capped Pt NPs, their activity toward oxygen reduction reaction was studied using cyclic voltammetry and rotating ring-disk electrode method. The results obtained showed that Pt NP NPs can catalyze the oxidation of organic substrates to the colored product and the reduction of oxygen to water through a four-electron exchange process. Because the aggregation of Pt NPs can inhibit their oxidase-like activity and protamine can recognize heparin, we prepared the protamine-modified Pt NPs through direct adsorption on the surface of citrate-capped Pt NPs. The electrostatic attraction between heparin and protamine-stabilized Pt NPs induced nanoparticle aggregation, inhibiting their catalytic activity. Therefore, the lowest detectable heparin concentrations through UV-vis absorption and by the naked eye were estimated to be 0.3 and 60nM, respectively. Moreover, the proposed system enabled the determination of the therapeutic heparin concentration in a single drop of blood. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Synthesis and structural study of two new heparin-like hexasaccharides.

    PubMed

    Lucas, Ricardo; Angulo, Jesús; Nieto, Pedro M; Martín-Lomas, Manuel

    2003-07-07

    Two new heparin-like hexasaccharides, 5 and 6, have been synthesised using a convergent block strategy and their solution conformations have been determined by NMR spectroscopy and molecular modelling. Both hexasaccharides contain the basic structural motif of the regular region of heparin but with negative charge distributions which have been designed to get insight into the mechanism of fibroblast growth factors (FGFs) activation.

  12. Facile preparation of heparinized polysulfone membrane assisted by polydopamine/polyethyleneimine co-deposition for simultaneous LDL selectivity and biocompatibility

    NASA Astrophysics Data System (ADS)

    Wang, Liwei; Fang, Fei; Liu, Yang; Li, Jing; Huang, Xiaojun

    2016-11-01

    Low-density lipoprotein (LDL) gains worldwide attention for decades as the key risk factor to atherosclerosis that progressively deteriorating into cardiovascular diseases. Until recent years, LDL-apheresis comes to be extensively used as a direct and efficient LDL removal method, with LDL adsorption materials particularly important. In this paper, a new strategy based on the co-deposition of polydopamine (PDA) with polyethylenimine (PEI) onto polysulfone (PSf) membranes, then subsequent heparinization by amino-carbonyl reactions, to achieve LDL selectivity and simultaneous biocompatibility, is proposed. Surface properties of modified PSf membranes are characterized by ATR-FTIR, XPS, FESEM, Zeta potential and WCA measurements. LDL adsorption ability is investigated by ELISA, while blood biocompatibility is evaluated by platelet adhesion experiments. Results suggest that heparin-modified PSf membranes show high selectivity for LDL removal and fine biocompatibility in contact with plasma, as excellent potential materials for LDL-apheresis.

  13. Biophysical investigations on the interaction of the major bovine seminal plasma protein, PDC-109, with heparin.

    PubMed

    Sankhala, Rajeshwer S; Damai, Rajani S; Anbazhagan, V; Kumar, C Sudheer; Bulusu, Gopalakrishnan; Swamy, Musti J

    2011-11-10

    PDC-109, the major bovine seminal plasma protein, binds to sperm plasma membrane and modulates capacitation in the presence of heparin. In view of this, the PDC-109/heparin interaction has been investigated employing various biophysical approaches. Isothermal titration calorimetric studies yielded the association constant and changes in enthalpy and entropy for the interaction at 25 °C (pH 7.4) as 1.92 (±0.2) × 10(5) M(-1), 18.6 (±1.6) kcal M(-1), and 86.5 (±5.1) cal M(-1) K(-1), respectively, whereas differential scanning calorimetric studies indicated that heparin binding results in a significant increase in the thermal stability of PDC-109. The affinity decreases with increase in pH and ionic strength, consistent with the involvement of electrostatic forces in this interaction. Circular dichroism spectroscopic studies indicated that PDC-109 retains its conformational features even up to 70-75 °C in the presence of heparin, whereas the native protein unfolds at about 55 °C. Atomic force microscopic studies demonstrated that large oligomeric structures are formed upon binding of PDC-109 to heparin, indicating an increase in the local density of the protein, which may be relevant to the ability of heparin to potentiate PDC-109 induced sperm capacitation.

  14. Formation of nanocrystalline diamond in polymer like carbon films deposited by plasma CVD.

    PubMed

    Bhaduri, A; Chaudhuri, P

    2009-09-01

    Conventional plasma enhanced chemical vapour deposition (PECVD) method is generally not suitable for the growth of nanocrystalline diamond (NCD) films. However, our study shows that conditions favourable for powder formation help to grow large amount of nanocrystallites in conventional PECVD. With CH4 as the carbon source gas, dilution with Ar and moderate (50 W) rf power enhances formations of powders (nanoparticles) and C2 dimers within the plasma. On the other hand, with pure CH4 or with hydrogen diluted CH4, powder formation as also NCD growth is hindered. It is proposed that the nanoparticles formed in the plasma act as the "islands" while the C2 dimers are the "seeds" for the NCD growth. The structure of the films deposited on the grounded anode under different conditions of dilution has been studied. It is observed that with high Ar dilution the films contain NCD embedded in polymer like carbon (PLC) matrix.

  15. Comparison of digoxin concentration in plastic serum tubes with clot activator and heparinized plasma tubes.

    PubMed

    Dukić, Lora; Simundić, Ana-Maria; Malogorski, Davorin

    2014-01-01

    Sample type recommended by the manufacturer for the digoxin Abbott assay is either serum collected in glass tubes or plasma (sodium heparin, lithium heparin, citrate, EDTA or oxalate as anticoagulant) collected in plastic tubes. In our hospital samples are collected in plastic tubes. Our hypothesis was that the serum sample collected in plastic serum tube can be used interchangeably with plasma sample for measurement of digoxin concentration. Our aim was verification of plastic serum tubes for determination of digoxin concentration. Concentration of digoxin was determined simultaneously in 26 venous blood plasma (plastic Vacuette, LH Lithium heparin) and serum (plastic Vacuette, Z Serum Clot activator; both Greiner Bio-One GmbH, Kremsmünster, Austria) samples, on Abbott AxSYM analyzer using the original Abbott Digoxin III assay (Abbott, Wiesbaden, Germany). Tube comparability was assessed using the Passing Bablok regression and Bland-Altman plot. Serum and plasma digoxin concentrations are comparable. Passing Bablok intercept (0.08 [95% CI = -0.10 to 0.20]) and slope (0.99 [95% CI = 0.92 to 1.11]) showed there is no constant or proportional error. Blood samples drawn in plastic serum tubes and plastic plasma tubes can be interchangeably used for determination of digoxin concentration.

  16. Comparison of digoxin concentration in plastic serum tubes with clot activator and heparinized plasma tubes

    PubMed Central

    Dukić, Lora; Šimundić, Ana-Maria; Malogorski, Davorin

    2014-01-01

    Introduction: Sample type recommended by the manufacturer for the digoxin Abbott assay is either serum collected in glass tubes or plasma (sodium heparin, lithium heparin, citrate, EDTA or oxalate as anticoagulant) collected in plastic tubes. In our hospital samples are collected in plastic tubes. Our hypothesis was that the serum sample collected in plastic serum tube can be used interchangeably with plasma sample for measurement of digoxin concentration. Our aim was verification of plastic serum tubes for determination of digoxin concentration. Materials and methods: Concentration of digoxin was determined simultaneously in 26 venous blood plasma (plastic Vacuette, LH Lithium heparin) and serum (plastic Vacuette, Z Serum Clot activator; both Greiner Bio-One GmbH, Kremsmünster, Austria) samples, on Abbott AxSYM analyzer using the original Abbott Digoxin III assay (Abbott, Wiesbaden, Germany). Tube comparability was assessed using the Passing Bablok regression and Bland-Altman plot. Results: Serum and plasma digoxin concentrations are comparable. Passing Bablok intercept (0.08 [95% CI = −0.10 to 0.20]) and slope (0.99 [95% CI = 0.92 to 1.11]) showed there is no constant or proportional error. Conclusion: Blood samples drawn in plastic serum tubes and plastic plasma tubes can be interchangeably used for determination of digoxin concentration. PMID:24627723

  17. [Heparin and antiheparin in childhood. 2. Clinical relevance of the phenomenon of heparin resistance].

    PubMed

    Domula, M; Weissbach, G

    1982-01-01

    Investigations of the content of platelet factor 4 in different thrombocyte lysates and platelet-rich plasma after induced release reaction were aimed at checking the efficiency of the own antiheparin measuring system. In this connection, the age dependent dynamics of platelet factor 4 could be first discovered. In platelet-poor plasma of healthy grown-up test persons there was an evidence of antiheparin titres which were five times higher as compared with those persons born maturely. All patients with disseminated intravascular coagulation processes of different aetiology, however, will have significantly increased values. As demonstrated in two children with hyperpyretic toxicosis, the liberated platelet factor 4 will only show a short plasma half decay period. From investigations made for refinding heparin in the plasma after in vitro addition the conclusion can be drawn that, in addition to platelet factor 4, even unspecific adhesions of heparin to certain plasma proteins may be responsible for increasing heparin resistance.

  18. Self-enhanced plasma discharge effect in the deposition of diamond-like carbon films on the inner surface of slender tube

    NASA Astrophysics Data System (ADS)

    Xu, Yi; Li, Liuhe; Luo, Sida; Lu, Qiuyuan; Gu, Jiabin; Lei, Ning; Huo, Chunqin

    2017-01-01

    Enhanced glow discharge plasma immersion ion implantation and deposition (EGD-PIII&D) have been proved to be highly effective for depositing diamond-like carbon (DLC) films on the inner surface of the slender quartz tube with a deposition rate of 1.3 μm/min. Such a high-efficiency DLC films deposition was explained previously as the short electrons mean free path to cause large collision frequency between electrons and neutral particles. However, in this paper, we found that the inner surface material of the tube itself play a vital role on the films deposition. To disclose the mechanism of this phenomenon, the effect of different inner surface materials on plasma discharge was experimentally and theoretically investigated. Then a self-enhancing plasma discharge is discovered. It is found that secondary electrons emitted from the inner surface material, whatever it is the tube inner surface or deposited DLC films, can dramatically enhance the plasma discharge to improve the DLC films deposition rate.

  19. 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.

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed Central

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

    2017-01-01

    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. PMID:28174207

  2. Sulfated polysaccharide from the leaves of Artemisia Princeps activates heparin cofactor II independently of the Lys173 and Arg189 residues of heparin cofactor II.

    PubMed

    Hayashi, T; Hayakawa, Y; Hayashi, T; Sasaki, H; Sakuragawa, N

    1997-07-01

    A sulfated polysaccharide (AFE-HCD) purified from the leaves of Artemisia princeps Pamp selectively accelerated the rate of thrombin inhibition by heparin cofactor II (HCII). By using plasma derived HCII and bacterial expressed recombinant HCII molecules, the interaction between each HCII molecule and AFE-HCD was analyzed. AFE-HCD accelerated thrombin inhibition by plasma derived HCII or bacterial expressed wild type HCII to the same extent (IC50: 0.056 micrograms/ml for plasma derived HCII and 0.066 micrograms/ml for recombinant HCII under the experimental condition). The recombinant HCII (rHCII) molecule with Lys173-->Leu or Arg189-->His substitution, which is defective in interactions with heparin and dermatan sulfate, respectively, is activated by AFE-HCD to inhibit thrombin in a manner similar to wild type rHCII. These results suggested that activation of HCII was independent of its Lys173 or Arg189 residue. Although AFE-HCD is a selective activator of HCII like dermatan sulfate, the amino acid residue required for the activation of HCII was distinct form that of dermatan sulfate as well as heparin.

  3. Ti-doped hydrogenated diamond like carbon coating deposited by hybrid physical vapor deposition and plasma enhanced chemical vapor deposition

    NASA Astrophysics Data System (ADS)

    Lee, Na Rae; Sle Jun, Yee; Moon, Kyoung Il; Sunyong Lee, Caroline

    2017-03-01

    Diamond-like carbon films containing titanium and hydrogen (Ti-doped DLC:H) were synthesized using a hybrid technique based on physical vapor deposition (PVD) and plasma enhanced chemical vapor deposition (PECVD). The film was deposited under a mixture of argon (Ar) and acetylene gas (C2H2). The amount of Ti in the Ti-doped DLC:H film was controlled by varying the DC power of the Ti sputtering target ranging from 0 to 240 W. The composition, microstructure, mechanical and chemical properties of Ti-doped DLC:H films with varying Ti concentrations, were investigated using Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), nano indentation, a ball-on-disk tribometer, a four-point probe system and dynamic anodic testing. As a result, the optimum composition of Ti in Ti-doped DLC:H film using our hybrid method was found to be a Ti content of 18 at. %, having superior electrical conductivity and high corrosion resistance, suitable for bipolar plates. Its hardness value was measured to be 25.6 GPa with a low friction factor.

  4. The effectiveness of heparin, platelet-rich plasma (PRP), and silver nanoparticles on prevention of postoperative peritoneal adhesion formation in rats.

    PubMed

    Makarchian, Hamid Reza; Kasraianfard, Amir; Ghaderzadeh, Pezhman; Javadi, Seyed Mohammad Reza; Ghorbanpoor, Manoochehr

    2017-01-01

    To assess the effectiveness of heparin, platelet-rich plasma (PRP), and silver nanoparticles on prevention of postoperative adhesion in animal models. Sixty males Albino Wistar rats aged 5 to 6 weeks were classified into five groups receiving none, heparin, PRP, silver nanoparticles, PRP plus silver nanoparticles intraperitoneally. After 2 weeks, the animals underwent laparotomy and the damaged site was assessed for peritoneal adhesions severity. The mean severity scores were 2.5 ± 0.9, 2.16 ± 0.7, 1.5 ± 0.5, 2.66 ± 0.88, and 2.25 ± 0.62 in the control, heparin, PRP, silver and PRP plus silver groups, respectively with significant intergroup difference (p = 0.004). The highest effective material for preventing adhesion formation was PRP followed by heparin and PRP plus silver. Moreover, compared to the controls, only use of PRP was significantly effective, in terms of adhesion severity (p = 0.01) . Platelet-rich plasma alone may have the highest efficacy for preventing postoperative peritoneal adhesions in comparison with heparin, silver nanoparticles and PRP plus silver nanoparticles.

  5. Synthesis of heparin-like oligosaccharides on polymer supports.

    PubMed

    Ojeda, Rafael; Terentí, Olimpia; de Paz, José-Luis; Martín-Lomas, Manuel

    2004-01-01

    The biological functions of a variety of proteins are regulated by heparan sulfate glycosaminoglycans. In order to facilitate the elucidation of the molecular basis of glycosaminoglycan-protein interactions we have developed syntheses of heparin-like oligosaccharides on polymer supports. A completely stereoselective strategy previously developed by us for the synthesis of these oligosaccharides in solution has been extended to the solid phase using an acceptor-bound approach. Both a soluble polymer support and a polyethylene glycol-grafted polystyrene resin have been used and different strategies for the attachment of the acceptor to the support have been explored. The attachment of fully protected disaccharide building blocks to a soluble support through the carboxylic group of the uronic acid unit by a succinic ester linkage, the use of trichloroacetimidates as glycosylating agents and of a functionalized Merryfield type resin for the capping process allowed for the construction of hexasaccharide and octasaccharide fragments containing the structural motif of the regular region of heparin. This strategy may facilitate the synthesis of glycosaminoglycan oligosaccharides by using the required building blocks in the glycosylation sequence.

  6. In Situ Nanocalorimetric Investigations of Plasma Assisted Deposited Poly(ethylene oxide)-like Films by Specific Heat Spectroscopy.

    PubMed

    Madkou, Sherif; Melnichu, Iurii; Choukourov, Andrei; Krakovsky, Ivan; Biederman, Hynek; Schönhals, Andreas

    2016-04-28

    In recent years, highly cross-linked plasma polymers have started to unveil their potential in numerous biomedical applications in thin-film form. However, conventional diagnostic methods often fail due to their diverse molecular dynamics conformations. Here, glassy dynamics and the melting transition of thin PEO-like plasma assisted deposited (ppPEO) films (thickness 100 nm) were in situ studied by a combination of specific heat spectroscopy, utilizing a pJ/K sensitive ac-calorimeter chip, and composition analytical techniques. Different cross-linking densities were obtained by different plasma powers during the deposition of the films. Glassy dynamics were observed for all values of the plasma power. It was found that the glassy dynamics slows down with increasing the plasma power. Moreover, the underlying relaxation time spectra broaden indicating that the molecular motions become more heterogeneous with increasing plasma power. In a second set of the experiment, the melting behavior of the ppPEO films was studied. The melting temperature of ppPEO was found to decrease with increasing plasma power. This was explained by a decrease of the order in the crystals due to formation of chemical defects during the plasma process.

  7. In vitro induction of protein complexes between bevacizumab, VEGF-A¹⁶⁵ and heparin: explanation for deposits observed on endothelial veins in monkey eyes.

    PubMed

    Julien, Sylvie; Biesemeier, Antje; Schraermeyer, Ulrich

    2013-04-01

    By investigating the effects of intravitreal bevacizumab on retinal vessels of monkeys, we found that bevacizumab accumulated locally at high concentration within individual blood vessels. It formed electron-dense fibrous deposits between endothelial cells and erythrocytes or granulocytes inducing retinal vein thrombosis. To better characterise the observed deposits, we investigated in vitro whether these deposits result from a complex between bevacizumab, vascular endothelial growth factor (VEGF)-A(165) and heparin. Cynomolgus monkeys were intravitreally injected with 1.25 mg bevacizumab. The eyes were enucleated between 1 and 14 days after injection and investigated by electron microscopy and immunohistochemistry. Human umbilical vein endothelial cells (HUVEC) were incubated with bevacizumab, VEGF-A(165) and heparin at different concentrations. Treatments with ranibizumab served as control. Bevacizumab and ranibizumab were detected immunohistochemically using Cy-3 or immunogold labelled antibodies. Treated animals showed bevacizumab locally at high concentration within retinal blood vessels. Electron-dense deposits inside retinal vessels and between erythrocytes were detected in three out of four treated monkeys. In vitro, many globular aggregates heavily stained with anti-human IgG were only observed with equimolar amounts (240 nM) of bevacizumab and VEGF-A(165) and 0.2 U/ml heparin and not after ranibizumab treatment. The immunogold labelling specifically localised ultrastructurally the complexes formed between bevacizumab, VEGF-A(165) and heparin at the surfaces of HUVEC cells. Heparin promotes bevacizumab immune complex deposition on to endothelial cells. Our in vitro results could explain the presence of deposits observed on endothelial veins in monkey eyes intravitreally injected with bevacizumab.

  8. Bovine and porcine heparins: different drugs with similar effects on human haemodialysis

    PubMed Central

    2013-01-01

    Background Heparins from porcine and bovine intestinal mucosa differ in their structure and also in their effects on coagulation, thrombosis and bleeding. However, they are used as undistinguishable drugs. Methods We compared bovine and porcine intestinal heparin administered to patients undergoing a particular protocol of haemodialysis. We compared plasma concentrations of these two drugs and also evaluated how they affect patients and the dialyzer used. Results Compared with porcine heparin, bovine heparin achieved only 76% of the maximum plasma concentration as IU mL-1. This observation is consistent with the activities observed in the respective pharmaceutical preparations. When the plasma concentrations were expressed on weight basis, bovine heparin achieved a maximum concentration 1.5 fold higher than porcine heparin. The reduced anticoagulant activity and higher concentration, on weight basis, achieved in the plasma of patients under dialysis using bovine instead of porcine heparin did not affect significantly the patients or the dialyzer used. The heparin dose is still in a range, which confers security and safety to the patients. Discussion Despite no apparent difference between bovine and porcine intestinal heparins in the haemodialysis practice, these two types of heparins should be used as distinct drugs due to their differences in structure and biological effects. Conclusions The reduced anticoagulant activity achieved in the plasma of patients under dialysis using bovine instead of porcine heparin did not affect significantly the patients or the dialyzer. PMID:23763719

  9. Preclinical Validation of the Heparin-Reactive Peptide p5+14 as a Molecular Imaging Agent for Visceral Amyloidosis

    DOE PAGES

    Wall, Jonathan; Martin, Emily B.; Richey, Tina; ...

    2015-04-27

    Amyloid is a complex pathologic matrix comprised principally of para-crystalline protein fibrils and heparan sulfate proteoglycans. Systemic amyloidoses are rare (~3500 new cases per year in the US); thus, routine diagnosis is often challenging, and effective treatment options are limited, resulting in high morbidity and mortality rates. Glycosaminoglycans contribute inextricably to the formation of amyloid fibrils and foster the deposition of amyloid in tissues. Those present in amyloid deposits are biochemically and electrochemically distinct from glycosaminoglycans found in the plasma membrane and extracellular matrices of healthy tissues due to the presence of a high degree of heparin-like hypersulfation. We havemore » exploited this unique property and evaluated heparin-reactive peptides, such as p5+14. Herein we show efficacious detection of murine systemic amyloid in vivo by using molecular imaging, and the specific targeting of the peptide to major forms of human amyloid in tissue sections. Furthermore, we have demonstrated that the peptide also binds synthetic amyloid fibrils that lack glycosaminoglycans implying that the dense anionic motif present on heparin is mimicked by the amyloid protein fibril itself. These biochemical and functional data support the translation of radiolabeled peptide p5+14 for the clinical imaging of amyloid in patients; thus, providing a novel technique for prognostication, patient stratification, and monitoring response to therapy.« less

  10. Evaluation of the Becton-Dickinson rapid serum tube: does it provide a suitable alternative to lithium heparin plasma tubes?

    PubMed

    Dimeski, Goce; Masci, Paul P; Trabi, Manuela; Lavin, Martin F; de Jersey, John

    2010-05-01

    Obtaining a suitable specimen for analysis in a timely manner is pivotal in clinical chemistry service provision. Serum is recognized as the preferred specimen for most assays, but because of time constraints for completion of clotting and an increasing number of patients on anti-coagulant therapy, latent clotting or no clotting is an outcome which can lead to errors and delay in delivery of critical results. Although lithium heparin plasma has unique problems, it has become an alternative in hospital-based laboratories. The Becton-Dickinson (BD) rapid serum tube (RST) was evaluated in a hospital environment using a total of 53 participants, both healthy and anticoagulated, for 31 analytes against BD PST II and BD SST II tubes measured with Beckman DxC800 and DxI800 analyzers. Most results from the RST tube were comparable with those from the SST II tube. Potassium results were closer to the PST II plasma concentrations. Incomplete and latent clotting was encountered in the RST specimens from participants (cardiac and dialysis) who had received a total of >7000 units of heparin [activated partial thromboplastin time (APTT) >150 s], warfarin/heparin combination, and specimens from cardiac surgery patients who had received a total of >25,000 units of heparin (APTT >200 s) at the time of collection of specimens. The RST tube provides a suitable alternative to lithium heparin plasma tubes for most patients in a hospital environment. However, latent clotting continued to occur in specimens collected from participants who had received high concentrations of anticoagulants.

  11. Heparin affinity purification of extracellular vesicles

    PubMed Central

    Balaj, Leonora; Atai, Nadia A.; Chen, Weilin; Mu, Dakai; Tannous, Bakhos A.; Breakefield, Xandra O.; Skog, Johan; Maguire, Casey A.

    2015-01-01

    Extracellular vesicles (EVs) are lipid membrane vesicles released by cells. They carry active biomolecules including DNA, RNA, and protein which can be transferred to recipient cells. Isolation and purification of EVs from culture cell media and biofluids is still a major challenge. The most widely used isolation method is ultracentrifugation (UC) which requires expensive equipment and only partially purifies EVs. Previously we have shown that heparin blocks EV uptake in cells, supporting a direct EV-heparin interaction. Here we show that EVs can be purified from cell culture media and human plasma using ultrafiltration (UF) followed by heparin-affinity beads. UF/heparin-purified EVs from cell culture displayed the EV marker Alix, contained a diverse RNA profile, had lower levels of protein contamination, and were functional at binding to and uptake into cells. RNA yield was similar for EVs isolated by UC. We were able to detect mRNAs in plasma samples with comparable levels to UC samples. In conclusion, we have discovered a simple, scalable, and effective method to purify EVs taking advantage of their heparin affinity. PMID:25988257

  12. [Study of the interrelations of ethmozine, cordarone and phenycaberan with heparin].

    PubMed

    Tolstopiatov, B I

    1981-01-01

    Cordarone, etmozin and phenycaberan form complexes with heparin. Etmozin and phenycaberan form complexes insoluble in an aqueous medium and exhibit a pronounced antiheparin action in in-vitro experiments. Cordarone and heparin form a complex which is soluble in an aqueous medium. This complex potentiates the biological activity of the anticoagulant. In experiments on rabbits cordarone and phenycaberan increase plasma tolerance to heparin followed by its lowering as compared with controls in experiments with phenycaberan. Etmozin decreases plasma tolerance to heparin.

  13. Heparin removal by ecteola-cellulose pre-treatment enables the use of plasma samples for accurate measurement of anti-Yellow fever virus neutralizing antibodies.

    PubMed

    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.

  14. Neutralization of heparin activity.

    PubMed

    Pai, Menaka; Crowther, Mark A

    2012-01-01

    Heparin is the mainstay in the treatment and prevention of thrombosis in such diverse clinical settings as venous thromboembolism, acute coronary syndrome, cardiopulmonary bypass, and hemodialysis. However, the major complication of heparin - like that of all anticoagulants - is bleeding. Heparin may need to be reversed in the following settings: clinically significant bleeding; prior to an invasive procedure; at the conclusion of a procedure involving extracorporeal circulation (e.g., cardiopulmonary bypass, dialysis). This chapter discusses protamine sulfate, as well as several other agents that are able to neutralize heparin, including their pharmacological properties, indications, dosing, and efficacy.

  15. Sticking non-stick: Surface and Structure control of Diamond-like Carbon in Plasma Enhanced Chemical Vapour Deposition

    NASA Astrophysics Data System (ADS)

    Jones, B. J.; Nelson, N.

    2016-10-01

    This short review article explores the practical use of diamond-like carbon (DLC) produced by plasma enhanced chemical vapour deposition (PECVD). Using as an example issues relating to the DLC coating of a hand-held surgical device, we draw on previous works using atomic force microscopy, X-ray photoelectron spectroscopy, Raman spectroscopy, scanning electron microscopy, tensiometry and electron paramagnetic resonance. Utilising data from these techniques, we examine the surface structure, substrate-film interface and thin film microstructure, such as sp2/sp3 ratio (graphitic/diamond-like bonding ratio) and sp2 clustering. We explore the variations in parameters describing these characteristics, and relate these to the final device properties such as friction, wear resistance, and diffusion barrier integrity. The material and device characteristics are linked to the initial plasma and substrate conditions.

  16. Change in blood coagulation indices as a function of the incubation period of plasma in a constant magnetic field. [considering heparin tolerance and recalcification

    NASA Technical Reports Server (NTRS)

    Yepishina, S. G.

    1974-01-01

    The influence of a constant magnetic field (CMF) with a strength of 250 and 2500 oersteds on the recalcification reaction and the tolerance of plasma to heparin was studied as a function of the exposure time of the plasma to the CMF. The maximum and reliable change in the activation of the coagulatory system of the blood was observed after a 20-hour incubation of the plasma in a CMF. As the exposure time increased, the recalcification reaction changed insigificantly; the difference between the mean arithmetic of the experiment and control values was not statistically reliable. The tolerance of the plasma to heparin as a function of the exposure time to the CMF of the plasma was considerably modified, an was statistically reliable.

  17. Plasma deposited composite coatings to control biological response of osteoblast-like MG-63 cells

    NASA Astrophysics Data System (ADS)

    Keremidarska, M.; Radeva, E.; Eleršič, K.; Iglič, A.; Pramatarova, L.; Krasteva, N.

    2014-12-01

    The successful osseointegration of a bone implant is greatly dependent on its ability to support cellular adhesion and functions. Deposition of thin composite coatings onto the implant surface is a promising approach to improve interactions with cells without compromising implant bulk properties. In this work, we have developed composite coatings, based on hexamethyldisiloxane (HMDS) and detonation nanodiamond (DND) particles and have studied adhesion, growth and function of osteoblast-like MG-63 cells. PPHMDS/DND composites are of interest for orthopedics because they combine superior mechanical properties and good biocompatibility of DND with high adherence of HMDS to different substrata including glass, metals and plastics. We have used two approaches of the implementation of DND particles into a polymer matrix: pre-mixture of both components followed by plasma polymerization and layer-by-layer deposition of HMDS and DND particles and found that the deposition approach affects significantly the surface properties of the resulting layers and cell behaviour. The composite, prepared by subsequent deposition of monomer and DND particles was hydrophilic, with a rougher surface and MG-63 cells demonstrated better spreading, growth and function compared to the other composite which was hydrophobic with a smooth surface similarly to unmodified polymer. Thus, by varying the deposition approach, different PPHMDS/DND composite coatings, enhancing or inhibiting osteoblast adhesion and functions, can be obtained. In addition, the effect of fibronectin pre-adsorption was studied and was found to increase greatly MG-63 cell spreading.

  18. Calculation of intrinsic stresses in the diamond-like coatings produced by plasma ion deposition in modes of DC and pulse bias potentials

    NASA Astrophysics Data System (ADS)

    Kalinichenko, A. A.; Perepelkin, S. S.; Strel'nitskij, V. E.

    2015-04-01

    The formula derivation for calculation of intrinsic stress in diamond-like coatings deposited from the ion flux in modes of continuous and pulsed potentials in view of process of defects formation is given. The criterion of applicability of obtained formula allowing to determine critical parameters of the pulsed potential mode is suggested. Results of calculation of stresses in diamond-like coatings at deposition of low-energy ions C+ from filtered vacuum arc plasma are adduced. The influence of the bias potential, repetition frequency and pulse duration, on the value of intrinsic stress is discussed. Qualitative agreement of calculated stress and experimental data is stated. The important role of deposition temperature in control of intrinsic stress in deposited coating is noted.

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

    PubMed Central

    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

  20. In vivo antithrombotic properties of a heparin from the oocyte test cells of the sea squirt Styela plicata(Chordata-Tunicata).

    PubMed

    Cardilo-Reis, L; Cavalcante, M C M; Silveira, C B M; Pavão, M S G

    2006-11-01

    In the ascidian Styela plicata, the oocytes are surrounded by two types of accessory cells named follicle cells and test cells. A heparin-like substance with an anticoagulant activity equivalent to 10% of mammalian heparin and about 5% as potent as the mammalian counterpart for the inhibition of thrombin by antithrombin was isolated from the oocyte test cells. In the present study, we compared the antithrombotic and hemorrhagic effects of sea squirt oocyte test cell heparin with those of porcine heparin in rat models of venous thrombosis and blood loss. Intravenous administration of the oocyte test cell heparin to Wistar rats (both sexes, weighing approximately 300 g, N = 4 in each group) at a dose of 5.0 mg/kg body weight, which produced a 1.8-fold increase in plasma activated partial thromboplastin time, inhibited thrombosis by 45 +/- 13.5% (mean +/- SD) without any bleeding effect. The same dose of porcine heparin inhibited thrombosis by 100 +/- 1.4%, but produced a blood loss three times greater than that of the saline-treated control. However, 10-fold reduction of the dose of porcine heparin to 0.5 mg/kg body weight, which produced a 5-fold increase in plasma-activated partial thromboplastin time, inhibited thrombosis by 70 +/- 13% without any bleeding effect. The antithrombotic properties of a new heparin isolated from test cells of the sea squirt S. plicata, reported here for the first time, indicate that, although sea squirt oocyte test cell heparin was a poor anticoagulant compared to porcine heparin, it had a significant antithrombotic effect without causing bleeding.

  1. Effects of heparin-binding epidermal growth factor-like growth factor on cell repopulation and signal transduction in periodontal ligament cells after scratch wounding in vitro.

    PubMed

    Lee, J S; Kim, J M; Hong, E K; Kim, S-O; Yoo, Y-J; Cha, J-H

    2009-02-01

    A growing amount of attention has been placed on periodontal regeneration and wound healing for periodontal therapy. This study was conducted in an effort to determine the effects of heparin-binding epidermal growth factor-like growth factor on cell repopulation and signal transduction in periodontal ligament cells after scratch wounding in vitro. Human periodontal ligament cells were acquired from explant tissue of human healthy periodontal ligament. After the wounding of periodontal ligament cells, the change in expression of heparin-binding epidermal growth factor-like growth factor and epidermal growth factor receptors 1-4 mRNA was assessed. The effects of heparin-binding epidermal growth factor-like growth factor on periodontal ligament cell proliferation and repopulation were assessed in vitro via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and by photographing the injuries, respectively. Extracellular signal-regulated kinase (Erk)1/2, p38 and Akt phosphorylation was characterized via western blotting. Scratch wounding resulted in a significant up-regulation of heparin-binding epidermal growth factor-like growth factor mRNA expression, whereas wounding had no effect on the expression levels of epidermal growth factor receptors 1-4. Interestingly, no expression of epidermal growth factor receptors 2 and 4 was detectable prior to or after wounding. Heparin-binding epidermal growth factor-like growth factor treatment promoted the proliferation and repopulation of periodontal ligament cells. The scratch wounding also stimulated the phosphorylation of Erk1/2 and p38, but not of Akt, in periodontal ligament cells, and heparin-binding epidermal growth factor-like growth factor treatment applied after wounding amplified and extended the activations of Erk1/2 and p38, but not of Akt. Furthermore, Erk1/2 inhibition blocked the process of cell repopulation induced by heparin-binding epidermal growth factor-like growth factor, whereas the

  2. The application of pulse modulated plasma to the plasma enhanced chemical vapor deposition of dielectric materials

    NASA Astrophysics Data System (ADS)

    Qi, Yu

    This dissertation work applied the pulse modulated plasma to the plasma enhanced chemical vapor deposition (PECVD) of two types of dielectric materials: SiO2-like coatings and Teflon-like coatings. SiO2-like coatings were firstly implemented with continuous plasma. It was proven that three different precursors: hexamethyldisiloxane (HMDSO), 1, 3, 5, 7-tetramethylcyclotetrasiloxane (TMCTS) and octamethylcyclotetrasiloxane (OMCTS) can be used to generate hard, clear and high density SiO2 deposition with coupled high growth rate and low processing temperature via PECVD. Under similar conditions, HMDSO has the lowest growth rate, lowest hardness and highest carbon content; TMCTS has the highest growth rate and hardness, and lowest carbon content; and OMCTS has moderate rates of these deposition qualities, but the best corrosion resistance. Substrate bias seems to have no effect on any deposition quality. High chamber pressure can significantly lower the carbon content in the thin films but does not affect any other qualities; the O2/precursor ratio is the most influential factor among all variables considered in this experiment. The deposition hardness and O:Si ratio always increase with this ratio while the carbon content always decreases. However, different precursors require different optimal ratios to achieve the highest growth rate. Pulse modulation was introduced into PECVD of SiO2-like coatings and OMCTS was selected as the precursor. It was demonstrated that pulse frequency, duty ratio and peak power have significant effects on deposition qualities. The proper combination of the pulse parameters and other traditional plasma parameters can significantly lower the processing temperature while retaining or even improving other deposition qualities, such as growth rate, corrosion resistance and elemental composition. Hardness is the only sacrifice of the lower time-average power caused by pulsing. Therefore, pulse modulation can effectively expand the possible

  3. Click-coated, heparinized, decellularized vascular grafts

    PubMed Central

    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; Linhardt, Robert J.

    2014-01-01

    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 ten-fold 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. XPS, NMR, MS and FTIR were used to characterize the synthesis steps, building the final heparin layered coatings. Continuity of the heparin coating was verified using fluorescent microscopy and histological analysis. Efficacy of heparin linkage was demonstrated with factor Xa antithrombogenic 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. PMID:25463496

  4. Synthesis of Diamond-Like Carbon Films on Planar and Non-Planar Geometries by the Atmospheric Pressure Plasma Chemical Vapor Deposition Method

    NASA Astrophysics Data System (ADS)

    Noborisaka, Mayui; Hirako, Tomoaki; Shirakura, Akira; Watanabe, Toshiyuki; Morikawa, Masashi; Seki, Masaki; Suzuki, Tetsuya

    2012-09-01

    Diamond-like carbon (DLC) films were synthesized by the dielectric barrier discharge-based plasma deposition at atmospheric pressure and their hardness and gas barrier properties were measured. A decrease in size of grains and heating substrate temperature improved nano-hardness up to 3.3 GPa. The gas barrier properties of DLC-coated poly(ethylene terephthalate) (PET) sheets were obtained by 3-5 times of non-coated PET with approximately 0.5 µm in film thickness. The high-gas-barrier DLC films deposited on PET sheets are expected to wrap elevated bridge of the super express and prevent them from neutralization of concrete. We also deposited DLC films inside PET bottles by the microwave surface-wave plasma chemical vapor deposition (CVD) method at near-atmospheric pressure. Under atmospheric pressure, the films were coated uniformly inside the PET bottles, but did not show high gas barrier properties. In this paper, we summarize recent progress of DLC films synthesized at atmospheric pressure with the aimed of food packaging and concrete pillar.

  5. Mechanism of high growth rate for diamond-like carbon films synthesized by helicon wave plasma chemical vapor deposition

    NASA Astrophysics Data System (ADS)

    Peiyu, JI; Jun, YU; Tianyuan, HUANG; Chenggang, JIN; Yan, YANG; Lanjian, ZHUGE; Xuemei, WU

    2018-02-01

    A high growth rate fabrication of diamond-like carbon (DLC) films at room temperature was achieved by helicon wave plasma chemical vapor deposition (HWP-CVD) using Ar/CH4 gas mixtures. The microstructure and morphology of the films were characterized by Raman spectroscopy and scanning electron microscopy. The diagnosis of plasma excited by a helicon wave was measured by optical emission spectroscopy and a Langmuir probe. The mechanism of high growth rate fabrication for DLC films by HWP-CVD has been discussed. The growth rate of the DLC films reaches a maximum value of 54 μm h-1 at the CH4 flow rate of 85 sccm, which is attributed to the higher plasma density during the helicon wave plasma discharge. The CH and H α radicals play an important role in the growth of DLC films. The results show that the H α radicals are beneficial to the formation and stabilization of C=C bond from sp2 to sp3.

  6. Pathway of oral absorption of heparin with sodium N-[8-(2-hydroxybenzoyl)amino] caprylate.

    PubMed

    Malkov, Dmitry; Wang, Huai-Zhen; Dinh, Steven; Gomez-Orellana, Isabel

    2002-08-01

    The oral bioavailability of heparin is negligible. Recent studies, however, have shown that sodium N-[8-(2-hydroxybenzoyl) amino]caprylate (SNAC) and other N-acylated amino acids enable oral heparin absorption. To investigate the mechanism by which heparin crosses the intestinal epithelium in the presence of SNAC, we have used fluorescence microscopy to follow the transport of heparin across Caco-2 cell monolayers. The experiments were carried out on Caco-2 monolayers and Caco-2 cells grown to confluence on culture dishes, using different concentrations of SNAC. The localization of fluorescently labeled heparin was determined using epi-fluorescence and confocal microscopy. DNA dyes were used to determine the effect of SNAC on the plasma membrane integrity. F-actin was labeled with fluorescent phalloidin to investigate the stability of perijunctional actin rings in the presence of SNAC. Heparin was detected in the cytoplasm only after incubation of the cells with heparin and SNAC. No DNA staining was observed in cells incubated with a DNA dye in the presence of SNAC concentrations at which heparin transport occurred. In addition, no signs of actin redistribution or perijunctional ring disbandment were observed during the transport of heparin. The results indicate that SNAC enables heparin transport across Caco-2 monolayers via the transcellular pathway. Heparin transport in the presence of SNAC is selective and does not involve permeabilization of the plasma membrane or tight junction disruption.

  7. Surface modification of silk fibroin fabric using layer-by-layer polyelectrolyte deposition and heparin immobilization for small-diameter vascular prostheses.

    PubMed

    Elahi, M Fazley; Guan, Guoping; Wang, Lu; Zhao, Xinzhe; Wang, Fujun; King, Martin W

    2015-03-03

    There is an urgent need to develop a biologically active implantable small-diameter vascular prosthesis with long-term patency. Silk-fibroin-based small-diameter vascular prosthesis is a promising candidate having higher patency rate; however, the surface modification is indeed required to improve its further hemocompatibility. In this study, silk fibroin fabric was modified by a two-stage process. First, the surface of silk fibroin fabric was coated using a layer-by-layer polyelectrolyte deposition technique by stepwise dipping the silk fibroin fabric into a solution of cationic poly(allylamine hydrochloride) (PAH) and anionic poly(acrylic acid) (PAA) solution. The dipping procedure was repeated to obtain the PAH/PAA multilayers deposited on the silk fibroin fabrics. Second, the polyelectrolyte-deposited silk fibroin fabrics were treated in EDC/NHS-activated low-molecular-weight heparin (LMWH) solution at 4 °C for 24 h, resulting in immobilization of LMWH on the silk fibroin fabrics surface. Scanning electron microscopy, atomic force microscopy, and energy-dispersive X-ray data revealed the accomplishment of LMWH immobilization on the polyelectrolyte-deposited silk fibroin fabric surface. The higher the number of PAH/PAA coating layers on the silk fibroin fabric, the more surface hydrophilicity could be obtained, resulting in a higher fetal bovine serum protein and platelets adhesion resistance properties when tested in vitro. In addition, compared with untreated sample, the surface-modified silk fibroin fabrics showed negligible loss of bursting strength and thus reveal the acceptability of polyelectrolytes deposition and heparin immobilization approach for silk-fibroin-based small-diameter vascular prostheses modification.

  8. The local clinical validation of a new lithium heparin tube with a barrier: BD Vacutainer® Barricor LH Plasma tube.

    PubMed

    Arslan, Fatma Demet; Karakoyun, Inanc; Basok, Banu Isbilen; Aksit, Merve Zeytinli; Baysoy, Anil; Ozturk, Yasemin Kilic; Guclu, Yusuf Adnan; Duman, Can

    2017-10-15

    Although serum-providing blood tubes with a barrier are still widely used due to their significant advantages, the use of blood tubes with a barrier to provide plasma is becoming widespread. We compared 22 analytes in a BD Vacutainer® Barricor LH Plasma tube for local clinical validation of this new lithium heparin tube with a barrier. Samples from 44 volunteers were collected in different tubes (Becton Dickinson and Company): Z tube without additive (reference), clot-activator tube with gel (SST), lithium heparin tube without gel (LiH), and lithium heparin tube with barrier (Barricor). Analyte concentrations in different tubes were compared with the reference tube. All tubes were also evaluated according to additional testing (different centrifugation durations, blood-sampling techniques and individual differences). Aspartate aminotransferase (AST), glucose (Glc), potassium (K), lactate dehydrogenase (LD), sodium (Na), and total protein (TP) had a significant bias in Barricor (9.19%, - 3.24%, - 4.88%, 21.60%, - 0.40%, 5.03%, respectively) relative to the reference tube. There was no statistical difference between different centrifugation durations and individual differences for AST, K and LD in LiH and/or Barricor (P > 0.05). There was a significant bias for LD between LiH and Barricor in terms of blood-sampling techniques (21.2% and 12.4%, respectively). Recently, the use of plasma has become prominent due to some of its advantages. In this study, plasma AST, K, LD, Glc and TP levels in Barricor were clinically different in comparison to serum. The results of additional tests showed that higher levels of LD in Barricor did not result from haemolysis, and they might be related to other factors including number of platelets, cellular fragility, or functional environment.

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

    PubMed

    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.

  10. Axial distribution of plasma fluctuations, plasma parameters, deposition rate and grain size during copper deposition

    NASA Astrophysics Data System (ADS)

    Gopikishan, S.; Banerjee, I.; Pathak, Anand; Mahapatra, S. K.

    2017-08-01

    Floating potential fluctuations, plasma parameters and deposition rate have been investigated as a function of axial distance during deposition of copper in direct current (DC) magnetron sputtering system. Fluctuations were analyzed using phase space, power spectra and amplitude bifurcation plots. It has been observed that the fluctuations are modified from chaotic to ordered state with increase in the axial distance from cathode. Plasma parameters such as electron density (ne), electron temperature (Te) and deposition rate (Dr) were measured and correlated with plasma fluctuations. It was found that more the deposition rate, greater the grain size, higher the electron density, higher the electron temperature and more chaotic the oscillations near the cathode. This observation could be helpful to the thin film technology industry to optimize the required film.

  11. Heparin-like entities from marine organisms.

    PubMed

    Colliec-Jouault, S; Bavington, C; Delbarre-Ladrat, C

    2012-01-01

    Polysaccharides are ubiquitous in animals and plant cells where they play a significant role in a number of physiological situations e.g. hydration, mechanical properties of cell walls and ionic regulation. This review concentrates on heparin-like entities from marine procaryotes and eukaryotes. Carbohydrates from marine prokaryotes offer a significant structural chemodiversity with novel material and biological properties. Cyanobacteria are Gram-negative photosynthetic prokaryotes considered as a rich source of novel molecules, and marine bacteria are a rich source of polysaccharides with novel structures, which may be a good starting point from which to synthesise heparinoid molecules. For example, some sulphated polysaccharides have been isolated from gamma-proteobacteria such as Alteromonas and Pseudoalteromonas sp. In contrast to marine bacteria, all marine algae contain sulphated wall polysaccharides, whereas such polymers are not found in terrestrial plants. In their native form, or after chemical modifications, a range of polysaccharides isolated from marine organisms have been described that have anticoagulant, anti-thrombotic, anti-tumour, anti-proliferative, anti-viral or anti-inflammatory activities.In spite of the enormous potential of sulphated oligosaccharides from marine sources, their technical and pharmaceutical usage is still limited because of the high complexity of these molecules. Thus, the production of tailor-made oligo- and polysaccharidic structures by biocatalysis is also a growing field of interest in biotechnology.

  12. Printed microfluidic filter for heparinized blood.

    PubMed

    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.

  13. RF-plasma vapor deposition of siloxane on paper. Part 1: Physical evolution of paper surface

    NASA Astrophysics Data System (ADS)

    Sahin, Halil Turgut

    2013-01-01

    An alternative, new approach to improve the hydrophobicity and barrier properties of paper was evaluated by radio-frequency (RF) plasma octamethylcyclotetrasiloxane (OMCTSO) vapor treatment. The interaction between OMCTSO and paper, causing the increased hydophobicity, is likely through covalent bonding. The deposited thin silicone-like polymeric layer from OMCTSO plasma treatment possessed desirable hydrophobic properties. The SEM micrographs showed uniformly distributed grainy particles with various shapes on the paper surface. Deposition of the silicone polymer-like layer with the plasma treatment affects the distribution of voids in the network structure and increases the barrier against water intake and air. The water absorptivity was reduced by 44% for the OMCTSO plasma treated sheet. The highest resistance to air flow was an approximately 41% lower air permeability than virgin paper.

  14. Polyguluronate sulfate, polymannuronate sulfate, and their oligosaccharides have antithrombin III- and heparin cofactor II-independent anticoagulant activity

    NASA Astrophysics Data System (ADS)

    Zeng, Xuan; Lan, Ying; Zeng, Pengjiao; Guo, Zhihua; Hao, Cui; Zhang, Lijuan

    2017-04-01

    Cardiovascular disease is the leading causes of death. However, the complications can be treated with heparin and heparinoids, such as heparin pentasaccharide Fondaparinux, dermatan sulfate, and PSS made from alginate extracted from brown seaweeds by chemical sulfation. Alginate is composed of a linear backbone of polymannuronate (PM), polyguluronate (PG), and alternate residues of mannuronic acid and guluronic acid. It is unknown if heparin and sulfated PG (PGS)/PM (PMS) have the same or different anticoagulant molecular targets. In the current study, the anticoagulant activities of PGS, PMS, and their oligosaccharides were directly compared to that of heparin, Fondaparinux, and dermatan sulfate by the activated partial thrombinplastin time (aPTT) assay using normal, antithrombin III (ATIII)-deficient, heparin co-factor II (HCII)-deficient, and ATIII- and HCII-double deficient human plasmas. Our results showed that PGS, PMS, and their oligosaccharides had better anticoagulant activity than that of Fondaparinux in all four human plasmas tested. As expected, heparin was the best anticoagulant in normal plasma. Moreover, PGS, PGS6, PGS12, PGS25, PMS6, PMS12, and PMS25 were better anticoagulants than dermatan sulfate in HCII-deficient plasma. Most strikingly, PGS, PGS12, PGS25, PMS6, PMS12, and PMS25 were better anticoagulants than that of heparin in ATIII- and HCII-double deficient human plasma. The results revealed for the first time that sulfated alginate had ATIII- and HCII-independent anticoagulant activities. Therefore, developing PGS and PMS-based anticoagulants might require to discover their major molecular targets and to develop target-specific anticoagulant assays.

  15. Structural and binding studies of SAP-1 protein with heparin.

    PubMed

    Yadav, Vikash K; Mandal, Rahul S; Puniya, Bhanwar L; Kumar, Rahul; Dey, Sharmistha; Singh, Sarman; Yadav, Savita

    2015-03-01

    SAP-1 is a low molecular weight cysteine protease inhibitor (CPI) which belongs to type-2 cystatins family. SAP-1 protein purified from human seminal plasma (HuSP) has been shown to inhibit cysteine and serine proteases and exhibit interesting biological properties, including high temperature and pH stability. Heparin is a naturally occurring glycosaminoglycan (with varied chain length) which interacts with a number of proteins and regulates multiple steps in different biological processes. As an anticoagulant, heparin enhances inhibition of thrombin by the serpin antithrombin III. Therefore, we have employed surface plasmon resonance (SPR) to improve our understanding of the binding interaction between heparin and SAP-1 (protease inhibitor). SPR data suggest that SAP-1 binds to heparin with a significant affinity (KD = 158 nm). SPR solution competition studies using heparin oligosaccharides showed that the binding of SAP-1 to heparin is dependent on chain length. Large oligosaccharides show strong binding affinity for SAP-1. Further to get insight into the structural aspect of interactions between SAP-1 and heparin, we used modelled structure of the SAP-1 and docked with heparin and heparin-derived polysaccharides. The results suggest that a positively charged residue lysine plays important role in these interactions. Such information should improve our understanding of how heparin, present in the reproductive tract, regulates cystatins activity. © 2014 John Wiley & Sons A/S.

  16. Liquid injection plasma deposition method and apparatus

    DOEpatents

    Kong, Peter C.; Watkins, Arthur D.

    1999-01-01

    A liquid injection plasma torch deposition apparatus for depositing material onto a surface of a substrate may comprise a plasma torch for producing a jet of plasma from an outlet nozzle. A plasma confinement tube having an inlet end and an outlet end and a central bore therethrough is aligned with the outlet nozzle of the plasma torch so that the plasma jet is directed into the inlet end of the plasma confinement tube and emerges from the outlet end of the plasma confinement tube. The plasma confinement tube also includes an injection port transverse to the central bore. A liquid injection device connected to the injection port of the plasma confinement tube injects a liquid reactant mixture containing the material to be deposited onto the surface of the substrate through the injection port and into the central bore of the plasma confinement tube.

  17. Liquid injection plasma deposition method and apparatus

    DOEpatents

    Kong, P.C.; Watkins, A.D.

    1999-05-25

    A liquid injection plasma torch deposition apparatus for depositing material onto a surface of a substrate may comprise a plasma torch for producing a jet of plasma from an outlet nozzle. A plasma confinement tube having an inlet end and an outlet end and a central bore therethrough is aligned with the outlet nozzle of the plasma torch so that the plasma jet is directed into the inlet end of the plasma confinement tube and emerges from the outlet end of the plasma confinement tube. The plasma confinement tube also includes an injection port transverse to the central bore. A liquid injection device connected to the injection port of the plasma confinement tube injects a liquid reactant mixture containing the material to be deposited onto the surface of the substrate through the injection port and into the central bore of the plasma confinement tube. 8 figs.

  18. Preparation Of Sources For Plasma Vapor Deposition

    NASA Technical Reports Server (NTRS)

    Waters, William J.; Sliney, Hal; Kowalski, D.

    1993-01-01

    Multicomponent metal targets serving as sources of vapor for plasma vapor deposition made in modified pressureless-sintering process. By use of targets made in modified process, one coats components with materials previously plasma-sprayed or sintered but not plasma-vapor-deposited.

  19. Heparin-induced thrombocytopenia

    PubMed Central

    Shaikh, Nissar

    2011-01-01

    In the last 7 decades heparin has remained the most commonly used anticoagulant. Its use is increasing, mainly due to the increase in the number of vascular interventions and aging population. The most feared complication of heparin use is heparin-induced thrombocytopenia (HIT). HIT is a clinicopathologic hypercoagulable, procoagulant prothrombotic condition in patients on heparin therapy, and decrease in platelet count by 50% or to less than 100,000, from 5 to 14 days of therapy. This prothrombotic hypercoagulable state in HIT patient is due to the combined effect of various factors, such as platelet activation, mainly the formation of PF4/heparin/IgG complex, stimulation of the intrinsic factor, and loss of anticoagulant effect of heparin. Diagnosis of HIT is done by clinical condition, heparin use, and timing of thrombocytopenia, and it is confirmed by either serotonin release assay or ELISA assay. Complications of HIT are venous/arterial thrombosis, skin gangrene, and acute platelet activation syndrome. Stopping heparin is the basic initial treatment, and Direct Thrombin Inhibitors (DTI) are medication of choice in these patients. A few routine but essential procedures performed by using heparin are hemodialysis, Percutaneous Coronary Intervention, and Cardiopulmonary Bypass; but it cannot be used if a patient develops HIT. HIT patients with unstable angina, thromboembolism, or indwelling devices, such as valve replacement or intraaortic balloon pump, will require alternative anticoagulation therapy. HIT can be prevented significantly by keeping heparin therapy shorter, avoiding bovine heparin, using low-molecular weight heparin, and stopping heparin use for flush and heparin lock. PMID:21633576

  20. The role of complement C3 and fibrinogen in monocyte adhesion to PEO like plasma deposited tetraglyme

    PubMed Central

    Szott, Luisa M.; Horbett, Thomas A.

    2010-01-01

    The role of complement C3 in mediating adhesion of monocytes to plasma deposited tetraglyme surfaces was studied. Although fibrinogen (Fg) is usually considered the main factor in mediating phagocyte attachment, plasma deposited PEO-like tetraethylene glycol dimethyl ether (tetraglyme) coatings that have ultra-low Fg adsorption (< 10 ng/cm2) from low concentration solutions and low monocyte adhesion in vitro still show high phagocyte adhesion after short implantations and later become encapsulated when tested in vivo. To test whether higher Fg adsorption under in vivo conditions could explain the higher in vivo reactivity, we again measured the resistance of tetraglyme films to Fg adsorption. We found a surprising and previously unreported increased amount of adsorbed Fg on tetraglyme surfaces from higher concentration protein solutions. However, monocyte adhesion to tetraglyme did not markedly increase despite the increased Fg adsorption. We thus suspected proteins other than Fg must be responsible for the increased in vivo reactivity. We found that on tetraglyme pre-adsorbed with C3-depleted serum, monocyte adhesion was greatly reduced as compared to samples adsorbed with normal serum. Addition of exogenous pure C3 to the serum used to pre-adsorb the surfaces restored monocyte adhesion to tetraglyme coatings. While Fg clearly plays an important role in mediating monocyte adhesion to tetraglyme surfaces, the results show an additional role for adsorbed C3 in monocyte adhesion. PMID:20939050

  1. Plasma deposition of antimicrobial coating on organic polymer

    NASA Astrophysics Data System (ADS)

    Rżanek-Boroch, Zenobia; Dziadczyk, Paulina; Czajkowska, Danuta; Krawczyk, Krzysztof; Fabianowski, Wojciech

    2013-02-01

    Organic materials used for packing food products prevent the access of microorganisms or gases, like oxygen or water vapor. To prolong the stability of products, preservatives such as sulfur dioxide, sulfites, benzoates, nitrites and many other chemical compounds are used. To eliminate or limit the amount of preservatives added to food, so-called active packaging is sought for, which would limit the development of microorganisms. Such packaging can be achieved, among others, by plasma modification of a material to deposit on its surface substances inhibiting the growth of bacteria. In this work plasma modification was carried out in barrier discharge under atmospheric pressure. Sulfur dioxide or/and sodium oxide were used as the coating precursors. As a result of bacteriological studies it was found that sulfur containing coatings show a 16% inhibition of Salmonella bacteria growth and 8% inhibition of Staphylococcus aureus bacteria growth. Sodium containing coatings show worse (by 10%) inhibiting properties. Moreover, films with plasma deposited coatings show good sealing properties against water vapor. Contribution to the Topical Issue "13th International Symposium on High Pressure Low Temperature Plasma Chemistry (Hakone XIII)", Edited by Nicolas Gherardi, Henryca Danuta Stryczewska and Yvan Ségui.

  2. Stability of Routine Biochemical Analytes in Whole Blood and Plasma From Lithium Heparin Gel Tubes During 6-hr Storage.

    PubMed

    Monneret, Denis; Godmer, Alexandre; Le Guen, Ronan; Bravetti, Clotilde; Emeraud, Cecile; Marteau, Anthony; Alkouri, Rana; Mestari, Fouzi; Dever, Sylvie; Imbert-Bismut, Françoise; Bonnefont-Rousselot, Dominique

    2016-09-01

    The stability of biochemical analytes has already been investigated, but results strongly differ depending on parameters, methodologies, and sample storage times. We investigated the stability for many biochemical parameters after different storage times of both whole blood and plasma, in order to define acceptable pre- and postcentrifugation delays in hospital laboratories. Twenty-four analytes were measured (Modular® Roche analyzer) in plasma obtained from blood collected into lithium heparin gel tubes, after 2-6 hr of storage at room temperature either before (n = 28: stability in whole blood) or after (n = 21: stability in plasma) centrifugation. Variations in concentrations were expressed as mean bias from baseline, using the analytical change limit (ACL%) or the reference change value (RCV%) as acceptance limit. In tubes stored before centrifugation, mean plasma concentrations significantly decreased after 3 hr for phosphorus (-6.1% [95% CI: -7.4 to -4.7%]; ACL 4.62%) and lactate dehydrogenase (LDH; -5.7% [95% CI: -7.4 to -4.1%]; ACL 5.17%), and slightly decreased after 6 hr for potassium (-2.9% [95% CI: -5.3 to -0.5%]; ACL 4.13%). In plasma stored after centrifugation, mean concentrations decreased after 6 hr for bicarbonates (-19.7% [95% CI: -22.9 to -16.5%]; ACL 15.4%), and moderately increased after 4 hr for LDH (+6.0% [95% CI: +4.3 to +7.6%]; ACL 5.17%). Based on RCV, all the analytes can be considered stable up to 6 hr, whether before or after centrifugation. This study proposes acceptable delays for most biochemical tests on lithium heparin gel tubes arriving at the laboratory or needing to be reanalyzed. © 2016 Wiley Periodicals, Inc.

  3. Comparison of Low-Molecular-Weight Heparins Prepared From Bovine Lung Heparin and Porcine Intestine Heparin.

    PubMed

    Guan, Yudong; Xu, Xiaohui; Liu, Xinyue; Sheng, Anran; Jin, Lan; Linhardt, Robert J; Chi, Lianli

    2016-06-01

    Currently porcine intestine is the only approved source for producing pharmaceutical heparin in most countries. Enoxaparin, prepared by benzylation and alkaline depolymerization from porcine intestine heparin, is prevalent in the anticoagulant drug market. It is predicted that porcine intestine heparin-derived enoxaparin (PIE) will encounter shortage, and expanding its production from heparins obtained from other animal tissues may, therefore, be inevitable. Bovine lung heparin is a potential alternative source for producing enoxaparin. Critical processing parameters for producing bovine lung heparin-derived enoxaparin (BLE) are discussed. Three batches of BLEs were prepared and their detailed structures were compared with PIEs using modern analytical techniques, including disaccharide composition, intact chain mapping by liquid chromatography-mass spectrometry and 2-dimensional nuclear magnetic resonance spectroscopy. The results suggested that the differences between PIEs and BLEs mainly result from N-acetylation differences derived from the parent heparins. In addition, bioactivities of BLEs were about 70% of PIEs based on anti-factor IIa and Xa chromogenic assays. We conclude that BLE has the potential to be developed as an analogue of PIE, although some challenges still remain. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  4. Heparin-induced thrombocytopenia

    PubMed Central

    2017-01-01

    Heparin-induced thrombocytopenia (HIT) is an immune complication of heparin therapy caused by antibodies to complexes of platelet factor 4 (PF4) and heparin. Pathogenic antibodies to PF4/heparin bind and activate cellular FcγRIIA on platelets and monocytes to propagate a hypercoagulable state culminating in life-threatening thrombosis. It is now recognized that anti-PF4/heparin antibodies develop commonly after heparin exposure, but only a subset of sensitized patients progress to life-threatening complications of thrombocytopenia and thrombosis. Recent scientific developments have clarified mechanisms underlying PF4/heparin immunogenicity, disease susceptibility, and clinical manifestations of disease. Insights from clinical and laboratory findings have also been recently harnessed for disease prevention. This review will summarize our current understanding of HIT by reviewing pathogenesis, essential clinical and laboratory features, and management. PMID:28416511

  5. Deposition And Characterization Of Ultra Thin Diamond Like Carbon Films

    NASA Astrophysics Data System (ADS)

    Tomcik, B.

    2010-07-01

    Amorphous hydrogenated and/or nitrogenated carbon films, a-C:H/a-C:N, in overall thickness up to 2 nm are materials of choice as a mechanical and corrosion protection layer of the magnetic media in modern hard disk drive disks. In order to obtain high density and void-free films the sputtering technology has been replaced by different plasma and ion beam deposition techniques. Hydrocarbon gas precursors, like C2H2 or CH4 with H2 and N2 as reactive gases are commonly used in Kaufman DC ion and RF plasma beam sources. Optimum incident energy of carbon ions, C+, is up to 100 eV while the typical ion current densities during the film formation are in the mA/cm2 range. Other carbon deposition techniques, like filtered cathodic arc, still suffer from co-deposition of fine nanosized carbon clusters (nano dust) and their improvements are moving toward arc excitation in the kHz and MHz frequency range. Non-destructive film analysis like μ-Raman optical spectroscopy, spectroscopic ellipsometry, FTIR and optical surface analysis are mainly used in the carbon film characterization. Due to extreme low film thicknesses the surface enhanced Raman spectroscopy (SERS) with pre-deposited layer of Au can reduce the signal collection time and minimize photon-induced damage during the spectra acquisition. Standard approach in the μ-Raman film evaluation is the measurement of the position (shift) and area of D and G-peaks under the deconvoluted overall carbon spectrum. Also, a slope of the carbon spectrum in the 1000-2000 cm-1 wavenumber range is used as a measure of the hydrogen intake within a film. Diamond like carbon (DLC) film should possess elasticity and self-healing properties during the occasional crash of the read-write head flying only couple of nanometers above the spinning film. Film corrosion protection capabilities are mostly evaluated by electrochemical tests, potentio-dynamic and linear polarization method and by business environmental method. Corrosion mechanism

  6. Plasma Spray-Physical Vapor Deposition (PS-PVD) of Ceramics for Protective Coatings

    NASA Technical Reports Server (NTRS)

    Harder, Bryan J.; Zhu, Dongming

    2011-01-01

    In order to generate advanced multilayer thermal and environmental protection systems, a new deposition process is needed to bridge the gap between conventional plasma spray, which produces relatively thick coatings on the order of 125-250 microns, and conventional vapor phase processes such as electron beam physical vapor deposition (EB-PVD) which are limited by relatively slow deposition rates, high investment costs, and coating material vapor pressure requirements. The use of Plasma Spray - Physical Vapor Deposition (PS-PVD) processing fills this gap and allows thin (< 10 microns) single layers to be deposited and multilayer coatings of less than 100 microns to be generated with the flexibility to tailor microstructures by changing processing conditions. Coatings of yttria-stabilized zirconia (YSZ) were applied to NiCrAlY bond coated superalloy substrates using the PS-PVD coater at NASA Glenn Research Center. A design-of-experiments was used to examine the effects of process variables (Ar/He plasma gas ratio, the total plasma gas flow, and the torch current) on chamber pressure and torch power. Coating thickness, phase and microstructure were evaluated for each set of deposition conditions. Low chamber pressures and high power were shown to increase coating thickness and create columnar-like structures. Likewise, high chamber pressures and low power had lower growth rates, but resulted in flatter, more homogeneous layers

  7. Dust cloud evolution in sub-stellar atmospheres via plasma deposition and plasma sputtering

    NASA Astrophysics Data System (ADS)

    Stark, C. R.; Diver, D. A.

    2018-04-01

    Context. In contemporary sub-stellar model atmospheres, dust growth occurs through neutral gas-phase surface chemistry. Recently, there has been a growing body of theoretical and observational evidence suggesting that ionisation processes can also occur. As a result, atmospheres are populated by regions composed of plasma, gas and dust, and the consequent influence of plasma processes on dust evolution is enhanced. Aim. This paper aims to introduce a new model of dust growth and destruction in sub-stellar atmospheres via plasma deposition and plasma sputtering. Methods: Using example sub-stellar atmospheres from DRIFT-PHOENIX, we have compared plasma deposition and sputtering timescales to those from neutral gas-phase surface chemistry to ascertain their regimes of influence. We calculated the plasma sputtering yield and discuss the circumstances where plasma sputtering dominates over deposition. Results: Within the highest dust density cloud regions, plasma deposition and sputtering dominates over neutral gas-phase surface chemistry if the degree of ionisation is ≳10-4. Loosely bound grains with surface binding energies of the order of 0.1-1 eV are susceptible to destruction through plasma sputtering for feasible degrees of ionisation and electron temperatures; whereas, strong crystalline grains with binding energies of the order 10 eV are resistant to sputtering. Conclusions: The mathematical framework outlined sets the foundation for the inclusion of plasma deposition and plasma sputtering in global dust cloud formation models of sub-stellar atmospheres.

  8. Characterization of PEG-Like Macromolecular Coatings on Plasma Modified NiTi Alloy

    NASA Astrophysics Data System (ADS)

    Yang, Jun; Gao, Jiacheng; Chang, Peng; Wang, Jianhua

    2008-04-01

    A poly (ethylene glycol) (PEG-like) coating was developed to improve the biocompatibility of Nickel-Titanium (NiTi) alloy implants. The PEG-like macromolecular coatings were deposited on NiTi substrates at a room temperature of 298 K through a ECR (electron-cyclotron resonance) cold-plasma enhanced chemical vapor deposition method using tetraglyme (CH3-O-(CH2-CH2-O)4-CH3) as a precursor. A power supply with a frequency of 2.45 GHz was applied to ignite the plasma with Ar(argon) used as the carrier gas. Based on the atomic force microscopy (AFM) studies, a thin smooth coating on NiTi substrates with highly amorphous functional groups on the modified NiTi surfaces were mainly the same accumulated stoichiometric ratio of C and O with PEG. The vitro studies showed that platelet-rich plasma (PRP) adsorption on the modified NiTi alloy surface was significantly reduced. This study indicated that plasma surface modification changes the surface components of NiTi alloy and subsequently improves its biocompatibility.

  9. A Self Consistent RF Discharge, Plasma Chemistry and Surface Model for Plasma Enhanced Chemical Vapor Deposition

    DTIC Science & Technology

    1988-06-30

    consists of three submodels for the electron kinetics, plasma chemistry , and surface deposition kinetics for a-Si:H deposited from radio frequency...properties. Plasma enhanced, Chemical vapor deposition, amorphous silicon, Modeling, Electron kinetics, Plasma chemistry , Deposition kinetics, Rf discharge, Silane, Film properties, Silicon.

  10. Vapor Phase Deposition Using Plasma Spray-PVD™

    NASA Astrophysics Data System (ADS)

    von Niessen, K.; Gindrat, M.; Refke, A.

    2010-01-01

    Plasma spray—physical vapor deposition (PS-PVD) is a low pressure plasma spray technology to deposit coatings out of the vapor phase. PS-PVD is a part of the family of new hybrid processes recently developed by Sulzer Metco AG (Switzerland) on the basis of the well-established low pressure plasma spraying (LPPS) technology. Included in this new process family are plasma spray—chemical vapor deposition (PS-CVD) and plasma spray—thin film (PS-TF) processes. In comparison to conventional vacuum plasma spraying and LPPS, these new processes use a high energy plasma gun operated at a work pressure below 2 mbar. This leads to unconventional plasma jet characteristics which can be used to obtain specific and unique coatings. An important new feature of PS-PVD is the possibility to deposit a coating not only by melting the feed stock material which builds up a layer from liquid splats, but also by vaporizing the injected material. Therefore, the PS-PVD process fills the gap between the conventional PVD technologies and standard thermal spray processes. The possibility to vaporize feedstock material and to produce layers out of the vapor phase results in new and unique coating microstructures. The properties of such coatings are superior to those of thermal spray and EB-PVD coatings. This paper reports on the progress made at Sulzer Metco to develop functional coatings build up from vapor phase of oxide ceramics and metals.

  11. Heparin-induced hyperkalemia.

    PubMed

    Thomas, C M; Thomas, J; Smeeton, F; Leatherdale, B A

    2008-05-01

    An 85-year-old lady with type 2 diabetes mellitus of 32 years duration with peripheral neuropathy was admitted under the vascular surgeons with extensive gangrene of her lower limb. She was on insulin for the last 7 years. Initial investigations showed normal serum electrolytes. She was started on antibiotics and unfractionated heparin, and her electrolytes showed hyperkalemia, which persisted on active treatment. Her short synacthen test showed good response, renin was normal with low aldosterone, urinary pH, sodium, potassium and osmolality was normal. On stopping heparin serum, potassium became normal. On restarting heparin (low molecular weight) during a suspected episode of pulmonary embolism, she developed hyperkalemia and heparin was stopped. Her potassium and aldosterone became normal on discontinuation of heparin. She developed hyperkalemia with both unfractionated and low molecular weight heparin.

  12. 78 FR 36786 - Linking Marketplace Heparin Product Attributes and Manufacturing Processes to Bioactivity and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-19

    ... heparin. The condition leads to formation of abnormal blood clots and concomitant complications associated... antibody formation although these smaller chain length heparins are much less likely to lead to clinical... components of heparin that lead to the pathogenesis of HIT is the lack of pure component heparin standards...

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

    PubMed

    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

  14. Diagnostics of capacitively-coupled hydrocarbon plasmas for deposition of diamond-like carbon films using quadrupole mass spectrometry and Langmuir probe

    NASA Astrophysics Data System (ADS)

    Oda, Akinori; Fukai, Shun; Kousaka, Hiroyuki; Ohta, Takayuki

    2015-09-01

    Diamond-like carbon (DLC) films are the hydrogenated amorphous carbon films, which contains a mixture of sp2- and sp3-bonded carbon. The DLC films have been widely used for various applications, such as automotive, semiconductors, medical devices, since have excellent material properties in lower friction, higher chemical stability, higher hardness, higher wear resistance. Until now, numerous investigations on the DLC films using plasma assisted chemical vapor deposition have been done. For precise control of coating technique of DLC films, it is enormously important to clarify the fundamental properties in hydrocarbon plasmas, as a source of hydrocarbon ions and radicals. In this paper, the fundamental properties in a low pressure radio-frequency hydrocarbon (Ar/CH4 (1 %) gas mixture) plasmas have been diagnosed using a quadrupole mass spectrometer (HIDEN ANARYTICAL Ltd., EQP-300) and Langmuir probe system (HIDEN ANARYTICAL Ltd., ESPion). This work was partly supported by KAKENHI (No.26420247), and a ``Grant for Advanced Industrial Technology Development (No.11B06004d)'' in 2011 from the New Energy and Industrial Technology Development Organization (NEDO) of Japan.

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

    PubMed Central

    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

  16. Heparin allergy: delayed-type non-IgE-mediated allergic hypersensitivity to subcutaneous heparin injection.

    PubMed

    Trautmann, Axel; Seitz, Cornelia S

    2009-08-01

    Itching erythematous or eczematous plaques around injection sites are quite frequent side effects of heparin treatment and clinical symptoms of delayed-type non-IgE-mediated allergic hypersensitivity (DTH) to heparin. For diagnosis, intradermal, patch, and subcutaneous challenge tests with heparins are suitable. In most cases, changing the subcutaneous therapy from unfractionated to low molecular weight heparin or treatment with heparinoids does not provide improvement because of extensive cross-reactivity. Hirudin polypeptides, which exhibit a different chemical structure, are a safe therapeutic alternative for subcutaneous application, however. Importantly, despite DTH to subcutaneously injected heparins, most patients tolerate heparin intravenously. Moreover, in case of therapeutic necessity and DTH to heparins, the simple shift from subcutaneous to intravenous heparin administration without prior testing may be justified.

  17. The effect of heparin rinse on the biocompatibility of continuous veno-venous hemodiafiltration.

    PubMed

    Opatrný, K; Polanská, K; Krouzecký, A; Vít, L; Novák, I; Kasal, E

    2002-06-01

    The aims of our cross-over randomized study were (1) to assess hemostasis in patients with acute renal failure (ARF) and (2) to determine whether or not the generally recommended heparin rinse of the extracorporeal circuit (ECC) prior to the procedure affects thrombogenicity, complement activation, and leukocyte count in blood during continuous venovenous hemodiafiltration (CVVHDF). Eleven critically ill ARF patients were treated, in random order, using CVVHDF in postdilution setup following ECC rinse with saline (A) with heparin at a concentration of 2,000 IU/L (10 procedures), (B) with heparin at a concentration of 10,000 IU/L (7 procedures), and (C) without heparin (9 procedures). Except for the rinse, anticoagulation therapy did not differ in individual patients during the procedures. Blood was withdrawn before, and at minutes 15, 60, and 360 invariably at diafilter inlet and outlet. Compared with healthy individuals, patients showed lower blood thrombocyte counts (153 vs 233*10(9)/L, p<0.01, arithmetic means, Student's t test), longer aPTT (44 vs 36 s, p<0.05), higher plasma levels of heparin (0.1 vs 0.0 U/mL, p<0.05), D-dimer (1129 vs 36 ng/mL, p<0.001) and beta-thromboglobulin (BTG) (159 vs 37 U/mL, p<0.001) prior to CVVHDF. The comparison of procedures with different rinsing technique did not reveal any significant difference in their effects on blood thrombocyte and leukocyte counts, aPTT, plasma levels of heparin, BTG, thrombin-antithrombin III complexes, D-dimer, or the C5a complement component. (1) Patients indicated for CVVHDF show impaired hemostasis involving thrombocytes, coagulation, and fibrinolysis, (2) no beneficial effect of heparin rinse on CVVHDF ECC thrombogenicity, complement activation or blood leukocyte counts was demonstrated.

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

    PubMed

    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.

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

    PubMed

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

  1. Diamond synthesis at atmospheric pressure by microwave capillary plasma chemical vapor deposition

    NASA Astrophysics Data System (ADS)

    Hemawan, Kadek W.; Gou, Huiyang; Hemley, Russell J.

    2015-11-01

    Polycrystalline diamond has been synthesized on silicon substrates at atmospheric pressure, using a microwave capillary plasma chemical vapor deposition technique. The CH4/Ar plasma was generated inside of quartz capillary tubes using 2.45 GHz microwave excitation without adding H2 into the deposition gas chemistry. Electronically excited species of CN, C2, Ar, N2, CH, Hβ, and Hα were observed in the emission spectra. Raman measurements of deposited material indicate the formation of well-crystallized diamond, as evidenced by the sharp T2g phonon at 1333 cm-1 peak relative to the Raman features of graphitic carbon. Field emission scanning electron microscopy images reveal that, depending on the growth conditions, the carbon microstructures of grown films exhibit "coral" and "cauliflower-like" morphologies or well-facetted diamond crystals with grain sizes ranging from 100 nm to 10 μm.

  2. Structural Snapshots of Heparin Depolymerization by Heparin Lyase I

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

    Han, Young-Hyun; Garron, Marie-Line; Kim, Hye-Yeon

    2010-01-12

    Heparin lyase I (heparinase I) specifically depolymerizes heparin, cleaving the glycosidic linkage next to iduronic acid. Here, we show the crystal structures of heparinase I from Bacteroides thetaiotaomicron at various stages of the reaction with heparin oligosaccharides before and just after cleavage and product disaccharide. The heparinase I structure is comprised of a {beta}-jellyroll domain harboring a long and deep substrate binding groove and an unusual thumb-resembling extension. This thumb, decorated with many basic residues, is of particular importance in activity especially on short heparin oligosaccharides. Unexpected structural similarity of the active site to that of heparinase II with anmore » ({alpha}/{alpha}){sub 6} fold is observed. Mutational studies and kinetic analysis of this enzyme provide insights into the catalytic mechanism, the substrate recognition, and processivity.« less

  3. Influence of Layer-by-Layer Polyelectrolyte Deposition and EDC/NHS Activated Heparin Immobilization onto Silk Fibroin Fabric

    PubMed Central

    Elahi, M. Fazley; Guan, Guoping; Wang, Lu; King, Martin W.

    2014-01-01

    To enhance the hemocompatibility of silk fibroin fabric as biomedical material, polyelectrolytes architectures have been assembled through the layer-by-layer (LbL) technique on silk fibroin fabric (SFF). In particular, 1.5 and 2.5 bilayer of oppositely charged polyelectrolytes were assembled onto SFF using poly(allylamine hydrochloride) (PAH) as polycationic polymer and poly(acrylic acid) (PAA) as polyanionic polymer with PAH topmost. Low molecular weight heparin (LMWH) activated with 1-ethyl-3-(dimethylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) was then immobilized on its surface. Alcian Blue staining, toluidine blue assay and X-ray photoelectron spectroscopy (XPS) confirmed the presence of heparin on modified SFF surfaces. The surface morphology of the modified silk fibroin fabric surfaces was characterized by scanning electron microscopy (SEM) and atomic force microscopy (AFM), and obtained increased roughness. Negligible hemolytic effect and a higher concentration of free hemoglobin by a kinetic clotting time test ensured the improved biological performance of the modified fibroin fabric. Overall, the deposition of 2.5 bilayer was found effective in terms of biological and surface properties of the modified fibroin fabric compared to 1.5 bilayer self-assembly technique. Therefore, this novel approach to surface modification may demonstrate long term patency in future in vivo animal trials of small diameter silk fibroin vascular grafts. PMID:28788601

  4. Plasma-Powder Feedstock Interaction During Plasma Spray-Physical Vapor Deposition

    NASA Astrophysics Data System (ADS)

    Anwaar, Aleem; Wei, Lianglinag; Guo, Hongbo; Zhang, Baopeng

    2017-02-01

    Plasma spray-physical vapor deposition is a new process developed to produce coatings from the vapor phase. To achieve deposition from the vapor phase, the plasma-feedstock interaction inside the plasma torch, i.e., from the powder injection point to the nozzle exit, is critical. In this work, the plasma characteristics and the momentum and heat transfer between the plasma and powder feedstock at different torch input power levels were investigated theoretically to optimize the net plasma torch power, among other important factors such as the plasma gas composition, powder feed rate, and carrier gas. The plasma characteristics were calculated using the CEA2 code, and the plasma-feedstock interaction was studied inside the torch nozzle at low-pressure (20-25 kPa) conditions. A particle dynamics model was introduced to compute the particle velocity, coupled with Xi Chen's drag model for nonevaporating particles. The results show that the energy transferred to the particles and the coating morphology are greatly influenced by the plasma gas characteristics and the particle dynamics inside the nozzle. The heat transfer between the plasma gas and feedstock material increased with the net torch power up to an optimum at 64 kW, at which a maximum of 3.4% of the available plasma energy was absorbed by the feedstock powder. Experimental results using agglomerated 7-8 wt.% yttria-stabilized zirconia (YSZ) powder as feedstock material confirmed the theoretical predictions.

  5. Effect of PEG-PDMAEMA Block Copolymer Architecture on Polyelectrolyte Complex Formation with Heparin.

    PubMed

    Välimäki, Salla; Khakalo, Alexey; Ora, Ari; Johansson, Leena-Sisko; Rojas, Orlando J; Kostiainen, Mauri A

    2016-09-12

    Heparin is a naturally occurring polyelectrolyte consisting of a sulfated polysaccharide backbone. It is widely used as an anticoagulant during major surgical operations. However, the associated bleeding risks require rapid neutralization after the operation. The only clinically approved antidote for heparin is protamine sulfate, which is, however, ineffective against low molecular weight heparin and can cause severe adverse reactions in patients. In this study, the facile synthesis of cationic-neutral diblock copolymers and their effective heparin binding is presented. Poly(ethylene glycol)-poly(2-(dimethylamino)ethyl methacrylate) (PEG-PDMAEMA) block copolymers were synthesized in two steps via atom-transfer radical polymerization (ATRP) using PEG as a macroinitiator. Solution state binding between heparin and a range of PEG-PDMAEMA block copolymers and one homopolymer was studied with dynamic light scattering and methylene blue displacement assay. Also in vitro binding in plasma was studied by utilizing a chromogenic heparin anti-Xa assay. Additionally, quartz crystal microbalance and multiparametric surface plasmon resonance were used to study the surface adsorption kinetics of the polymers on a heparin layer. It was shown that the block copolymers and heparin form electrostatically bound complexes with varying colloidal properties, where the block lengths play a key role in controlling the heparin binding affinity, polyelectrolyte complex size and surface charge. With the optimized polymers (PEG114PDMAEMA52 and PEG114PDMAEMA100), heparin could be neutralized in a dose-dependent manner, and bound efficiently into small neutral complexes, with a hydrodynamic radius less than 100 nm. These complexes had only a limited effect on cell viability. Based on these studies, our approach paves the way for the development of new polymeric heparin binding agents.

  6. Improvement in hemocompatibility of chitosan/soy protein composite membranes by heparinization.

    PubMed

    Wang, Xiaomei; Shi, Na; Chen, Yan; Li, Chen; Du, Xinshen; Jin, Weihua; Chen, Yun; Chang, Peter R

    2012-01-01

    To improve the hemocompatibility of chitosan/soy protein isolate composite membranes by heparinization. Chitosan/soy protein isolate membranes (ChS-n, n=0, 10 and 30, corresponding to the soy protein isolate content in the membranes) and heparinized ChS-n membranes (HChS-n) were prepared by blending in dilute HAc/NaAc solution. The hemocompatibility of ChS-n and HChS-n membranes were comparatively evaluated by measuring surface heparin density, blood platelet adhesion, plasma recalcification time (PRT), thrombus formation and hemolysis assay. The surface heparin density analysis showed that heparinized chitosan/SPI soy protein isolate membranes have been successfully prepared by blending. The density of heparin on the surface of HChS-n membranes was in the range of 0.67-1.29 μg/cm2. The results of platelet adhesion measurement showed that the platelet adhesion numbers of HChS-n membranes were lower than those of the corresponding ChS-n membranes. The PRT of the HChS-0, HChS-10 and HChS-30 membranes were around 292, 306 and 295 s, respectively, which were longer than the corresponding ChS-0 (152 s), ChS-10 (204 s) and ChS-30 (273 s) membranes. The hemolysis rate of HChS-n membranes was lower than 1%. The hemocompatibility of ChS membranes could be improved by blending with heparin. Compared with ChS membranes, HChS membranes showed lower platelet adhesion, longer PRT, higher BCI, significant thromboresistivity and a lower hemolysis rate due to the heparinization. This widens the application of chitosan and soy protein-based biomaterials that may come in contact with blood.

  7. Interactions between nattokinase and heparin/GAGs.

    PubMed

    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.

  8. Particle formation in SiOx film deposition by low frequency plasma enhanced chemical vapor deposition

    NASA Astrophysics Data System (ADS)

    Yamaguchi, Tomoyo; Sakamoto, Naoshi; Shimozuma, Mitsuo; Yoshino, Masaki; Tagashira, Hiroaki

    1998-01-01

    Dust particle formation dynamics in the process of SiOx film deposition from a SiH4 and N2O gas mixture by a low frequency plasma enhanced chemical vapor deposition have been investigated using scanning electron microscopy and laser light scattering. The deposited films are confirmed to be SiOx from the measurements of Auger electron spectroscopy, x-ray photoelectron spectroscopy, and Fourier transform infrared spectroscopy. It is observed by scanning electron microscopy that particles are deposited on Si substrate at the plasma power frequency f=5 kHz and above both with and without substrate heating (400 °C), while no particle is deposited below f=1 kHz. Moreover, the laser light scattering indicates that particles are generated at the plasma power frequency of f=3 kHz and above in the gas phase, and that they are not generated in the gas phase at below f=3 kHz. Properties (the refractive index, resistivity, and Vickers hardness) of the films with particles are inferior to those of the films without particles. This article has revealed experimentally the effect of plasma power frequency on SiOx particle formation and makes a contribution to the explication of the particle formation mechanism. We suggest that high-quality film deposition with the low frequency plasma enhanced chemical vapor deposition method is attained at f=1 kHz or less without substrate heating.

  9. Nebulized heparin is associated with fewer days of mechanical ventilation in critically ill patients: a randomized controlled trial.

    PubMed

    Dixon, Barry; Schultz, Marcus J; Smith, Roger; Fink, James B; Santamaria, John D; Campbell, Duncan J

    2010-01-01

    Prolonged mechanical ventilation has the potential to aggravate or initiate pulmonary inflammation and cause lung damage through fibrin deposition. Heparin may reduce pulmonary inflammation and fibrin deposition. We therefore assessed whether nebulized heparin improved lung function in patients expected to require prolonged mechanical ventilation. Fifty patients expected to require mechanical ventilation for more than 48 hours were enrolled in a double-blind randomized placebo-controlled trial of nebulized heparin (25,000 U) or placebo (normal saline) 4 or 6 hourly, depending on patient height. The study drug was continued while the patient remained ventilated to a maximum of 14 days from randomization. Nebulized heparin was not associated with a significant improvement in the primary end-point, the average daily partial pressure of oxygen to inspired fraction of oxygen ratio while mechanically ventilated, but was associated with improvement in the secondary end-point, ventilator-free days amongst survivors at day 28 (22.6 ± 4.0 versus 18.0 ± 7.1, treatment difference 4.6 days, 95% CI 0.9 to 8.3, P = 0.02). Heparin administration was not associated with any increase in adverse events. Nebulized heparin was associated with fewer days of mechanical ventilation in critically ill patients expected to require prolonged mechanical ventilation. Further trials are required to confirm these findings. The Australian Clinical Trials Registry (ACTR-12608000121369).

  10. Dual frequency diffuse dielectric barrier discharge in atmospheric-pressure air-like gas mixture for thin film deposition

    NASA Astrophysics Data System (ADS)

    Liu, Yaoge; Starostin, Serguei; Welzel, Stefan; van de Sanden, M. C. M.; de Vries, Hindrik; Fom Institute-Differ Team; Eindhoven University Of Technology Team; Fujifilm Manufacturing Europe B. v. Team

    2016-09-01

    A dual frequency (DF) diffuse discharge was obtained in an atmospheric-pressure dielectric barrier discharge reactor in air-like gas mixtures. By adding a radio frequency (RF) voltage to a low frequency (LF) voltage, we aim to increase the plasma power density. In this study, the discussion is mainly focused on the discharge characteristics and the thin film deposition. According to the spatio-temporal emission, the discharge shows a glow-like structure with both LF and DF voltages. By fitting the spectral lines of the second positive system of N2, the gas temperature was estimated which does not obviously increase with the extra RF signal. Moreover, SiO2-like film was deposited from TEOS using the DF power supply. Thin film properties such as surface morphology, microstructure and stoichiometry were analyzed by AFM, FTIR and XPS, respectively. Because of the higher plasma power density, the DF power supply can be an efficient approach to improve the properties and to increase the throughput of the thin film deposition.

  11. Spontaneous heparin-induced thrombocytopenia (HIT) syndrome: HIT without any heparin exposure.

    PubMed

    Miyata, Shigeki

    2016-01-01

    Heparin-induced thrombocytopenia (HIT) is a pro-thrombotic side effect of heparin therapy caused by HIT antibodies with platelet-activating properties. Recent advances in understanding of spontaneous HIT syndrome, which can occur even without any heparin exposure despite its clinical and serological characteristics being similar to those of HIT, reveal the following HIT clinical features atypical for an immune-mediated disease. Heparin-naïve patients can develop IgG antibodies as early as day 4, as in a secondary immune response. Evidence for an anamnestic response upon heparin re-exposure is lacking. In addition, HIT antibodies are relatively short-lived, unlike those in a secondary immune response. Antigen immunoassays are commonly used worldwide for serological diagnosis of HIT. However, such assays do not indicate whether HIT antibodies have platelet-activating properties, leading to low diagnostic specificity for HIT. The detection of platelet-activating antibodies using a washed platelet activation assay is crucial for making a HIT diagnosis. These atypical clinical and serological features should be carefully considered while appropriately diagnosing HIT, which leads to appropriate therapy such as immediate administration of an alternative anticoagulant for preventing thromboembolic events and re-administration of heparin during surgery involving cardiopulmonary bypass when HIT antibodies are no longer detectable.

  12. Molecular dynamics-based model of VEGF-A and its heparin interactions.

    PubMed

    Uciechowska-Kaczmarzyk, Urszula; Babik, Sándor; Zsila, Ferenc; Bojarski, Krzysztof Kamil; Beke-Somfai, Tamás; Samsonov, Sergey A

    2018-06-01

    We present a computational model of the Vascular Endothelial Growth Factor (VEGF), an important regulator of blood vessels formation, which function is affected by its heparin interactions. Although structures of a receptor binding (RBD) and a heparin binding domain (HBD) of VEGF are known, there are structural data neither on the 12 amino acids interdomain linker nor on its complexes with heparin. We apply molecular docking and molecular dynamics techniques combined with circular dichroism spectroscopy to model the full structure of the dimeric VEGF and to propose putative molecular mechanisms underlying the function of VEGF/VEGF receptors/heparin system. We show that both the conformational flexibility of the linker and the formation of HBD-heparin-HBD sandwich-like structures regulate the mutual disposition of HBDs and so affect the VEGF-mediated signalling. Copyright © 2018 Elsevier Inc. All rights reserved.

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

    PubMed

    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

  14. Transdermal delivery of heparin: Physical enhancement techniques.

    PubMed

    Ita, Kevin

    2015-12-30

    Thromboembolic complications are the most common preventable cause of mortality and morbidity in trauma patients. Thrombosis is also the common cause of ischemic heart disease (acute coronary syndrome), stroke, and venous thromboembolism. Heparin, as a potent anticoagulant, has been used in clinical practice for more than five decades and remains the major medicine for the prevention and treatment of venous thromboembolism. However it binds to the endothelium and has a high affinity for plasma proteins resulting in a short half-life and unpredictable bioavailability. Transdermal drug delivery can address the problems of short half-life and unpredictable bioavailability. Other advantages of transdermal drug delivery include convenience, improved patient compliance, prompt termination of dosing and avoidance of the first-pass effect. This review focuses on different approaches used for transdermal delivery of heparin. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Delivering heparin-binding insulin-like growth factor 1 with self-assembling peptide hydrogels.

    PubMed

    Florine, Emily M; Miller, Rachel E; Liebesny, Paul H; Mroszczyk, Keri A; Lee, Richard T; Patwari, Parth; Grodzinsky, Alan J

    2015-02-01

    Heparin-binding insulin-like growth factor 1 (HB-IGF-1) is a fusion protein of IGF-1 with the HB domain of heparin-binding epidermal growth factor-like growth factor. A single dose of HB-IGF-1 has been shown to bind specifically to cartilage and to promote sustained upregulation of proteoglycan synthesis in cartilage explants. Achieving strong integration between native cartilage and tissue-engineered cartilage remains challenging. We hypothesize that if a growth factor delivered by the tissue engineering scaffold could stimulate enhanced matrix synthesis by both the cells within the scaffold and the adjacent native cartilage, integration could be enhanced. In this work, we investigated methods for adsorbing HB-IGF-1 to self-assembling peptide hydrogels to deliver the growth factor to encapsulated chondrocytes and cartilage explants cultured with growth factor-loaded hydrogels. We tested multiple methods for adsorbing HB-IGF-1 in self-assembling peptide hydrogels, including adsorption prior to peptide assembly, following peptide assembly, and with/without heparan sulfate (HS, a potential linker between peptide molecules and HB-IGF-1). We found that HB-IGF-1 and HS were retained in the peptide for all tested conditions. A subset of these conditions was then studied for their ability to stimulate increased matrix production by gel-encapsulated chondrocytes and by chondrocytes within adjacent native cartilage. Adsorbing HB-IGF-1 or IGF-1 prior to peptide assembly was found to stimulate increased sulfated glycosaminoglycan per DNA and hydroxyproline content of chondrocyte-seeded hydrogels compared with basal controls at day 10. Cartilage explants cultured adjacent to functionalized hydrogels had increased proteoglycan synthesis at day 10 when HB-IGF-1 was adsorbed, but not IGF-1. We conclude that delivery of HB-IGF-1 to focal defects in cartilage using self-assembling peptide hydrogels is a promising technique that could aid cartilage repair via enhanced matrix

  16. Heparin-Binding Protein Measurement Improves the Prediction of Severe Infection With Organ Dysfunction in the Emergency Department

    PubMed Central

    Arnold, Ryan; Boyd, John H.; Zindovic, Marko; Zindovic, Igor; Lange, Anna; Paulsson, Magnus; Nyberg, Patrik; Russell, James A.; Pritchard, David; Christensson, Bertil; Åkesson, Per

    2015-01-01

    Objectives: Early identification of patients with infection and at risk of developing severe disease with organ dysfunction remains a difficult challenge. We aimed to evaluate and validate the heparin-binding protein, a neutrophil-derived mediator of vascular leakage, as a prognostic biomarker for risk of progression to severe sepsis with circulatory failure in a multicenter setting. Design: A prospective international multicenter cohort study. Setting: Seven different emergency departments in Sweden, Canada, and the United States. Patients: Adult patients with a suspected infection and at least one of three clinical systemic inflammatory response syndrome criteria (excluding leukocyte count). Intervention: None. Measurements and Main Results: Plasma levels of heparin-binding protein, procalcitonin, C-reactive protein, lactate, and leukocyte count were determined at admission and 12–24 hours after admission in 759 emergency department patients with suspected infection. Patients were defined depending on the presence of infection and organ dysfunction. Plasma samples from 104 emergency department patients with suspected sepsis collected at an independent center were used to validate the results. Of the 674 patients diagnosed with an infection, 487 did not have organ dysfunction at enrollment. Of these 487 patients, 141 (29%) developed organ dysfunction within the 72-hour study period; 78.0% of the latter patients had an elevated plasma heparin-binding protein level (> 30 ng/mL) prior to development of organ dysfunction (median, 10.5 hr). Compared with other biomarkers, heparin-binding protein was the best predictor of progression to organ dysfunction (area under the receiver operating characteristic curve = 0.80). The performance of heparin-binding protein was confirmed in the validation cohort. Conclusion: In patients presenting at the emergency department, heparin-binding protein is an early indicator of infection-related organ dysfunction and a strong predictor

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

    PubMed

    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.

  18. Heparin pharmacovigilance in Brazil.

    PubMed

    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.

  19. Interactions between nattokinase and heparin/GAGs

    PubMed Central

    Zhang, Fuming

    2015-01-01

    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 a 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. PMID:26412225

  20. Characterization of Diamond-like Carbon (DLC) films deposited by RF ICP PECVD method

    NASA Astrophysics Data System (ADS)

    Oleszkiewicz, Waldemar; Kijaszek, Wojciech; Gryglewicz, Jacek; Zakrzewski, Adrian; Gajewski, Krzysztof; Kopiec, Daniel; Kamyczek, Paulina; Popko, Ewa; Tłaczała, Marek

    2013-07-01

    The work presents the results of a research carried out with Plasmalab Plus 100 system, manufactured by Oxford Instruments Company. The system was configured for deposition of diamond-like carbon films by ICP PECVD method. The deposition processes were carried out in CH4 or CH4/H2 atmosphere and the state of the plasma was investigated by the OES method. The RF plasma was capacitively coupled by 13.56 MHz generator with supporting ICP generator (13.56 Mhz). The deposition processes were conducted in constant value of RF generator's power and resultant value of the DC Bias. The power values of RF generator was set at 70 W and the power values of ICP generator was set at 300 W. In this work we focus on the influence of DLC film's thickness on optical, electrical and structural properties of the deposited DLC films. The quality of deposited DLC layers was examined by the Raman spectroscopy, AFM microscopy and spectroscopic ellipsometry. In the investigated DLC films the calculated sp3 content was ranging from 60 % to 70 %. The films were characterized by the refractive index ranging from 2.03 to 2.1 and extinction coefficient ranging from 0.09 to 0.12.

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

    PubMed

    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

  2. Heparin: Past, Present, and Future.

    PubMed

    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.

  3. Optimizing the vacuum plasma spray deposition of metal, ceramic, and cermet coatings using designed experiments

    NASA Astrophysics Data System (ADS)

    Kingswell, R.; Scott, K. T.; Wassell, L. L.

    1993-06-01

    The vacuum plasma spray (VPS) deposition of metal, ceramic, and cermet coatings has been investigated using designed statistical experiments. Processing conditions that were considered likely to have a significant influence on the melting characteristics of the precursor powders and hence deposition efficiency were incorporated into full and fractional factorial experimental designs. The processing of an alumina powder was very sensitive to variations in the deposition conditions, particularly the injection velocity of the powder into the plasma flame, the plasma gas composition, and the power supplied to the gun. Using a combination of full and fractional factorial experimental designs, it was possible to rapidly identify the important spraying variables and adjust these to produce a deposition efficiency approaching 80 percent. The deposition of a nickel-base alloy metal powder was less sensitive to processing conditions. Generally, however, a high degree of particle melting was achieved for a wide range of spray conditions. Preliminary experiments performed using a tungsten carbide/cobalt cermet powder indicated that spray efficiency was not sensitive to deposition conditions. However, microstructural analysis revealed considerable variations in the degree of tungsten carbide dissolution. The structure and properties of the optimized coatings produced in the factorial experiments are also discussed.

  4. In vitro and in vivo characterization of a reversible synthetic heparin analog.

    PubMed

    Whelihan, Matthew F; Cooley, Brian; Xu, Yongmei; Pawlinski, Rafal; Liu, Jian; Key, Nigel S

    2016-02-01

    The global supply of unfractionated heparin (UFH) and all commercially available low molecular weight heparins (LMWH) remain dependent on animal sources, such as porcine intestine or bovine lung. Recent experience has shown that contamination of the supply chain (with over-sulfated chondroitin sulfates) can result in lethal toxicity. Fondaparinux is currently the only commercially available synthetic analog of heparin. We recently described a new class of chemoenzymatically synthesized heparin analogs. One of these compounds (S12-mer) is a dodecasaccharide consisting of an antithrombin-binding moiety with repeating units of IdoA2S-GlcNS6S and two 3-O-sulfate groups that confer the ability to bind protamine. We sought to further characterize this new compound in vitro using biochemical and global coagulation assays and in vivo using thrombosis and hemostasis assays. The anticoagulant activities of the Super 12-mer (S12-mer) and Enoxaparin in anti-factor Xa and plasma-based thrombin generation assays were roughly equivalent with a 50% reduction in peak thrombin generation occurring at approximately 325nM. When protamine was titrated against a fixed concentration of S12-mer in plasma or blood, the S12-mer displayed a significant restitution of thrombin generation and clot formation. In vivo, S12-mer inhibited venous thrombosis to a similar extent as Enoxaparin, with similar bleeding profiles. These data show that the S12-mer has almost identical efficacy to Enoxaparin in terms of FXa inhibition, while displaying significant reversibility with protamine. Taken together with the ability to ensure purity and homogeneity from batch to batch, the S12-mer is a promising new synthetic heparin analog with a potentially enhanced safety profile. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Comparison of Low-Molecular-Weight Heparins Prepared From Bovine Heparins With Enoxaparin.

    PubMed

    Liu, Xinyue; St Ange, Kalib; Fareed, Jawed; Hoppensteadt, Debra; Jeske, Walter; Kouta, Ahmed; Chi, Lianli; Jin, Caijuan; Jin, Yongsheng; Yao, Yiming; Linhardt, Robert J

    2017-09-01

    Heparin and its low-molecular-weight heparin (LMWH) derivatives are widely used clinical anticoagulants. These drugs are critical for the practice of medicine in applications including kidney dialysis, cardiopulmonary bypass, and in the management of venous thromboembolism. Currently, these drugs are derived from livestock, primarily porcine intestine. The worldwide dependence on a single animal species has made the supply chain for this critical drug quite fragile, leading to the search for other sources of these drugs, including bovine tissues such as bovine intestine or lung. A number of laboratories are currently examining the similarities and differences between heparins prepared from porcine and bovine tissues. The current study is designed to compare LMWH prepared from bovine heparins through chemical β-elimination, a process currently used to prepare the LMWH, enoxaparin, from porcine heparin. Using top-down, bottom-up, compositional analysis and bioassays, LMWHs, derived from bovine lung and intestine, are shown to closely resemble enoxaparin.

  6. Systematic Evaluation of the Use of Human Plasma and Serum for Mass-Spectrometry-Based Shotgun Proteomics.

    PubMed

    Lan, Jiayi; Núñez Galindo, Antonio; Doecke, James; Fowler, Christopher; Martins, Ralph N; Rainey-Smith, Stephanie R; Cominetti, Ornella; Dayon, Loïc

    2018-04-06

    Over the last two decades, EDTA-plasma has been used as the preferred sample matrix for human blood proteomic profiling. Serum has also been employed widely. Only a few studies have assessed the difference and relevance of the proteome profiles obtained from plasma samples, such as EDTA-plasma or lithium-heparin-plasma, and serum. A more complete evaluation of the use of EDTA-plasma, heparin-plasma, and serum would greatly expand the comprehensiveness of shotgun proteomics of blood samples. In this study, we evaluated the use of heparin-plasma with respect to EDTA-plasma and serum to profile blood proteomes using a scalable automated proteomic pipeline (ASAP 2 ). The use of plasma and serum for mass-spectrometry-based shotgun proteomics was first tested with commercial pooled samples. The proteome coverage consistency and the quantitative performance were compared. Furthermore, protein measurements in EDTA-plasma and heparin-plasma samples were comparatively studied using matched sample pairs from 20 individuals from the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study. We identified 442 proteins in common between EDTA-plasma and heparin-plasma samples. Overall agreement of the relative protein quantification between the sample pairs demonstrated that shotgun proteomics using workflows such as the ASAP 2 is suitable in analyzing heparin-plasma and that such sample type may be considered in large-scale clinical research studies. Moreover, the partial proteome coverage overlaps (e.g., ∼70%) showed that measures from heparin-plasma could be complementary to those obtained from EDTA-plasma.

  7. Plasma spraying method for forming diamond and diamond-like coatings

    DOEpatents

    Holcombe, C.E.; Seals, R.D.; Price, R.E.

    1997-06-03

    A method and composition is disclosed for the deposition of a thick layer of diamond or diamond-like material. The method includes high temperature processing wherein a selected composition including at least glassy carbon is heated in a direct current plasma arc device to a selected temperature above the softening point, in an inert atmosphere, and is propelled to quickly quenched on a selected substrate. The softened or molten composition crystallizes on the substrate to form a thick deposition layer comprising at least a diamond or diamond-like material. The selected composition includes at least glassy carbon as a primary constituent and may include at least one secondary constituent. Preferably, the secondary constituents are selected from the group consisting of at least diamond powder, boron carbide (B{sub 4}C) powder and mixtures thereof. 9 figs.

  8. Plasma spraying method for forming diamond and diamond-like coatings

    DOEpatents

    Holcombe, Cressie E.; Seals, Roland D.; Price, R. Eugene

    1997-01-01

    A method and composition for the deposition of a thick layer (10) of diamond or diamond-like material. The method includes high temperature processing wherein a selected composition (12) including at least glassy carbon is heated in a direct current plasma arc device to a selected temperature above the softening point, in an inert atmosphere, and is propelled to quickly quenched on a selected substrate (20). The softened or molten composition (18) crystallizes on the substrate (20) to form a thick deposition layer (10) comprising at least a diamond or diamond-like material. The selected composition (12) includes at least glassy carbon as a primary constituent (14) and may include at least one secondary constituent (16). Preferably, the secondary constituents (16) are selected from the group consisting of at least diamond powder, boron carbide (B.sub.4 C) powder and mixtures thereof.

  9. Spontaneous heparin-induced thrombocytopenia presenting as bilateral adrenal hemorrhages and pulmonary embolism after total knee arthroplasty.

    PubMed

    Elshoury, Amro; Khedr, Maha; Abousayed, Mostafa M; Mehdi, Syed

    2015-09-01

    Heparin-induced thrombocytopenia syndrome is an acquired potentially life-threatening prothrombotic disorder caused by antibodies that recognize complexes of platelet factor 4 bound to heparin or heparin-like molecules. It typically occurs after exposure to unfractionated heparin, to a lesser extent after exposure to low-molecular-weight heparins, and rarely after exposure to fondaparinux. Herein, we report the case of a 48-year-old woman who developed severe thrombocytopenia, bilateral pulmonary embolism, and bilateral adrenal hemorrhages after total knee arthroplasty without evidence of heparin exposure. Antibodies to the heparin-platelet factor 4 complex and serotonin-release assay were positive. Spontaneous heparin-induced thrombocytopenia syndrome should be considered in patients with unexplained thrombocytopenia after knee replacement surgery even without heparin exposure, and a high index of suspicion for adrenal hemorrhage is needed in patients with fever, abdominal pain, and shock.

  10. Energy deposition of heavy ions in the regime of strong beam-plasma correlations.

    PubMed

    Gericke, D O; Schlanges, M

    2003-03-01

    The energy loss of highly charged ions in dense plasmas is investigated. The applied model includes strong beam-plasma correlation via a quantum T-matrix treatment of the cross sections. Dynamic screening effects are modeled by using a Debye-like potential with a velocity dependent screening length that guarantees the known low and high beam velocity limits. It is shown that this phenomenological model is in good agreement with simulation data up to very high beam-plasma coupling. An analysis of the stopping process shows considerably longer ranges and a less localized energy deposition if strong coupling is treated properly.

  11. Diamond deposition using a planar radio frequency inductively coupled plasma

    NASA Astrophysics Data System (ADS)

    Bozeman, S. P.; Tucker, D. A.; Stoner, B. R.; Glass, J. T.; Hooke, W. M.

    1995-06-01

    A planar radio frequency inductively coupled plasma has been used to deposit diamond onto scratched silicon. This plasma source has been developed recently for use in large area semiconductor processing and holds promise as a method for scale up of diamond growth reactors. Deposition occurs in an annulus which coincides with the area of most intense optical emission from the plasma. Well-faceted diamond particles are produced when the substrate is immersed in the plasma.

  12. The anticoagulant effect of heparin during radiofrequency ablation (RFA) in patients taking apixaban or rivaroxaban.

    PubMed

    Brendel, L C; Dobler, F; Hessling, G; Michel, J; Braun, S L; Steinsiek, A L; Groha, P; Eckl, R; Deisenhofer, I; Hyseni, A; Roest, M; Ott, I; Steppich, B

    2017-09-01

    Measuring the anticoagulant effect of heparin during radiofrequency ablation (RFA) in patients taking apixaban and rivaroxaban is challenging, since the activated coagulation time (ACT) does not seem to reflect the true anticoagulant activity of these drugs. We therefore evaluated coagulation properties of apixaban and rivaroxaban during RFA by different coagulation assays to better monitor periprocedural hemostasis. The study included 90 patients (61 ± 12 years) with atrial fibrillation who underwent RFA procedures. Patients received 20 mg rivaroxaban (n = 73) once or 5 mg apixaban (n = 17) twice daily 4 weeks prior to the procedure. During RFA, unfractionated heparin i.v. was given to maintain an ACT of 250-300 s. Blood samples were taken before and 10, 60, and 360 min after heparin administration. Heparin displayed a lower anti-Xa activity in rivaroxaban-treated patients compared to apixaban-treated patients. In contrast, D-dimer and prothrombin fragment F1+2 plasma levels indicated a higher activation of the coagulation cascade in apixaban/heparin than in rivaroxaban/heparin patients. This discordant coagulative state measured in vitro had no clinical impact in terms of bleeding or thromboembolic complications. We found different biochemical responses to rivaroxaban/heparin and apixaban/heparin during RFA. Precaution is necessary when monitoring periprocedural hemostasis in DOAC patients to avoid mismanagement.

  13. Plasma deposited diamondlike carbon on GaAs and InP

    NASA Technical Reports Server (NTRS)

    Warner, J. D.; Pouch, J. J.; Alterovitz, S. A.; Liu, D. C.; Lanford, W. A.

    1984-01-01

    The properties of diamond like carbon films grown by RF flow discharge 30 kHz plasma using methane are reported. The Cls XPS line shape of films showed localized hybrid carbon bonds as low as 40 to as high as 95 percent. Infrared spectroscopy and N(15) nuclear reaction profiling data indicated 35 to 42 percent hydrogen, depending inversely on deposition temperature. The deposition rate of films on Si falls off exponentially with substrate temperature, and nucleation does not occur above 200 C on GaAs and InP. Optical data of the films showed bandgap values of 2.0 to 2.4 eV increasing monotonically with CH4 flow rate.

  14. Inhibition of Crystal Growth during Plasma Enhanced Atomic Layer Deposition by Applying BIAS

    PubMed Central

    Ratzsch, Stephan; Kley, Ernst-Bernhard; Tünnermann, Andreas; Szeghalmi, Adriana

    2015-01-01

    In this study, the influence of direct current (DC) biasing on the growth of titanium dioxide (TiO2) layers and their nucleation behavior has been investigated. Titania films were prepared by plasma enhanced atomic layer deposition (PEALD) using Ti(OiPr)4 as metal organic precursor. Oxygen plasma, provided by remote inductively coupled plasma, was used as an oxygen source. The TiO2 films were deposited with and without DC biasing. A strong dependence of the applied voltage on the formation of crystallites in the TiO2 layer is shown. These crystallites form spherical hillocks on the surface which causes high surface roughness. By applying a higher voltage than the plasma potential no hillock appears on the surface. Based on these results, it seems likely, that ions are responsible for the nucleation and hillock growth. Hence, the hillock formation can be controlled by controlling the ion energy and ion flux. The growth per cycle remains unchanged, whereas the refractive index slightly decreases in the absence of energetic oxygen ions. PMID:28793679

  15. Shaping thin film growth and microstructure pathways via plasma and deposition energy: a detailed theoretical, computational and experimental analysis.

    PubMed

    Sahu, Bibhuti Bhusan; Han, Jeon Geon; Kersten, Holger

    2017-02-15

    Understanding the science and engineering of thin films using plasma assisted deposition methods with controlled growth and microstructure is a key issue in modern nanotechnology, impacting both fundamental research and technological applications. Different plasma parameters like electrons, ions, radical species and neutrals play a critical role in nucleation and growth and the corresponding film microstructure as well as plasma-induced surface chemistry. The film microstructure is also closely associated with deposition energy which is controlled by electrons, ions, radical species and activated neutrals. The integrated studies on the fundamental physical properties that govern the plasmas seek to determine their structure and modification capabilities under specific experimental conditions. There is a requirement for identification, determination, and quantification of the surface activity of the species in the plasma. Here, we report a detailed study of hydrogenated amorphous and crystalline silicon (c-Si:H) processes to investigate the evolution of plasma parameters using a theoretical model. The deposition processes undertaken using a plasma enhanced chemical vapor deposition method are characterized by a reactive mixture of hydrogen and silane. Later, various contributions of energy fluxes on the substrate are considered and modeled to investigate their role in the growth of the microstructure of the deposited film. Numerous plasma diagnostic tools are used to compare the experimental data with the theoretical results. The film growth and microstructure are evaluated in light of deposition energy flux under different operating conditions.

  16. Deposition of hard and adherent diamond-like carbon films inside steel tubes using a pulsed-DC discharge.

    PubMed

    Trava-Airoldi, Vladimir Jesus; Capote, Gil; Bonetti, Luís Francisco; Fernandes, Jesum; Blando, Eduardo; Hübler, Roberto; Radi, Polyana Alves; Santos, Lúcia Vieira; Corat, Evaldo José

    2009-06-01

    A new, low cost, pulsed-DC plasma-enhanced chemical vapor deposition system that uses a bipolar, pulsed power supply was designed and tested to evaluate its capacity to produce quality diamond-like carbon films on the inner surface of steel tubes. The main focus of the study was to attain films with low friction coefficients, low total stress, a high degree of hardness, and very good adherence to the inner surface of long metallic tubes at a reasonable growth rate. In order to enhance the diamond-like carbon coating adhesion to metallic surfaces, four steps were used: (1) argon ion sputtering; (2) plasma nitriding; (3) a thin amorphous silicon interlayer deposition, using silane as the precursor gas; and (4) diamond-like carbon film deposition using methane atmosphere. This paper presents various test results as functions of the methane gas pressure and of the coaxial metal anode diameter, where the pulsed-DC voltage constant is kept constant. The influence of the coaxial metal anode diameter and of the methane gas pressure is also demonstrated. The results obtained showed the possibilities of using these DLC coatings for reduced friction and to harden inner surface of the steel tubes.

  17. Radio frequency and microwave plasma for optical thin-film deposition

    NASA Astrophysics Data System (ADS)

    Otto, Juergen; Paquet, Volker; Kersten, Ralf T.; Etzkorn, Heinz-Werner; Brusasco, Raymond M.; Britten, Jerald A.; Campbell, Jack H.; Thorsness, J. B.

    1990-12-01

    For the next generation of fusion lasers reflecting mirrors with laser damage thresholds of at least 40 J/cm2 for 1 0 ns laser pulses at 1 .064 pm are needed. Up to now, no deposition technique has been developed to produce such mirrors. Best R&D-values realized today are around 30 J/cm2 for e-beam evaporated mirrors. R&D on conventional e-beam coating processes over the last 1 0 years has come up with marginal improvements in laser damage thresholds only. However, new technologies, like PICVD (Plasma-Impulse CVD) developed for the fabrication of ultra-low loss fiber preforms, seem to offer the potential to solve this problem. First results have been reported already [1-3]. It is well known that fused silica produced by CVD processes can have laser damage thresholds as high as 80 J/cm2. However, the thickness of a single deposited film is in the pm-range for most of the CVD-processes used for preform manufacturing; since interference optics need films in the ; /4n range (where n is the refractive index of the dielectric material) the use of preform-fabrication processes for the purpose of interference mirror fabrication is limited to a few plasma based CVD technologies, namely PCVD (Plasma-CVD, Philips [4]; PICVD, SCHOTT [5]). Especially PICVD is a very powerful technology to fabricate thin film multilayers for interference mirrors, because this technique is able to produce films down to monolayer thickness with nearly perfect stoichiometry and morphology. In first and preliminary experiments the usual deposition in a circular tube at high temperatures has been used for simplicity. However, to produce large area high quality laser mirrors this principle know-how has to be transfered from circular to planar geometry. Experiments showed, that there may be some limitations with respect to the homogeneity of a planar deposition using microwave excitation for the plasma. Therefore experiments have been performed in parallel with both RF and microwave excitation for

  18. Structural Characterization of the E2 Domain of APL-1, a C. Elegans Homolog of Human Amyloid Precursor Protein, and its Heparin Binding Site

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

    Hoopes, J.; Liu, X; Xu, X

    2010-01-01

    The amyloid {beta}-peptide deposit found in the brain tissue of patients with Alzheimer disease is derived from a large heparin-binding protein precursor APP. The biological function of APP and its homologs is not precisely known. Here we report the x-ray structure of the E2 domain of APL-1, an APP homolog in Caenorhabditis elegans, and compare it to the human APP structure. We also describe the structure of APL-1 E2 in complex with sucrose octasulfate, a highly negatively charged disaccharide, which reveals an unexpected binding pocket between the two halves of E2. Based on the crystal structure, we are able tomore » map, using site-directed mutagenesis, a surface groove on E2 to which heparin may bind. Our biochemical data also indicate that the affinity of E2 for heparin is influenced by pH: at pH 5, the binding appears to be much stronger than that at neutral pH. This property is likely caused by histidine residues in the vicinity of the mapped heparin binding site and could be important for the proposed adhesive function of APL-1.« less

  19. Analysis and characterization of heparin impurities.

    PubMed

    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.

  20. Cellular immune responses to platelet factor 4 and heparin complexes in patients with heparin-induced thrombocytopenia.

    PubMed

    Nazy, Ishac; Clare, Rumi; Staibano, Phillip; Warkentin, Theodore E; Larche, Mark; Moore, Jane C; Smith, James W; Whitlock, Richard P; Kelton, John G; Arnold, Donald M

    2018-05-03

    Heparin-induced thrombocytopenia (HIT) is an adverse reaction to heparin characterized by thrombocytopenia and thrombotic complications. HIT is caused by pathogenic antibodies that bind to complexes of platelet factor 4 and heparin (PF4/heparin) leading to platelet activation and inducing a hypercoagulable state. Previous studies have shown immunity to PF4/heparin occurs early in life even before heparin exposure; however, the immunogenesis of HIT is not well characterized. The aim of this study was to investigate cellular proliferation in response to PF4/heparin complexes in patients with HIT. Peripheral blood mononuclear cells (PBMCs) from healthy controls (n = 30), postoperative cardiac surgery patients who underwent cardiopulmonary bypass (CPB, n = 17), and patients with confirmed HIT (n = 41) were cultured with PF4 and PF4/heparin. Cellular proliferation was assessed by 3 H-thymidine uptake and 5-ethynyl-2'-deoxyuridine (EdU) detection. PBMCs proliferated in the presence of PF4 and was enhanced by the addition of heparin in all study groups. CPB and HIT patients exhibited significantly higher proliferative responses compared to healthy controls. PBMC proliferation was antigen-specific, depended on the presence of platelets, and only CD14 + cells were identified as proliferating cells. Culture supernatants were tested for the levels of regulatory cytokines and both CPB and HIT patients produced significantly lower levels of IL-10 and TGF-β1 compared to healthy controls. These findings further demonstrate that cellular immune sensitization to PF4/heparin occurs before heparin exposure and suggests that immune dysregulation can contribute to the immunogenesis of HIT. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  1. Heparin Resistance and Anticoagulation Failure in a Challenging Case of Cerebral Venous Sinus Thrombosis.

    PubMed

    King, Adam B; O'Duffy, Anne E; Kumar, Avinash B

    2016-07-01

    We report a challenging case of cerebral venous sinus thrombosis (multiple etiologic factors) that was complicated by heparin resistance secondary to suspected antithrombin III (ATIII) deficiency. A 20-year-old female previously healthy and currently 8 weeks pregnant presented with worsening headaches, nausea, and decreasing Glasgow Coma Scale/Score (GCS), necessitating mechanical ventilatory support. Imaging showed extensive clots in multiple cerebral venous sinuses including the superior sagittal sinus, transverse, sigmoid, jugular veins, and the straight sinus. She was started on systemic anticoagulation and underwent mechanical clot removal and catheter-directed endovascular thrombolysis with limited success. Complicating the intensive care unit care was the development of heparin resistance, with an inability to reach the target partial thomboplastin time (PTT) of 60 to 80 seconds. At her peak heparin dose, she was receiving >35 000 units/24 h, and her PTT was subtherapeutic at <50 seconds. Deficiency of ATIII was suspected as a possible etiology of her heparin resistance. Fresh frozen plasma was administered for ATIII level repletion. Given her high thrombogenic risk and challenges with conventional anticoagulation regimens, we transitioned to argatroban for systemic anticoagulation. Heparin produces its major anticoagulant effect by inactivating thrombin and factor X through an AT-dependent mechanism. For inhibition of thrombin, heparin must bind to both the coagulation enzyme and the AT. A deficiency of AT leads to a hypercoagulable state and decreased efficacy of heparin that places patients at high risk of thromboembolism. Heparin resistance, especially in the setting of critical illness, should raise the index of suspicion for AT deficiency. Argatroban is an alternate agent for systemic anticoagulation in the setting of heparin resistance.

  2. [Influence of deposition time on chromatics during nitrogen-doped diamond like carbon coating on pure titanium].

    PubMed

    Yin, Lu; Yao, Jiang-wu; Xu, De-wen

    2010-10-01

    The aim of this study was to observed the influence of deposition time on chromatics during nitrogen-doped diamond like carbon coating (N-DLC) on pure titanium by multi impulse are plasma plating machine. Applying multi impulse are plasma plating machine to produce TiN coatings on pure titanium in nitrogen atmosphere, then filming with nitrogen-doped DLC on TiN in methane (10-80 min in every 5 min). The colors of N-DLC were evaluated in the CIE1976 L*a*b* uniform color scale and Mussell notation. The surface morphology of every specimen was analyzed using scanning electron microscope (SEM) and X-ray photoelectron spectroscopy (XPS). When changing the time of N-DLC coating deposition, N-DLC surface showed different color. Golden yellow was presented when deposition time was 30 min. SEM showed that crystallization was found in N-DLC coatings, the structure changed from stable to clutter by varying the deposition time. The chromatics of N-DLC coatings on pure titanium could get golden yellow when deposition time was 30 min, then the crystallized structure was stable.

  3. 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.

    PubMed

    Laville, Maurice; Dorval, Marc; Fort Ros, Joan; Fay, Renaud; Cridlig, Joëlle; Nortier, Joëlle L; Juillard, Laurent; Dębska-Ślizień, Alicja; Fernández Lorente, Loreto; Thibaudin, Damien; Franssen, Casper; Schulz, Michael; Moureau, Frédérique; Loughraieb, Nathalie; Rossignol, Patrick

    2014-12-01

    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 non-inferiority of a heparin grafted dialyzer (NCT01318486). A total of 251 maintenance hemodialysis patients at increased risk of hemorrhage were randomly allocated for up to three heparin-free hemodialysis sessions using a heparin-grafted dialyzer or the center standard-of-care consisting of regular saline flushes or pre-dilution. The first heparin-free hemodialysis session was considered successful when there was neither complete occlusion of air traps or dialyzer, nor additional saline flushes, changes of dialyzer or bloodlines, or premature termination. The current standard-of-care resulted in high failure rates (50%). The success rate in the heparin-grafted membrane arm was significantly higher than in the control group (68.5% versus 50.4%), which was consistent for both standard-of-care modalities. The absolute difference between the heparin-grafted membrane and the controls was 18.2%, with a lower bound of the 90% confidence interval equal to plus 7.9%. The hypothesis of the non-inferiority at the minus 15% level was accepted, although superiority at the plus 15% level was not reached. Thus, use of a heparin-grafted membrane is a safe, helpful, and easy-to-use method for heparin-free hemodialysis in patients at increased risk of hemorrhage.

  4. Enhancement of trophoblast differentiation and survival by low molecular weight heparin requires heparin-binding EGF-like growth factor.

    PubMed

    Bolnick, Alan D; Bolnick, Jay M; Kohan-Ghadr, Hamid-Reza; Kilburn, Brian A; Pasalodos, Omar J; Singhal, Pankaj K; Dai, Jing; Diamond, Michael P; Armant, D Randall; Drewlo, Sascha

    2017-06-01

    Does low molecular weight heparin (LMWH) require heparin-binding epidermal growth factor (EGF)-like growth factor (HBEGF) signaling to induce extravillous trophoblast differentiation and decrease apoptosis during oxidative stress? LMWH increased HBEGF expression and secretion, and HBEGF signaling was required to stimulate trophoblast extravillous differentiation, increase invasion in vitro and reduce trophoblast apoptosis during oxidative stress. Abnormal trophoblast differentiation and survival contribute to placental insufficiency syndromes, including preeclampsia and intrauterine growth restriction. Preeclampsia often manifests as a pro-thrombotic state, with unsuccessful transformation of the spiral arteries that reduces oxygen supply and can produce placental infarction. LMWH improves placental function by increasing blood flow. Recent data suggest that the actions of LMWH transcend its anti-coagulative properties, but the molecular mechanism is unknown. There is evidence that LMWH alters the expression of human HBEGF in trophoblast cells, which regulates human trophoblast pathophysiology. HBEGF, itself, is capable of increasing trophoblast survival and invasiveness. First-trimester placental explants and the HTR-8/SVneo cell line, established using extravillous trophoblast outgrowths from first-trimester villous explants, were treated in vitro with LMWH to examine the effects on HBEGF signaling and trophoblast function under normal physiological and pathological conditions. A highly specific antagonist of HBEGF and other inhibitors of HBEGF downstream signaling were used to determine the relationship between LMWH treatment and HBEGF. Placental tissues (n = 5) were obtained with IRB approval and patient consent from first-trimester terminations. Placental explants and HTR-8/SVneo cells were cultured on plastic or Matrigel™ and treated with a therapeutic dose of LMWH (Enoxaparin; 10 IU/ml), with or without CRM197, pan Erb-B2 Receptor Tyrosine Kinase (ERBB

  5. Effect of switching unfractionated heparin to low-molecular-weight heparin on serum potassium in hemodialysis patients.

    PubMed

    Ezzatzadegan Jahromi, Shahrokh; Mahmoodi, Mohammad Saleh; Behroozi, Fatemeh; Roozbeh, Jamshid; Emamghoreishi, Fatemeh

    2014-11-01

    Unfractionated (UF) heparin is the most common anticoagulant used during hemodialysis. Failure of the kidneys to excrete potassium as well as heparin-induced reduction of aldosterone synthesis put hemodialysis patients at risk of hyperkalemia. It has not yet been clearly known whether hyperkalemia is also induced by low-molecular-weight (LMW) heparins. This study aimed to evaluate the effect of switching UF heparin to LMW heparin enoxaparin, as an anticoagulant during hemodialysis, on serum potassium level in patients on hemodialysis. In two hemodialysis units, 58 patients were randomly assigned into two groups, to receive two different anticoagulation protocols for 3 weeks; one group continued to receive their routine dose of UF heparin, 5000 units, and the other received enoxaparin, 0.5 mg/kg, at the beginning of each hemodialysis session. While there was no significant difference between baseline blood measurements of the two groups in terms of kidney function tests and electrolytes, following 3 weeks of the study, the mean serum potassium level decreased from 4.9 ± 0.8 mEq/L to 4.5 ± 0.5 mEq/L in the LMW heparin group (P = .001); however, there was no change in the mean serum potassium level in those who continued to receive their usual dose of UF heparin. In a subgroup analysis, diabetic patients in the enoxaparin group did not experience significant reduction in serum potassium levels. Our study revealed the role of LMW heparins as a potential alternative to UF heparins in the hemodialysis patients with hyperkalemia.

  6. Plasma deposited rider rings for hot displacer

    DOEpatents

    Kroebig, Helmut L.

    1976-01-01

    A hot cylinder for a cryogenic refrigerator having two plasma spray deposited rider rings of a corrosion and abrasion resistant material provided in the rider ring grooves, wherein the rider rings are machined to the desired diameter and width after deposition. The rider rings have gas flow flats machined on their outer surface.

  7. Erosion and deposition in the JET divertor during the second ITER-like wall campaign

    NASA Astrophysics Data System (ADS)

    Mayer, M.; Krat, S.; Baron-Wiechec, A.; Gasparyan, Yu; Heinola, K.; Koivuranta, S.; Likonen, J.; Ruset, C.; de Saint-Aubin, G.; Widdowson, A.; Contributors, JET

    2017-12-01

    Erosion of plasma-facing materials and successive transport and redeposition of eroded material are crucial processes determining the lifetime of plasma-facing components and the trapped tritium inventory in redeposited material layers. Erosion and deposition in the JET divertor were studied during the second JET ITER-like wall campaign ILW-2 in 2013-2014 by using a poloidal row of specially prepared divertor marker tiles including the tungsten bulk tile 5. The marker tiles were analyzed using elastic backscattering with 3-4.5 MeV incident protons and nuclear reaction analysis using 0.8-4.5 MeV 3He ions before and after the campaign. The erosion/deposition pattern observed during ILW-2 is qualitatively comparable to the first campaign ILW-1 in 2011-2012: deposits consist mainly of beryllium with 5-20 at.% of carbon and oxygen and small amounts of Ni and W. The highest deposition with deposited layer thicknesses up to 30 μm per campaign is still observed on the upper and horizontal parts of the inner divertor. Outer divertor tiles 5, 6, 7 and 8 are net W erosion areas. The observed D inventory is roughly comparable to the inventory observed during ILW-1. The results obtained during ILW-2 therefore confirm the positive results observed in ILW-1 with respect to reduced material deposition and hydrogen isotopes retention in the divertor.

  8. Heparin-induced thrombocytopenia: real-world issues.

    PubMed

    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.

  9. Method For Plasma Source Ion Implantation And Deposition For Cylindrical Surfaces

    DOEpatents

    Fetherston, Robert P. , Shamim, Muhammad M. , Conrad, John R.

    1997-12-02

    Uniform ion implantation and deposition onto cylindrical surfaces is achieved by placing a cylindrical electrode in coaxial and conformal relation to the target surface. For implantation and deposition of an inner bore surface the electrode is placed inside the target. For implantation and deposition on an outer cylindrical surface the electrode is placed around the outside of the target. A plasma is generated between the electrode and the target cylindrical surface. Applying a pulse of high voltage to the target causes ions from the plasma to be driven onto the cylindrical target surface. The plasma contained in the space between the target and the electrode is uniform, resulting in a uniform implantation or deposition of the target surface. Since the plasma is largely contained in the space between the target and the electrode, contamination of the vacuum chamber enclosing the target and electrodes by inadvertent ion deposition is reduced. The coaxial alignment of the target and the electrode may be employed for the ion assisted deposition of sputtered metals onto the target, resulting in a uniform coating of the cylindrical target surface by the sputtered material. The independently generated and contained plasmas associated with each cylindrical target/electrode pair allows for effective batch processing of multiple cylindrical targets within a single vacuum chamber, resulting in both uniform implantation or deposition, and reduced contamination of one target by adjacent target/electrode pairs.

  10. Synthetic heparin-binding factor analogs

    DOEpatents

    Pena, Louis A [Poquott, NY; Zamora, Paul O [Gaithersburg, MD; Lin, Xinhua [Plainview, NY; Glass, John D [Shoreham, NY

    2010-04-20

    The invention provides synthetic heparin-binding growth factor analogs having at least one peptide chain, and preferably two peptide chains branched from a dipeptide branch moiety composed of two trifunctional amino acid residues, which peptide chain or chains bind a heparin-binding growth factor receptor and are covalently bound to a non-signaling peptide that includes a heparin-binding domain, preferably by a linker, which may be a hydrophobic linker. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

  11. Adaption of a microwave plasma source for low temperature diamond deposition

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

    Ulczynski, M.; Reinhard, D.K.; Asmussen, J.

    1996-12-31

    This report describes the adaption of a microwave plasma reactor for low temperature diamond deposition. The reactor is of a resonant cavity design. Three approaches have been taken to establish plasma conditions for diamond deposition on substrates which are in the range of 450 C to 550 C. In the first, the substrate is heated only by the plasma and the source is operated at pressures on the order of 10 torr, such that the volumetric power density is sufficiently low to achieve these temperatures. In the second, the plasma pressure and microwave input power were reduced and a substratemore » heater was used to maintain the desired deposition temperatures. In the third approach, the plasma pressure and microwave power were increased and a substrate cooler was used to keep the substrate temperature in the desired range. Reactor performance and deposition results will be described for the three configurations. For the plasma heated substrate assembly, substrate dimensions were up to 10 cm diameter. For the heated and cooled substrate assemblies, substrate dimensions were up to 7.5 cm diameter. Deposition results on a variety of substrates will be reported including low-temperature substrates such as borosilicate glass.« less

  12. Characteristics of Diamond-Like Carbon Films Deposited on Polymer Dental Materials

    NASA Astrophysics Data System (ADS)

    Ohtake, Naoto; Uchi, Tomio; Yasuhara, Toshiyuki; Takashima, Mai

    2012-09-01

    Characterizations of diamond-like carbon (DLC) deposited on a polymer artificial tooth were performed. DLC films were deposited on dental parts made of poly(methyl methacrylate) (PMMA) resin by dc-pulse plasma chemical vapor deposition (CVD) from methane. Wear resistance test results revealed that a DLC-coated resin tooth has a very high wear resistance against tooth brushing, and endures 24 h brushing without a marked weight decrease. Cell cultivation test results show that DLC plays an important role in preventing cell death. Moreover, a biocompatibility test using a rabbit revealed that a connective tissue in the vicinity of DLC-coated PMMA is significantly thinner than that of noncoated PMMA. The numbers of inflammatory cells in the vicinity of DLC-coated and noncoated surfaces are 0 and 508 cells/mm2, respectively. These results led us to conclude that DLC films are an excellent material for use as the coating of a polymer artificial tooth in terms of not only high wear resistance but also biocompatibility.

  13. Binding affinities of vascular endothelial growth factor (VEGF) for heparin-derived oligosaccharides

    PubMed Central

    Zhao, Wenjing; McCallum, Scott A.; Xiao, Zhongping; Zhang, Fuming; Linhardt, Robert J.

    2011-01-01

    Heparin and heparan sulphate (HS) exert their wide range of biological activities by interacting with extracellular protein ligands. Among these important protein ligands are various angiogenic growth factors and cytokines. HS-binding to vascular endothelial growth factor (VEGF) regulates multiple aspects of vascular development and function through its specific interaction with HS. Many studies have focused on HS-derived or HS-mimicking structures for the characterization of VEGF165 interaction with HS. Using a heparinase 1-prepared small library of heparin-derived oligosaccharides ranging from hexasaccharide to octadecasaccharide, we systematically investigated the heparin-specific structural features required for VEGF binding. We report the apparent affinities for the association between the heparin-derived oligosaccharides with both VEGF165 and VEGF55, a peptide construct encompassing exclusively the heparin-binding domain of VEGF165. An octasaccharide was the minimum size of oligosaccharide within the library to efficiently bind to both forms of VEGF and that a tetradecasaccharide displayed an effective binding affinity to VEGF165 comparable to unfractionated heparin. The range of relative apparent binding affinities among VEGF and the panel of heparin-derived oligosaccharides demonstrate that VEGF binding affinity likely depends on the specific structural features of these oligosaccharides including their degree of sulphation and sugar ring stereochemistry and conformation. Notably, the unique 3-O-sulpho group found within the specific antithrombin binding site of heparin is not required for VEGF165 binding. These findings afford new insight into the inherent kinetics and affinities for VEGF association with heparin and heparin-derived oligosaccharides with key residue specific modifications and may potentially benefit the future design of oligosaccharide-based anti-angiogenesis drugs. PMID:21658003

  14. Effect of heparin bonding on catheter-induced fibrin formation and platelet activation.

    PubMed

    Nichols, A B; Owen, J; Grossman, B A; Marcella, J J; Fleisher, L N; Lee, M M

    1984-11-01

    Pathologic and experimental evidence indicates that platelet activation and fibrin formation contribute to the pathogenesis of angina pectoris, coronary vasospasm and myocardial infarction. Detection of localized intravascular platelet activation and fibrin formation in vivo by selective blood sampling requires catheters that do not induce coagulation ex vivo. We studied the effect of heparin bonding of catheter surfaces on activation of the coagulation system by cardiovascular catheters. Woven Dacron, polyvinylchloride, and polyurethane catheters were tested and compared with identical catheters with heparin-bonded surfaces in 47 patients undergoing percutaneous cardiac catheterization. Platelet activation was measured by radioimmunoassay of plasma platelet factor 4 (PF4), beta-thromboglobulin (BTG), and thromboxane B2 (TXB2) in blood samples withdrawn through catheters, and fibrin formation was assessed by determination of fibrinopeptide A (FPA) levels. In blood samples collected through conventional catheters, FPA, PF4, BTG, and TXB2 levels were markedly elevated; blood sampling through heparin-bonded catheters had no significant effect on FPA, PF4, BTG, or TXB2 levels. Scanning electron microscopy disclosed extensive platelet aggregates and fibrin strands adherent to the surface of conventional catheters but not to heparin-bonded catheter surfaces. This study demonstrates that (1) collection of blood samples through cardiovascular catheters causes artifactual elevation of FPA, PF4, BTG, and TXB2 levels, and (2) heparin-bonded catheter surfaces effectively prevent catheter-induced platelet alpha-granule release and fibrin formation on catheter surfaces. Heparin-bonded catheters will facilitate investigation of the role of intravascular coagulation in coronary artery disease by eliminating catheter-induced fibrin formation and platelet activation.

  15. Synthetic heparin-binding growth factor analogs

    DOEpatents

    Pena, Louis A.; Zamora, Paul; Lin, Xinhua; Glass, John D.

    2007-01-23

    The invention provides synthetic heparin-binding growth factor analogs having at least one peptide chain that binds a heparin-binding growth factor receptor, covalently bound to a hydrophobic linker, which is in turn covalently bound to a non-signaling peptide that includes a heparin-binding domain. The synthetic heparin-binding growth factor analogs are useful as soluble biologics or as surface coatings for medical devices.

  16. Ti film deposition process of a plasma focus: Study by an experimental design

    NASA Astrophysics Data System (ADS)

    Inestrosa-Izurieta, M. J.; Moreno, J.; Davis, S.; Soto, L.

    2017-10-01

    The plasma generated by plasma focus (PF) devices have substantially different physical characteristics from another plasma, energetic ions and electrons, compared with conventional plasma devices used for plasma nanofabrication, offering new and unique opportunities in the processing and synthesis of Nanomaterials. This article presents the use of a plasma focus of tens of joules, PF-50J, for the deposition of materials sprayed from the anode by the plasma dynamics in the axial direction. This work focuses on the determination of the most significant effects of the technological parameters of the system on the obtained depositions through the use of a statistical experimental design. The results allow us to give a qualitative understanding of the Ti film deposition process in our PF device depending on four different events provoked by the plasma dynamics: i) an electric erosion of the outer material of the anode; ii) substrate ablation generating an interlayer; iii) electron beam deposition of material from the center of the anode; iv) heat load provoking clustering or even melting of the deposition surface.

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

    PubMed

    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 seconds with > 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.

  18. 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.

    PubMed

    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.

  19. Low incidence of heparin-induced skin lesions in orthopedic surgery patients with low-molecular-weight heparins.

    PubMed

    Schindewolf, M; Paulik, M; Kroll, H; Kaufmann, R; Wolter, M; Boehncke, W-H; Lindhoff-Last, E; Recke, A; Ludwig, R J

    2018-04-23

    Heparins are widely prescribed for prevention and therapy of arterial and venous thromboembolic diseases. Heparin-induced skin lesions are the most frequent adverse effects of subcutaneous heparin treatment in non-surgical patients (7.5-39.8%); no data exist on surgical patients. Commonly, they are due to a delayed-type hypersensitivity reaction (DTH), but may also be a manifestation of life-threatening heparin-induced thrombocytopenia (HIT). Lesions of both entities resemble initially. The risk of HIT is highest among heparin-anticoagulated orthopedic surgery patients. To determine incidence and causes of heparin-induced skin lesions in major orthopedic surgery patients. In a prospective cohort study consecutive patients with subcutaneous low-molecular-weight heparin (LMWH) treatment were examined for cutaneous adverse effects. Further diagnostics (skin biopsy, clinical/laboratory assessment for thrombosis, bleeding, HIT, cross-allergies) were performed. Six of 316 enrolled patients (1.9%; 95% CI 0.4%-3.4%) developed heparin-induced skin lesions. All were caused by a DTH reaction, none was due to HIT or other rare heparin-associated skin diseases. Therapeutic use (dosage) of LMWH was identified as only risk factor (odds ratio: 3.1, 95%CI: 1.4-4.9; p=0.00141). In addition to DTH, 5 thromboembolic, 4 major bleeding complications but no cases of HIT or cross-allergies were observed. Orthopedic surgery patients have - unlike non-surgical patients - a low risk for heparin-induced skin lesions during LMWH treatment; all lesions were due to a DTH reaction. The risk for DTH differs considerably between individual patient cohorts. No association with HIT was observed. These data help to tailor anticoagulatory treatment individually and to increase patient safety. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  20. Nanostructure iron-silicon thin film deposition using plasma focus device

    NASA Astrophysics Data System (ADS)

    Kotb, M.; Saudy, A. H.; Hassaballa, S.; Eloker, M. M.

    2013-03-01

    The presented study in this paper reports the deposition of nano-structure iron-silicon thin film on a glass substrate using 3.3 KJ Mather-type plasma focus device. The iron-silicon powder was put on the top of hollow copper anode electrode. The deposition was done under different experimental conditions such as numbers of electric discharge shots and angular position of substrate. The film samples were exposed to energetic argon ions generated by plasma focus device at different distances from the top of the central electrode. The exposed samples were then analyzed for their structure and optical properties using X-ray diffraction (XRD) and UV-visible spectroscopy. The structure of iron-silicon thin films deposited using plasma focus device depends on the distance from the anode, the number of focus deposition shots and the angular position of the sample

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

    PubMed

    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.

  2. Solid coatings deposited from liquid methyl methacrylate via Plasma Polymerization

    NASA Astrophysics Data System (ADS)

    Wurlitzer, Lisa; Maus-Friedrichs, Wolfgang; Dahle, Sebastian

    2016-09-01

    The polymerization of methyl methacrylate via plasma discharges is well known today. Usually, plasma-enhanced chemical vapor deposition (PECVD) is used to deposit polymer coatings. Solid coatings are formed out of the liquid phase from methyl methacrylate via dielectric barrier discharge. The formation of the coating proceeds in the gas and the liquid phase. To learn more about the reactions in the two phases, the coatings from MMA monomer will be compared to those from MMA resin. Finally, attenuated total reflection infrared spectroscopy, confocal laser scanning microscopy and X-ray photoelectron spectroscopy are employed to characterize the solid coatings. In conclusion, the plasma enhanced chemical solution deposition is compared to the classical thermal polymerization of MMA.

  3. Recovery From Amiodarone-Induced Cornea Verticillata by Application of Topical Heparin.

    PubMed

    Frings, Andreas; Schargus, Marc

    2017-11-01

    To report a case of amiodarone-induced vortex keratopathy-associated anatomical findings and subjective visual perception before and after treatment with topical heparin eye drops. Case report. A 76-year-old man complained of halos in his vision in both his eyes due to prominent bilateral cornea verticillata. For treatment of cornea verticillata, we prescribed unpreserved eye drops of a sterile, phosphate-free solution of 0.1% sodium hyaluronate with 1300 IU/mL heparin sodium 3 times daily to the left eye, whereas the other side served as the control. The area of corneal deposits was measured by 2 examiners before and at the 1- and 3-month examination. At last follow-up, cornea verticillata had been reduced from 6 to 2 mm in area by approximately 66% from grade-III to grade-II amiodarone keratopathy. In patients using amiodarone, clearing of cornea verticillata may be achieved by topical use of unpreserved eye drops of a sterile, phosphate-free solution of 0.1% sodium hyaluronate with 1300 IU/mL heparin sodium.

  4. Electrowetting on plasma-deposited fluorocarbon hydrophobic films for biofluid transport in microfluidics

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

    Bayiati, P.; Tserepi, A.; Petrou, P. S.

    2007-05-15

    The present work focuses on the plasma deposition of fluorocarbon (FC) films on surfaces and the electrostatic control of their wettability (electrowetting). Such films can be employed for actuation of fluid transport in microfluidic devices, when deposited over patterned electrodes. Here, the deposition was performed using C{sub 4}F{sub 8} and the plasma parameters that permit the creation of films with optimized properties desirable for electrowetting were established. The wettability of the plasma-deposited surfaces was characterized by means of contact angle measurements (in the static and dynamic mode). The thickness of the deposited films was probed in situ by means ofmore » spectroscopic ellipsometry, while the surface roughness was provided by atomic force microscopy. These plasma-deposited FC films in combination with silicon nitride, a material of high dielectric constant, were used to create a dielectric structure that requires reduced voltages for successful electrowetting. Electrowetting experiments using protein solutions were conducted on such optimized dielectric structures and were compared with similar structures bearing commercial spin-coated Teflon registered amorphous fluoropolymer (AF) film as the hydrophobic top layer. Our results show that plasma-deposited FC films have desirable electrowetting behavior and minimal protein adsorption, a requirement for successful transport of biological solutions in 'digital' microfluidics.« less

  5. Study on deposition of Al2O3 films by plasma-assisted atomic layer with different plasma sources

    NASA Astrophysics Data System (ADS)

    Haiying, WEI; Hongge, GUO; Lijun, SANG; Xingcun, LI; Qiang, CHEN

    2018-04-01

    In this paper, Al2O3 thin films are deposited on a hydrogen-terminated Si substrate by using two home-built electron cyclotron resonance (ECR) and magnetic field enhanced radio frequency plasma-assisted atomic layer deposition (PA-ALD) devices with Al(CH3)3 (trimethylaluminum, TMA) and oxygen plasma used as precursor and oxidant, respectively. The thickness, chemical composition, surface morphology and group reactions are characterized by in situ spectroscopic ellipsometer, x-ray photoelectric spectroscopy, atomic force microscopy, scanning electron microscopy, a high-resolution transmission electron microscope and in situ mass spectrometry (MS), respectively. We obtain that both ECR PA-ALD and the magnetic field enhanced PA-ALD can deposit thin films with high density, high purity, and uniformity at a high deposition rate. MS analysis reveals that the Al2O3 deposition reactions are not simple reactions between TMA and oxygen plasma to produce alumina, water and carbon dioxide. In fact, acetylene, carbon monoxide and some other by-products also appear in the exhaustion gas. In addition, the presence of bias voltage has a certain effect on the deposition rate and surface morphology of films, which may be attributed to the presence of bias voltage controlling the plasma energy and density. We conclude that both plasma sources have a different deposition mechanism, which is much more complicated than expected.

  6. Heparin-binding EGF-like growth factor is present in human amniotic fluid and breast milk.

    PubMed

    Michalsky, M P; Lara-Marquez, M; Chun, L; Besner, G E

    2002-01-01

    Heparin-binding EGF-like growth factor (HB-EGF) is a member of the epidermal growth factor (EGF) family that has been implicated in the healing of various organ injuries. Endogenous HB-EGF production is upregulated in response to injury to the kidney, liver, brain, skin, and intestine. Exogenous administration of HB-EGF protects against intestinal epithelial cell apoptosis and necrosis and intestinal ischemia/reperfusion (I/R) injury. This study examines the presence of endogenous HB-EGF in human amniotic fluid and breast milk, fluids that are in intimate contact with the developing and neonatal gastrointestinal tract. Breast milk samples were collected from lactating women and amniotic fluid was gathered from full-term uteri (cesarian sections) or preterm uteri (amniocentesis). Crude and partially purified breast milk and amniotic fluid samples were analyzed for HB-EGF levels using an HB-EGF-specific enzyme-linked immunosorbent assay (ELISA). Analysis results showed detectable HB-EGF levels in human amniotic fluid and breast milk, ranging from 0.2 to 230 pg/mL. Breast milk and amniotic fluid subjected to heparin affinity or HB-EGF-affinity column chromatography showed bioactivity eluting at positions consistent with those known for native HB-EGF. This study represents the first report of detectable HB-EGF in human amniotic fluid and breast milk. The presence of HB-EGF in these fluids may serve a role in the development of the gastrointestinal tract in utero, and in protection against gut mucosal injury after birth. Copyright 2002 by W.B. Saunders Company.

  7. The non-anticoagulant heparin-like K5 polysaccharide derivative K5-N,OSepi attenuates myocardial ischaemia/reperfusion injury

    PubMed Central

    Collino, Massimo; Pini, Alessandro; Mastroianni, Rosanna; Benetti, Elisa; Lanzi, Cecilia; Bani, Daniele; Chini, Jacopo; Manoni, Marco; Fantozzi, Roberto; Masini, Emanuela

    2012-01-01

    Heparin and low molecular weight heparins have been demonstrated to reduce myocardial ischaemia/reperfusion (I/R) injury, although their use is hampered by the risk of haemorrhagic and thrombotic complications. Chemical and enzymatic modifications of K5 polysaccharide have shown the possibility of producing heparin-like compounds with low anticoagulant activity and strong anti-inflammatory effects. Using a rat model of regional myocardial I/R, we investigated the effects of an epimerized N-,O-sulphated K5 polysaccharide derivative, K5-N,OSepi, on infarct size and histological signs of myocardial injury caused by 30 min. ligature of the left anterior descending coronary artery followed by 1 or 24 h reperfusion. K5-N,OSepi (0.1–1 mg/kg given i.v. 15 min. before reperfusion) significantly reduced the extent of myocardial damage in a dose-dependent manner. Furthermore, we investigated the potential mechanism(s) of the cardioprotective effect(s) afforded by K5-N,OSepi. In left ventricular samples, I/R induced mast cell degranulation and a robust increase in lipid peroxidation, free radical-induced DNA damage and calcium overload. Markers of neutrophil infiltration and activation were also induced by I/R in rat hearts, specifically myeloperoxidase activity, intercellular-adhesion-molecule-1 expression, prostaglandin-E2 and tumour-necrosis-factor-α production. The robust increase in oxidative stress and inflammatory markers was blunted by K5-N,OSepi, in a dose-dependent manner, with maximum at 1 mg/kg. Furthermore, K5-N,OSepi administration attenuated the increase in caspase 3 activity, Bid and Bax activation and ameliorated the decrease in expression of Bcl-2 within the ischaemic myocardium. In conclusion, we demonstrate that the cardioprotective effect of the non-anticoagulant K5 derivative K5-N,OSepi is secondary to a combination of anti-apoptotic and anti-inflammatory effects. PMID:22248092

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

    PubMed

    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.

  9. Novel Family of Insect Salivary Inhibitors Blocks Contact Pathway Activation by Binding to Polyphosphate, Heparin, and Dextran Sulfate

    PubMed Central

    Alvarenga, Patricia H.; Xu, Xueqing; Oliveira, Fabiano; Chagas, Andrezza C.; Nascimento, Clarissa R.; Francischetti, Ivo M.B.; Juliano, Maria A.; Juliano, Luiz; Scharfstein, Julio; Valenzuela, Jesus G.; Ribeiro, José M.C.; Andersen, John F.

    2014-01-01

    Objective Polyphosphate and heparin are anionic polymers released by activated mast cells and platelets that are known to stimulate the contact pathway of coagulation. These polymers promote both the autoactivation of factor XII and the assembly of complexes containing factor XI, prekallikrein, and high-molecular-weight kininogen. We are searching for salivary proteins from blood-feeding insects that counteract the effect of procoagulant and proinflammatory factors in the host, including elements of the contact pathway. Approach and Results Here, we evaluate the ability of the sand fly salivary proteins, PdSP15a and PdSP15b, to inhibit the contact pathway by disrupting binding of its components to anionic polymers. We attempt to demonstrate binding of the proteins to polyphosphate, heparin, and dextran sulfate. We also evaluate the effect of this binding on contact pathway reactions. We also set out to determine the x-ray crystal structure of PdSP15b and examine the determinants of relevant molecular interactions. Both proteins bind polyphosphate, heparin, and dextran sulfate with high affinity. Through this mechanism they inhibit the autoactivation of factor XII and factor XI, the reciprocal activation of factor XII and prekallikrein, the activation of factor XI by thrombin and factor XIIa, the cleavage of high-molecular-weight kininogen in plasma, and plasma extravasation induced by polyphosphate. The crystal structure of PdSP15b contains an amphipathic helix studded with basic side chains that forms the likely interaction surface. Conclusions The results of these studies indicate that the binding of anionic polymers by salivary proteins is used by blood feeders as an antihemostatic/anti-inflammatory mechanism. PMID:24092749

  10. Plasma-deposited amorphous hydrogenated carbon films and their tribological properties

    NASA Technical Reports Server (NTRS)

    Miyoshi, Kazuhisa; Pouch, John J.; Alterovitz, Samuel A.

    1989-01-01

    Recent work on the properties of diamondlike carbon films and their dependence on preparation conditions are reviewed. The results of the study indicate that plasma deposition enables one to deposit a variety of amorphous hydrogenated carbon (a-C:H ) films exhibiting more diamondlike behavior to more graphitic behavior. The plasma-deposited a-C:H can be effectively used as hard, wear-resistant, and protective lubricating films on ceramic materials such as Si(sub 3)N(sub 4) under a variety of environmental conditions such as moist air, dry nitrogrn, and vacuum.

  11. PF4/heparin antibody testing and treatment of heparin-induced thrombocytopenia in the intensive care unit.

    PubMed

    Wanat, Matthew; Fitousis, Kalliopi; Hall, Jeff; Rice, Lawrence

    2013-06-01

    The diagnosis of heparin-induced thrombocytopenia (HIT) may be challenging in critically ill patients, as heparin exposures are ubiquitous, and thrombocytopenia is common. Unwarranted ordering and incorrect interpretation of heparin antibody tests can expose a patient to adverse drug events and imposes a significant economic burden on our health care system. A prospective, observational study was performed over 4 months on all adult patients located in 5 intensive care units, with a heparin antibody test ordered. A platelet factor 4/heparin enzyme-linked immunosorbent assay (ELISA) test was ordered in 131 patients. In total, 110 patients had a low 4Ts score (0-3), and of these 103 had a negative ELISA result. In patients with a low 4Ts score, 0 (0%) of 110 had an optical density value >1.0. One hundred twenty-nine patients (98%) had another possible cause of thrombocytopenia identified. In critically ill patients, low 4Ts scores indicate a low probability of HIT, and heparin antibody testing in these patients is not useful.

  12. Plasma deposition of amorphous metal alloys

    DOEpatents

    Hays, Auda K.

    1986-01-01

    Amorphous metal alloy coatings are plasma-deposited by dissociation of vapors of organometallic compounds and metalloid hydrides in the presence of a reducing gas, using a glow discharge. Tetracarbonylnickel, phosphine, and hydrogen constitute a typical reaction mixture of the invention, yielding a NiPC alloy.

  13. Plasma deposition of amorphous metal alloys

    DOEpatents

    Hays, A.K.

    1979-07-18

    Amorphous metal alloy coatings are plasma-deposited by dissociation of vapors of organometallic compounds and metalloid hydrides in the presence of a reducing gas, using a glow discharge. Tetracarbonylnickel, phosphine, and hydrogen constitute a typical reaction mixture of the invention, yielding a NiPC alloy.

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

    PubMed

    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.

  15. Two dimensional radial gas flows in atmospheric pressure plasma-enhanced chemical vapor deposition

    NASA Astrophysics Data System (ADS)

    Kim, Gwihyun; Park, Seran; Shin, Hyunsu; Song, Seungho; Oh, Hoon-Jung; Ko, Dae Hong; Choi, Jung-Il; Baik, Seung Jae

    2017-12-01

    Atmospheric pressure (AP) operation of plasma-enhanced chemical vapor deposition (PECVD) is one of promising concepts for high quality and low cost processing. Atmospheric plasma discharge requires narrow gap configuration, which causes an inherent feature of AP PECVD. Two dimensional radial gas flows in AP PECVD induces radial variation of mass-transport and that of substrate temperature. The opposite trend of these variations would be the key consideration in the development of uniform deposition process. Another inherent feature of AP PECVD is confined plasma discharge, from which volume power density concept is derived as a key parameter for the control of deposition rate. We investigated deposition rate as a function of volume power density, gas flux, source gas partial pressure, hydrogen partial pressure, plasma source frequency, and substrate temperature; and derived a design guideline of deposition tool and process development in terms of deposition rate and uniformity.

  16. NKG2D and CD94 bind to heparin and sulfate-containing polysaccharides.

    PubMed

    Higai, Koji; Imaizumi, Yuzo; Suzuki, Chiho; Azuma, Yutaro; Matsumoto, Kojiro

    2009-09-04

    Killer lectin-like receptors NKG2D and CD94 on natural killer cells trigger cytotoxicity through binding of glycans on target cells including sialyl Lewis X antigen. We previously reported that NKG2D and CD94 recognize alpha2,3-linked NeuAc on multi-antennary N-glycans. Here we further investigated polysaccharide binding by these receptors, using glutathione-S-transferase-fused extracellular domains of NKG2D AA 73-216 (rNKG2Dlec) and CD94 AA 68-179 (rCD94lec). We found that rNKG2Dlec and rCD94lec bind in a dose-dependent manner to plates coated with heparin-conjugated bovine serum albumin (heparin-BSA). Binding to heparin-BSA was suppressed by soluble sulfate-containing polysaccharides, but minimally impacted by 2-O-, 6-O-, and 2-N-desulfated heparin. Mutagenesis revealed that (152)Y and (199)Y of NKG2D and (144)F, (160)N, and (166)C of CD94 were critical for binding to heparin-BSA. The present manuscript provides the first evidence that NKG2D and CD94 bind to heparin and sulfate-containing polysaccharides.

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

    PubMed

    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.

  18. Surface modification of biomaterials by pulsed laser ablation deposition and plasma/gamma polymerization

    NASA Astrophysics Data System (ADS)

    Rau, Kaustubh R.

    Surface modification of stainless-steel was carried out by two different methods: pulsed laser ablation deposition (PLAD) and a combined plasma/gamma process. A potential application was the surface modification of endovascular stents, to enhance biocompatibility. The pulsed laser ablation deposition process, had not been previously reported for modifying stents and represented a unique and potentially important method for surface modification of biomaterials. Polydimethylsiloxane (PDMS) elatomer was studied using the PLAD technique. Cross- linked PDMS was deemed important because of its general use for biomedical implants and devices as well as in other fields. Furthermore, PDMS deposition using PLAD had not been previously studied and any information gained on its ablation characteristics could be important scientifically and technologically. The studies reported here showed that the deposited silicone film properties had a dependence on the laser energy density incident on the target. Smooth, hydrophobic, silicone-like films were deposited at low energy densities (100-150 mJ/cm2). At high energy densities (>200 mJ/cm2), the films had an higher oxygen content than PDMS, were hydrophilic and tended to show a more particulate morphology. It was also determined that (1)the deposited films were stable and extremely adherent to the substrate, (2)silicone deposition exhibited an `incubation effect' which led to the film properties changing with laser pulse number and (3)films deposited under high vacuum were similar to films deposited at low vacuum levels. The mechanical properties of the PLAD films were determined by nanomechanical measurements which are based on the Atomic Force Microscope (AFM). From these measurements, it was possible to determine the modulus of the films and also study their scratch resistance. Such measurement techniques represent a significant advance over current state-of-the-art thin film characterization methods. An empirical model for

  19. Developing a Highly Active Blood Anticoagulant—a Heparin Complex with Glutamic Acid—by Simulating Chemical Equilibria Based on pH-Metric Data

    NASA Astrophysics Data System (ADS)

    Nikolaeva, L. S.; Semenov, A. N.

    2018-02-01

    The anticoagulant activity of high-molecular-weight heparin is increased by developing a new highly active heparin complex with glutamate using the thermodynamic model of chemical equilibria based on pH-metric data. The anticoagulant activity of the developed complexes is estimated in the pH range of blood plasma according to the drop in the calculated equilibrium Ca2+ concentration associated with the formation of mixed ligand complexes of Ca2+ ions, heparin (Na4hep), and glutamate (H2Glu). A thermodynamic model is calculated by mathematically modelling chemical equilibria in the CaCl2-Na4hep-H2Glu-H2O-NaCl system in the pH range of 2.30 ≤ pH ≤ 10.50 in diluted saline that acts as a background electrolyte (0.154 M NaCl) at 37°C and initial concentrations of the main components of ν × 10-3 M, where n ≤ 4. The thermodynamic model is used to determine the main complex of the monomeric unit of heparin with glutamate (HhepGlu5-) and the most stable mixed ligand complex of Ca2+ with heparin and glutamate (Ca2hepGlu2-) in the pH range of blood plasma (6.80 ≤ pH ≤ 7.40). It is concluded that the Ca2hepGlu2- complex reduces the Ca2+ concentration 107 times more than the Ca2+ complex with pure heparin. The anticoagulant effect of the developed HhepGlu5- complex is confirmed in vitro and in vivo via coagulation tests on the blood plasma of laboratory rats. Additional antithrombotic properties of the developed complex are identified. The new highly active anticoagulant, HhepGlu5- complex with additional antithrombotic properties, is patented.

  20. Modulated plasma deposition of super hydrophobic fluorinated coatings

    NASA Astrophysics Data System (ADS)

    Favia, Pietro

    2002-10-01

    Modulated (pulsed) RF glow discharges fed with unsaturated fluorocarbons originate often films with superior characteristics and remarkable monomer structure retention degree. Properties such as low dielectric constant, low friction coefficient, high flexibility and high hydrophobic character can be granted by such coatings, as well as applications in textiles, packaging, biomaterials, microelectronics and other fields [1-4]. Albeit the surface chemistry of fluorinated films has been extensively analysed, very few works deal with the investigation of the plasma phase and of the material morphology and crystalline. We present our last results on the plasma deposition of coatings from modulated glow discharges fed with tetrafluoroethylene. Period and Duty Cycle (DC) have been changed in the range 20-200 ms and 2-100%, respectively. Chemical composition and structure of the coatings were determined by means of XPS, SIMS, FT-IR and XRD measurements; SEM and AFM allowed morphological investigations. The diagnostics of the gas phase was carried out by time resolved (TR) OES [5] and by IR-AS diagnostics [6]. At low DC (< 10%) a unique morphology is observed at the surface of the films, in form of ribbon-like features many microns long and hundreds of nanometers wide, whose surface density increases at lower DC values. XPS has been used to determine the surface fluorine to carbon ratio of the coatings; best-fitting procedures of the C1s signals have been also carried out. XPS and SIMS results show a high F/C ratio and a chemical structure close to conventional PTFE for samples with ribbon-like features. Due to the combined presence of structures and high fluorination degree, structured surfaces revealed very high hydrophobic character (Water Contact Angle > 150^o). XRD patterns of the structured coatings exhibited a diffraction peak at 2Θ = 18^o, characteristic of crystalline PTFE [4, 6]; this finding, and the presence of the structures, open questions about the

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

    PubMed

    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.

  2. Evidence for a reduced heparin cofactor II biological activity in diabetes.

    PubMed

    Ceriello, A; Quatraro, A; Dello Russo, P; Marchi, E; Milani, M R; Giugliano, D

    1990-01-01

    A reduction of heparin cofactor II (HCII) biological activity, despite its normal plasma concentration, is reported in insulin-dependent diabetic patients. A good linear correlation between HCII activity and concentration is present in normal controls but not in diabetics. In these subjects HCII activity correlates inversely with fasting blood glucose and glycated proteins but not with Hb A1. These data demonstrate the presence of a depressed HCII activity in the presence of its normal plasma concentration in insulin-dependent diabetics and suggest a role for short-term metabolic control in conditioning this phenomenon.

  3. The clinical evaluation of low-dose heparin in haemodialysis: a prospective study using the heparin-coated AN69 ST membrane.

    PubMed

    Chanard, Jacques; Lavaud, Sylvie; Maheut, Hervé; Kazes, Isabelle; Vitry, Fabien; Rieu, Philippe

    2008-06-01

    The AN69 ST haemodialysis membrane, a new membrane resulting from coating polyethyleneimine upon the polyacrylonitrile surface, binds heparin. In patients at risk of bleeding, a pilot study has demonstrated the efficient anticoagulant effect of this heparin-coated membrane. Study design. In chronic haemodialyzed patients, we evaluated whether this anticoagulant effect can be validated in a controlled, prospective, open study. Pragmatically, we tested the hypothesis of no difference of the massive clotting rate in two groups of patients haemodialyzed either with 50% reduced standard doses of nonfractionated heparin using the heparin-coated AN69 ST or with a full dose of heparin (100%) using another type of dialysis membrane that does not bind heparin. Secondary objectives included evaluation of partial clotting, changes in haemoglobin levels, erythropoietin consumption and dialyzer performances. One hundred and eighty-four patients were elected and 170 finally included in an 18-month follow-up study. They were allocated to one of the two arms of the study. In the heparin-reduced group (n = 85, mean age: 73 +/- 11 years), 12 472 sessions were performed after priming the AN69 ST dialyzer with 2 L of heparinized saline (5000 IU/L heparin) and using 50% reduced doses of previously administered heparin. In the control group with standard heparin (n = 85, mean age: 74 +/- 13 years), 14 154 sessions were analysed (NS), and mean heparin doses were 2718 +/- 1388 and 4800 +/- 1564 IU per session, respectively (P < 0.001). In the heparin-reduced group, massive clotting occurred in 1.4 per 1000 sessions, whereas it occurred in 1.6 per 1000 sessions in the standard heparin group (P < 0.05). Mild to moderate partial clotting in the venous drip chamber and in the dialyzer was evaluated in a subset of patients, on a visual scale. It was more frequent in the experimental group than in the control group (P < 0.001). Platelets, haemoglobin levels, erythropoietin needs and dialyzer

  4. Heparin Characterization: Challenges and Solutions

    NASA Astrophysics Data System (ADS)

    Jones, Christopher J.; Beni, Szabolcs; Limtiaco, John F. K.; Langeslay, Derek J.; Larive, Cynthia K.

    2011-07-01

    Although heparin is an important and widely prescribed pharmaceutical anticoagulant, its high degree of sequence microheterogeneity and size polydispersity make molecular-level characterization challenging. Unlike nucleic acids and proteins that are biosynthesized through template-driven assembly processes, heparin and the related glycosaminoglycan heparan sulfate are actively remodeled during biosynthesis through a series of enzymatic reactions that lead to variable levels of O- and N-sulfonation and uronic acid epimers. As summarized in this review, heparin sequence information is determined through a bottom-up approach that relies on depolymerization reactions, size- and charge-based separations, and sensitive mass spectrometric and nuclear magnetic resonance experiments to determine the structural identity of component oligosaccharides. The structure-elucidation process, along with its challenges and opportunities for future analytical improvements, is reviewed and illustrated for a heparin-derived hexasaccharide.

  5. Inappropriate documentation of heparin allergy in the medical record because of misdiagnosis of heparin-induced thrombocytopenia: frequency and consequences.

    PubMed

    McMahon, C M; Tanhehco, Y C; Cuker, A

    2017-02-01

    Essentials Misdiagnosis of heparin-induced thrombocytopenia (HIT) may be associated with adverse outcomes. We conducted a study of patients with a heparin allergy in the chart due to misdiagnosis of HIT. 42% of patients with a heparin allergy due to suspected HIT were clearly HIT-negative. 68% were unnecessarily treated with an alternative anticoagulant, 66% of whom had major bleeding. Background It is recommended that heparin be added to the allergy list of patients with heparin-induced thrombocytopenia (HIT). Misdiagnosis of HIT could lead to inappropriate documentation of a heparin allergy and adverse outcomes. Objectives To determine the frequency and consequences of inappropriate documentation of a heparin allergy because of misdiagnosis of HIT. Methods We conducted a cohort study of patients with an inappropriate heparin allergy listed in the electronic medical record (EMR) because of misdiagnosis of HIT. We searched the EMR for patients with a new heparin allergy. Patients were eligible if the reason for allergy listing was suspected acute HIT and laboratory testing for HIT was performed within 60 days. Subjects were defined as 'HIT-negative' if they had a 4Ts score of ≤ 3 or negative laboratory test results. Results Of 239 subjects with a new heparin allergy documented because of concern regarding HIT, 100 (42%) met the prespecified definition of HIT-negative. Sixty-eight (68%) HIT-negative subjects unnecessarily received an alternative parenteral anticoagulant for a median duration of 10.5 days. Among these 68 patients, 45 (66%) met criteria for major bleeding. Sixty-eight (68%) of the 100 HIT-negative subjects had an inappropriate allergy to heparin documented that persisted in the EMR for > 3 years beyond the index hospitalization. Conclusions Inappropriate listing of heparin as an allergy in the EMR because of misdiagnosis of HIT is common, is associated with substantial rates of unnecessary alternative anticoagulant use and major bleeding, and tends

  6. Interpretation of plasma impurity deposition probes. Analytic approximation

    NASA Astrophysics Data System (ADS)

    Stangeby, P. C.

    1987-10-01

    Insertion of a probe into the plasma induces a high speed flow of the hydrogenic plasma to the probe which, by friction, accelerates the impurity ions to velocities approaching the hydrogenic ion acoustic speed, i.e., higher than the impurity ion thermal speed. A simple analytic theory based on this effect provides a relation between impurity fluxes to the probe Γimp and the undisturbed impurity ion density nimp, with the hydrogenic temperature and density as input parameters. Probe size also influences the collection process and large probes are found to attract a higher flux density than small probes in the same plasma. The quantity actually measured, cimp, the impurity atom surface density (m-2) net-deposited on the probe, is related to Γimp and thus to nimp by taking into account the partial removal of deposited material caused by sputtering and the redeposition process.

  7. The role of heparins and nano-heparins as therapeutic tool in breast cancer.

    PubMed

    Afratis, Nikos A; Karamanou, Konstantina; Piperigkou, Zoi; Vynios, Demitrios H; Theocharis, Achilleas D

    2017-06-01

    Glycosaminoglycans are integral part of the dynamic extracellular matrix (ECM) network that control crucial biochemical and biomechanical signals required for tissue morphogenesis, differentiation, homeostasis and cancer development. Breast cancer cells communicate with stromal ones to modulate ECM mainly through release of soluble effectors during cancer progression. The intracellular cross-talk between cell surface receptors and estrogen receptors is important for the regulation of breast cancer cell properties and production of ECM molecules. In turn, reorganized ECM-cell surface interface modulates signaling cascades, which regulate almost all aspects of breast cell behavior. Heparan sulfate chains present on cell surface and matrix proteoglycans are involved in regulation of breast cancer functions since they are capable of binding numerous matrix molecules, growth factors and inflammatory mediators thus modulating their signaling. In addition to its anticoagulant activity, there is accumulating evidence highlighting various anticancer activities of heparin and nano-heparin derivatives in numerous types of cancer. Importantly, heparin derivatives significantly reduce breast cancer cell proliferation and metastasis in vitro and in vivo models as well as regulates the expression profile of major ECM macromolecules, providing strong evidence for therapeutic targeting. Nano-formulations of the glycosaminoglycan heparin are possibly novel tools for targeting tumor microenvironment. In this review, the role of heparan sulfate/heparin and its nano-formulations in breast cancer biology are presented and discussed in terms of future pharmacological targeting.

  8. Be ITER-like wall at the JET tokamak under plasma

    NASA Astrophysics Data System (ADS)

    Tsavalas, P.; Lagoyannis, A.; Mergia, K.; Rubel, M.; Triantou, K.; Harissopulos, S.; Kokkoris, M.; Petersson, P.; Contributors, JET

    2017-12-01

    The JET tokamak is operated with beryllium and tungsten plasma-facing components to prepare for the exploitation of ITER. To determine beryllium erosion and migration in JET a set of markers were installed. Specimens from different beryllium marker tiles of the main wall of the ITER-like wall (ILW) JET tokamak from the first and the second D-D campaign were analyzed with nuclear reaction analysis, x-ray fluorescence spectroscopy, scanning electron microscopy and x-ray diffraction (XRD). Emphasis was on the determination of carbon plasma impurities deposited on beryllium surfaces. The 12C(d, p0)13C reaction was used to quantify carbon deposition and to determine depth profiles. Carbon quantities on the surface of the Be tiles are low, varying from (0.35 ± 0.07) × 1017 to (11.8 ± 0.6) × 1017 at cm-2 in the deposition depth from 0.4 to 6.7 μm, respectively. In the 0.4-0.5 mm wide grooves of castellation sides the carbon content is found up to (14.3 ± 2.5) × 1017 at cm-2 while it is higher (up to (38 ± 4) × 1017 at cm-2) in wider gaps (0.8 mm) separating tile segments. Oxygen (O), titanium (Ti), chromium (Cr), manganese (Mn), iron (Fe), nickel (Ni) and tungsten (W) were detected in all samples exposed to plasma and the reference one but at lower quantities at the latter. In the central part of the Inner Wall Guard Limiter from the first ILW campaign and in the Outer Poloidal Limiter from the second ILW campaign the Ni interlayer has been completely eroded. XRD shows the formation of BeNi in most specimens.

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

    PubMed

    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.

  10. Towards molecular modeling of the impact of heparin-derived oligosaccharides on hIFN-γ binding

    NASA Astrophysics Data System (ADS)

    Lilkova, E.; Petkov, P.; Ilieva, N.; Litov, L.

    2015-10-01

    Human interferon gamma (hIFN-γ) is an important signalling molecule, which plays a key role in the formation and modulation of immune response. The role of the cytokine C-termini in the formation of a complex with the extracellular receptor is still controversial due to the lack of structural information about this domain. Moreover, the C-termini are also responsible for the high affinity interaction of hIFN-γ with the glycosaminoglicans heparan sulfate and heparin. This interaction can drastically change the properties and behaviour of the protein. We performed molecular dynamics simulations in order to model the structure of the hIFN-γ C-terminal part and the interaction of the cytokine with heparin-derived oligosaccharides. For this purpose we reconstructed the missing C-terminal amino acid residues and performed folding simulations to determine their conformation. In order to simulate the interaction with heparin-like fragments, we developed CHARMM 36 compatible force field for the sulfamate anion group that is present in the glucosamine sugar to complete the heparin and heparan sulfate force field. The new topology and parameters reproduce the available experimental structural properties of heparin-like fragments. The simulations show that the oligosaccharides quickly bind the IFN-γ C-termini and reduce their solvent accessible surface area.

  11. Carbon Nanotubes/Nanofibers by Plasma Enhanced Chemical Vapour Deposition

    NASA Technical Reports Server (NTRS)

    Teo, K. B. K.; Hash, D. B.; Bell, M. S.; Chhowalla, M.; Cruden, B. A.; Amaratunga, G. A. J.; Meyyappan, M.; Milne, W. I.

    2005-01-01

    Plasma enhanced chemical vapour deposition (PECVD) has been recently used for the production of vertically aligned carbon nanotubedfibers (CN) directly on substrates. These structures are potentially important technologically as electron field emitters (e.g. microguns, microwave amplifiers, displays), nanoelectrodes for sensors, filter media, superhydrophobic surfaces and thermal interface materials for microelectronics. A parametric study on the growth of CN grown by glow discharge dc-PECVD is presented. In this technique, a substrate containing thin film Ni catalyst is exposed to C2H2 and NH3 gases at 700 C. Without plasma, this process is essentially thermal CVD which produces curly spaghetti-like CN as seen in Fig. 1 (a). With the plasma generated by biasing the substrate at -6OOV, we observed that the CN align vertically during growth as shown in Fig. l(b), and that the magnitude of the applied substrate bias affects the degree of alignment. The thickness of the thin film Ni catalyst was found to determine the average diameter and inversely the length of the CN. The yield and density of the CN were controlled by the use of different diffusion barrier materials under the Ni catalyst. Patterned CN growth [Fig. l(c)], with la variation in CN diameter of 4.1% and 6.3% respectively, is achieved by lithographically defining the Ni thin film prior to growth. The shape of the structures could be varied from very straight nanotube-like to conical tip-like nanofibers by increasing the ratio of C2H2 in the gas flow. Due to the plasma decomposition of C2H2, amorphous carbon (a-C) is an undesirable byproduct which could coat the substrate during CN growth. Using a combination of depth profiled Auger electron spectroscopy to study the substrate and in-situ mass spectroscopy to examine gas phase neutrals and ions, the optimal conditions for a-C free growth of CN is determined.

  12. Soil-like deposits observed by Sojourner, the Pathfinder rover

    USGS Publications Warehouse

    Moore, Henry J.; Bickler, Donald B.; Crisp, Joy A.; Eisen, Howard J.; Gensler, Jeffrey A.; Haldemann, Albert F.C.; Matijevic, Jacob R.; Reid, Lisa K.; Pavlics, Ferenc

    1999-01-01

    Most of the soil-like materials at the Pathfinder landing site behave like moderately dense soils on Earth with friction angles near 34°-39° and are called cloddy deposits. Cloddy deposits appear to be poorly sorted with dust-sized to granule-sized mineral or rock grains; they may contain pebbles, small rock fragments, and clods. Thin deposits of porous, compressible drifts with friction angles near 26°-28° are also present. Drifts are fine grained. Cohesions of both types of deposits are small. There may be indurated soil-like deposits and/or coated or crusted rocks. Cloddy deposits may be fluvial sediments of the Ares-Tiu floods, but other origins, such as ejecta from nearby impact craters, should be considered. Drifts are probably dusts that settled from the Martian atmosphere. Remote-sensing signatures of the deposits inferred from rover observations are consistent with those observed from orbit and Earth.

  13. Single-molecule dynamic force spectroscopy of the fibronectin-heparin interaction

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

    Mitchell, Gabriel; Lamontagne, Charles-Antoine; Lebel, Rejean

    2007-12-21

    The integrity of cohesive tissues strongly depends on the presence of the extracellular matrix, which provides support and anchorage for cells. The fibronectin protein and the heparin-like glycosaminoglycans are key components of this dynamic structural network. In this report, atomic force spectroscopy was used to gain insight into the compliance and the resistance of the fibronectin-heparin interaction. We found that this interaction can be described by an energetic barrier width of 3.1 {+-} 0.2 A and an off-rate of 0.2 {+-} 0.1 s{sup -1}. These dissociation parameters are similar to those of other carbohydrate-protein interactions and to off-rate values reportedmore » for more complex interactions between cells and extracellular matrix components. Our results indicate that the function of the fibronectin-heparin interaction is supported by its capacity to sustain significant deformations and considerable external mechanical forces.« less

  14. Radio-frequency oxygen-plasma-enhanced pulsed laser deposition of IGZO films

    NASA Astrophysics Data System (ADS)

    Chou, Chia-Man; Lai, Chih-Chang; Chang, Chih-Wei; Wen, Kai-Shin; Hsiao, Vincent K. S.

    2017-07-01

    We demonstrate the crystalline structures, optical transmittance, surface and cross-sectional morphologies, chemical compositions, and electrical properties of indium gallium zinc oxide (IGZO)-based thin films deposited on glass and silicon substrates through pulsed laser deposition (PLD) incorporated with radio-frequency (r.f.)-generated oxygen plasma. The plasma-enhanced pulsed laser deposition (PEPLD)-based IGZO thin films exhibited a c-axis-aligned crystalline (CAAC) structure, which was attributed to the increase in Zn-O under high oxygen vapor pressure (150 mTorr). High oxygen vapor pressure (150 mTorr) and low r.f. power (10 W) are the optimal deposition conditions for fabricating IGZO thin films with improved electrical properties.

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

    PubMed

    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.

  16. Microwave plasma induced surface modification of diamond-like carbon films

    NASA Astrophysics Data System (ADS)

    Rao Polaki, Shyamala; Kumar, Niranjan; Gopala Krishna, Nanda; Madapu, Kishore; Kamruddin, Mohamed; Dash, Sitaram; Tyagi, Ashok Kumar

    2017-12-01

    Tailoring the surface of diamond-like carbon (DLC) film is technically relevant for altering the physical and chemical properties, desirable for useful applications. A physically smooth and sp3 dominated DLC film with tetrahedral coordination was prepared by plasma-enhanced chemical vapor deposition technique. The surface of the DLC film was exposed to hydrogen, oxygen and nitrogen plasma for physical and chemical modifications. The surface modification was based on the concept of adsorption-desorption of plasma species and surface entities of films. Energetic chemical species of microwave plasma are adsorbed, leading to desorbtion of the surface carbon atoms due to energy and momentum exchange. The interaction of such reactive species with DLC films enhanced the roughness, surface defects and dangling bonds of carbon atoms. Adsorbed hydrogen, oxygen and nitrogen formed a covalent network while saturating the dangling carbon bonds around the tetrahedral sp3 valency. The modified surface chemical affinity depends upon the charge carriers and electron covalency of the adsorbed atoms. The contact angle of chemically reconstructed surface increases when a water droplet interacts either through hydrogen or van dear Waals bonding. These weak interactions influenced the wetting property of the DLC surface to a great extent.

  17. Hemocompatibility and oxygenation performance of polysulfone membranes grafted with polyethylene glycol and heparin by plasma-induced surface modification.

    PubMed

    Wang, Weiping; Zheng, Zhi; Huang, Xin; Fan, Wenling; Yu, Wenkui; Zhang, Zhibing; Li, Lei; Mao, Chun

    2017-10-01

    Polyethylene glycol (PEG) and heparin (Hep) were grafted onto polysulfone (PSF) membrane by plasma-induced surface modification to prepare PSF-PEG-Hep membranes used for artificial lung. The effects of plasma treatment parameters, including power, gas type, gas flow rate, and treatment time, were investigated, and different PEG chains were bonded covalently onto the surface in the postplasma grafting process. Membrane surfaces were characterized by water contact angle, PEG grafting degree, attenuated total reflectance-Fourier transform infrared spectroscopy, ultraviolet-visible spectrophotometry, X-ray photoelectron spectroscopy, critical water permeability pressure, and scanning electron microscopy. Protein adsorption, platelet adhesion, and coagulation tests showed significant improvement in the hemocompatibility of PSF-PEG-Hep membranes compared to pristine PSF membrane. Gas exchange tests through PSF-PEG6000-Hep membrane showed that when the flow rate of porcine blood reached 5.0 L/min, the permeation fluxes of O 2 and CO 2 reached 192.6 and 166.9 mL/min, respectively, which were close to the gas exchange capacity of a commercial membrane oxygenator. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1737-1746, 2017. © 2016 Wiley Periodicals, Inc.

  18. Delayed-onset heparin-induced skin necrosis: a rare complication of perioperative heparin therapy.

    PubMed

    Gan, Weh Kiat

    2017-11-03

    An uncommon case of delayed-onset dalteparin-induced skin necrosis in an 83-year-old Caucasian female patient associated with heparin-induced thrombocytopaenia (HIT) presenting on day 30 following dalteparin therapy is reported. Investigations revealed mild thrombocytopaenia with normal protein C, protein S, coagulation screen and positive test for heparin-platelet factor-4 antibody. Clinical diagnosis of heparin-induced skin necrosis with HIT was made. Dalteparin injection was discontinued promptly and substituted with fondaparinux therapy. The patient achieved good recovery following cessation of dalteparin therapy and was subsequently discharged. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  19. Addressing endotoxin issues in bioengineered heparin.

    PubMed

    Suwan, Jiraporn; Torelli, Amanda; Onishi, Akihiro; Dordick, Jonathan S; Linhardt, Robert J

    2012-01-01

    Heparin is a widely used clinical anticoagulant that is prepared from pig intestine. A contamination of heparin in 2008 has led to a reexamination of animal-derived pharmaceuticals. A bioengineered heparin prepared by bacterial fermentation and chemical and enzymatic processing is currently under development. This study examines the challenges of reducing or removing endotoxins associated with this process that are necessary to proceed with preclinical in vivo evaluation of bioengineered heparin. The current process is assessed for endotoxin levels, and strategies are examined for endotoxin removal from polysaccharides and enzymes involved in this process. © 2012 International Union of Biochemistry and Molecular Biology, Inc.

  20. Study on effect of plasma surface treatments for diamond deposition by DC arc plasmatron.

    PubMed

    Kang, In-Je; Joa, Sang-Beom; Lee, Heon-Ju

    2013-11-01

    To improve the thermal conductivity and wear resistance of ceramic materials in the field of renewable energy technologies, diamond coating by plasma processing has been carried out in recent years. This study's goal is to improve diamond deposition on Al2O3 ceramic substrates by plasma surface treatments. Before diamond deposition was carried out in a vacuum, plasma surface treatments using Ar gas were conducted to improve conditions for deposition. We also conducted plasma processing for diamond deposition on Al2O3 ceramic substrates using a DC arc Plasmatron. The Al2O3 ceramic substrates with diamond film (5 x 15 mm2), were investigated by SEM (Scanning Electron Microscopy), AFM (Atomic Force Microscopy) and XRD (X-ray Diffractometer). Then, the C-H stretching of synthetic diamond films by FTIR (Fourier Transform Infrared Spectroscopy) was studied. We identified nanocrystalline diamond films on the Al2O3 ceramic substrates. The results showed us that the deposition rate of diamond films was 2.3 microm/h after plasma surface treatments. Comparing the above result with untreated ceramic substrates, the deposition rate improved with the surface roughness of the deposited diamond films.

  1. Outbreak of Adverse Reactions Associated with Contaminated Heparin

    PubMed Central

    Blossom, David B.; Kallen, Alexander J.; Patel, Priti R.; Elward, Alexis; Robinson, Luke; Gao, Ganpan; Langer, Robert; Perkins, Kiran M.; Jaeger, Jennifer L.; Kurkjian, Katie M.; Jones, Marilyn; Schillie, Sarah F.; Shehab, Nadine; Ketterer, Daniel; Venkataraman, Ganesh; Kishimoto, Takashi Kei; Shriver, Zachary; McMahon, Ann W.; Austen, K. Frank; Kozlowski, Steven; Srinivasan, Arjun; Turabelidze, George; Gould, Carolyn V.; Arduino, Matthew J.; Sasisekharan, Ram

    2013-01-01

    BACKGROUND In January 2008, the Centers for Disease Control and Prevention began a nationwide investigation of severe adverse reactions that were first detected in a single hemodialysis facility. Preliminary findings suggested that heparin was a possible cause of the reactions. METHODS Information on clinical manifestations and on exposure was collected for patients who had signs and symptoms that were consistent with an allergic-type reaction after November 1, 2007. Twenty-one dialysis facilities that reported reactions and 23 facilities that reported no reactions were included in a case–control study to identify facility-level risk factors. Unopened heparin vials from facilities that reported reactions were tested for contaminants. RESULTS A total of 152 adverse reactions associated with heparin were identified in 113 patients from 13 states from November 19, 2007, through January 31, 2008. The use of heparin manufactured by Baxter Healthcare was the factor most strongly associated with reactions (present in 100.0% of case facilities vs. 4.3% of control facilities, P<0.001). Vials of heparin manufactured by Baxter from facilities that reported reactions contained a contaminant identified as oversulfated chondroitin sulfate (OSCS). Adverse reactions to the OSCS-contaminated heparin were often characterized by hypotension, nausea, and shortness of breath occurring within 30 minutes after administration. Of 130 reactions for which information on the heparin lot was available, 128 (98.5%) occurred in a facility that had OSCS-contaminated heparin on the premises. Of 54 reactions for which the lot number of administered heparin was known, 52 (96.3%) occurred after the administration of OSCS-contaminated heparin. CONCLUSIONS Heparin contaminated with OSCS was epidemiologically linked to adverse reactions in this nationwide outbreak. The reported clinical features of many of the cases further support the conclusion that contamination of heparin with OSCS was the cause

  2. LMW Heparin Prevents Increased Kidney Expression of Proinflammatory Mediators in (NZBxNZW)F1 Mice

    PubMed Central

    Kanapathippillai, Premasany; Rekvig, Ole Petter; Fenton, Kristin Andreassen

    2013-01-01

    We have previously demonstrated that continuous infusion of low molecular weight (LMW) heparin delays autoantibody production and development of lupus nephritis in (NZBxNZW)F1 (B/W) mice. In this study we investigated the effect of LMW heparin on renal cytokine and chemokine expression and on nucleosome-mediated activation of nucleosome-specific splenocytes. Total mRNA extracted from kidneys of heparin-treated or -untreated B/W mice was analysed by qPCR for the expression of several cytokines, chemokines, and Toll-like receptors. Splenocytes taken from B/W mice were stimulated with nucleosomes with or without the presence of heparin. Splenocyte cell proliferation as thymidine incorporation and the expression of costimulatory molecules and cell activation markers were measured. Heparin treatment of B/W mice reduced the in vivo expression of CCR2, IL1β, and TLR7 compared to untreated B/W mice. Nucleosome-induced cell proliferation of splenocytes was not influenced by heparin. The expression of CD80, CD86, CD69, CD25, CTLA-4, and TLR 2, 7, 8, and 9 was upregulated upon stimulation by nucleosomes, irrespective of whether heparin was added to the cell culture or not. In conclusion, treatment with heparin lowers the kidney expression of proinflammatory mediators in B/W mice but does not affect nucleosomal activation of splenocytes. PMID:24151519

  3. Surface immobilization of heparin on functional polyisobutylene-based thermoplastic elastomer as a potential artificial vascular graft

    NASA Astrophysics Data System (ADS)

    Wu, Yi-Bo; Li, Kang; Xiang, Dong; Zhang, Min; Yang, Dan; Zhang, Jin-Han; Mao, Jing; Wang, Hao; Guo, Wen-Li

    2018-07-01

    Polyisobutylene-based thermoplastic elastomer (TPE) is a new soft biomaterial. Hydroxyl functional dendritic polyisobutylene-based TPEs (arb-SIBS-OH), which satisfy the design requirements for small-diameter vascular substitutes, were synthesized by controlled carbocationic polymerization. Creep property, which is the destructive weakness of polyisobutylene-based TPEs, was significantly improved with the formation of a "double network" promoted by branched structure and microphase separation. Compatibility of arb-SIBS-OH with rabbit blood was markedly enhanced by modifying heparin grafted from these hydroxyl functional groups. Application of "click chemistry" to immobilize heparin on arb-SIBS-OH surface was apparently effective in enhancing the bioactivity of heparin. Immobilized heparin, which directly bonded by ester bonds, was more likely to form multi-point binding on arb-SIBS-OH surface. This process hindered the accessibility of the heparin active sequence to antithrombin.

  4. Effect of catalyst on deposition of vanadium oxide in plasma ambient

    NASA Astrophysics Data System (ADS)

    Singh, Megha; Kumar, Prabhat; Saini, Sujit K.; Reddy, G. B.

    2018-05-01

    In this paper, we have studied effect of catalyst (buffer layer) on structure, morphology, crystallinity, uniformity of nanostructured thin films deposited in nitrogen plasma ambient keeping all other process parameters constant. The process used for deposition is novel known as Plasma Assisted Sublimation Process (PASP). Samples were then studied using SEM, TEM, HRTEM, Raman spectroscopy. By structural analysis it was found out that samples deposited on Ni layer composed chiefly of α-V2O5 but minor amount of other phases were present in the sample. Samples deposited on Al catalyst layer revealed different phase of V2O5, where sample deposited on Ag was composed chiefly of VO2±x phase. Further analysis revealed that morphology of samples is also affected by catalyst. While samples deposited in Al and Ag layer tend to have reasonably defined geometry, sample deposited on Ni layer were irregular in shape and size. All the results well corroborate with each other.

  5. Surface Passivation of Silicon Using HfO2 Thin Films Deposited by Remote Plasma Atomic Layer Deposition System.

    PubMed

    Zhang, Xiao-Ying; Hsu, Chia-Hsun; Lien, Shui-Yang; Chen, Song-Yan; Huang, Wei; Yang, Chih-Hsiang; Kung, Chung-Yuan; Zhu, Wen-Zhang; Xiong, Fei-Bing; Meng, Xian-Guo

    2017-12-01

    Hafnium oxide (HfO 2 ) thin films have attracted much attention owing to their usefulness in equivalent oxide thickness scaling in microelectronics, which arises from their high dielectric constant and thermodynamic stability with silicon. However, the surface passivation properties of such films, particularly on crystalline silicon (c-Si), have rarely been reported upon. In this study, the HfO 2 thin films were deposited on c-Si substrates with and without oxygen plasma pretreatments, using a remote plasma atomic layer deposition system. Post-annealing was performed using a rapid thermal processing system at different temperatures in N 2 ambient for 10 min. The effects of oxygen plasma pretreatment and post-annealing on the properties of the HfO 2 thin films were investigated. They indicate that the in situ remote plasma pretreatment of Si substrate can result in the formation of better SiO 2 , resulting in a better chemical passivation. The deposited HfO 2 thin films with oxygen plasma pretreatment and post-annealing at 500 °C for 10 min were effective in improving the lifetime of c-Si (original lifetime of 1 μs) to up to 67 μs.

  6. Coaxial carbon plasma gun deposition of amorphous carbon films

    NASA Technical Reports Server (NTRS)

    Sater, D. M.; Gulino, D. A.; Rutledge, S. K.

    1984-01-01

    A unique plasma gun employing coaxial carbon electrodes was used in an attempt to deposit thin films of amorphous diamond-like carbon. A number of different structural, compositional, and electrical characterization techniques were used to characterize these films. These included scanning electron microscopy, scanning transmission electron microscopy, X ray diffraction and absorption, spectrographic analysis, energy dispersive spectroscopy, and selected area electron diffraction. Optical absorption and electrical resistivity measurements were also performed. The films were determined to be primarily amorphous, with poor adhesion to fused silica substrates. Many inclusions of particulates were found to be present as well. Analysis of these particulates revealed the presence of trace impurities, such as Fe and Cu, which were also found in the graphite electrode material. The electrodes were the source of these impurities. No evidence of diamond-like crystallite structure was found in any of the film samples. Details of the apparatus, experimental procedure, and film characteristics are presented.

  7. Heparin use in a rat hemorrhagic shock model induces biologic activity in mesenteric lymph separate from shock

    PubMed Central

    Qin, Yong; Prescott, Lauriston M.; Deitch, Edwin A.; Kaiser, Vicki L.

    2011-01-01

    Experimental data has shown that mesenteric lymph from rats subjected to trauma-hemorrhagic shock (THS) but not trauma-sham shock (TSS) induces neutrophil activation, cytotoxicity, decreased red blood cell deformability and bone marrow colony growth suppression. These data have lead to the hypothesis that gut factors produced from THS enter the systemic circulation via the mesenteric lymphatics and contribute to the progression of Multiple Organ Failure (MOF) following THS. Ongoing studies designed to identify bioactive lymph agents implicated factors associated with the heparin use in the THS procedure. We investigated if heparin itself was responsible for reported toxicity to human umbilical vein endothelial cells (HUVECs). HUVEC toxicity was not induced by lymph when alternate anti-coagulants (citrate and EDTA) were used in THS. HUVEC toxicity was induced by lymph after heparin but not saline or citrate injection into TSS and naïve animals and was dose dependent. Activities of both heparin-releasable lipases (lipoprotein (LPL) and hepatic (HL)) were detected in the plasma and lymph from THS and naïve animals receiving heparin but not citrate or saline. Lymph-induced HUVEC toxicity correlated with lymph lipase activities. Finally, incubation of HUVECs with purified LPL added to naïve lymph induced toxicity in vitro. These data show that heparin, not THS, is responsible for the reported lymph-mediated HUVEC toxicity through its release of lipases into the lymph. These findings can provide alternative explanations for several of the THS effects reported in the literature using heparin models thus necessitating a review of previous work in this field. PMID:21063238

  8. Heparin use in a rat hemorrhagic shock model induces biologic activity in mesenteric lymph separate from shock.

    PubMed

    Qin, Yong; Prescott, Lauriston M; Deitch, Edwin A; Kaiser, Vicki L

    2011-04-01

    Experimental data have shown that mesenteric lymph from rats subjected to trauma-hemorrhagic shock (THS) but not trauma-sham shock induces neutrophil activation, cytotoxicity, decreased red blood cell (RBC) deformability, and bone marrow colony growth suppression. These data have led to the hypothesis that gut factors produced from THS enter the systemic circulation via the mesenteric lymphatics and contribute to the progression of multiple organ failure after THS. Ongoing studies designed to identify bioactive lymph agents implicated factors associated with the heparin use in the THS procedure. We investigated if heparin itself was responsible for reported toxicity to human umbilical vein endothelial cells (HUVECs). Human umbilical vein endothelial cell toxicity was not induced by lymph when alternate anticoagulants (citrate and EDTA) were used in THS. Human umbilical vein endothelial cell toxicity was induced by lymph after heparin but not saline or citrate injection into trauma-sham shock and naive animals and was dose dependent. Activities of both heparin-releasable lipases (lipoprotein and hepatic) were detected in the plasma and lymph from THS and naive animals receiving heparin but not citrate or saline. Lymph-induced HUVEC toxicity correlated with lymph lipase activities. Finally, incubation of HUVECs with purified lipoprotein lipase added to naive lymph-induced toxicity in vitro. These data show that heparin, not THS, is responsible for the reported lymph-mediated HUVEC toxicity through its release of lipases into the lymph. These findings can provide alternative explanations for several of the THS effects reported in the literature using heparin models, thus necessitating a review of previous work in this field.

  9. Biotechnological engineering of heparin/heparan sulphate: a novel area of multi-target drug discovery.

    PubMed

    Rusnati, Marco; Oreste, Pasqua; Zoppetti, Giorgio; Presta, Marco

    2005-01-01

    Heparin is a sulphated glycosaminoglycan currently used as an anticoagulant and antithrombotic drug. It consists largely of 2-O-sulphated IdoA not l&r arrow N, 6-O-disulphated GlcN disaccharide units. Other disaccharides containing unsulphated IdoA or GlcA and N-sulphated or N-acetylated GlcN are also present as minor components. This heterogeneity is more pronounced in heparan sulphate (HS), where the low-sulphated disaccharides are the most abundant. Heparin/HS bind to a variety of biologically active polypeptides, including enzymes, growth factors and cytokines, and viral proteins. This capacity can be exploited to design multi-target heparin/HS-derived drugs for pharmacological interventions in a variety of pathologic conditions besides coagulation and thrombosis, including neoplasia and viral infection. The capsular K5 polysaccharide from Escherichia coli has the same structure as the heparin precursor N-acetyl heparosan. The possibility of producing K5 polysaccharide derivatives by chemical and enzymatic modifications, thus generating heparin/HS-like compounds, has been demonstrated. These K5 polysaccharide derivatives are endowed with different biological properties, including anticoagulant/antithrombotic, antineoplastic, and anti-AIDS activities. Here, the literature data are discussed and the possible therapeutic implications for this novel class of multi-target "biotechnological heparin/HS" molecules are outlined.

  10. Heparin-Mimicking Polymers: Synthesis and Biological Applications

    PubMed Central

    2016-01-01

    Heparin is a naturally occurring, highly sulfated polysaccharide that plays a critical role in a range of different biological processes. Therapeutically, it is mostly commonly used as an injectable solution as an anticoagulant for a variety of indications, although it has also been employed in other forms such as coatings on various biomedical devices. Due to the diverse functions of this polysaccharide in the body, including anticoagulation, tissue regeneration, anti-inflammation, and protein stabilization, and drawbacks of its use, analogous heparin-mimicking materials are also widely studied for therapeutic applications. This review focuses on one type of these materials, namely, synthetic heparin-mimicking polymers. Utilization of these polymers provides significant benefits compared to heparin, including enhancing therapeutic efficacy and reducing side effects as a result of fine-tuning heparin-binding motifs and other molecular characteristics. The major types of the various polymers are summarized, as well as their applications. Because development of a broader range of heparin-mimicking materials would further expand the impact of these polymers in the treatment of various diseases, future directions are also discussed. PMID:27739666

  11. Heparin-Mimicking Polymers: Synthesis and Biological Applications.

    PubMed

    Paluck, Samantha J; Nguyen, Thi H; Maynard, Heather D

    2016-11-14

    Heparin is a naturally occurring, highly sulfated polysaccharide that plays a critical role in a range of different biological processes. Therapeutically, it is mostly commonly used as an injectable solution as an anticoagulant for a variety of indications, although it has also been employed in other forms such as coatings on various biomedical devices. Due to the diverse functions of this polysaccharide in the body, including anticoagulation, tissue regeneration, anti-inflammation, and protein stabilization, and drawbacks of its use, analogous heparin-mimicking materials are also widely studied for therapeutic applications. This review focuses on one type of these materials, namely, synthetic heparin-mimicking polymers. Utilization of these polymers provides significant benefits compared to heparin, including enhancing therapeutic efficacy and reducing side effects as a result of fine-tuning heparin-binding motifs and other molecular characteristics. The major types of the various polymers are summarized, as well as their applications. Because development of a broader range of heparin-mimicking materials would further expand the impact of these polymers in the treatment of various diseases, future directions are also discussed.

  12. The mechanisms how heparin affects the tumor cell induced VEGF and chemokine release from platelets to attenuate the early metastatic niche formation

    PubMed Central

    Ponert, Jan Moritz; Schwarz, Svenja; Haschemi, Reza; Müller, Jens; Pötzsch, Bernd; Bendas, Gerd

    2018-01-01

    Metastasis is responsible for the majority of cancer associated fatalities. Tumor cells leaving the primary tumor and entering the blood flow immediately interact with platelets. Activated platelets contribute in different ways to cancer cell survival and proliferation, e.g. in formation of the early metastatic niche by release of different growth factors and chemokines. Here we show that a direct interaction between platelets and MV3 melanoma or MCF7 breast cancer cells induces platelet activation and a VEGF release in citrated plasma that cannot be further elevated by the coagulation cascade and generated thrombin. In contrast, the release of platelet-derived chemokines CXCL5 and CXCL7 depends on both, a thrombin-mediated platelet activation and a direct interaction between tumor cells and platelets. Preincubation of platelets with therapeutic concentrations of unfractionated heparin reduces the tumor cell initiated VEGF release from platelets. In contrast, tumor cell induced CXCL5 and CXCL7 release from platelets was not impacted by heparin pretreatment in citrated plasma. In defibrinated, recalcified plasma, on the contrary, heparin is able to reduce CXCL5 and CXCL7 release from platelets by thrombin inhibition. Our data indicate that different chemokines and growth factors in diverse platelet granules are released in tightly regulated processes by various trigger mechanisms. We show for the first time that heparin is able to reduce the mediator release induced by different tumor cells both in a contact and coagulation dependent manner. PMID:29346400

  13. Plasma marinobufagenin-like and ouabain-like immunoreactivity during saline volume expansion in anesthetized dogs.

    PubMed

    Bagrov, A Y; Fedorova, O V; Dmitrieva, R I; French, A W; Anderson, D E

    1996-02-01

    This study investigated effects of acute plasma volume expansion on plasma levels and urinary output of two endogenous Na,K-ATPase inhibitors, marinobufagenin-like and ouabain-like immunoreactive substances. Plasma volume was expanded for 3 h via intravenous saline infusion in three groups of anesthetized dogs--nontreated (n = 5); pretreated with rabbit antidigoxin (n = 5); and pretreated with rabbit antimouse (control) antibody (n = 4). Plasma marinobufagenin-like immunoreactivity increased to 11.87 +/- 3.16 nmol.l-1 (vs. 0.30 +/- 0.16 nmol.l-1) within 10 min of volume expansion, in parallel with a 15% increase in LVdP/dt, then decreased to 2.21 +/- 0.59 nmol.l-1, and in 90 min increased to 11.8 +/- 2.8 nmol.l-1, in parallel with the maximal natriuretic response. Plasma concentrations of ouabain-like immunoreactive material were increased after 90 min of saline infusion (0.019 +/- 0.004 nmol.l-1 vs. 0.139 +/- 0.056 nmol.l-1). Pretreatment of the animals with antidigoxin antibody blocked the positive inotropic and reduced natriuretic response to volume expansion, and decreased the urinary release of marinobufagenin-like, but not ouabain-like, material. These results show the presence of marinobufagenin-like immunoreactive substance in dog plasma and suggest that mammalian EDLF may have a bufodienolide nature. Endogenous marinobufagenin-like immunoreactive substance, which is likely to cross-react with antidigoxin antibody, is involved in the natriuretic and positive inotropic responses to plasma volume expansion.

  14. Niobium thin film coating on a 500-MHz copper cavity by plasma deposition

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

    Haipeng Wang; Genfa Wu; H. Phillips

    2005-05-16

    A system using an Electron Cyclotron Resonance (ECR) plasma source for the deposition of a thin niobium film inside a copper cavity for superconducting accelerator applications has been designed and is being constructed. The system uses a 500-MHz copper cavity as both substrate and vacuum chamber. The ECR plasma will be created to produce direct niobium ion deposition. The central cylindrical grid is DC biased to control the deposition energy. This paper describes the design of several subcomponents including the vacuum chamber, RF supply, biasing grid and magnet coils. Operational parameters are compared between an operating sample deposition system andmore » this system. Engineering work progress toward the first plasma creation will be reported here.« less

  15. Plasma enhanced chemical vapor deposition of titanium nitride thin films using cyclopentadienyl cycloheptatrienyl titanium

    NASA Astrophysics Data System (ADS)

    Charatan, R. M.; Gross, M. E.; Eaglesham, D. J.

    1994-10-01

    The use of a low oxidation state Ti compound, cyclopentadienyl cycloheptatrienyl titanium, (C5H5) Ti(C7H7) (CPCHT), as a potential source for TiN and Ti in plasma enhanced chemical vapor deposition processes has been investigated. This precursor provides us with a new chemical vapor deposition route to TiN films that offer an interesting contrast to films deposited from Ti(IV) precursors. Film depositions were carried out by introducing CPCHT, with H2 carrier gas, into the downstream region of a NH3, N2, H2, or mixed H2/N2 plasma. Low resistivity (100-250 micro-ohm cm) nitrogen-rich TiN films with little carbon or oxygen incorporation and good conformality were deposited with activated N2 or NH3 at deposition temperatures of 300-600 C, inclusive. Mixed H2/N2 plasmas resulted in more stoichiometric TiN films with similar properties. The most striking feature of these films is the absence of columnar grain growth, in contrast to TiN films deposited using TiCl4 or Ti(NR(2))(4). Although the film texture was influenced by the plasma gas, the average grain size of the films deposited using activated N2 and NH3 was similar. The TiN films that we deposited were effective diffusion barriers between aluminum and silicon up to 575 C. Depositions using activated H2 resulted in films with significantly less carbon than CPCHT, but still having a minimum of 2.7:1 C:Ti. The lower oxidation state of the precursor did not facilitate the deposition of a Ti-rich film. No depositions were observed with any of the reactant gases in the absence of plasmas activation.

  16. Optical in situ monitoring of plasma-enhanced atomic layer deposition process

    NASA Astrophysics Data System (ADS)

    Zeeshan Arshad, Muhammad; Jo, Kyung Jae; Kim, Hyun Gi; Jeen Hong, Sang

    2018-06-01

    An optical in situ process monitoring method for the early detection of anomalies in plasma process equipment is presented. Cyclic process steps of precursor treatment and plasma reaction for the deposition of an angstrom-scale film increase their complexity to ensure the process quality. However, a small deviation in process parameters, for instance, gas flow rate, process temperature, or RF power, may jeopardize the deposited film quality. As a test vehicle for the process monitoring, we have investigated the aluminum-oxide (Al2O3) encapsulation process in plasma-enhanced atomic layer deposition (PEALD) to form a moisture and oxygen diffusion barrier in organic-light emitting diodes (OLEDs). By optical in situ monitoring, we successfully identified the reduction in oxygen flow rates in the reaction steps, which resulted in a 2.67 times increase in the water vapor transmission ratio (WVTR) of the deposited Al2O3 films. Therefore, we are convinced that the suggested in situ monitoring method is useful for the detection of process shifts or drifts that adversely affect PEALD film quality.

  17. Plasma Diagnostics For The Investigation of Silane Based Glow Discharge Deposition Processes

    NASA Astrophysics Data System (ADS)

    Mataras, Dimitrios

    2001-10-01

    In this work is presented the study of microcrystalline silicon PECVD process through highly diluted silane in hydrogen discharges. The investigation is performed by applying different non intrusive plasma diagnostics (electrical, optical, mass spectrometric and laser interferometric measurements). Each of these measurements is related to different plasma sub-processes (gas physics, plasma chemistry and plasma surface interaction) and compose a complete set, proper for the investigation of the effect of external discharge parameters on the deposition processes. In the specific case these plasma diagnostics are applied for prospecting the optimal experimental conditions from the ic-Si:H deposition rate point of view. Namely, the main characteristics of the effect of frequency, discharge geometry, power consumption and total gas pressure on the deposition process are presented successively. Special attention is given to the study of the frequency effect (13.56 MHz 50 MHz) indicating that the correct way to compare results of different driving frequency discharges is by maintaining constant the total power dissipation in the discharge. The important role of frequency in the achievement of high deposition rates and on the optimization of all other parameters is underlined. Finally, the proper combination of experimental conditions that result from the optimal choice of each of the above-mentioned discharge parameters and lead to high microcrystalline silicon deposition rates (7.5 Å/sec) is presented. The increase of silane dissociation rate towards neutral radicals (frequency effect), the contribution of highly sticking to the surface radicals (discharge geometry optimum) and the controlled production of higher radicals through secondary gas phase reactions (total gas pressure), are presented as prerequisites for the achievement of high deposition rates.

  18. Selective activation of heparin cofactor II by a sulfated polysaccharide isolated from the leaves of Artemisia princeps.

    PubMed

    Hayakawa, Y; Hayashi, T; Hayashi, T; Niiya, K; Sakuragawa, N

    1995-10-01

    While checking anticoagulant activities in crude fractions from Wakan-Yakus (traditional herbal drugs), we detected antithrombin activity in the polysaccharide fraction of the leaves of Artemisia princeps Pamp. A sulfated polysaccharide purified from the crude fractions by ion-exchange chromatography on DEAE-cellulose and gel filtration on Sepharose 6B potentiated the heparin cofactor II (HC II)-dependent antithrombin activity but not the antithrombin activity of antithrombin III (AT III). The polysaccharide enhanced the HC II-thrombin reaction more than 6000-fold. The apparent second-order rate constant of thrombin inhibition by HC II increased from 3.8 x 10(4) (in the absence of the polysaccharide) to 2.5 x 10(8) M-1 min-1 in the presence of 25-125 micrograms/ml of the polysaccharide. In human plasma, the polysaccharide accelerated the formation of thrombin-HC II complex. The stimulating effect on HC II-dependent antithrombin activity was almost totally abolished by treatment with chondroitinase AC I, heparinase or heparitinase, while chondroitinase ABC or chondroitinase AC II had little or no effect. These results suggest that the polysaccharide is a glycosaminoglycan-like material with properties that are quite distinct from heparin or dermatan sulfate.

  19. Modelling of plasma generation and thin film deposition by a non-thermal plasma jet at atmospheric pressure

    NASA Astrophysics Data System (ADS)

    Sigeneger, F.; Becker, M. M.; Foest, R.; Loffhagen, D.

    2016-09-01

    The gas flow and plasma in a miniaturized non-thermal atmospheric pressure plasma jet for plasma enhanced chemical vapour deposition has been investigated by means of hydrodynamic modelling. The investigation focuses on the interplay between the plasma generation in the active zone where the power is supplied by an rf voltage to the filaments, the transport of active plasma particles due to the gas flow into the effluent, their reactions with the thin film precursor molecules and the transport of precursor fragments towards the substrate. The main features of the spatially two-dimensional model used are given. The results of the numerical modelling show that most active particles of the argon plasma are mainly confined within the active volume in the outer capillary of the plasma jet, with the exception of molecular argon ions which are transported remarkably into the effluent together with slow electrons. A simplified model of the precursor kinetics yields radial profiles of precursor fragment fluxes onto the substrate, which agree qualitatively with the measured profiles of thin films obtained by static film deposition experiments.

  20. Effects of Deposition Parameters on Thin Film Properties of Silicon-Based Electronic Materials Deposited by Remote Plasma-Enhanced Chemical-Vapor Deposition

    NASA Astrophysics Data System (ADS)

    Theil, Jeremy Alfred

    The motivation of this thesis is to discuss the major issues of remote plasma enhanced chemical vapor deposition (remote PECVD) that affect the properties Si-based thin films. In order to define the issues required for process optimization, the behavior of remote PECVD process must be understood. The remote PECVD process is defined as having four segments: (1) plasma generation, (2) excited species extraction, (3) excited species/downstream gas mixing, and (4) surface reaction. The double Langmuir probe technique is employed to examine plasma parameters under 13.56 MHz and 2.54 GHz excitation. Optical emission spectroscopy is used to determine changes in the excited states of radiating species in the plasma afterglow. Mass spectrometry is used to determine the excitation and consumption of process gases within the reactor during film growth. Various analytical techniques such as infrared absorption spectroscopy, (ir), high resolution transmission electron microscopy, (HRTEM), and reflected high energy electron diffraction, (RHEED), are used to ascertain film properties. The results of the Langmuir probe show that plasma coupling is frequency dependent and that the capacitive coupling mode is characterized by orders of magnitude higher electron densities in the reactor than inductive coupling. These differences can be manifested in the degree to which a hydrogenated amorphous silicon, a-Si:H, component co-deposition reaction affects film stoichiometry. Mass spectrometry shows that there is an additional excitation source in the downstream glow. In addition the growth of microcrystalline silicon, muc-Si, is correlated with the decrease in the production of disilane and heavier Si-containing species. Chloronium, H_2 Cl^{+}, a super acid ion is identified for the first time in a CVD reactor. It forms from plasma fragmentation of SiH_2 Cl_2, and H_2 . Addition of impurity gases was shown not to affect the electron temperature of the plasma. By products of deposition

  1. Direct fabrication of 3D graphene on nanoporous anodic alumina by plasma-enhanced chemical vapor deposition

    PubMed Central

    Zhan, Hualin; Garrett, David J.; Apollo, Nicholas V.; Ganesan, Kumaravelu; Lau, Desmond; Prawer, Steven; Cervenka, Jiri

    2016-01-01

    High surface area electrode materials are of interest for a wide range of potential applications such as super-capacitors and electrochemical cells. This paper describes a fabrication method of three-dimensional (3D) graphene conformally coated on nanoporous insulating substrate with uniform nanopore size. 3D graphene films were formed by controlled graphitization of diamond-like amorphous carbon precursor films, deposited by plasma-enhanced chemical vapour deposition (PECVD). Plasma-assisted graphitization was found to produce better quality graphene than a simple thermal graphitization process. The resulting 3D graphene/amorphous carbon/alumina structure has a very high surface area, good electrical conductivity and exhibits excellent chemically stability, providing a good material platform for electrochemical applications. Consequently very large electrochemical capacitance values, as high as 2.1 mF for a sample of 10 mm3, were achieved. The electrochemical capacitance of the material exhibits a dependence on bias voltage, a phenomenon observed by other groups when studying graphene quantum capacitance. The plasma-assisted graphitization, which dominates the graphitization process, is analyzed and discussed in detail. PMID:26805546

  2. Direct fabrication of 3D graphene on nanoporous anodic alumina by plasma-enhanced chemical vapor deposition.

    PubMed

    Zhan, Hualin; Garrett, David J; Apollo, Nicholas V; Ganesan, Kumaravelu; Lau, Desmond; Prawer, Steven; Cervenka, Jiri

    2016-01-25

    High surface area electrode materials are of interest for a wide range of potential applications such as super-capacitors and electrochemical cells. This paper describes a fabrication method of three-dimensional (3D) graphene conformally coated on nanoporous insulating substrate with uniform nanopore size. 3D graphene films were formed by controlled graphitization of diamond-like amorphous carbon precursor films, deposited by plasma-enhanced chemical vapour deposition (PECVD). Plasma-assisted graphitization was found to produce better quality graphene than a simple thermal graphitization process. The resulting 3D graphene/amorphous carbon/alumina structure has a very high surface area, good electrical conductivity and exhibits excellent chemically stability, providing a good material platform for electrochemical applications. Consequently very large electrochemical capacitance values, as high as 2.1 mF for a sample of 10 mm(3), were achieved. The electrochemical capacitance of the material exhibits a dependence on bias voltage, a phenomenon observed by other groups when studying graphene quantum capacitance. The plasma-assisted graphitization, which dominates the graphitization process, is analyzed and discussed in detail.

  3. Heparin increases food intake through AgRP neurons

    USDA-ARS?s Scientific Manuscript database

    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...

  4. Growth of ultrananocrystalline diamond film by DC Arcjet plasma enhanced chemical vapor deposition

    NASA Astrophysics Data System (ADS)

    Chen, G. C.; Li, B.; Yan, Z. Q.; Liu, J.; Lu, F. X.; Ye, H.

    2012-06-01

    Self-standing diamond films were grown by DC Arcjet plasma enhanced chemical vapor deposition (CVD). The feed gasses were Ar/H2/CH4, in which the flow ratio of CH4 to H2 (F/F) was varied from 5% to 20%. Two distinct morphologies were observed by scanning electron microscope (SEM), i.e. the "pineapple-like" morphology and the "cauliflower-like" morphology. It was found that the morphologies of the as-grown films are strongly dependent on the flow ratio of CH4 to H2 in the feed gasses. High resolution transmission electron microscope (HRTEM) survey results revealed that there were nanocrystalline grains within the "pineapple-like" films whilst there were ultrananocrystalline grains within "cauliflower-like" films. X-ray diffraction (XRD) results suggested that (110) crystalline plane was the dominant surface in the "cauliflower-like" films whilst (100) crystalline plane was the dominant surface in the "pineapple-like" films. Raman spectroscopy revealed that nanostructured carbon features could be observed in both types of films. Plasma diagnosis was carried out in order to understand the morphology dependent growth mechanism. It could be concluded that the film morphology was strongly influenced by the density of gas phases. The gradient of C2 radical was found to be different along the growth direction under the different growth conditions.

  5. Scaling relations for a needle-like electron beam plasma from the self-similar behavior in beam propagation

    NASA Astrophysics Data System (ADS)

    Bai, Xiaoyan; Chen, Chen; Li, Hong; Liu, Wandong; Chen, Wei

    2017-10-01

    Scaling relations of the main parameters of a needle-like electron beam plasma (EBP) to the initial beam energy, beam current, and discharge pressures are presented. The relations characterize the main features of the plasma in three parameter space and can provide great convenience in plasma design with electron beams. First, starting from the self-similar behavior of electron beam propagation, energy and charge depositions in beam propagation were expressed analytically as functions of the three parameters. Second, according to the complete coupled theoretical model of an EBP and appropriate assumptions, independent equations controlling the density and space charges were derived. Analytical expressions for the density and charges versus functions of energy and charge depositions were obtained. Finally, with the combination of the expressions derived in the above two steps, scaling relations of the density and potential to the three parameters were constructed. Meanwhile, numerical simulations were used to test part of the scaling relations.

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

    PubMed

    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 < .0001). Binding of SRA-positive antibodies to platelets was inhibited by chondroitinase ABC digestion (P < .05) and by the addition of chondroitin-4-sulfate (CS) or heparin in excess quantities. The findings suggest that although all 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.

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

    PubMed Central

    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 < .0001). Binding of SRA-positive antibodies to platelets was inhibited by chondroitinase ABC digestion (P < .05) and by the addition of chondroitin-4-sulfate (CS) or heparin in excess quantities. The findings suggest that although all 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. PMID:25342714

  8. Biopolymer-modified graphite oxide nanocomposite films based on benzalkonium chloride-heparin intercalated in graphite oxide

    NASA Astrophysics Data System (ADS)

    Meng, Na; Zhang, Shuang-Quan; Zhou, Ning-Lin; Shen, Jian

    2010-05-01

    Heparin is a potent anticoagulant agent that interacts strongly with antithrombin III to prevent the formation of fibrin clots. In the present work, poly(dimethylsiloxane)(PDMS)/graphite oxide-benzalkonium chloride-heparin (PDMS/modified graphite oxide) nanocomposite films were obtained by the solution intercalation technique as a possible drug delivery system. The heparin-benzalkonium chloride (BAC-HEP) was intercalated into graphite oxide (GO) layers to form GO-BAC-HEP (modified graphite oxide). Nanocomposite films were characterized by XRD, SEM, TEM, ATR-FTIR and TGA. The modified graphite oxide was observed to be homogeneously dispersed throughout the PDMS matrix. The effect of modified graphite oxide on the mechanical properties of the nanocomposite film was investigated. When the modified graphite oxide content was lower than 0.2 wt%, the nanocomposites showed excellent mechanical properties. Furthermore, nanocomposite films become delivery systems that release heparin slowly to make the nanocomposite films blood compatible. The in vitro studies included hemocompatibility testing for effects on platelet adhesion, platelet activation, plasma recalcification profiles, and hemolysis. Results from these studies showed that the anticoagulation properties of PDMS/GO-BCA-HEP nanocomposite films were greatly superior to those for no treated PDMS. Cell culture assay indicated that PDMS/GO-BCA-HEP nanocomposite films showed enhanced cell adhesion.

  9. Glow discharge plasma deposition of thin films

    DOEpatents

    Weakliem, Herbert A.; Vossen, Jr., John L.

    1984-05-29

    A glow discharge plasma reactor for deposition of thin films from a reactive RF glow discharge is provided with a screen positioned between the walls of the chamber and the cathode to confine the glow discharge region to within the region defined by the screen and the cathode. A substrate for receiving deposition material from a reactive gas is positioned outside the screened region. The screen is electrically connected to the system ground to thereby serve as the anode of the system. The energy of the reactive gas species is reduced as they diffuse through the screen to the substrate. Reactive gas is conducted directly into the glow discharge region through a centrally positioned distribution head to reduce contamination effects otherwise caused by secondary reaction products and impurities deposited on the reactor walls.

  10. Characterization of Interactions between Heparin/Glycosaminoglycan and Adeno-associated Virus

    PubMed Central

    Zhang, Fuming; Aguilera, Javier; Beaudet, Julie M.; Xie, Qing; Lerch, Thomas F.; Davulcu, Omar; Colón, Wilfredo; Chapman, Michael S.; Linhardt, Robert J.

    2013-01-01

    Adeno-associated virus (AAV) is a key candidate in the development of gene therapy. In this report, we used surface plasmon resonance spectroscopy to study the interaction between AAV and heparin and other glycosaminoglycans. Surface plasmon resonance results revealed that heparin binds to AAV with extremely high affinity. Solution competition studies shows that AAV binding to heparin is chain length dependent. AAV prefers to bind full chain heparin. All sulfo groups (especially N-sulfo and 6-O-sulfo groups) on heparin are important for the AAV- heparin interaction. Higher levels of sulfo group substitution in GAGs enhance their binding affinities. Atomic force microscopy was also performed to image AAV-2 complexed with heparin. PMID:23952613

  11. Non-enzymatic glycation reduces heparin cofactor II anti-thrombin activity.

    PubMed

    Ceriello, A; Marchi, E; Barbanti, M; Milani, M R; Giugliano, D; Quatraro, A; Lefebvre, P

    1990-04-01

    The effects of non-enzymatic glycation on heparin cofactor II activity, at glucose concentrations which might be expected in physiological or diabetic conditions have been evaluated in this study. Radiolabelled glucose incorporation was associated with a loss of heparin cofactor anti-thrombin activity. The heparin cofactor heparin and dermatan sulfate-dependent inhibition of thrombin was significantly reduced, showing a remarkable decrease of the maximum second order rate constant. This study shows that heparin cofactor can be glycated at glucose concentrations found in the blood, and that this phenomenon produces a loss of heparin cofactor-antithrombin activity. These data suggest, furthermore, a possible link between heparin cofactor glycation and the pathogenesis of thrombosis in diabetes mellitus.

  12. SPATHOLOBUS SUBERECTUS STEM EXTRACT IMPROVES THE PROTECTIVE EFFECT OF HEPARIN ON CERULEIN-INDUCED PANCREATITIS.

    PubMed

    Shao, Zhengyi

    2017-01-01

    The present study evaluates the effect of Spatholobus suberectus stem extract (SS) in the management of pancreatitis alone and in combination with heparin. Pancreatitis was induced pancreatitis by cerulean (50μg/kg, i.p.) five times at an interval of 1 h without any pretreatment of drug. Rats were treated with SS (100 and 200 mg/kg, p. o.) and heparin (150 U/kg, i.p.) alone and in combination for the duration of a week. Later pancreatic weight and blood flow was estimated and different biochemical parameters like concentration of D-dimer and Interleukin 1β (IL-Ιβ) and activity of amylase and lipase were determined in blood of pancreatitis rats. Moreover effect of drug treatment on DNA synthesis and histopathology was also estimated on cerulean induced pancreatitis rats. Results of this study suggest that treatment with SS alone and in combination with heparin significantly increase in prothrombin time and pancreatic blood flow than negative control group. There was significant decrease in concentration of IL-Ιβ and D-dimer and activity of amylase and lipase in SS and heparin treated group than negative control group. Pancreatic DNA synthesis was also found to be reduced in SS and heparin alone and in combination treated group. Histopathology study also reveals that treatment with SS and heparin alone and in combination reduces edema, hemorrhages, leukocyte infiltration in the TS of pancreatic tissues. Present study concludes that treatment with SS alone effectively manages the pancreatitis by ceasing the inflammatory pathway and potentiates the effect of heparin in the management of pancreatitis.

  13. Heparins from porcine and bovine intestinal mucosa: Are they similar drugs?

    PubMed

    Aquino, Rafael S; Pereira, Mariana S; Vairo, Bruno C; Cinelli, Leonardo P; Santos, Gustavo R C; Fonseca, Roberto J C; Mourão, Paulo A S

    2010-05-01

    Increasing reports of bleeding and peri- or post-operative blood dyscrasias in Brazil were possibly associated with the use of heparin from bovine instead of porcine intestine. These two pharmaceutical grade heparins were analysed for potential differences. NMR analyses confirmed that porcine heparin is composed of mainly trisulfated disaccharides -->4-alpha-IdoA2S-1-->4-alpha-GlcNS6S-1-->. Heparin from bovine intestine is also composed of highly 2-sulfated alpha-iduronic acid residues, but the sulfation of the alpha-glucosamine units vary significantly: approximately 50% are 6- and N -disulfated, as in porcine heparin, while approximately 36% are 6-desulfated and approximately 14% N -acetylated. These heparins differ significantly in their effects on coagulation, thrombosis and bleeding. Bovine heparin acts mostly through factor Xa. Compared to porcine heparin on a weight basis, bovine heparin exhibited approximately half of the anticoagulant and antithrombotic effects, but similar effect on bleeding. These two heparins also differ in their protamine neutralisation curves. The doses of heparin from bovine intestine required for effective antithrombotic protection and the production of adverse bleeding effects are closer than those for porcine heparin. This observation may explain the increasing bleeding observed among Brazilian patients. Our results suggest that these two types of heparin are not equivalent drugs.

  14. Structural characterization of pharmaceutical heparins prepared from different animal tissues.

    PubMed

    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.

  15. Room temperature deposition of silicon nanodot clusters by plasma-enhanced chemical vapor deposition.

    PubMed

    Kim, Jae-Kwan; Kim, Jun Young; Yoon, Jae-Sik; Lee, Ji-Myon

    2013-10-01

    The formation of nanometer-scale (ns)-Si dots and clusters on p-GaN layers has been studied by controlling the early stage of growth during plasma-enhanced chemical vapor deposition (PECVD) at room temperature. We found that ns-Si dots and clusters formed on the p-GaN surface, indicating that growth was the Volmer-Weber mode. The deposition parameters such as radio frequency (RF) power and processing time mainly influenced the size of the ns-Si dots (40 nm-160 nm) and the density of the ns-Si dot clusters.

  16. Effects of Chitosan Derivative N-[(2-Hydroxy-3-Trimethylammonium)Propyl]Chloride on Anticoagulant Activity of Guinea Pig Plasma.

    PubMed

    Drozd, N N; Shagdarova, B Ts; Il'ina, A V; Varlamov, V P

    2017-07-01

    Intravenous injection of protamine sulfate or quarternized chitosan derivative to guinea pigs after injection of 70 aIIa U/kg non-fractionated heparin shortened plasma clotting time (shown by partial activated thromboplastin time, thrombin time, and prothrombin time). Intravenous injection of protamine sulfate or quarternized chitosan derivative to guinea pigs after injection of 1 mg/kg (100 aXa U/kg) low-molecular-weight heparin (clexane) led to shortening of plasma clotting time in the ReaClot Heparin test and to prolongation of plasma amidolytic activity in the factor Xa chromogenic substrate test.

  17. Hydrazinolysis of heparin and other glycosaminoglycans.

    PubMed Central

    Shaklee, P N; Conrad, H E

    1984-01-01

    Heparin, carboxy-group-reduced heparin, several sulphated monosaccharides and disaccharides formed from heparin, and a tetrasaccharide prepared from chondroitin sulphate were treated at 100 degrees C with hydrazine containing 1% hydrazine sulphate for periods sufficient to cause complete N-deacetylation of the N-acetylhexosamine residues. Under these hydrazinolysis conditions both the N-sulphate and the O-sulphate substituents on these compounds were completely stable. However, the uronic acid residues were converted into their hydrazide derivatives at rates that depended on the uronic acid structures. Unsubstituted L-iduronic acid residues reacted much more slowly than did unsubstituted D-glucuronic acid or 2-O-sulphated L-iduronic acid residues. The chemical modification of the carboxy groups resulted in a low rate of C-5 epimerization of the uronic acid residues. The hydrazinolysis reaction also caused a partial depolymerization of heparin but not of carboxy-group-reduced heparin. Treatment of the hydrazinolysis products with HNO2 at either pH 4 or pH 1.5 or with HIO3 converted the uronic acid hydrazides back into uronic acid residues. The use of the hydrazinolysis reaction in studies of the structures of uronic acid-containing polymers and the implications of the uronic acid hydrazide formation are discussed. PMID:6421280

  18. Binding affinities of NKG2D and CD94 to sialyl Lewis X-expressing N-glycans and heparin.

    PubMed

    Higai, Koji; Suzuki, Chiho; Imaizumi, Yuzo; Xin, Xin; Azuma, Yutaro; Matsumoto, Kojiro

    2011-01-01

    Lectin-like receptors natural killer group 2D (NKG2D) and CD94 on natural killer (NK) cells bind to α2,3-NeuAc-containing N-glycans and heparin/heparan sulfate (HS). Using recombinant glutathione S-transferase-fused extracellular lectin-like domains of NKG2D (rGST-NKG2Dlec) and CD94 (rGST-CD94lec), we evaluated their binding affinities (K(d)) to high sialyl Lewis X (sLeX)-expressing transferrin secreted by HepG2 cells (HepTf) and heparin-conjugated bovine serum albumin (Heparin-BSA), using quartz crystal microbalance (QCM) and enzyme immunoassay (EIA) microplate methods. K(d) values obtained by linear reciprocal plots revealed good coincidence between the two methods. K(d) values of rGST-NKG2Dlec obtained by QCM and EIA, respectively, were 1.19 and 1.11 µM for heparin-BSA >0.30 and 0.20 µM for HepTf, while those of rGST-CD94lec were 1.31 and 1.45 µM for HepTf >0.37 and 0.36 µM for heparin-BSA. These results suggested that these glycans can interact with NKG2D and CD94 to modulate NK cell-dependent cytotoxicity.

  19. Adhesion, friction, and wear of plasma-deposited thin silicon nitride films at temperatures to 700 C

    NASA Technical Reports Server (NTRS)

    Miyoshi, K.; Pouch, J. J.; Alterovitz, S. A.; Pantic, D. M.; Johnson, G. A.

    1988-01-01

    The adhesion, friction, and wear behavior of silicon nitride films deposited by low- and high-frequency plasmas (30 kHz and 13.56 MHz) at various temperatures to 700 C in vacuum were examined. The results of the investigation indicated that the Si/N ratios were much greater for the films deposited at 13.56 MHz than for those deposited at 30 kHz. Amorphous silicon was present in both low- and high-frequency plasma-deposited silicon nitride films. However, more amorphous silicon occurred in the films deposited at 13.56 MHz than in those deposited at 30 kHz. Temperature significantly influenced adhesion, friction, and wear of the silicon nitride films. Wear occurred in the contact area at high temperature. The wear correlated with the increase in adhesion and friction for the low- and high-frequency plasma-deposited films above 600 and 500 C, respectively. The low- and high-frequency plasma-deposited thin silicon nitride films exhibited a capability for lubrication (low adhesion and friction) in vacuum at temperatures to 500 and 400 C, respectively.

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

    PubMed

    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.

  1. Dual chain synthetic heparin-binding growth factor analogs

    DOEpatents

    Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY

    2012-04-24

    The invention provides synthetic heparin-binding growth factor analogs having two peptide chains each branched from a branch moiety, such as trifunctional amino acid residues, the branch moieties separated by a first linker of from 3 to about 20 backbone atoms, which peptide chains bind a heparin-binding growth factor receptor and are covalently bound to a non-signaling peptide that includes a heparin-binding domain, preferably by a second linker, which may be a hydrophobic second linker. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

  2. Dual chain synthetic heparin-binding growth factor analogs

    DOEpatents

    Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY

    2009-10-06

    The invention provides synthetic heparin-binding growth factor analogs having two peptide chains each branched from a branch moiety, such as trifunctional amino acid residues, the branch moieties separated by a first linker of from 3 to about 20 backbone atoms, which peptide chains bind a heparin-binding growth factor receptor and are covalently bound to a non-signaling peptide that includes a heparin-binding domain, preferably by a second linker, which may be a hydrophobic second linker. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

  3. Myocardial and Peripheral Ischemia Causes an Increase in Circulating Pregnancy-Associated Plasma Protein-A in Non-atherosclerotic, Non-heparinized Pigs.

    PubMed

    Steffensen, Lasse Bach; Poulsen, Christian Bo; Shim, Jeong; Bek, Marie; Jacobsen, Kevin; Conover, Cheryl A; Bentzon, Jacob Fog; Oxvig, Claus

    2015-12-01

    The usefulness of circulating pregnancy-associated plasma protein-A (PAPP-A) as a biomarker for acute coronary syndrome (ACS) is widely debated. We used the pig as a model to assess PAPP-A dynamics in the setting of myocardial ischemia. Induction of myocardial ischemia by ligation of the left anterior descending (LAD) coronary artery caused a systemic rise in PAPP-A. However, the ischemic myocardium was excluded as the source of PAPP-A. Interestingly, induction of ischemia in peripheral tissues by ligation of the left femoral artery caused a systemic rise in PAPP-A originating from the left hind limb. This is the first study to demonstrate PAPP-A elevations in the absence of atherosclerosis or heparin during myocardial ischemia. Our findings thus add to the current discussion of the usefulness of PAPP-A as a biomarker for ACS.

  4. Influence of Human Leukocyte Antigen (HLA) Alleles and Killer Cell Immunoglobulin-Like Receptors (KIR) Types on Heparin-Induced Thrombocytopenia (HIT).

    PubMed

    Karnes, Jason H; Shaffer, Christian M; Cronin, Robert; Bastarache, Lisa; Gaudieri, Silvana; James, Ian; Pavlos, Rebecca; Steiner, Heidi E; Mosley, Jonathan D; Mallal, Simon; Denny, Joshua C; Phillips, Elizabeth J; Roden, Dan M

    2017-09-01

    Heparin-induced thrombocytopenia (HIT) is an unpredictable, life-threatening, immune-mediated reaction to heparin. Variation in human leukocyte antigen (HLA) genes is now used to prevent immune-mediated adverse drug reactions. Combinations of HLA alleles and killer cell immunoglobulin-like receptors (KIR) are associated with multiple autoimmune diseases and infections. The objective of this study is to evaluate the association of HLA alleles and KIR types, alone or in the presence of different HLA ligands, with HIT. HIT cases and heparin-exposed controls were identified in BioVU, an electronic health record coupled to a DNA biobank. HLA sequencing and KIR type imputation using Illumina OMNI-Quad data were performed. Odds ratios for HLA alleles and KIR types and HLA*KIR interactions using conditional logistic regressions were determined in the overall population and by race/ethnicity. Analysis was restricted to KIR types and HLA alleles with a frequency greater than 0.01. The p values for HLA and KIR association were corrected by using a false discovery rate q<0.05 and HLA*KIR interactions were considered significant at p<0.05. Sixty-five HIT cases and 350 matched controls were identified. No statistical differences in baseline characteristics were observed between cases and controls. The HLA-DRB3*01:01 allele was significantly associated with HIT in the overall population (odds ratio 2.81 [1.57-5.02], p=2.1×10 -4 , q=0.02) and in individuals with European ancestry, independent of other alleles. No KIR types were associated with HIT, although a significant interaction was observed between KIR2DS5 and the HLA-C1 KIR binding group (p=0.03). The HLA-DRB3*01:01 allele was identified as a potential risk factor for HIT. This class II HLA gene and allele represent biologically plausible candidates for influencing HIT pathogenesis. We found limited evidence of the role of KIR types in HIT pathogenesis. Replication and further study of the HLA-DRB3*01:01 association is

  5. Tissue factor-expressing monocytes inhibit fibrinolysis through a TAFI-mediated mechanism, and make clots resistant to heparins

    PubMed Central

    Semeraro, Fabrizio; Ammollo, Concetta T.; Semeraro, Nicola; Colucci, Mario

    2009-01-01

    Background Thrombin is the main activator of the fibrinolysis inhibitor TAFI (thrombin activatable fibrinolysis inhibitor) and heightened clotting activation is believed to impair fibrinolysis through the increase of thrombin activatable fibrinolysis inhibitor activation. However, the enhancement of thrombin generation by soluble tissue factor was reported to have no effect on plasma fibrinolysis and it is not known whether the same is true for cell-associated tissue factor. The aim of this study was to evaluate the effect of tissue factor-expressing monocytes on plasma fibrinolysis in vitro. Design and Methods Tissue factor expression by human blood mononuclear cells (MNC) and monocytes was induced by LPS stimulation. Fibrinolysis was spectrophotometrically evaluated by measuring the lysis time of plasma clots containing LPS-stimulated or control cells and a low concentration of exogenous tissue plasminogen activator. Results LPS-stimulated MNC (LPS-MNC) prolonged fibrinolysis time as compared to unstimulated MNC (C-MNC) in contact-inhibited but not in normal citrated plasma. A significantly prolonged lysis time was observed using as few as 30 activated cells/μL. Fibrinolysis was also impaired when clots were generated on adherent LPS-stimulated monocytes. The antifibrinolytic effect of LPS-MNC or LPS-monocytes was abolished by an anti-tissue factor antibody, by an antibody preventing thrombin-mediated thrombin activatable fibrinolysis inhibitor activation, and by a TAFIa inhibitor (PTCI). Assays of thrombin and TAFIa in contact-inhibited plasma confirmed the greater generation of these enzymes in the presence of LPS-MNC. Finally, the profibrinolytic effect of unfractionated heparin and enoxaparin was markedly lower (~50%) in the presence of LPS-MNC than in the presence of a thromboplastin preparation displaying an identical tissue factor activity. Conclusions Our data indicate that LPS-stimulated monocytes inhibit fibrinolysis through a tissue factor

  6. Profiling Heparin-Chemokine Interactions Using Synthetic Tools

    PubMed Central

    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

  7. Heparin bridge therapy and post-polypectomy bleeding

    PubMed Central

    Kubo, Toshiyuki; Yamashita, Kentaro; Onodera, Kei; Iida, Tomoya; Arimura, Yoshiaki; Nojima, Masanori; Nakase, Hiroshi

    2016-01-01

    AIM To identify risk factors for post-polypectomy bleeding (PPB), focusing on antithrombotic agents. METHODS This was a case-control study based on medical records at a single center. PPB was defined as bleeding that occurred 6 h to 10 d after colonoscopic polypectomy and required endoscopic hemostasis. As risk factors for PPB, patient-related factors including anticoagulants, antiplatelets and heparin bridge therapy as well as polyp- and procedure-related factors were evaluated. All colonoscopic hot polypectomies, endoscopic mucosal resections and endoscopic submucosal dissections performed between January 2011 and December 2014 were reviewed. RESULTS PPB occurred in 29 (3.7%) of 788 polypectomies performed during the study period. Antiplatelet or anticoagulant agents were prescribed for 210 (26.6%) patients and were ceased before polypectomy except for aspirin and cilostazol in 19 cases. Bridging therapy using intravenous unfractionated heparin was adopted for 73 patients. The univariate analysis revealed that anticoagulants, heparin bridge, and anticoagulants plus heparin bridge were significantly associated with PPB (P < 0.0001) whereas antiplatelets and antiplatelets plus heparin were not. None of the other factors including age, gender, location, size, shape, number of resected polyps, prophylactic clipping and resection method were correlated with PPB. The multivariate analysis demonstrated that anticoagulants and anticoagulants plus heparin bridge therapy were significant risk factors for PPB (P < 0.0001). Of the 29 PPB cases, 4 required transfusions and none required surgery. A thromboembolic event occurred in a patient who took anticoagulant. CONCLUSION Patients taking anticoagulants have an increased risk of PPB, even if the anticoagulants are interrupted before polypectomy. Heparin-bridge therapy might be responsible for the increased PPB in patients taking anticoagulants. PMID:28018108

  8. Heparin bridge therapy and post-polypectomy bleeding.

    PubMed

    Kubo, Toshiyuki; Yamashita, Kentaro; Onodera, Kei; Iida, Tomoya; Arimura, Yoshiaki; Nojima, Masanori; Nakase, Hiroshi

    2016-12-07

    To identify risk factors for post-polypectomy bleeding (PPB), focusing on antithrombotic agents. This was a case-control study based on medical records at a single center. PPB was defined as bleeding that occurred 6 h to 10 d after colonoscopic polypectomy and required endoscopic hemostasis. As risk factors for PPB, patient-related factors including anticoagulants, antiplatelets and heparin bridge therapy as well as polyp- and procedure-related factors were evaluated. All colonoscopic hot polypectomies, endoscopic mucosal resections and endoscopic submucosal dissections performed between January 2011 and December 2014 were reviewed. PPB occurred in 29 (3.7%) of 788 polypectomies performed during the study period. Antiplatelet or anticoagulant agents were prescribed for 210 (26.6%) patients and were ceased before polypectomy except for aspirin and cilostazol in 19 cases. Bridging therapy using intravenous unfractionated heparin was adopted for 73 patients. The univariate analysis revealed that anticoagulants, heparin bridge, and anticoagulants plus heparin bridge were significantly associated with PPB ( P < 0.0001) whereas antiplatelets and antiplatelets plus heparin were not. None of the other factors including age, gender, location, size, shape, number of resected polyps, prophylactic clipping and resection method were correlated with PPB. The multivariate analysis demonstrated that anticoagulants and anticoagulants plus heparin bridge therapy were significant risk factors for PPB ( P < 0.0001). Of the 29 PPB cases, 4 required transfusions and none required surgery. A thromboembolic event occurred in a patient who took anticoagulant. Patients taking anticoagulants have an increased risk of PPB, even if the anticoagulants are interrupted before polypectomy. Heparin-bridge therapy might be responsible for the increased PPB in patients taking anticoagulants.

  9. 21 CFR 864.7525 - Heparin assay.

    Code of Federal Regulations, 2010 CFR

    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...

  10. 21 CFR 864.7525 - Heparin assay.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 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...

  11. 21 CFR 864.7525 - Heparin assay.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 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...

  12. 21 CFR 864.7525 - Heparin assay.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 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...

  13. 21 CFR 864.7525 - Heparin assay.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 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...

  14. Modulatory effects of heparin and short-length oligosaccharides of heparin on the metastasis and growth of LMD MDA-MB 231 breast cancer cells in vivo

    PubMed Central

    Mellor, P; Harvey, J R; Murphy, K J; Pye, D; O'Boyle, G; Lennard, T W J; Kirby, J A; Ali, S

    2007-01-01

    Expression of the chemokine receptor CXCR4 allows breast cancer cells to migrate towards specific metastatic target sites which constitutively express CXCL12. In this study, we determined whether this interaction could be disrupted using short-chain length heparin oligosaccharides. Radioligand competition binding assays were performed using a range of heparin oligosaccharides to compete with polymeric heparin or heparan sulphate binding to I125 CXCL12. Heparin dodecasaccharides were found to be the minimal chain length required to efficiently bind CXCL12 (71% inhibition; P<0.001). These oligosaccharides also significantly inhibited CXCL12-induced migration of CXCR4-expressing LMD MDA-MB 231 breast cancer cells. In addition, heparin dodecasaccharides were found to have less anticoagulant activity than either a smaller quantity of polymeric heparin or a similar amount of the low molecular weight heparin pharmaceutical product, Tinzaparin. When given subcutaneously in a SCID mouse model of human breast cancer, heparin dodecasaccharides had no effect on the number of lung metastases, but did however inhibit (P<0.05) tumour growth (lesion area) compared to control groups. In contrast, polymeric heparin significantly inhibited both the number (P<0.001) and area of metastases, suggesting a differing mechanism for the action of polymeric and heparin-derived oligosaccharides in the inhibition of tumour growth and metastases. PMID:17726466

  15. Microwave remote plasma enhanced-atomic layer deposition system with multicusp confinement chamber

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

    Dechana, A.; Thamboon, P.; Boonyawan, D., E-mail: dheerawan.b@cmu.ac.th

    A microwave remote Plasma Enhanced-Atomic Layer Deposition system with multicusp confinement chamber is established at the Plasma and Beam Physics research facilities, Chiang Mai, Thailand. The system produces highly-reactive plasma species in order to enhance the deposition process of thin films. The addition of the multicusp magnetic fields further improves the plasma density and uniformity in the reaction chamber. Thus, the system is more favorable to temperature-sensitive substrates when heating becomes unwanted. Furthermore, the remote-plasma feature, which is generated via microwave power source, offers tunability of the plasma properties separately from the process. As a result, the system provides highmore » flexibility in choice of materials and design experiments, particularly for low-temperature applications. Performance evaluations of the system were carried on coating experiments of Al{sub 2}O{sub 3} layers onto a silicon wafer. The plasma characteristics in the chamber will be described. The resulted Al{sub 2}O{sub 3} films—analyzed by Rutherford Backscattering Spectrometry in channeling mode and by X-ray Photoelectron Spectroscopy techniques—will be discussed.« less

  16. Microwave remote plasma enhanced-atomic layer deposition system with multicusp confinement chamber

    NASA Astrophysics Data System (ADS)

    Dechana, A.; Thamboon, P.; Boonyawan, D.

    2014-10-01

    A microwave remote Plasma Enhanced-Atomic Layer Deposition system with multicusp confinement chamber is established at the Plasma and Beam Physics research facilities, Chiang Mai, Thailand. The system produces highly-reactive plasma species in order to enhance the deposition process of thin films. The addition of the multicusp magnetic fields further improves the plasma density and uniformity in the reaction chamber. Thus, the system is more favorable to temperature-sensitive substrates when heating becomes unwanted. Furthermore, the remote-plasma feature, which is generated via microwave power source, offers tunability of the plasma properties separately from the process. As a result, the system provides high flexibility in choice of materials and design experiments, particularly for low-temperature applications. Performance evaluations of the system were carried on coating experiments of Al2O3 layers onto a silicon wafer. The plasma characteristics in the chamber will be described. The resulted Al2O3 films—analyzed by Rutherford Backscattering Spectrometry in channeling mode and by X-ray Photoelectron Spectroscopy techniques—will be discussed.

  17. Microwave remote plasma enhanced-atomic layer deposition system with multicusp confinement chamber.

    PubMed

    Dechana, A; Thamboon, P; Boonyawan, D

    2014-10-01

    A microwave remote Plasma Enhanced-Atomic Layer Deposition system with multicusp confinement chamber is established at the Plasma and Beam Physics research facilities, Chiang Mai, Thailand. The system produces highly-reactive plasma species in order to enhance the deposition process of thin films. The addition of the multicusp magnetic fields further improves the plasma density and uniformity in the reaction chamber. Thus, the system is more favorable to temperature-sensitive substrates when heating becomes unwanted. Furthermore, the remote-plasma feature, which is generated via microwave power source, offers tunability of the plasma properties separately from the process. As a result, the system provides high flexibility in choice of materials and design experiments, particularly for low-temperature applications. Performance evaluations of the system were carried on coating experiments of Al2O3 layers onto a silicon wafer. The plasma characteristics in the chamber will be described. The resulted Al2O3 films-analyzed by Rutherford Backscattering Spectrometry in channeling mode and by X-ray Photoelectron Spectroscopy techniques-will be discussed.

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

    PubMed

    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.

  19. Electrophoresis for the analysis of heparin purity and quality

    PubMed Central

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

    2012-01-01

    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. PMID:22736353

  20. Development of hydrophilic interaction chromatography with quadruple time-of-flight mass spectrometry for heparin and low molecular weight heparin disaccharide analysis.

    PubMed

    Ouyang, Yilan; Wu, Chengling; Sun, Xue; Liu, Jianfen; Linhardt, Robert J; Zhang, Zhenqing

    2016-01-30

    Heparin and low molecular weight heparin (LMWH) are widely used as clinical anticoagulants. The determination of their composition and structural heterogeneity still challenges analysts. Disaccharide compositional analysis, utilizing heparinase-catalyzed depolymerization, is one of the most important ways to evaluate the sequence, structural composition and quality of heparin and LMWH. Hydrophilic interaction chromatography coupled with quadruple time-of-flight mass spectrometry (HILIC/QTOFMS) has been developed to analyze the resulting digestion products. HILIC shows good resolution and excellent MS compatibility. Digestion products of heparin and LMWHs afforded up to 16 compounds that were separated using HILIC and analyzed semi-quantitatively. These included eight common disaccharides, two disaccharides derived from chain termini, three 3-O-sulfo-group-containing tetrasaccharides, along with three linkage region tetrasaccharides and their derivatives. Structures of these digestion products were confirmed by mass spectral analysis. The disaccharide compositions of a heparin, two batches of the LMWH, enoxaparin, and two batches of the LMWH, nadroparin, were compared. In addition to identifying disaccharides, 3-O-sulfo-group-containing tetrasaccharides, linkage region tetrasaccharides were observed having slightly different compositions and contents in these heparin products suggesting that they had been prepared using different starting materials or production processes. Thus, compositional analysis using HILIC/QTOFMS offers a unique insight into different heparin products. Copyright © 2015 John Wiley & Sons, Ltd.

  1. Reduced chemical warfare agent sorption in polyurethane-painted surfaces via plasma-enhanced chemical vapor deposition of perfluoroalkanes.

    PubMed

    Gordon, Wesley O; Peterson, Gregory W; Durke, Erin M

    2015-04-01

    Perfluoralkalation via plasma chemical vapor deposition has been used to improve hydrophobicity of surfaces. We have investigated this technique to improve the resistance of commercial polyurethane coatings to chemicals, such as chemical warfare agents. The reported results indicate the surface treatment minimizes the spread of agent droplets and the sorption of agent into the coating. The improvement in resistance is likely due to reduction of the coating's surface free energy via fluorine incorporation, but may also have contributing effects from surface morphology changes. The data indicates that plasma-based surface modifications may have utility in improving chemical resistance of commercial coatings.

  2. Development of plasma assisted thermal vapor deposition technique for high-quality thin film.

    PubMed

    Lee, Kang-Il; Choi, Yong Sup; Park, Hyun Jae

    2016-12-01

    The novel technique of Plasma-Assisted Vapor Deposition (PAVD) is developed as a new deposition method for thin metal films. The PAVD technique yields a high-quality thin film without any heating of the substrate because evaporated particles acquire energy from plasma that is confined to the inside of the evaporation source. Experiments of silver thin film deposition have been carried out in conditions of pressure lower than 10 -3 Pa. Pure silver plasma generation is verified by the measurement of the Ag-I peak using optical emission spectroscopy. A four point probe and a UV-VIS spectrophotometer are used to measure the electrical and optical properties of the silver film that is deposited by PAVD. For an ultra-thin silver film with a thickness of 6.5 nm, we obtain the result of high-performance silver film properties, including a sheet resistance <20 Ω sq -1 and a visible-range transmittance >75%. The PAVD-film properties show a low sheet resistance of 30% and the same transmittance with conventional thermal evaporation film. In the PAVD source, highly energetic particles and UV from plasma do not reach the substrate because the plasma is completely shielded by the optimized nozzle of the crucible. This new PAVD technique could be a realistic solution to improve the qualities of transparent electrodes for organic light emission device fabrication without causing damage to the organic layers.

  3. Development of plasma assisted thermal vapor deposition technique for high-quality thin film

    NASA Astrophysics Data System (ADS)

    Lee, Kang-Il; Choi, Yong Sup; Park, Hyun Jae

    2016-12-01

    The novel technique of Plasma-Assisted Vapor Deposition (PAVD) is developed as a new deposition method for thin metal films. The PAVD technique yields a high-quality thin film without any heating of the substrate because evaporated particles acquire energy from plasma that is confined to the inside of the evaporation source. Experiments of silver thin film deposition have been carried out in conditions of pressure lower than 10-3 Pa. Pure silver plasma generation is verified by the measurement of the Ag-I peak using optical emission spectroscopy. A four point probe and a UV-VIS spectrophotometer are used to measure the electrical and optical properties of the silver film that is deposited by PAVD. For an ultra-thin silver film with a thickness of 6.5 nm, we obtain the result of high-performance silver film properties, including a sheet resistance <20 Ω sq-1 and a visible-range transmittance >75%. The PAVD-film properties show a low sheet resistance of 30% and the same transmittance with conventional thermal evaporation film. In the PAVD source, highly energetic particles and UV from plasma do not reach the substrate because the plasma is completely shielded by the optimized nozzle of the crucible. This new PAVD technique could be a realistic solution to improve the qualities of transparent electrodes for organic light emission device fabrication without causing damage to the organic layers.

  4. Electrophoresis for the analysis of heparin purity and quality.

    PubMed

    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.

  5. High growth rate homoepitaxial diamond film deposition at high temperatures by microwave plasma-assisted chemical vapor deposition

    NASA Technical Reports Server (NTRS)

    Vohra, Yogesh K. (Inventor); McCauley, Thomas S. (Inventor)

    1997-01-01

    The deposition of high quality diamond films at high linear growth rates and substrate temperatures for microwave-plasma chemical vapor deposition is disclosed. The linear growth rate achieved for this process is generally greater than 50 .mu.m/hr for high quality films, as compared to rates of less than 5 .mu.m/hr generally reported for MPCVD processes.

  6. One-step microwave plasma enhanced chemical vapor deposition (MW-PECVD) for transparent superhydrophobic surface

    NASA Astrophysics Data System (ADS)

    Thongrom, Sukrit; Tirawanichakul, Yutthana; Munsit, Nantakan; Deangngam, Chalongrat

    2018-02-01

    We demonstrate a rapid and environmental friendly fabrication technique to produce optically clear superhydrophobic surfaces using poly (dimethylsiloxane) (PDMS) as a sole coating material. The inert PDMS chain is transformed into a 3-D irregular solid network through microwave plasma enhanced chemical vapor deposition (MW-PECVD) process. Thanks to high electron density in the microwave-activated plasma, coating can be done in just a single step with rapid deposition rate, typically much shorter than 10 s. Deposited layers show excellent superhydrophobic properties with water contact angles of ∼170° and roll-off angles as small as ∼3°. The plasma-deposited films can be ultrathin with thicknesses under 400 nm, greatly diminishing the optical loss. Moreover, with appropriate coating conditions, the coating layer can even enhance the transmission over the entire visible spectrum due to a partial anti-reflection effect.

  7. Formation of microchannels from low-temperature plasma-deposited silicon oxynitride

    DOEpatents

    Matzke, Carolyn M.; Ashby, Carol I. H.; Bridges, Monica M.; Manginell, Ronald P.

    2000-01-01

    A process for forming one or more fluid microchannels on a substrate is disclosed that is compatible with the formation of integrated circuitry on the substrate. The microchannels can be formed below an upper surface of the substrate, above the upper surface, or both. The microchannels are formed by depositing a covering layer of silicon oxynitride over a mold formed of a sacrificial material such as photoresist which can later be removed. The silicon oxynitride is deposited at a low temperature (.ltoreq.100.degree. C.) and preferably near room temperature using a high-density plasma (e.g. an electron-cyclotron resonance plasma or an inductively-coupled plasma). In some embodiments of the present invention, the microchannels can be completely lined with silicon oxynitride to present a uniform material composition to a fluid therein. The present invention has applications for forming microchannels for use in chromatography and electrophoresis. Additionally, the microchannels can be used for electrokinetic pumping, or for localized or global substrate cooling.

  8. Heparin-coated extracorporeal circulation systems in heart surgery.

    PubMed

    Tagarakis, Georgios I; Tsilimingas, Nikolaos B

    2009-11-01

    Despite the progress accomplished in the field of off-pump heart surgery, the vast majority of cardiac operations are still performed with the use of extracorporeal circulation, otherwise known as "heart-lung machine." This valuable tool, however, is connected with various complications, partly deriving from the application of intravenous heparin, necessary for the extracorporeal circuits to function. In order to deal with these complications, which among others include postoperative hemorrhage and systemic inflammatory response, several extracorporeal circulation systems, which contain a heparin-coating on their blood-contacting surfaces, have been developed with patents. The philosophy behind the creation of these systems is that with the controlled absorption and interaction of this heparin with the blood elements, adequate intraoperative anticoagulation with lower doses of systemic heparin and fewer systemic complications can be achieved. The idea of the use of heparin coatings has also been applied in other settings, such as in renal dialysis catheters, ECMO (extracorporeal membrane oxygenation), MECC (minimized extracorporeal circulation) and left ventricle assist devices.

  9. Low-temperature SiON films deposited by plasma-enhanced atomic layer deposition method using activated silicon precursor

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

    Suh, Sungin; Kim, Jun-Rae; Kim, Seongkyung

    2016-01-15

    It has not been an easy task to deposit SiN at low temperature by conventional plasma-enhanced atomic layer deposition (PE-ALD) since Si organic precursors generally have high activation energy for adsorption of the Si atoms on the Si-N networks. In this work, in order to achieve successful deposition of SiN film at low temperature, the plasma processing steps in the PE-ALD have been modified for easier activation of Si precursors. In this modification, the efficiency of chemisorption of Si precursor has been improved by additional plasma steps after purging of the Si precursor. As the result, the SiN films preparedmore » by the modified PE-ALD processes demonstrated higher purity of Si and N atoms with unwanted impurities such as C and O having below 10 at. % and Si-rich films could be formed consequently. Also, a very high step coverage ratio of 97% was obtained. Furthermore, the process-optimized SiN film showed a permissible charge-trapping capability with a wide memory window of 3.1 V when a capacitor structure was fabricated and measured with an insertion of the SiN film as the charge-trap layer. The modified PE-ALD process using the activated Si precursor would be one of the most practical and promising solutions for SiN deposition with lower thermal budget and higher cost-effectiveness.« less

  10. Correlations between plasma variables and the deposition process of Si films from chlorosilanes in low pressure RF plasma of argon and hydrogen

    NASA Technical Reports Server (NTRS)

    Avni, R.; Carmi, U.; Grill, A.; Manory, R.; Grossman, E.

    1984-01-01

    The dissociation of chlorosilanes to silicon and its deposition on a solid substrate in a RF plasma of mixtures of argon and hydrogen were investigated as a function of the macrovariables of the plasma. The dissociation mechanism of chlorosilanes and HCl as well as the formation of Si in the plasma state were studied by sampling the plasma with a quadrupole mass spectrometer. Macrovariables such as pressure, net RF power input and locations in the plasma reactor strongly influence the kinetics of dissociation. The deposition process of microcrystalline silicon films and its chlorine contamination were correlated to the dissociation mechanism of chlorosilanes and HCl.

  11. Silicon solar cell performance deposited by diamond like carbon thin film ;Atomic oxygen effects;

    NASA Astrophysics Data System (ADS)

    Aghaei, Abbas Ail; Eshaghi, Akbar; Karami, Esmaeil

    2017-09-01

    In this research, a diamond-like carbon thin film was deposited on p-type polycrystalline silicon solar cell via plasma-enhanced chemical vapor deposition method by using methane and hydrogen gases. The effect of atomic oxygen on the functioning of silicon coated DLC thin film and silicon was investigated. Raman spectroscopy, field emission scanning electron microscopy, atomic force microscopy and attenuated total reflection-Fourier transform infrared spectroscopy were used to characterize the structure and morphology of the DLC thin film. Photocurrent-voltage characteristics of the silicon solar cell were carried out using a solar simulator. The results showed that atomic oxygen exposure induced the including oxidation, structural changes, cross-linking reactions and bond breaking of the DLC film; thus reducing the optical properties. The photocurrent-voltage characteristics showed that although the properties of the fabricated thin film were decreased after being exposed to destructive rays, when compared with solar cell without any coating, it could protect it in atomic oxygen condition enhancing solar cell efficiency up to 12%. Thus, it can be said that diamond-like carbon thin layer protect the solar cell against atomic oxygen exposure.

  12. Helium-like magnesium embedded in strongly coupled plasma

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

    Bhattacharyya, Sukhamoy

    2016-05-06

    In recent days, with the advent of the x-ray free electron laser (FEL) with Linac coherent light source (LCLS) and the Orion laser, experimental studies on atomic systems within strongly coupled plasma environment with remarkable improvement in accuracy as compared to earlier experiments have become possible. In these kinds of experiments, hydrogen-like and helium-like spectral lines are used for determination of plasma parameters such as temperature, density. Accurate theoretical calculations are, therefore, necessary for such kind of studies within a dense plasma environment. In this work, ab initio calculations are carried out in the framework of the Rayleigh-Ritz variation principlemore » to estimate the ground state energy of helium-like magnesium within strongly coupled plasma environment. Explicitly correlated wave functions in Hylleraas coordinates have been used to incorporate the effect of electron correlation. The ion-sphere model potential that confines the central positive ion in a finite domain filled with plasma electrons has been adopted to mimic the strongly coupled plasma environment. Thermodynamic pressure ’felt’ by the ion in the ground states due to the confinement inside the ion spheres is also estimated.« less

  13. Platelet factor 4/heparin antibodies in blood bank donors.

    PubMed

    Hursting, Marcie J; Pai, Poulomi J; McCracken, Julianna E; Hwang, Fred; Suvarna, Shayela; Lokhnygina, Yuliya; Bandarenko, Nicholas; Arepally, Gowthami M

    2010-11-01

    Platelet factor 4 (PF4)/heparin antibody, typically associated with heparin therapy, is reported in some heparin-naive people. Seroprevalence in the general population, however, remains unclear. We prospectively evaluated PF4/heparin antibody in approximately 4,000 blood bank donors using a commercial enzyme-linked immunosorbent assay for initial and then repeated (confirmatory) testing. Antibody was detected initially in 249 (6.6%; 95% confidence interval [CI], 5.8%-7.4%) of 3,795 donors and repeatedly in 163 (4.3%; 95% CI, 3.7%-5.0%) of 3,789 evaluable donors. "Unconfirmed" positives were mostly (93%) low positives (optical density [OD] = 0.40-0.59). Of 163 repeatedly positive samples, 116 (71.2%) were low positives, and 124 (76.1%) exhibited heparin-dependent binding. Predominant isotypes of intermediate to high seropositive samples (OD >0.6) were IgG (20/39 [51%]), IgM (9/39 [23%]), and indeterminate (10/39 [26%]). The marked background seroprevalence of PF4/heparin antibody (4.3%-6.6%) with the preponderance of low (and frequently nonreproducible) positives in blood donors suggests the need for further assay calibration, categorization of antibody level, and studies evaluating clinical relevance of "naturally occurring" PF4/heparin antibodies.

  14. Quantitative PCR and disaccharide profiling to characterize the animal origin of low-molecular-weight heparins.

    PubMed

    Houiste, Céline; Auguste, Cécile; Macrez, Céline; Dereux, Stéphanie; Derouet, Angélique; Anger, Pascal

    2009-02-01

    Low-molecular-weight heparins (LMWHs) are widely used in the management of thrombosis and acute coronary syndromes. They are obtained by the enzymatic or chemical depolymerization of porcine intestinal heparin. Enoxaparin sodium, a widely used LMWH, has a unique and reproducible oligosaccharide profile which is determined by the origin of the starting material and a tightly controlled manufacturing process. Although other enoxaparin-like LMWHs do exist, specific release criteria including the origin of the crude heparin utilized for their production, have not been established. A quantitative polymerase chain reaction method has been developed to ensure the purity of the porcine origin of crude heparin, with a DNA detection limit as low as 1 ppm for bovine, or 10 ppm for ovine contaminants. This method is routinely used as the release acceptance criterion during enoxaparin sodium manufacturing. Furthermore, when the process removes DNA, other analytical techniques can be used to assess any contamination. Disaccharide profiling after exhaustive depolymerization can determine the presence of at least 10% bovine or 20% ovine material; multivariate analysis is useful to perform the data analysis. Consistent with the availability of newer technology, these methods should be required as acceptance criteria for crude heparins used in the manufacture of LMWHs to ensure their safety, quality, and immunologic profile.

  15. High-density plasma deposition manufacturing productivity improvement

    NASA Astrophysics Data System (ADS)

    Olmer, Leonard J.; Hudson, Chris P.

    1999-09-01

    High Density Plasma (HDP) deposition provides a means to deposit high quality dielectrics meeting submicron gap fill requirements. But, compared to traditional PECVD processing, HDP is relatively expensive due to the higher capital cost of the equipment. In order to keep processing costs low, it became necessary to maximize the wafer throughput of HDP processing without degrading the film properties. The approach taken was to optimize the post deposition microwave in-situ clean efficiency. A regression model, based on actual data, indicated that number of wafers processed before a chamber clean was the dominant factor. Furthermore, a design change in the ceramic hardware, surrounding the electrostatic chuck, provided thermal isolation resulting in an enhanced clean rate of the chamber process kit. An infra-red detector located in the chamber exhaust line provided a means to endpoint the clean and in-film particle data confirmed the infra-red results. The combination of increased chamber clean frequency, optimized clean time and improved process.

  16. Role of positive ions in determining the deposition rate and film chemistry of continuous wave hexamethyl disiloxane plasmas.

    PubMed

    Michelmore, Andrew; Bryant, Paul M; Steele, David A; Vasilev, Krasimir; Bradley, James W; Short, Robert D

    2011-10-04

    New data shed light on the mechanisms of film growth from low power, low pressure plasmas of organic compounds. These data rebalance the widely held view that plasma polymer formation is due to radical/neutral reactions only and that ions play no direct role in contributing mass at the surface. Ion reactions are shown to play an important role in both the plasma phase and at the surface. The mass deposition rate and ion flux in continuous wave hexamethyl disiloxane (HMDSO) plasmas have been studied as a function of pressure and applied RF power. Both the deposition rate and ion flux were shown to increase with applied power; however, the deposition rate increased with pressure while the ion flux decreased. Positive ion mass spectrometry of the plasma phase demonstrates that the dominant ionic species is the (HMDSO-CH(3))(+) ion at m/z 147, but significant fragmentation and subsequent oligomerization was also observed. Chemical analysis of the deposits by X-ray photoelectron spectroscopy and secondary ion mass spectrometry show that the deposits were consistent with deposits reported by previous workers grown from plasma and hyperthermal (HMDSO-CH(3))(+) ions. Increasing coordination of silicon with oxygen in the plasma deposits reveals the role of ions in the growth of plasma polymers. Comparing the calculated film thicknesses after a fixed total fluence of 1.5 × 10(19) ions/m(2) to results for hyperthermal ions shows that ions can contribute significantly to the total absorbed mass in the deposits. © 2011 American Chemical Society

  17. Plasma deposition of silver nanoparticles on ultrafiltration membranes: antibacterial and anti-biofouling properties.

    PubMed

    Cruz, Mercedes Cecilia; Ruano, Gustavo; Wolf, Marcus; Hecker, Dominic; Vidaurre, Elza Castro; Schmittgens, Ralph; Rajal, Verónica Beatriz

    2015-02-01

    A novel and versatile plasma reactor was used to modify Polyethersulphone commercial membranes. The equipment was applied to: i) functionalize the membranes with low-temperature plasmas, ii) deposit a film of poly(methyl methacrylate) (PMMA) by Plasma Enhanced Chemical Vapor Deposition (PECVD) and, iii) deposit silver nanoparticles (SNP) by Gas Flow Sputtering. Each modification process was performed in the same reactor consecutively, without exposure of the membranes to atmospheric air. Scanning electron microscopy and transmission electron microscopy were used to characterize the particles and modified membranes. SNP are evenly distributed on the membrane surface. Particle fixation and transport inside membranes were assessed before- and after-washing assays by X-ray photoelectron spectroscopy depth profiling analysis. PMMA addition improved SNP fixation. Plasma-treated membranes showed higher hydrophilicity. Anti-biofouling activity was successfully achieved against Gram-positive ( Enterococcus faecalis ) and -negative ( Salmonella Typhimurium) bacteria. Therefore, disinfection by ultrafiltration showed substantial resistance to biofouling. The post-synthesis functionalization process developed provides a more efficient fabrication route for anti-biofouling and anti-bacterial membranes used in the water treatment field. To the best of our knowledge, this is the first report of a gas phase condensation process combined with a PECVD procedure in order to deposit SNP on commercial membranes to inhibit biofouling formation.

  18. Plasma deposition of silver nanoparticles on ultrafiltration membranes: antibacterial and anti-biofouling properties

    PubMed Central

    Cruz, Mercedes Cecilia; Ruano, Gustavo; Wolf, Marcus; Hecker, Dominic; Vidaurre, Elza Castro; Schmittgens, Ralph; Rajal, Verónica Beatriz

    2015-01-01

    A novel and versatile plasma reactor was used to modify Polyethersulphone commercial membranes. The equipment was applied to: i) functionalize the membranes with low-temperature plasmas, ii) deposit a film of poly(methyl methacrylate) (PMMA) by Plasma Enhanced Chemical Vapor Deposition (PECVD) and, iii) deposit silver nanoparticles (SNP) by Gas Flow Sputtering. Each modification process was performed in the same reactor consecutively, without exposure of the membranes to atmospheric air. Scanning electron microscopy and transmission electron microscopy were used to characterize the particles and modified membranes. SNP are evenly distributed on the membrane surface. Particle fixation and transport inside membranes were assessed before- and after-washing assays by X-ray photoelectron spectroscopy depth profiling analysis. PMMA addition improved SNP fixation. Plasma-treated membranes showed higher hydrophilicity. Anti-biofouling activity was successfully achieved against Gram-positive (Enterococcus faecalis) and -negative (Salmonella Typhimurium) bacteria. Therefore, disinfection by ultrafiltration showed substantial resistance to biofouling. The post-synthesis functionalization process developed provides a more efficient fabrication route for anti-biofouling and anti-bacterial membranes used in the water treatment field. To the best of our knowledge, this is the first report of a gas phase condensation process combined with a PECVD procedure in order to deposit SNP on commercial membranes to inhibit biofouling formation. PMID:26166926

  19. Characterization of DC Magnetron Sputtering Plasma Used for Deposition of Amorphous Carbon Nitride

    NASA Astrophysics Data System (ADS)

    Camps, Enrique; Escobar-Alarcón, Luis; López, J.; Zambrano, G.; Prieto, P.

    2006-12-01

    Amorphous carbon nitride (a-CNx) thin films are attractive due to their potential applications, in different areas. This material can be hard and used as a protective coating, or can be soft and porous and used as the active element in gas sensors, it can also be used as a radiation detector due to its thermoluminescent response. The use of this material for one or another application, will depend on the material's structure, which can be changed by changing the deposition parameters. When using the d.c. magnetron sputtering technique it means mainly the change of discharge power, type of Ar/N2 gas mixture, and the working gas pressure. The variation of these deposition parameters has an important influence on the characteristics of the plasma formed in the discharge. In this work we studied the plasma characteristics, such as the type of excited species, plasma density, and electron temperature under different deposition conditions, using Optical Emission Spectroscopy (OES), and a single Langmuir probe. These parameters were correlated with the properties of a-CNx films deposited under those characterized regimes, in order to establish the role that the plasma parameters play on the formation of the different structures of CNx films.

  20. CMAS Interactions with Advanced Environmental Barrier Coatings Deposited via Plasma Spray- Physical Vapor Deposition

    NASA Technical Reports Server (NTRS)

    Harder, B. J.; Wiesner, V. L.; Zhu, D.; Johnson, N. S.

    2017-01-01

    Materials for advanced turbine engines are expected to have temperature capabilities in the range of 1370-1500C. At these temperatures the ingestion of sand and dust particulate can result in the formation of corrosive glass deposits referred to as CMAS. The presence of this glass can both thermomechanically and thermochemically significantly degrade protective coatings on metallic and ceramic components. Plasma Spray- Physical Vapor Deposition (PS-PVD) was used to deposit advanced environmental barrier coating (EBC) systems for investigation on their interaction with CMAS compositions. Coatings were exposed to CMAS and furnace tested in air from 1 to 50 hours at temperatures ranging from 1200-1500C. Coating composition and crystal structure were tracked with X-ray diffraction and microstructure with electron microscopy.

  1. Radio frequency plasma power dependence of the moisture permeation barrier characteristics of Al{sub 2}O{sub 3} films deposited by remote plasma atomic layer deposition

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

    Jung, Hyunsoo; Samsung Display Co. Ltd., Tangjeong, Chungcheongnam-Do 336-741; Choi, Hagyoung

    2013-11-07

    In the present study, we investigated the gas and moisture permeation barrier properties of Al{sub 2}O{sub 3} films deposited on polyethersulfone films (PES) by capacitively coupled plasma (CCP) type Remote Plasma Atomic Layer Deposition (RPALD) at Radio Frequency (RF) plasma powers ranging from 100 W to 400 W in 100 W increments using Trimethylaluminum [TMA, Al(CH{sub 3}){sub 3}] as the Al source and O{sub 2} plasma as the reactant. To study the gas and moisture permeation barrier properties of 100-nm-thick Al{sub 2}O{sub 3} at various plasma powers, the Water Vapor Transmission Rate (WVTR) was measured using an electrical Ca degradationmore » test. WVTR decreased as plasma power increased with WVTR values for 400 W and 100 W of 2.6 × 10{sup −4} gm{sup −2}day{sup −1} and 1.2 × 10{sup −3} gm{sup −2}day{sup −1}, respectively. The trends for life time, Al-O and O-H bond, density, and stoichiometry were similar to that of WVTR with improvement associated with increasing plasma power. Further, among plasma power ranging from 100 W to 400 W, the highest power of 400 W resulted in the best moisture permeation barrier properties. This result was attributed to differences in volume and amount of ion and radical fluxes, to join the ALD process, generated by O{sub 2} plasma as the plasma power changed during ALD process, which was determined using a plasma diagnosis technique called the Floating Harmonic Method (FHM). Plasma diagnosis by FHM revealed an increase in ion flux with increasing plasma power. With respect to the ALD process, our results indicated that higher plasma power generated increased ion and radical flux compared with lower plasma power. Thus, a higher plasma power provides the best gas and moisture permeation barrier properties.« less

  2. Mass spectrometric studies of SiO2 deposition in an indirect plasma enhanced LPCVD system

    NASA Technical Reports Server (NTRS)

    Iyer, R.; Lile, D. L.; Mcconica, C. M.

    1993-01-01

    Reaction pathways for the low temperature deposition of SiO2 from silane and indirect plasma-excited oxygen-nitrogen mixtures are proposed based on experimental evidence gained from mass spectrometry in an indirect plasma enhanced chemical vapor deposition chamber. It was observed that about 80-85 percent of the silane was oxidized to byproduct hydrogen and only about 15-20 percent to water. Such conversion levels have led us to interpret that silanol (SiH3OH) could be the precursor for SiO2 film deposition, rather than siloxane /(SiH3)2O/ which has generally been cited in the literature. From mass spectrometry, we have also shown the effects of the plasma, and of mixing small amounts of N2 with the oxygen flow, in increasing the deposition rate of SiO2. Free radical reaction of nitric oxide, synthesized from the reaction of oxygen and nitrogen in the plasma chamber, and an *ncrease in atomic oxygen concentration, are believed to be the reasons for these SiO2 deposition rate increases. Through mass spectrometry we have, in addition, been able to identify products, presumably originating from terminating reactions, among a sequence of chemical reactions proposed for the deposition of SiO2.

  3. Distinctive features of kinetics of plasma at high specific energy deposition

    NASA Astrophysics Data System (ADS)

    Lepikhin, Nikita; Popov, Nikolay; Starikovskaia, Svetlana

    2016-09-01

    A nanosecond capillary discharge in pure nitrogen at moderate pressures is used as an experimental tool for plasma kinetics studies at conditions of high specific deposited energy up to 1 eV/molecule. Experimental observations based on electrical (back current shunts, capacitive probe) and spectroscopic measurements (quenching rates; translational, rotational and vibrational temperature measurements) demonstrate that high specific deposited energy, at electric fields of 200-300 Td, can significantly change gas kinetics in the discharge and in the afterglow. The numerical calculations in 1D axially symmetric geometry using experimental data as input parameters show that changes in the plasma kinetics are caused by extremely high excitation degree: up to 10% of molecular nitrogen is electronically excited at present conditions. Distinctive features of kinetics of plasma at high specific energy deposition as well as details of the experimental technique and numerical calculations will be present. The work was partially supported by French National Agency, ANR (PLASMAFLAME Project, 2011 BS09 025 01), AOARD AFOSR, FA2386-13-1-4064 grant (Program Officer Prof. Chiping Li), LabEx Plas@Par and Linked International Laboratory LIA KaPPA (France-Russia).

  4. Growth of diamond by RF plasma-assisted chemical vapor deposition

    NASA Technical Reports Server (NTRS)

    Meyer, Duane E.; Ianno, Natale J.; Woollam, John A.; Swartzlander, A. B.; Nelson, A. J.

    1988-01-01

    A system has been designed and constructed to produce diamond particles by inductively coupled radio-frequency, plasma-assisted chemical vapor deposition. This is a low-pressure, low-temperature process used in an attempt to deposit diamond on substrates of glass, quartz, silicon, nickel, and boron nitride. Several deposition parameters have been varied including substrate temperature, gas concentration, gas pressure, total gas flow rate, RF input power, and deposition time. Analytical methods employed to determine composition and structure of the deposits include scanning electron microscopy, absorption spectroscopy, scanning Auger microprobe spectroscopy, and Raman spectroscopy. Analysis indicates that particles having a thin graphite surface, as well as diamond particles with no surface coatings, have been deposited. Deposits on quartz have exhibited optical bandgaps as high as 4.5 eV. Scanning electron microscopy analysis shows that particles are deposited on a pedestal which Auger spectroscopy indicates to be graphite. This is a phenomenon that has not been previously reported in the literature.

  5. Capillary Electrophoresis-Mass Spectrometry for the Analysis of Heparin Oligosaccharides and Low Molecular Weight Heparin.

    PubMed

    Sun, Xiaojun; Lin, Lei; Liu, Xinyue; Zhang, Fuming; Chi, Lianli; Xia, Qiangwei; Linhardt, Robert J

    2016-02-02

    Heparins, highly sulfated, linear polysaccharides also known as glycosaminoglycans, are among the most challenging biopolymers to analyze. Hyphenated techniques in conjunction with mass spectrometry (MS) offer rapid analysis of complex glycosaminoglycan mixtures, providing detailed structural and quantitative data. Previous analytical approaches have often relied on liquid chromatography (LC)-MS, and some have limitations including long separation times, low resolution of oligosaccharide mixtures, incompatibility of eluents, and often require oligosaccharide derivatization. This study examines the analysis of glycosaminoglycan oligosaccharides using a novel electrokinetic pump-based capillary electrophoresis (CE)-MS interface. CE separation and electrospray were optimized using a volatile ammonium bicarbonate electrolyte and a methanol-formic acid sheath fluid. The online analyses of highly sulfated heparin oligosaccharides, ranging from disaccharides to low molecular weight heparins, were performed within a 10 min time frame, offering an opportunity for higher-throughput analysis. Disaccharide compositional analysis as well as top-down analysis of low molecular weight heparin was demonstrated. Using normal polarity CE separation and positive-ion electrospray ionization MS, excellent run-to-run reproducibility (relative standard deviation of 3.6-5.1% for peak area and 0.2-0.4% for peak migration time) and sensitivity (limit of quantification of 2.0-5.9 ng/mL and limit of detection of 0.6-1.8 ng/mL) could be achieved.

  6. The Heparan and Heparin Metabolism Pathway is Involved in Regulation of Fatty Acid Composition

    USDA-ARS?s Scientific Manuscript database

    Six genes involved in the heparan sulfate and heparin metabolism pathway, DSEL (dermatan sulfate epimerase-like), EXTL1 (exostoses (multiple)-like 1), HS6ST1 (heparan sulfate 6-O-sulfotransferase 1), HS6ST3 (heparan sulfate 6-O-sulfotransferase 3), NDST3 (N-deacetylase/N-sulfotransferase (heparan gl...

  7. Low-molecular-weight heparin for thromboprophylaxis.

    PubMed

    Camporese, Giuseppe; Bernardi, Enrico

    2009-09-01

    Venous thromboembolism represents a potentially threatening complication in surgical and medical patients. Thromboprophylaxis showed a significant reduction of venous thromboembolic events, and low-molecular-weight heparins have been considered the standardized prophylactic regimen for a long time. The purpose of this review is to provide updated evidence on the use of low-molecular-weight heparins for prevention of venous thromboembolism after the publication of the latest American College of Chest Physicians Evidence-Based Clinical Practice Guidelines on antithrombotic and thrombolytic therapy. Low-molecular-weight heparins, used as comparator or investigational drug, have been investigated in several studies not included in the analysis of the latest American College of Chest Physicians Guidelines on Antithrombotic and Thrombolytic Therapy. Data gathered from studies published from December 2007 up to May 2009 dealing with surgical and medical patients have been collected and discussed. Low-molecular-weight heparins are expanding their application, but progressively they will be replaced by other new antithrombotics for the prophylaxis of venous thromboembolism. Surgical patients undergo a more concerted approach to thromboprophylaxis than medical patients. Future research should aim at improving prophylaxis in the latter setting in order to significantly reduce the rate of venous thromboembolic events.

  8. A solid-state nuclear magnetic resonance study of post-plasma reactions in organosilicone microwave plasma-enhanced chemical vapor deposition (PECVD) coatings.

    PubMed

    Hall, Colin J; Ponnusamy, Thirunavukkarasu; Murphy, Peter J; Lindberg, Mats; Antzutkin, Oleg N; Griesser, Hans J

    2014-06-11

    Plasma-polymerized organosilicone coatings can be used to impart abrasion resistance and barrier properties to plastic substrates such as polycarbonate. Coating rates suitable for industrial-scale deposition, up to 100 nm/s, can be achieved through the use of microwave plasma-enhanced chemical vapor deposition (PECVD), with optimal process vapors such as tetramethyldisiloxane (TMDSO) and oxygen. However, it has been found that under certain deposition conditions, such coatings are subject to post-plasma changes; crazing or cracking can occur anytime from days to months after deposition. To understand the cause of the crazing and its dependence on processing plasma parameters, the effects of post-plasma reactions on the chemical bonding structure of coatings deposited with varying TMDSO-to-O2 ratios was studied with (29)Si and (13)C solid-state magic angle spinning nuclear magnetic resonance (MAS NMR) using both single-pulse and cross-polarization techniques. The coatings showed complex chemical compositions significantly altered from the parent monomer. (29)Si MAS NMR spectra revealed four main groups of resonance lines, which correspond to four siloxane moieties (i.e., mono (M), di (D), tri (T), and quaternary (Q)) and how they are bound to oxygen. Quantitative measurements showed that the ratio of TMDSO to oxygen could shift the chemical structure of the coating from 39% to 55% in Q-type bonds and from 28% to 16% for D-type bonds. Post-plasma reactions were found to produce changes in relative intensities of (29)Si resonance lines. The NMR data were complemented by Fourier transform infrared (FTIR) spectroscopy. Together, these techniques have shown that the bonding environment of Si is drastically altered by varying the TMDSO-to-O2 ratio during PECVD, and that post-plasma reactions increase the cross-link density of the silicon-oxygen network. It appears that Si-H and Si-OH chemical groups are the most susceptible to post-plasma reactions. Coatings produced at a

  9. Facilitation of learning and modulation of frontal cortex acetylcholine by ventral pallidal injection of heparin glucosaminoglycan.

    PubMed

    De Souza Silva, M A; Jezek, K; Weth, K; Müller, H W; Huston, J P; Brandao, M L; Hasenöhrl, R U

    2002-01-01

    We examined the effects of heparin on learning and frontal cortex acetylcholine parameters following injection of the glucosaminoglycan into the ventral pallidum. In Experiment 1, possible mnemoactive effects of intrapallidal heparin injection were assessed. Rats with chronically implanted cannulae were administered heparin (0.1, 1.0, 10 ng) or vehicle (0.5 microl) and were tested on a one-trial step-through avoidance task. Two retention tests were carried out in each animal, one at 1.5 h after training to measure short-term memory and another at 24 h to measure long-term memory. Post-trial intrapallidal injection of 1.0 ng heparin improved both short- and long-term retention of the task, whereas the lower and the higher dose of the glucosaminoglycan had no effect. When the effective dose of heparin was injected 5 h, rather than immediately after training, it no longer facilitated long-term retention of the conditioned avoidance response. In Experiment 2, the effects of ventral pallidal heparin injection on frontal cortex acetylcholine and choline concentrations were investigated with in vivo microdialysis in anaesthetized rats. Heparin, administered in the dose of 1.0 ng, which was effective in facilitating avoidance performance, produced a delayed increase in cortical acetylcholine levels ipsi- and contralaterally to the side of intrabasalis injection, resembling the known neurochemical effects obtained for another glycosaminoglycan, chondroitin sulfate, which recently was shown to facilitate inhibitory avoidance learning and to increase frontal cortex acetylcholine. The present findings indicate that heparin, like other extracellular matrix proteoglycans, can exert beneficial effects on memory and strengthen the presumptive relationship between such promnestic effects of proteoglycans and basal forebrain cholinergic mechanisms. The data are discussed with respect to the presumed roles of matrix molecules in extrasynaptic volume transmission and in the 'cross

  10. Heparin: new life for an old drug.

    PubMed

    Aláez-Versón, Carlos Raúl; Lantero, Elena; Fernàndez-Busquets, Xavier

    2017-07-01

    Heparin is one of the oldest drugs, which nevertheless remains in widespread clinical use as an inhibitor of blood coagulation. The history of its identification a century ago unfolded amid one of the most fascinating scientific controversies turning around the distribution of credit for its discovery. The composition, purification and structure-function relationship of this naturally occurring glycosaminoglycan regarding its classical role as anticoagulant will be dealt with before proceeding to discuss its therapeutic potential in, among other, inflammatory and infectious disease, cancer treatment, cystic fibrosis and Alzheimer's disease. The first bibliographic reference hit using the words 'nanomedicine' and 'heparin' is as recent as 2008. Since then, nanomedical applications of heparin have experienced an exponential growth that will be discussed in detail, with particular emphasis on its antimalarial activity. Some of the most intriguing potential applications of heparin nanomedicines will be exposed, such as those contemplating the delivery of drugs to the mosquito stages of malaria parasites.

  11. Cerebral Venous Sinus Thrombosis Due to Low-molecular-weight Heparin-induced Thrombocytopenia.

    PubMed

    Gleichgerrcht, Ezequiel; Lim, Ming Y; Turan, Tanya N

    2017-11-01

    Heparin-induced thrombocytopenia (HIT) is an immune-mediated complication of heparin exposure. A limited number of studies have reported cerebral venous sinus thrombosis (CVST) as the presenting thrombotic event induced by HIT, only one of which occurred with exposure to low-molecular-weight heparin (LMWH), with death as outcome. Here, we present a unique case of LMWH-induced HIT leading to CVST but resulting in good clinical outcome. A 52-year-old woman received subcutaneous LMWH for deep vein thrombosis prophylaxis while in rehabilitation following kyphoplasty for spinal fracture related to recent trauma. On postoperative day 15, she developed acute onset altered mental status with significant agitation and nonsensical speech and was found to have brain imaging findings suggestive of CVST. Work-up revealed a drop in platelets associated with HIT, which did not improve off heparin products and with steroids, requiring intravenous immunoglobulin therapy, likely due to an overlapping immune thrombocytopenic purpura. Patient was managed on an argatroban drip until platelet count normalized and was able to transition to warfarin. Her clinical outcome was very favorable with near-normal neurological exam except for subtle cognitive changes. This unique case of LMWH-induced HIT leading to CVST but resulting in good clinical outcome highlights the importance of linking CVST with HIT and of establishing the need for early alternative antithrombotic therapeutic strategies.

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

    PubMed

    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.

  13. Atmospheric pressure plasma deposition of antimicrobial coatings on non-woven textiles

    NASA Astrophysics Data System (ADS)

    Nikiforov, Anton Yu.; Deng, Xiaolong; Onyshchenko, Iuliia; Vujosevic, Danijela; Vuksanovic, Vineta; Cvelbar, Uros; De Geyter, Nathalie; Morent, Rino; Leys, Christophe

    2016-08-01

    A simple method for preparation of nanoparticle incorporated non-woven fabric with high antibacterial efficiency has been proposed based on atmospheric pressure plasma process. In this work direct current plasma jet stabilized by fast nitrogen flow was used as a plasma deposition source. Three different types of the nanoparticles (silver, copper and zinc oxide nanoparticles) were employed as antimicrobial agents. X-ray photoelectron spectroscopy (XPS) measurements have shown a positive chemical shift observed for Ag 3d 5/2 (at 368.1 eV) suggests that silver nanoparticles (AgNPs) are partly oxidized during the deposition. The surface chemistry and the antibacterial activity of the samples against Staphylococcus aureus and Escherichia coli were investigated and analyzed. It is shown that the samples loaded with nanoparticles of Ag and Cu and having the barrier layer of 10 nm characterized by almost 97% of bacterial reduction whereas the samples with ZnO nanoparticles provide 86% reduction of Staphylococcus aureus. Contribution to the topical issue "6th Central European Symposium on Plasma Chemistry (CESPC-6)", edited by Nicolas Gherardi, Ester Marotta and Cristina Paradisi

  14. Structure, mechanical, and frictional properties of hydrogenated fullerene-like amorphous carbon film prepared by direct current plasma enhanced chemical vapor deposition

    NASA Astrophysics Data System (ADS)

    Wang, Yongfu; Gao, Kaixiong; Zhang, Junyan

    2016-07-01

    In this study, fullerene like carbon (FL-C) is introduced in hydrogenated amorphous carbon (a-C:H) film by employing a direct current plasma enhanced chemical vapor deposition. The film has a low friction and wear, such as 0.011 and 2.3 × 10-9mm3/N m in the N2, and 0.014 and 8.4 × 10-8mm3/N m in the humid air, and high hardness and elasticity (25.8 GPa and 83.1%), to make further engineering applications in practice. It has several nanometers ordered domains consisting of less frequently cross-linked graphitic sheet stacks. We provide new evidences for understanding the reported Raman fit model involving four vibrational frequencies from five, six, and seven C-atom rings of FL-C structures, and discuss the structure evolution before or after friction according to the change in the 1200 cm-1 Raman band intensity caused by five- and seven-carbon rings. Friction inevitably facilitates the transformation of carbon into FL-C nanostructures, namely, the ultra low friction comes from both such structures within the carbon film and the sliding induced at friction interface.

  15. In vivo distribution and antitumor activity of heparin-stabilized doxorubicin-loaded liposomes.

    PubMed

    Han, Hee Dong; Lee, Aeri; Song, Chung Kil; Hwang, Taewon; Seong, Hasoo; Lee, Chong Ock; Shin, Byung Cheol

    2006-04-26

    The purpose of this study was to investigate the effect of heparin conjugation to the surface of doxorubicin (DOX)-loaded liposomes on the circulation time, biodistribution and antitumor activity after intravenous injection in murine B16F10 melanoma tumor-bearing mice. The heparin-conjugated liposomes (heparin-liposomes) were prepared by fixation of the negatively charged heparin to the positively charged liposomes. The existence of heparin on the liposomal surface was confirmed by measuring the changes in the particle size, zeta potential and heparin amount of the liposomes. The stability of the heparin-liposomes in serum was higher than that of the control liposomes, due to the heparin-liposomes being better protected from the adsorption of serum proteins. The DOX-loaded heparin-liposomes showed high drug levels for up to 64 h after the intravenous injection and the half-life of DOX was approximately 8.4- or 1.5-fold higher than that of the control liposomes or polyethyleneglycol-fixed liposomes (PEG-liposomes), respectively. The heparin-liposomes accumulated to a greater extent in the tumor than the control or PEG-liposomes as a result of their lower uptake by the reticuloendothelial system cells in the liver and spleen. In addition, the DOX-loaded heparin-liposomes retarded the growth of the tumor effectively compared with the control or PEG-liposomes. These results indicate the promising potential of heparin-liposomes as a new sterically stabilized liposomal delivery system for the enhancement of the therapeutic efficacy of chemotherapeutic agents.

  16. Low temperature growth of gallium oxide thin films via plasma enhanced atomic layer deposition.

    PubMed

    O'Donoghue, Richard; Rechmann, Julian; Aghaee, Morteza; Rogalla, Detlef; Becker, Hans-Werner; Creatore, Mariadriana; Wieck, Andreas Dirk; Devi, Anjana

    2017-12-21

    Herein we describe an efficient low temperature (60-160 °C) plasma enhanced atomic layer deposition (PEALD) process for gallium oxide (Ga 2 O 3 ) thin films using hexakis(dimethylamido)digallium [Ga(NMe 2 ) 3 ] 2 with oxygen (O 2 ) plasma on Si(100). The use of O 2 plasma was found to have a significant improvement on the growth rate and deposition temperature when compared to former Ga 2 O 3 processes. The process yielded the second highest growth rates (1.5 Å per cycle) in terms of Ga 2 O 3 ALD and the lowest temperature to date for the ALD growth of Ga 2 O 3 and typical ALD characteristics were determined. From in situ quartz crystal microbalance (QCM) studies and ex situ ellipsometry measurements, it was deduced that the process is initially substrate-inhibited. Complementary analytical techniques were employed to investigate the crystallinity (grazing-incidence X-ray diffraction), composition (Rutherford backscattering analysis/nuclear reaction analysis/X-ray photoelectron spectroscopy), morphology (X-ray reflectivity/atomic force microscopy) which revealed the formation of amorphous, homogeneous and nearly stoichiometric Ga 2 O 3 thin films of high purity (carbon and nitrogen <2 at.%) under optimised process conditions. Tauc plots obtained via UV-Vis spectroscopy yielded a band gap of 4.9 eV and the transmittance values were more than 80%. Upon annealing at 1000 °C, the transformation to oxygen rich polycrystalline β-gallium oxide took place, which also resulted in the densification and roughening of the layer, accompanied by a slight reduction in the band gap. This work outlines a fast and efficient method for the low temperature ALD growth of Ga 2 O 3 thin films and provides the means to deposit Ga 2 O 3 upon thermally sensitive polymers like polyethylene terephthalate.

  17. Low-molecular-weight heparins: differential characterization/physical characterization.

    PubMed

    Guerrini, Marco; Bisio, Antonella

    2012-01-01

    Low-molecular-weight heparins (LMWHs), derived from unfractionated heparin (UFH) through different depolymerization processes, have advantages with respect to the parent heparin in terms of pharmacokinetics, convenience of administration, and reduced side effects. Each LMWH can be considered as an independent drug with its own activity profile, placing significance on their biophysical characterization, which will also enable a better understanding of their structure-function relationship. Several chemical and physical methods, some involving sample modification, are now available and are reviewed.

  18. A ToF-SIMS and XPS study of protein adsorption and cell attachment across PEG-like plasma polymer films with lateral compositional gradients

    NASA Astrophysics Data System (ADS)

    Menzies, Donna J.; Jasieniak, Marek; Griesser, Hans J.; Forsythe, John S.; Johnson, Graham; McFarland, Gail A.; Muir, Benjamin W.

    2012-12-01

    In this work we report a detailed X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) study of poly(ethylene glycol) PEG-like chemical gradients deposited via plasma enhanced chemical vapour deposition (PECVD) at two different load powers using diethylene glycol dimethyl ether (DG) as a monomer. Principal component analysis (PCA) was applied to the ToF-SIMS data both before and after protein adsorption on the plasma polymer thin films. Results of the PCA loadings indicated a higher content of hydrocarbon fragments across the higher load power gradient, which adsorbed higher amounts of proteins. Gradients deposited at a lower load power retained a higher degree of monomer like functionality as did the central region directly underneath the knife edge electrode. Analysis of the adsorption of serum proteins (human serum albumin and fetal bovine serum) was monitored across the gradient films and increased with decreasing ether (PEG-like) film chemistries. The effect of protein incubation time on the levels adsorbed fetal bovine serum on the plasma polymer films was critical, with significantly more protein adsorbing after 24 hour incubation times on both gradient films. The attachment of HeLa cells on the gradients appeared to be dictated not only by the surface chemistry, but also by the adsorption of serum proteins. XPS analysis revealed that at surface ether concentrations of less than 70% in the gradient films, significant increases in protein and cell attachment were observed.

  19. Engineering of routes to heparin and related polysaccharides.

    PubMed

    Bhaskar, Ujjwal; Sterner, Eric; Hickey, Anne Marie; Onishi, Akihiro; Zhang, Fuming; Dordick, Jonathan S; Linhardt, Robert J

    2012-01-01

    Anticoagulant heparin has been shown to possess important biological functions that vary according to its fine structure. Variability within heparin's structure occurs owing to its biosynthesis and animal tissue-based recovery and adds another dimension to its complex polymeric structure. The structural variations in chain length and sulfation patterns mediate its interaction with many heparin-binding proteins, thereby eliciting complex biological responses. The advent of novel chemical and enzymatic approaches for polysaccharide synthesis coupled with high throughput combinatorial approaches for drug discovery have facilitated an increased effort to understand heparin's structure-activity relationships. An improved understanding would offer potential for new therapeutic development through the engineering of polysaccharides. Such a bioengineering approach requires the amalgamation of several different disciplines, including carbohydrate synthesis, applied enzymology, metabolic engineering, and process biochemistry.

  20. Radiative transition of hydrogen-like ions in quantum plasma

    NASA Astrophysics Data System (ADS)

    Hu, Hongwei; Chen, Zhanbin; Chen, Wencong

    2016-12-01

    At fusion plasma electron temperature and number density regimes of 1 × 103-1 × 107 K and 1 × 1028-1 × 1031/m3, respectively, the excited states and radiative transition of hydrogen-like ions in fusion plasmas are studied. The results show that quantum plasma model is more suitable to describe the fusion plasma than the Debye screening model. Relativistic correction to bound-state energies of the low-Z hydrogen-like ions is so small that it can be ignored. The transition probability decreases with plasma density, but the transition probabilities have the same order of magnitude in the same number density regime.

  1. Heparin Stimulates Elastogenesis: Application to Silk-Based Vascular Grafts

    PubMed Central

    Baughman, Cassandra; Kaplan, David L.; Castellot, John J.

    2013-01-01

    With over 500,000 coronary artery bypass grafts (CABG) performed annually in the United States alone, there is a significant clinical need for a small diameter tissue engineered vascular graft. A principle goal in tissue engineering is to develop materials and growth conditions that encourage appropriate re-cellularization and extracellular matrix formation in vivo. A particular challenge in vascular tissue engineering results from the inability of adult cells to produce elastin, as its expression is developmentally limited. We investigated factors to stimulate elastogenesis in vitro, and found that heparin treatment of adult human vascular smooth muscle cells promoted the formation of elastic fibers. This effect was heparin-specific, and dependent on cell density and growth state. We then applied this information to a silk-based construct, and found that immobilized heparin showed essentially identical biological effects to that of soluble heparin. These findings indicate that heparinized vascular grafts may promote elastin formation and regulate restenosis, in addition to heparin’s well-established antithrombotic properties. Given the increase in elastin mRNA level and the increase in extracellular elastin present, our data suggests that there may be multiple levels of elastin regulation that are mediated by heparin treatment. PMID:21600981

  2. Plasma Spray-PVD: A New Thermal Spray Process to Deposit Out of the Vapor Phase

    NASA Astrophysics Data System (ADS)

    von Niessen, Konstantin; Gindrat, Malko

    2011-06-01

    Plasma spray-physical vapor deposition (PS-PVD) is a low pressure plasma spray technology recently developed by Sulzer Metco AG (Switzerland). Even though it is a thermal spray process, it can deposit coatings out of the vapor phase. The basis of PS-PVD is the low pressure plasma spraying (LPPS) technology that has been well established in industry for several years. In comparison to conventional vacuum plasma spraying (VPS) or low pressure plasma spraying (LPPS), the new proposed process uses a high energy plasma gun operated at a reduced work pressure of 0.1 kPa (1 mbar). Owing to the high energy plasma and further reduced work pressure, PS-PVD is able to deposit a coating not only by melting the feed stock material which builds up a layer from liquid splats but also by vaporizing the injected material. Therefore, the PS-PVD process fills the gap between the conventional physical vapor deposition (PVD) technologies and standard thermal spray processes. The possibility to vaporize feedstock material and to produce layers out of the vapor phase results in new and unique coating microstructures. The properties of such coatings are superior to those of thermal spray and electron beam-physical vapor deposition (EB-PVD) coatings. In contrast to EB-PVD, PS-PVD incorporates the vaporized coating material into a supersonic plasma plume. Owing to the forced gas stream of the plasma jet, complex shaped parts such as multi-airfoil turbine vanes can be coated with columnar thermal barrier coatings using PS-PVD. Even shadowed areas and areas which are not in the line of sight of the coating source can be coated homogeneously. This article reports on the progress made by Sulzer Metco in developing a thermal spray process to produce coatings out of the vapor phase. Columnar thermal barrier coatings made of Yttria-stabilized Zircona (YSZ) are optimized to serve in a turbine engine. This process includes not only preferable coating properties such as strain tolerance and erosion

  3. Suspensions Plasma Spraying of Ceramics with Hybrid Water-Stabilized Plasma Technology

    NASA Astrophysics Data System (ADS)

    Musalek, Radek; Medricky, Jan; Tesar, Tomas; Kotlan, Jiri; Pala, Zdenek; Lukac, Frantisek; Chraska, Tomas; Curry, Nicholas

    2017-01-01

    Technology of water-stabilized plasma torch was recently substantially updated through introduction of a so-called hybrid concept that combines benefits of water stabilization and gas stabilization principles. The high-enthalpy plasma provided by the WSP-H ("hybrid") torch may be used for thermal spraying of powders as well as liquid feedstocks with high feed rates. In this study, results from three selected experiments with suspension plasma spraying with WSP-H technology are presented. Possibility of deposition of coatings with controlled microstructures was demonstrated for three different ceramics (YSZ—yttria-stabilized zirconia, YAG—yttrium aluminum garnet and Al2O3) introduced into ethanol-based suspensions. Shadowgraphy was used for optimization of suspension injection and visualization of the liquid fragmentation in the plasma jet. Coatings were deposited onto substrates attached to the rotating carousel with integrated temperature monitoring and air cooling, which provided an excellent reproducibility of the deposition process. Deposition of columnar-like YSZ and dense YAG and Al2O3 coatings was successfully achieved. Deposition efficiency reached more than 50%, as evaluated according to EN ISO 17 836 standard.

  4. Metabolic aspects and viability of heparin/CPDA-1-stored red cell concentrate as a by-product of a high-yield factor VIII production method.

    PubMed

    de Jonge, J; Smit Sibinga, C T; Das, P C

    1983-01-01

    As a by-product of a new high-yield method of production of freeze-dried factor VIII, red cell concentrate (RCC) containing a small amount of heparin besides CPDA-1 was studied. Compared to CPDA-1 stored RCC no difference was found in hematology parameters and 2,3-DPG levels during 28 days storage. Although still in the normal range for transfusion, ATP levels were significantly lower compared to CPDA-1-stored RCC after 30 days shelf life. A survival study with 51Cr-labelled red cells showed good recovery and normal red cell half-life. Rapid transfusion of heparin/CPDA-1 RCC in 6 volunteers did not have any effect on aPTT. Heparin could not be detected in posttransfusion plasma samples.

  5. [Low molecular weight heparin and non valvular atrial fibrillation].

    PubMed

    Ederhy, S; Di Angelantonio, E; Meuleman, C; Janower, S; Boccara, F; Cohen, A

    2006-12-01

    Low molecular weight heparin (LMWH) are obtained through chemical or enzyme depolymerisation of unfractioned heparins (UFH). LMWHs present several advantages over UFH: they exhibit a smaller interindividual variability of the anticoagulant effect, they have a greater bioavailability, a longer plasma half-life and do not require monitoring of the anticoagulant effect. LMWH have restrictive indications in AF patients, cardioversion (II level C and TEE for ACC/AHA/ESC and 2C for ACCP guidelines) or use as a bridge therapy (IIB, level C for ACC/AHA/ESC). The ACE study (Anticoagulation for cardioversion using enoxaparin), showed a reduction, though not statistically significant, of 42% of the composite end point (embolic event, major bleeding and death) 2.8% under enoxaparin vs. 4.8 % under conventional treatment, relative risk 0.58, CI 95% 0.23-1.46). Other studies, using dalteparin, confirmed that an anticoagulant treatment using LMWH followed by warfarin was at least as good as conventional management. ACUTE II (Assessment of cardioversion using transesophageal echochardiography), a randomized multicenter trial, compared the efficacy and tolerance of enoxaparin (1 mg/kg every 12 hours) and UFH in 155 patients eligible for a TEE-guided cardioversion. These patients were administered LMWH or UFH for 24 hours before TEE or cardioversion. There were no significative differences regarding the incidence of the study end points, in particular stroke and bleeding, and no death occurred. HAEST (Heparin in acute embolic stroke trial), a randomized, placebo-controlled, double blind trial failed to show the LMWH superiority over aspirin in patients with acute ischemic stroke and atrial fibrillation. Finally, LMWH have been proposed as a bridge therapy in patients under chronic VKA prior to surgery or invasive procedures. This strategy resulted in a low rate of thromboembolic events and major bleedings.

  6. Novel Prospects for Plasma Spray-Physical Vapor Deposition of Columnar Thermal Barrier Coatings

    NASA Astrophysics Data System (ADS)

    Anwaar, Aleem; Wei, Lianglinag; Guo, Qian; Zhang, Baopeng; Guo, Hongbo

    2017-12-01

    Plasma spray-physical vapor deposition (PS-PVD) is an emerging coating technique that can produce columnar thermal barrier coatings from vapor phase. Feedstock treatment at the start of its trajectory in the plasma torch nozzle is important for such vapor-phase deposition. This study describes the effects of the plasma composition (Ar/He) on the plasma characteristics, plasma-particle interaction, and particle dynamics at different points spatially distributed inside the plasma torch nozzle. The results of calculations show that increasing the fraction of argon in the plasma gas mixture enhances the momentum and heat flow between the plasma and injected feedstock. For the plasma gas combination of 45Ar/45He, the total enthalpy transferred to a representative powder particle inside the plasma torch nozzle is highest ( 9828 kJ/kg). Moreover, due to the properties of the plasma, the contribution of the cylindrical throat, i.e., from the feed injection point (FIP) to the start of divergence (SOD), to the total transferred energy is 69%. The carrier gas flow for different plasma gas mixtures was also investigated by optical emission spectroscopy (OES) measurements of zirconium emissions. Yttria-stabilized zirconia (YSZ) coating microstructures were produced when using selected plasma gas compositions and corresponding carrier gas flows; structural morphologies were found to be in good agreement with OES and theoretical predictions. Quasicolumnar microstructure was obtained with porosity of 15% when applying the plasma composition of 45Ar/45He.

  7. Surface and corrosion characteristics of carbon plasma implanted and deposited nickel-titanium alloy

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

    Poon, R.W.Y.; Liu, X.Y.; Chung, C.Y.

    2005-05-01

    Nickel-titanium shape memory alloys (NiTi) are potentially useful in orthopedic implants on account of their super-elastic and shape memory properties. However, the materials are prone to surface corrosion and the most common problem is out-diffusion of harmful Ni ions from the substrate into body tissues and fluids. In order to improve the corrosion resistance and related surface properties, we used the technique of plasma immersion ion implantation and deposition to deposit an amorphous hydrogenated carbon coating onto NiTi and implant carbon into NiTi. Both the deposited amorphous carbon film and carbon plasma implanted samples exhibit much improved corrosion resistances andmore » surface mechanical properties and possible mechanisms are suggested.« less

  8. Chemically treated plasma Aβ is a potential blood-based biomarker for screening cerebral amyloid deposition.

    PubMed

    Park, Jong-Chan; Han, Sun-Ho; Cho, Hyun Jin; Byun, Min Soo; Yi, Dahyun; Choe, Young Min; Kang, Seokjo; Jung, Eun Sun; Won, Su Jin; Kim, Eun Hye; Kim, Yu Kyeong; Lee, Dong Young; Mook-Jung, Inhee

    2017-03-22

    Plasma β-amyloid (Aβ) is a potential candidate for an Alzheimer's disease (AD) biomarker because blood is an easily accessible bio-fluid, which can be collected routinely, and Aβ is one of the major hallmarks of AD pathogenesis in the brain. However, the association between plasma Aβ levels and AD diagnosis is still unclear due to the instability and inaccurate measurements of plasma Aβ levels in the blood of patients with AD. If a consistent value of plasma Aβ from the blood can be obtained, this might help determine whether plasma Aβ is a potential biomarker for AD diagnosis. We predicted the brain amyloid deposit by measuring the plasma Aβ levels. This cross-sectional study included 353 participants (215 cognitively normal, 79 with mild cognitive impairment, and 59 with AD dementia) who underwent Pittsburgh-compound B positron emission tomography (PiB-PET) scans. We treated a mixture of protease inhibitors and phosphatase inhibitors (MPP) and detected plasma Aβ42 and Aβ40 (MPP-Aβ42 and MPP-Aβ40) in a stable manner using xMAP technology. MPP-Aβ40 and MPP-Aβ42/40 (MPP-Aβs) were significantly different between subjects with positive amyloid deposition (PiB+) and those with negative amyloid deposition (PiB-) (P < 0.0001). Furthermore, MPP-Aβ40 (P < 0.0001, r = 0.23) and MPP-Aβ42/40 ratio (P < 0.0001, r = -0.23) showed significant correlation with global PiB deposition (standardized uptake value ratio). In addition, our integrated multivariable (MPP-Aβ42/40, gender, age, and apolipoprotein E genotypes) logistic regression model proposes a new standard for the prediction of cerebral amyloid deposition. MPP-Aβ might be one of the potential blood biomarkers for the prediction of PiB-PET positivity in the brain.

  9. Study on re-sputtering during CN{sub x} film deposition through spectroscopic diagnostics of plasma

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

    Liang, Peipei; Yang, Xu; Li, Hui

    2015-10-15

    A nitrogen-carbon plasma was generated during the deposition of carbon nitride (CN{sub x}) thin films by pulsed laser ablation of a graphite target in a discharge nitrogen plasma, and the optical emission of the generated nitrogen-carbon plasma was measured for the diagnostics of the plasma and the characterization of the process of CN{sub x} film deposition. The nitrogen-carbon plasma was recognized to contain various species including nitrogen molecules and molecular ions excited in the ambient N{sub 2} gas, carbon atoms and atomic ions ablated from the graphite target and CN radicals. The temporal evolution and spatial distribution of the CNmore » emission and their dependence on the substrate bias voltage show two groups of CN radicals flying in opposite directions. One represents the CN radicals formed as the products of the reactions occurring in the nitrogen-carbon plasma, revealing the reactive deposition of CN{sub x} film due to the reactive expansion of the ablation carbon plasma in the discharge nitrogen plasma and the effective formation of gaseous CN radicals as precursors for CN{sub x} film growth. The other one represents the CN radicals re-sputtered from the growing CN{sub x} film by energetic plasma species, evidencing the re-sputtering of the growing film accompanying film growth. And, the re-sputtering presents ion-induced sputtering features.« less

  10. Heparin free coating on PLA membranes for enhanced hemocompatibility via iCVD

    NASA Astrophysics Data System (ADS)

    Wang, Hui; Shi, Xiao; Gao, Ailin; Lin, Haibo; Chen, Yongliang; Ye, Yumin; He, Jidong; Liu, Fu; Deng, Gang

    2018-03-01

    In the present work, we report one-step immobilization of nano-heparin coating on PLA membranes via initiated chemical vapor deposition (iCVD) for enhanced hemocompatibility. The nano-coating introduced onto the membrane surface via the crosslinking of P(MAA-EGDA) was confirmed by the FTIR, SEM and weight measurement respectively. The negative carboxyl groups could form the hydration interaction with the protein and platelets and electrostatic interaction with amide groups of thrombin by the mediation of antithrombin, which is similar but different with heparin. The P(MAA-EGDA) coated membranes showed suppressed platelet adhesion and prolonged clotting time (APTTs increased to 59 s, PTs increased to 20.4 s, TTs increased to 17.5 s, and the FIBs declined by 30 mg/dL). Moreover, the complement activation tests demonstrated the formation of C3a and C5a was inhibited. All results demonstrated that the nano-coating of P(MAA-EGDA) via iCVD significantly enhanced the hemocompatibility of PLA membranes, which is also applicable for various membranes.

  11. The cell-penetrating peptide domain from human heparin-binding epidermal growth factor-like growth factor (HB-EGF) has anti-inflammatory activity in vitro and in vivo.

    PubMed

    Lee, Jue-Yeon; Seo, Yoo-Na; Park, Hyun-Jung; Park, Yoon-Jeong; Chung, Chong-Pyoung

    2012-03-23

    A heparin-binding peptide (HBP) sequence from human heparin-binding epidermal growth factor-like growth factor (HB-EGF) was identified and was shown to exhibit cell penetration activity. This cell penetration induced an anti-inflammatory reaction in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. HBP penetrated the cell membrane during the 10 min treatment and reduced the LPS-induced production of nitric oxide (NO), inducible nitric oxide synthase (iNOS), and cytokines (TNF-α and IL-6) in a concentration-dependent manner. Additionally, HBP inhibited the LPS-induced upregulation of cytokines, including TNF-α and IL-6, and decreased the interstitial infiltration of polymorphonuclear leukocytes in a lung inflammation model. HBP inhibited NF-κB-dependent inflammatory responses by directly blocking the phosphorylation and degradation of IκBα and by subsequently inhibiting the nuclear translocation of the p65 subunit of NF-κB. Taken together, this novel HBP may be potentially useful candidate for anti-inflammatory treatments and can be combined with other drugs of interest to transport attached molecules into cells. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Plasma deposition and surface modification techniques for wear resistance

    NASA Technical Reports Server (NTRS)

    Spalvins, T.

    1982-01-01

    The ion-assisted or plasma coating technology is discussed as it applies to the deposition of hard, wear resistant refractory compound films. Of the many sputtering and ion plating modes and configurations the reactive magnetron sputtering and the reactive triode ion plating techniques are the preferred ones to deposit wear resistant coatings for tribological applications. Both of these techniques incorporate additional means to enhance the ionization efficiency and chemical reaction to precision tailor desirable tribological characteristics. Interrelationships between film formation, structure, and ribological properties are strictly controlled by the deposition parameters and the substrate condition. The enhanced ionization contributes to the excellent adherence and coherence, reduced internal stresses and improved structural growth to form dense, cohesive, equiaxed grain structure for improved wear resistance and control.

  13. High Temperature Multilayer Environmental Barrier Coatings Deposited Via Plasma Spray-Physical Vapor Deposition

    NASA Technical Reports Server (NTRS)

    Harder, Bryan James; Zhu, Dongming; Schmitt, Michael P.; Wolfe, Douglas E.

    2014-01-01

    Si-based ceramic matrix composites (CMCs) require environmental barrier coatings (EBCs) in combustion environments to avoid rapid material loss. Candidate EBC materials have use temperatures only marginally above current technology, but the addition of a columnar oxide topcoat can substantially increase the durability. Plasma Spray-Physical Vapor Deposition (PS-PVD) allows application of these multilayer EBCs in a single process. The PS-PVD technique is a unique method that combines conventional thermal spray and vapor phase methods, allowing for tailoring of thin, dense layers or columnar microstructures by varying deposition conditions. Multilayer coatings were deposited on CMC specimens and assessed for durability under high heat flux and load. Coated samples with surface temperatures ranging from 2400-2700F and 10 ksi loads using the high heat flux laser rigs at NASA Glenn. Coating morphology was characterized in the as-sprayed condition and after thermomechanical loading using electron microscopy and the phase structure was tracked using X-ray diffraction.

  14. Development and in vivo evaluation of an oral delivery system for low molecular weight heparin based on thiolated polycarbophil.

    PubMed

    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.

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

    PubMed

    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.

  16. Selective deposition for ''chamber clean-free'' processes using tailored voltage waveform plasmas

    NASA Astrophysics Data System (ADS)

    Wang, Junkang; v. Johnson, Erik

    2016-09-01

    Tailored Voltage Waveforms (TVWs) have been proven capable of creating plasma asymmetries in otherwise symmetric CCP reactors. Particularly, sawtooth TVWs (described as having strong slope-asymmetry due to different voltage rise/fall slope) can lead to different sheath dynamics, thus generating strongly asymmetric ionization near each electrode. To date, research concerning the slope-asymmetry has only focused on single-gas plasmas. Herein, we present a study looking at SiF4/H2/Ar mixtures to investigate silicon thin film deposition. The resulting surface process depends strongly on multiple precursors, and the deposition requires a specific balance between surface arrival rates of SiFx and H. For a certain gas flow ratio, we can obtain a deposition rate of 0.82Å/s on one electrode and an etching rate of 1.2Å/s on the other. Moreover, the deposition/etching balance can be controlled by H2 flow and waveform amplitude. This is uniquely possible due to the mixed-gas nature of the process and localized ionization generated by sawtooth TVWs. This encourages the prospect that one could choose process conditions to achieve a variety of desired depositions on one electrode, while leaving the other pristine.

  17. Current Trends in Heparin Use During Arterial Vascular Interventional Radiology

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

    Durran, Alexandra C., E-mail: durranjobs@hotmail.com; Watts, Christopher, E-mail: Christopher.watts@salisbury.nhs.uk

    2012-12-15

    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 ofmore » 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 {approx}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.« less

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

    PubMed

    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.

  19. A comparative study: Effect of plasma on V2O5 nanostructured thin films

    NASA Astrophysics Data System (ADS)

    Singh, Megha; Kumar, Prabhat; Sharma, Rabindar K.; Reddy, G. B.

    2016-05-01

    Vanadium pentoxide nanostructured thin films (NSTs) have been studied to analyze the effect of plasma on nanostructures grown and morphology of films deposited using sublimation process. Nanostructured thin films were deposited on glass substrates, one in presence of oxygen plasma and other in oxygen environment (absence of plasma). Films were characterized using XRD, Raman spectroscopy, SEM and HRTEM. XRD studies revealed α-V2O5 films (orthorhombic phase) with good crystallinity. However, film deposited in presence of plasma have higher peak intensities as compared to those deposited in absence of plasma. Raman studies also support these finding following same trends of considerable increase in intensity in case of film deposited in presence of plasma. SEM micrographs makes the difference more visible, as film deposited in plasma have well defined plate like structures whereas other film have not-clearly-defined petal-like structures. HRTEM results show orthorhombic phase with 0.39 nm interplanar spacing, as reported by XRD. Results are hereby in good agreement with each other.

  20. Heparin-functionalized polymeric biomaterials in tissue engineering and drug delivery applications

    PubMed Central

    Liang, Yingkai; Kiick, Kristi L.

    2014-01-01

    Heparin plays an important role in many biological processes, via its interaction with various proteins, and hydrogels and nanoparticles comprising heparin exhibit attractive properties such as anticoagulant activity, growth factor binding, as well as antiangiogenic and apoptotic effects, making them great candidates for emerging applications. Accordingly, this review summarizes recent efforts in the preparation of heparin-based hydrogels and formation of nanoparticles, as well as the characterization of their properties and applications. The challenges and future perspectives for heparin-based materials are also discussed. Prospects are promising for heparin-containing polymeric biomaterials in diverse applications ranging from cell carriers for promoting cell differentiation to nanoparticle therapeutics for cancer treatment. PMID:23911941

  1. Filters for blocking macroparticles in plasma deposition apparatus

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

    Anders, Andre; Kolbeck, Jonathan

    This disclosure provides systems, methods, and apparatus related to blocking macroparticles in deposition processes utilizing plasmas. In one aspect, an apparatus includes a cathode, a substrate holder, a first magnet, a second magnet, and a structure. The cathode is configured to generate a plasma. The substrate holder is configured to hold a substrate. The first magnet is disposed proximate a first side of the cathode. The second magnet is disposed proximate a second side of the substrate holder. A magnetic field exists between the first magnet and the second magnet and a flow of the plasma substantially follows the magneticmore » field. The structure is disposed between the second side of the cathode and the first side of the substrate holder and is positioned proximate a region where the magnetic field between the first magnet and the second magnet is weak.« less

  2. Laser ablation and deposition of wide bandgap semiconductors: plasma and nanostructure of deposits diagnosis

    NASA Astrophysics Data System (ADS)

    Sanz, M.; López-Arias, M.; Rebollar, E.; de Nalda, R.; Castillejo, M.

    2011-12-01

    Nanostructured CdS and ZnS films on Si (100) substrates were obtained by nanosecond pulsed laser deposition at the wavelengths of 266 and 532 nm. The effect of laser irradiation wavelength on the surface structure and crystallinity of deposits was characterized, together with the composition, expansion dynamics and thermodynamic parameters of the ablation plume. Deposits were analyzed by environmental scanning electron microscopy, atomic force microscopy and X-ray diffraction, while in situ monitoring of the plume was carried out with spectral, temporal and spatial resolution by optical emission spectroscopy. The deposits consist of 25-50 nm nanoparticle assembled films but ablation in the visible results in larger aggregates (150 nm) over imposed on the film surface. The aggregate free films grown at 266 nm on heated substrates are thicker than those grown at room temperature and in the former case they reveal a crystalline structure congruent with that of the initial target material. The observed trends are discussed in reference to the light absorption step, the plasma composition and the nucleation processes occurring on the substrate.

  3. Improved Survival of Full-Thickness Skin Graft With Low-Molecular Weight Heparin-Protamine Micro/Nanoparticles Including Platelet-Rich Plasma.

    PubMed

    Takabayashi, Yuki; Ishihara, Masayuki; Kuwabara, Masahiro; Takikawa, Makoto; Nakamura, Shingo; Hattori, Hidemi; Kiyosawa, Tomoharu

    2017-05-01

    Activated platelet-rich plasma secrets many growth factors (GFs), and low-molecular weight heparin-protamine micro/nanoparticles (LMWH-P M/NPs) significantly interact with, enhance, and stabilize the secreted GFs. The purpose of this study was to evaluate the effects of LMWH-P M/NPs and GFs (from platelet-rich plasma) on full-thickness skin graft (FTSG). A total of 96 inbred male rats were anesthetized and 4-cm full-thickness skin wound were created on dorsal skin of rats. LMWH-P M/NPs and GFs, LMWH-P M/NPs, GFs and saline (control) were then injected evenly into cutaneous muscles at the wound. The next day, the rats underwent FTSG. On the indicated days after FTSG, blood flow of FTSG site (wound bed and FTSG) was examined by 2-dimensional laser Doppler blood flowmeter. On 10 days, pictures of FTSG site were taken and FTSG survival rate was evaluated. Histologic analyses of skin samples were performed on 4, 7, and 10 days. Treatment of full-thickness skin wound with LMWH-P M/NPs and GFs effectively promoted survival rate of FTSG and blood flow of FTSG site compared with those treated with GFs, LMWH-P M/NPs, and control. LMWH-P M/NPs and GFs also promoted new vessel formation at FTSG site. The prior injection of LMWH-P M/NPs and GFs into wound bed increases FTSG survival rate, and promotes blood flow and angiogenesis at FTSG site.

  4. Relationship between lipoprotein lipase activity and plasma sex steroid level in obese women.

    PubMed

    Iverius, P H; Brunzell, J D

    1988-09-01

    In obese women (n = 16) at their weight, fasting adipose tissue lipoprotein lipase (LPL) activity, obtained by elution with serum and heparin at 4 degrees and 37 degrees C, was inversely correlated to plasma estradiol levels (r = -0.724; P = 0.002) and (r = -0.641; P = 0.010), respectively. Furthermore, fasting postheparin plasma LPL activity during a heparin infusion, showed an even stronger inverse correlation to plasma estradiol when measured at 60 min (r = -0.815; P less than 0.001). None of the above parameters was correlated to the body mass index. Postprandial LPL activity in postheparin plasma, measured 10 min after a heparin injection, showed a strong positive correlation with plasma free testosterone (r = 0.780; P = 0.001). Neither of these parameters was correlated with the body mass index. The origin of this LPL activity is presently unknown but could conceivably represent a pool of LPL from skeletal muscle. Since it has been shown convincingly that estrogen decreases adipose tissue LPL activity in the rat, the present studies strongly suggest that estradiol is a major negative regulator of fasting adipose tissue LPL activity in women.

  5. Identification of PDC-109-like protein(s) in buffalo seminal plasma.

    PubMed

    Harshan, Hiron M; Sankar, Surya; Singh, L P; Singh, Manish Kumar; Sudharani, S; Ansari, M R; Singh, S K; Majumdar, A C; Joshi, P

    2009-10-01

    The FN-2 family of seminal plasma proteins represents the major protein fraction of bovine seminal plasma. These proteins also constitute the major seminal plasma proteins fraction in horse, goat and bison seminal plasma and are present in pig, rat, mouse, hamster and human seminal plasma. BSP-A1 and BSP-A2, the predominant proteins of the FN-2 family, are collectively termed as PDC-109. Fn-2 proteins play an important role in fertilization, including sperm capacitation and formation of oviductal sperm reservoirs. Significantly, BSP proteins were also shown to have negative effects in the context of sperm storage. No conclusive evidence for the presence of buffalo seminal plasma protein(s) similar to PDC-109 exists. Studies with buffalo seminal plasma indicated that isolation and identification of PDC-109-like protein(s) from buffalo seminal plasma by conventional methods might be difficult. Thus, antibodies raised against PDC-109 isolated, and purified from cattle seminal plasma, were used for investigating the presence of PDC-109-like protein(s) in buffalo seminal plasma. Buffalo seminal plasma proteins were resolved on SDS-PAGE, blotted to nitro cellulose membranes and probed for the presence of PDC-109-like protein(s) using the PDC-109 antisera raised in rabbits. A distinct immunoreactive band well below the 20-kDa regions indicated the presence of PDC-109-like protein(s) in buffalo seminal plasma.

  6. Enoxaparin versus unfractionated heparin with fibrinolysis for ST-elevation myocardial infarction.

    PubMed

    Antman, Elliott M; Morrow, David A; McCabe, Carolyn H; Murphy, Sabina A; Ruda, Mikhail; Sadowski, Zygmunt; Budaj, Andrzej; López-Sendón, Jose L; Guneri, Sema; Jiang, Frank; White, Harvey D; Fox, Keith A A; Braunwald, Eugene

    2006-04-06

    Unfractionated heparin is often used as adjunctive therapy with fibrinolysis in patients with ST-elevation myocardial infarction. We compared a low-molecular-weight heparin, enoxaparin, with unfractionated heparin for this purpose. We randomly assigned 20,506 patients with ST-elevation myocardial infarction who were scheduled to undergo fibrinolysis to receive enoxaparin throughout the index hospitalization or weight-based unfractionated heparin for at least 48 hours. The primary efficacy end point was death or nonfatal recurrent myocardial infarction through 30 days. The primary end point occurred in 12.0 percent of patients in the unfractionated heparin group and 9.9 percent of those in the enoxaparin group (17 percent reduction in relative risk, P<0.001). Nonfatal reinfarction occurred in 4.5 percent of the patients receiving unfractionated heparin and 3.0 percent of those receiving enoxaparin (33 percent reduction in relative risk, P<0.001); 7.5 percent of patients given unfractionated heparin died, as did 6.9 percent of those given enoxaparin (P=0.11). The composite of death, nonfatal reinfarction, or urgent revascularization occurred in 14.5 percent of patients given unfractionated heparin and 11.7 percent of those given enoxaparin (P<0.001); major bleeding occurred in 1.4 percent and 2.1 percent, respectively (P<0.001). The composite of death, nonfatal reinfarction, or nonfatal intracranial hemorrhage (a measure of net clinical benefit) occurred in 12.2 percent of patients given unfractionated heparin and 10.1 percent of those given enoxaparin (P<0.001). In patients receiving fibrinolysis for ST-elevation myocardial infarction, treatment with enoxaparin throughout the index hospitalization is superior to treatment with unfractionated heparin for 48 hours but is associated with an increase in major bleeding episodes. These findings should be interpreted in the context of net clinical benefit. (ClinicalTrials.gov number, NCT00077792.). Copyright 2006

  7. Atmospheric pulsed laser deposition of plasmonic nanoparticle films of silver with flowing gas and flowing atmospheric plasma

    NASA Astrophysics Data System (ADS)

    Khan, T. M.; Pokle, A.; Lunney, J. G.

    2018-04-01

    Two methods of atmospheric pulsed laser deposition of plasmonic nanoparticle films of silver are described. In both methods the ablation plume, produced by a 248 nm, 20 ns excimer laser in gas, is strongly confined near the target and forms a nanoparticle aerosol. For both the flowing gas, and the atmospheric plasma from a dielectric barrier discharge plasma source, the aerosol is entrained in the flow and carried to a substrate for deposition. The nanoparticle films produced by both methods were examined by electron microscopy and optical absorption spectroscopy. With plasma assistance, the deposition rate was significantly enhanced and the film morphology altered. With argon gas, isolated nanoparticles of 20 nm size were obtained, whereas in argon plasma, the nanoparticles are aggregated in clusters of 90 nm size. Helium gas also leads to the deposition of isolated nanoparticles, but with helium plasma, two populations of nanoparticles are observed: one of rounded particles with a mean size of 26 nm and the other of faceted particles with a mean size 165 nm.

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

    PubMed

    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.

  9. Modelling of plasma-wall interaction and impurity transport in fusion devices and prompt deposition of tungsten as application

    NASA Astrophysics Data System (ADS)

    Kirschner, A.; Tskhakaya, D.; Brezinsek, S.; Borodin, D.; Romazanov, J.; Ding, R.; Eksaeva, A.; Linsmeier, Ch

    2018-01-01

    Main processes of plasma-wall interaction and impurity transport in fusion devices and their impact on the availability of the devices are presented and modelling tools, in particular the three-dimensional Monte-Carlo code ERO, are introduced. The capability of ERO is demonstrated on the example of tungsten erosion and deposition modelling. The dependence of tungsten deposition on plasma temperature and density is studied by simulations with a simplified geometry assuming (almost) constant plasma parameters. The amount of deposition increases with increasing electron temperature and density. Up to 100% of eroded tungsten can be promptly deposited near to the location of erosion at very high densities (˜1 × 1014 cm-3 expected e.g. in the divertor of ITER). The effect of the sheath characteristics on tungsten prompt deposition is investigated by using particle-in-cell (PIC) simulations to spatially resolve the plasma parameters inside the sheath. Applying PIC data instead of non-resolved sheath leads in general to smaller tungsten deposition, which is mainly due to a density and temperature decrease towards the surface within the sheath. Two-dimensional tungsten erosion/deposition simulations, assuming symmetry in toroidal direction but poloidally spatially varying plasma parameter profiles, have been carried out for the JET divertor. The simulations reveal, similar to experimental findings, that tungsten gross erosion is dominated in H-mode plasmas by the intra-ELM phases. However, due to deposition, the net tungsten erosion can be similar within intra- and inter-ELM phases if the inter-ELM electron temperature is high enough. Also, the simulated deposition fraction of about 84% in between ELMs is in line with spectroscopic observations from which a lower limit of 50% has been estimated.

  10. Plasma-assisted deposition of microcapsule containing Aloe vera extract for cosmeto-textiles

    NASA Astrophysics Data System (ADS)

    Nascimento do Carmo, S.; Zille, A.; Souto, A. P.

    2017-10-01

    Dielectric Barrier Discharge (DBD) atmospheric-pressure plasma was employed to enhance the deposition of commercial microcapsules (MCs) containing Aloe vera extract onto a cotton/polyester (50:50) fabric. DBD conditions were optimized in term of energy dosage and contact angle. The MCs were applied by padding and printing methods and the coatings were characterized in terms of SEM and FTIR. MCs display a spherical shape with size between 2 and 8 μm with an average wall thickness of 0.5 μm. The MCs applied by printing and pretreated with a plasma dosage of 1.6 kW m2 min-1 showed the best results with an increased adhesion of 200% and significant penetration of MCs into the fibres network. Plasma printed fabric retained 230% more MCs than untreated fabric after 10 washing cycles. However, the coating resistance between unwashed and washed samples was only improved by 5%. Considering the fact that no binder or crosslinking agents were used, the DBD plasma-assisted deposition of MCs revealed to be a promising environmental safe and low cost coating technology.

  11. Plasma-enhanced atomic layer deposition for plasmonic TiN

    NASA Astrophysics Data System (ADS)

    Otto, Lauren M.; Hammack, Aaron T.; Aloni, Shaul; Ogletree, D. Frank; Olynick, Deirdre L.; Dhuey, Scott; Stadler, Bethanie J. H.; Schwartzberg, Adam M.

    2016-09-01

    This work presents the low temperature plasma-enhanced atomic layer deposition (PE-ALD) of TiN, a promising plasmonic synthetic metal. The plasmonics community has immediate needs for alternatives to traditional plasmonic materials (e.g. Ag and Au), which lack chemical, thermal, and mechanical stability. Plasmonic alloys and synthetic metals have significantly improved stability, but their growth can require high-temperatures (>400 °C), and it is difficult to control the thickness and directionality of the resulting film, especially on technologically important substrates. Such issues prevent the application of alternative plasmonic materials for both fundamental studies and large-scale industrial applications. Alternatively, PE-ALD allows for conformal deposition on a variety of substrates with consistent material properties. This conformal coating will allow the creation of exotic three-dimensional structures, and low-temperature deposition techniques will provide unrestricted usage across a variety of platforms. The characterization of this new plasmonic material was performed with in-situ spectroscopic ellipsometry as well as Auger electron spectroscopy for analysis of TiN film sensitivity to oxide cross-contamination. Plasmonic TiN films were fabricated, and a chlorine plasma etch was found to pattern two dimensional gratings as a test structure. Optical measurements of 900 nm period gratings showed reasonable agreement with theoretical modeling of the fabricated structures, indicating that ellipsometry models of the TiN were indeed accurate.

  12. Heparin conjugated quantum dots for in vitro imaging applications.

    PubMed

    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.

  13. Metalorganic Chemical Vapor Deposition of Ruthenium-Doped Diamond like Carbon Films

    NASA Technical Reports Server (NTRS)

    Sunkara, M. K.; Ueno, M.; Lian, G.; Dickey, E. C.

    2001-01-01

    We investigated metalorganic precursor deposition using a Microwave Electron Cyclotron Resonance (ECR) plasma for depositing metal-doped diamondlike carbon films. Specifically, the deposition of ruthenium doped diamondlike carbon films was investigated using the decomposition of a novel ruthenium precursor, Bis(ethylcyclopentadienyl)-ruthenium (Ru(C5H4C2H5)2). The ruthenium precursor was introduced close to the substrate stage. The substrate was independently biased using an applied RF power. Films were characterized using Fourier Transform Infrared Spectroscopy (FTIR), Transmission Electron Microscopy (TEM) and Four Point Probe. The conductivity of the films deposited using ruthenium precursor showed strong dependency on the deposition parameters such as pressure. Ruthenium doped sample showed the presence of diamond crystallites with an average size of approx. 3 nm while un-doped diamondlike carbon sample showed the presence of diamond crystallites with an average size of 11 nm. TEM results showed that ruthenium was atomically dispersed within the amorphous carbon network in the films.

  14. Structure, mechanical, and frictional properties of hydrogenated fullerene-like amorphous carbon film prepared by direct current plasma enhanced chemical vapor deposition

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

    Wang, Yongfu; University of Chinese Academy of Sciences, Beijing 100049; Gao, Kaixiong

    In this study, fullerene like carbon (FL-C) is introduced in hydrogenated amorphous carbon (a-C:H) film by employing a direct current plasma enhanced chemical vapor deposition. The film has a low friction and wear, such as 0.011 and 2.3 × 10{sup −9}mm{sup 3}/N m in the N{sub 2}, and 0.014 and 8.4 × 10{sup −8}mm{sup 3}/N m in the humid air, and high hardness and elasticity (25.8 GPa and 83.1%), to make further engineering applications in practice. It has several nanometers ordered domains consisting of less frequently cross-linked graphitic sheet stacks. We provide new evidences for understanding the reported Raman fit model involving four vibrational frequenciesmore » from five, six, and seven C-atom rings of FL-C structures, and discuss the structure evolution before or after friction according to the change in the 1200 cm{sup −1} Raman band intensity caused by five- and seven-carbon rings. Friction inevitably facilitates the transformation of carbon into FL-C nanostructures, namely, the ultra low friction comes from both such structures within the carbon film and the sliding induced at friction interface.« less

  15. Covalent Binding of Heparin to Functionalized PET Materials for Improved Haemocompatibility

    PubMed Central

    Kolar, Metod; Mozetič, Miran; Stana-Kleinschek, Karin; Fröhlich, Mirjam; Turk, Boris; Vesel, Alenka

    2015-01-01

    The hemocompatibility of vascular grafts made from poly(ethylene terephthalate) (PET) is insufficient due to the rapid adhesion and activation of blood platelets that occur upon incubation with whole blood. PET polymer was treated with NHx radicals created by passing ammonia through gaseous plasma formed by a microwave discharge, which allowed for functionalization with amino groups. X-ray photoelectron spectroscopy characterization using derivatization with 4-chlorobenzaldehyde indicated that approximately 4% of the –NH2 groups were associated with the PET surface after treatment with the gaseous radicals. The functionalized polymers were coated with an ultra-thin layer of heparin and incubated with fresh blood. The free-hemoglobin technique, which is based on the haemolysis of erythrocytes, indicated improved hemocompatibility, which was confirmed by imaging the samples using confocal optical microscopy. A significant decrease in number of adhered platelets was observed on such samples. Proliferation of both human umbilical vein endothelial cells and human microvascular endothelial cells was enhanced on treated polymers, especially after a few hours of cell seeding. Thus, the technique represents a promising substitute for wet-chemical modification of PET materials prior to coating with heparin. PMID:28788016

  16. Thromboembolic Prophylaxis with Heparin in Patients with Blunt Solid Organ Injuries Undergoing Non-operative Treatment.

    PubMed

    Khatsilouskaya, Tatsiana; Haltmeier, Tobias; Cathomas, Marionna; Eberle, Barbara; Candinas, Daniel; Schnüriger, Beat

    2017-05-01

    Patients with blunt solid organ injuries (SOI) are at risk for venous thromboembolism (VTE), and VTE prophylaxis is crucial. However, little is known about the safety of early prophylactic administration of heparin in these patients. This is a retrospective study including adult trauma patients with SOI (liver, spleen, kidney) undergoing non-operative management (NOM) from 01/01/2009 to 31/12/2014. Three groups were distinguished: prophylactic heparin (low molecular weight heparin or low-dose unfractionated heparin) ≤72 h after admission ('early heparin group'), >72 h after admission ('late heparin group'), and no heparin ('no heparin group'). Patient and injury characteristics, transfusion requirements, and outcomes (failed NOM, VTE, and mortality) were compared between the three groups. Overall, 179 patients were included; 44.7% in the 'early heparin group,' 34.6% in the 'late heparin group,' and 20.8% in the 'no heparin group.' In the 'late heparin group,' the ISS was significantly higher than in the 'early' and 'no heparin groups' (median 29.0 vs. 17.0 vs. 19.0; p < 0.001). The overall NOM failure rate was 3.9%. Failed NOM was significantly more frequent in the 'no heparin group' compared to the 'early' and 'late heparin groups' (10.8 vs. 3.2 vs. 1.3%; p = 0.043). In the 'early heparin group' 27.5% patients suffered from a high-grade SOI; none of these patients failed NOM. Mortality did not differ significantly. Although not statistically significant, VTE were more frequent in the 'no heparin group' compared to the 'early' and 'late heparin groups' (10.8 vs. 4.8 vs. 1.3%; p = 0.066). In patients with SOI, heparin was administered early in a high percentage of patients and was not associated with an increased NOM failure rate or higher in-hospital mortality.

  17. Heparin-Induced Thrombocytopenia with Associated Thrombosis in Children after the Fontan Operation

    PubMed Central

    Porcelli, Rosalia; Moskowitz, Bonnie C.; Cetta, Frank; Graham, Lynn C.; Godwin, John E.; Eidem, Benjamin W.; Prechel, M. Margaret; Walenga, Jeanine M.

    2003-01-01

    Heparin-induced thrombocytopenia is a widely recognized clinical disorder. The spectrum of disease ranges from clinically insignificant to severe thrombosis (heparin-induced thrombocytopenia with associated thrombosis). Overall, thrombosis occurs in approximately 33% of adults diagnosed with heparin-induced thrombocytopenia and has been associated with high morbidity and mortality rates. Diagnostic testing for this disorder is not standard in children with thrombocytopenia who are receiving heparin, despite the fact that children with congenital heart disease may be exposed to heparin frequently. There are few reported cases of heparin-induced thrombocytopenia with associated thrombosis in children; herein, we describe the cases of 2 children who developed this disorder after undergoing a Fontan operation. (Tex Heart Inst J 2003;30:58–61) PMID:12638673

  18. Heparin in acute ischemic stroke revisited.

    PubMed

    Chamorro, A

    2008-10-01

    The evidence gathered in clinical trials of low molecular weight heparins (LMWHs) or with unfractionated heparin (UH) given subcutaneously at low or medium doses to patients with acute stroke cannot be extrapolated to the insufficiently tested effects of intravenous, weight-adjusted UH. Recent small studies have provided encouraging results but are potentially confounded and deserve confirmation in larger randomized controlled trials. In accordance with the current understanding of the biology of acute ischemic stroke and the pharmacology of UH, the new randomized controlled trials on heparin should give appropriate credit to the importance of a short therapeutic window, adequate dose adjustment of the drug, intravenous administration, and close monitoring of biological effects. UH is an orphan drug and only an academic driven trial would be able to face such an enterprise. Meanwhile, recommendations against the value of "early" anticoagulation with full dose of weight adjusted UH in the setting of acute ischemic stroke are not based on direct evidence but on extrapolations.

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

    PubMed

    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.

  20. Treatment and Prevention of Heparin-Induced Thrombocytopenia

    PubMed Central

    Dans, Antonio L.; Moores, Lisa K.; Bona, Robert; Davidson, Bruce L.; Schulman, Sam; Crowther, Mark

    2012-01-01

    Background: Heparin-induced thrombocytopenia (HIT) is an antibody-mediated adverse drug reaction that can lead to devastating thromboembolic complications, including pulmonary embolism, ischemic limb necrosis necessitating limb amputation, acute myocardial infarction, and stroke. Methods: The methods of this guideline follow the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. Results: Among the key recommendations for this article are the following: For patients receiving heparin in whom clinicians consider the risk of HIT to be > 1%, we suggest that platelet count monitoring be performed every 2 or 3 days from day 4 to day 14 (or until heparin is stopped, whichever occurs first) (Grade 2C). For patients receiving heparin in whom clinicians consider the risk of HIT to be < 1%, we suggest that platelet counts not be monitored (Grade 2C). In patients with HIT with thrombosis (HITT) or isolated HIT who have normal renal function, we suggest the use of argatroban or lepirudin or danaparoid over other nonheparin anticoagulants (Grade 2C). In patients with HITT and renal insufficiency, we suggest the use of argatroban over other nonheparin anticoagulants (Grade 2C). In patients with acute HIT or subacute HIT who require urgent cardiac surgery, we suggest the use of bivalirudin over other nonheparin anticoagulants or heparin plus antiplatelet agents (Grade 2C). Conclusions: Further studies evaluating the role of fondaparinux and the new oral anticoagulants in the treatment of HIT are needed. PMID:22315270

  1. Transition energies and polarizabilities of hydrogen like ions in plasma

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

    Das, Madhusmita

    2012-09-15

    Effect of plasma screening on various properties like transition energy, polarizability (dipole and quadrupole), etc. of hydrogen like ions is studied. The bound and free state wave functions and transition matrix elements are obtained by numerically integrating the radial Schrodinger equation for appropriate plasma potential. We have used adaptive step size controlled Runge-Kutta method to perform the numerical integration. Debye-Huckel potential is used to investigate the variation in transition lines and polarizabilities (dipole and quadrupole) with increasing plasma screening. For a strongly coupled plasma, ion sphere potential is used to show the variation in excitation energy with decreasing ion spheremore » radius. It is observed that plasma screening sets in phenomena like continuum lowering and pressure ionization, which are unique to ions in plasma. Of particular interest is the blue (red) shift in transitions conserving (non-conserving) principal quantum number. The plasma environment also affects the dipole and quadrupole polarizability of ions in a significant manner. The bound state contribution to polarizabilities decreases with increase in plasma density whereas the continuum contribution is significantly enhanced. This is a result of variation in the behavior of bound and continuum state wave functions in the presence of plasma. We have compared the results with existing theoretical and experimental data wherever present.« less

  2. Induction of anti-PF4/heparin antibodies after arthroplasty for rheumatic diseases.

    PubMed

    Migita, Kiyoshi; Asano, Tomoyuki; Sato, Shuzo; Motokawa, Satoru

    2018-04-17

    Heparin-induced thrombocytopenia (HIT) is an immune complication of heparin therapy caused by antibodies to complexes of platelet factor 4 (PF4) and heparin. These pathogenic antibodies against PF4/heparin bind and activate cellular FcγRIIa on platelets to induce a hypercoagulable state culminating in thrombosis. Recent studies indicate several conditions, including joint surgery, induce spontaneous HIT, which can occur without exposure to heparin. To determine the real-world evidences concerning the incidences of venous thromboembolism (VTE) after total joint arthroplasty for rheumatic disease, we conducted a multicenter cohort study (J-PSVT) designed to document the VTE and seroconversion rates of anti-PF4/heparin antibody in 34 Japanese National hospital organization (NHO) hospitals. J-PSVT indicated that prophylaxis with fondaparinux, not enoxaparin, reduces the risk of deep vein thrombosis in patients undergoing arthroplasty. Multivariate analysis revealed that dynamic mechanical thromboprophylaxis (intermittent plantar device) was an independent risk factor for seroconversion of anti-PF4/heparin antibodies, which was also confirmed by propensity-score matching. Seroconversion rates of anti-PF4/heparin antibodies were significantly reduced in rheumatoid arthritis (RA) patients compared with osteoarthritis (OA) patients, which may link with the findings that IgG fractions isolated from RA patients not OA patients contained PF4. Our study indicated that a unique profile of anti-PF4/heparin antibodies is induced by arthroplasty for rheumatic diseases.

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

    PubMed Central

    Tebbe, David; Thull, Roger; Gbureck, Uwe

    2007-01-01

    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-(Trimethoxysilyl)propyl]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. Furthermore, the

  4. Growth of vertically aligned carbon nanofibers by low-pressure inductively coupled plasma-enhanced chemical vapor deposition

    NASA Astrophysics Data System (ADS)

    Caughman, J. B. O.; Baylor, L. R.; Guillorn, M. A.; Merkulov, V. I.; Lowndes, D. H.; Allard, L. F.

    2003-08-01

    Vertically aligned carbon nanofibers (VACNFs) have been grown using a low-pressure, plasma-enhanced, chemical vapor deposition process. The nanofibers are grown from a nickel catalyst that can be patterned to form arrays of individual, isolated VACNFs. The fibers are grown at pressures below 100 mTorr, using an inductively coupled plasma source with a radio-frequency bias on the sample substrate to allow for independent control of the ion energies. Plasma conditions are related to growth results by comparing optical emission from the plasma to the physical structure of the nanofibers. We find that the ratio of etching species in the plasma to depositing species is critical to the final shape of the carbon structures that are formed.

  5. Experience on divertor fuel retention after two ITER-Like Wall campaigns

    NASA Astrophysics Data System (ADS)

    Heinola, K.; Widdowson, A.; Likonen, J.; Ahlgren, T.; Alves, E.; Ayres, C. F.; Baron-Wiechec, A.; Barradas, N.; Brezinsek, S.; Catarino, N.; Coad, P.; Guillemaut, C.; Jepu, I.; Krat, S.; Lahtinen, A.; Matthews, G. F.; Mayer, M.; Contributors, JET

    2017-12-01

    The JET ITER-Like Wall experiment, with its all-metal plasma-facing components, provides a unique environment for plasma and plasma-wall interaction studies. These studies are of great importance in understanding the underlying phenomena taking place during the operation of a future fusion reactor. Present work summarizes and reports the plasma fuel retention in the divertor resulting from the two first experimental campaigns with the ITER-Like Wall. The deposition pattern in the divertor after the second campaign shows same trend as was observed after the first campaign: highest deposition of 10-15 μm was found on the top part of the inner divertor. Due to the change in plasma magnetic configurations from the first to the second campaign, and the resulted strike point locations, an increase of deposition was observed on the base of the divertor. The deuterium retention was found to be affected by the hydrogen plasma experiments done at the end of second experimental campaign.

  6. Temporally and Spatially Resolved Plasma Spectroscopy in Pulsed Laser Deposition of Ultra-Thin Boron Nitride Films (Postprint)

    DTIC Science & Technology

    2015-04-24

    AFRL-RX-WP-JA-2016-0196 TEMPORALLY AND SPATIALLY RESOLVED PLASMA SPECTROSCOPY IN PULSED LASER DEPOSITION OF ULTRA-THIN BORON NITRIDE...AND SPATIALLY RESOLVED PLASMA SPECTROSCOPY IN PULSED LASER DEPOSITION OF ULTRA-THIN BORON NITRIDE FILMS (POSTPRINT) 5a. CONTRACT NUMBER FA8650...distributions within a PVD plasma plume ablated from a boron nitride (BN) target by a KrF laser at different pressures of nitrogen gas were investigated

  7. Microstructural Effects and Properties of Non-line-of-Sight Coating Processing via Plasma Spray-Physical Vapor Deposition

    NASA Astrophysics Data System (ADS)

    Harder, Bryan J.; Zhu, Dongming; Schmitt, Michael P.; Wolfe, Douglas E.

    2017-08-01

    Plasma spray-physical vapor deposition (PS-PVD) is a unique processing method that bridges the gap between conventional thermal spray and vapor phase methods, and enables highly tailorable coatings composed of a variety of materials in thin, dense layers or columnar microstructures with modification of the processing conditions. The strengths of this processing technique are material and microstructural flexibility, deposition speed, and potential for non-line-of-sight (NLOS) capability by vaporization of the feedstock material. The NLOS capability of PS-PVD is investigated here using yttria-stabilized zirconia and gadolinium zirconate, which are materials of interest for turbine engine applications. PS-PVD coatings were applied to static cylindrical substrates approximately 6-19 mm in diameter to study the coating morphology as a function of angle. In addition, coatings were deposited on flat substrates under various impingement configurations. Impingement angle had significant effects on the deposition mode, and microscopy of coatings indicated that there was a shift in the deposition mode at approximately 90° from incidence on the cylindrical samples, which may indicate the onset of more turbulent flow and PVD-like growth. Coatings deposited at non-perpendicular angles exhibited a higher density and nearly a 2× improvement in erosion performance when compared to coatings deposited with the torch normal to the surface.

  8. The heparin-binding site in tetranectin is located in the N-terminal region and binding does not involve the carbohydrate recognition domain.

    PubMed Central

    Lorentsen, R H; Graversen, J H; Caterer, N R; Thogersen, H C; Etzerodt, M

    2000-01-01

    Tetranectin is a homotrimeric plasma and extracellular-matrix protein that binds plasminogen and complex sulphated polysaccharides including heparin. In terms of primary and tertiary structure, tetranectin is related to the collectin family of Ca(2+)-binding C-type lectins. Tetranectin is encoded in three exons. Exon 3 encodes the carbohydrate recognition domain, which binds to kringle 4 in plasminogen at low levels of Ca(2+). Exon 2 encodes an alpha-helix, which is necessary and sufficient to govern the trimerization of tetranectin by assembling into a triple-helical coiled-coil structural element. Here we show that the heparin-binding site in tetranectin resides not in the carbohydrate recognition domain but within the N-terminal region, comprising the 16 amino acid residues encoded by exon 1. In particular, the lysine residues in the decapeptide segment KPKKIVNAKK (tetranectin residues 6-15) are shown to be of primary importance in heparin binding. PMID:10727405

  9. The heparin-binding site in tetranectin is located in the N-terminal region and binding does not involve the carbohydrate recognition domain.

    PubMed

    Lorentsen, R H; Graversen, J H; Caterer, N R; Thogersen, H C; Etzerodt, M

    2000-04-01

    Tetranectin is a homotrimeric plasma and extracellular-matrix protein that binds plasminogen and complex sulphated polysaccharides including heparin. In terms of primary and tertiary structure, tetranectin is related to the collectin family of Ca(2+)-binding C-type lectins. Tetranectin is encoded in three exons. Exon 3 encodes the carbohydrate recognition domain, which binds to kringle 4 in plasminogen at low levels of Ca(2+). Exon 2 encodes an alpha-helix, which is necessary and sufficient to govern the trimerization of tetranectin by assembling into a triple-helical coiled-coil structural element. Here we show that the heparin-binding site in tetranectin resides not in the carbohydrate recognition domain but within the N-terminal region, comprising the 16 amino acid residues encoded by exon 1. In particular, the lysine residues in the decapeptide segment KPKKIVNAKK (tetranectin residues 6-15) are shown to be of primary importance in heparin binding.

  10. Influence of deposition rate on the structural properties of plasma-enhanced CVD epitaxial silicon.

    PubMed

    Chen, Wanghua; Cariou, Romain; Hamon, Gwenaëlle; Léal, Ronan; Maurice, Jean-Luc; Cabarrocas, Pere Roca I

    2017-03-06

    Solar cells based on epitaxial silicon layers as the absorber attract increasing attention because of the potential cost reduction. In this work, we studied the influence of the deposition rate on the structural properties of epitaxial silicon layers produced by plasma-enhanced chemical vapor deposition (epi-PECVD) using silane as a precursor and hydrogen as a carrier gas. We found that the crystalline quality of epi-PECVD layers depends on their thickness and deposition rate. Moreover, increasing the deposition rate may lead to epitaxy breakdown. In that case, we observe the formation of embedded amorphous silicon cones in the epi-PECVD layer. To explain this phenomenon, we develop a model based on the coupling of hydrogen and built-in strain. By optimizing the deposition conditions to avoid epitaxy breakdown, including substrate temperatures and plasma potential, we have been able to synthesize epi-PECVD layers up to a deposition rate of 8.3 Å/s. In such case, we found that the incorporation of hydrogen in the hydrogenated crystalline silicon can reach 4 at. % at a substrate temperature of 350 °C.

  11. Ion-substituted calcium phosphate coatings deposited by plasma-assisted techniques: A review.

    PubMed

    Graziani, Gabriela; Bianchi, Michele; Sassoni, Enrico; Russo, Alessandro; Marcacci, Maurilio

    2017-05-01

    One of the main critical aspects behind the failure or success of an implant resides in its ability to fast bond with the surrounding bone. To boost osseointegration, the ideal implant material should exhibit composition and structure similar to those of biological apatite. To this aim, the most common approach is to coat the implant surface with a coating of hydroxyapatite (HA), resembling the main component of mineralized tissues. However, bone apatite is a non-stoichiometric, multi-substituted poorly-crystalline apatite, containing significant amounts of foreign ions, with high biological relevance. Ion-substituted HAs can be deposited by so called "wet methods", which are however poorly reproducible and hardly industrially feasible; at the same time bioactive coatings realized by plasma assisted method, interesting for industrial applications, are generally made of stoichiometric (i.e. un-substituted) HA. In this work, the literature concerning plasma-assisted deposition methods used to deposit ion-substituted HA was reviewed and the last advances in this field discussed. The ions taken into exam are those present in mineralized tissues and possibly having biological relevance. Notably, literature about this topic is scarce, especially relating to in vivo animal and clinical trials; further on, available studies evaluate the performance of substituted coatings from different points of view (mechanical properties, bone growth, coating dissolution, etc.) which hinders a proper evaluation of the real efficacy of ion-doped HA in promoting bone regeneration, compared to stoichiometric HA. Moreover, results obtained for plasma sprayed coatings (which is the only method currently employed for deposition at the industrial scale) were collected and compared to those of novel plasma-assisted techniques, that are expected to overcome its limitations. Data so far available on the topic were discussed to highlight advantages, limitations and possible perspectives of these

  12. Authentication of animal origin of heparin and low molecular weight heparin including ovine, porcine and bovine species using 1D NMR spectroscopy and chemometric tools.

    PubMed

    Monakhova, Yulia B; Diehl, Bernd W K; Fareed, Jawed

    2018-02-05

    High resolution (600MHz) nuclear magnetic resonance (NMR) spectroscopy is used to distinguish heparin and low-molecular weight heparins (LMWHs) produced from porcine, bovine and ovine mucosal tissues as well as their blends. For multivariate analysis several statistical methods such as principal component analysis (PCA), factor discriminant analysis (FDA), partial least squares - discriminant analysis (PLS-DA), linear discriminant analysis (LDA) were utilized for the modeling of NMR data of more than 100 authentic samples. Heparin and LMWH samples from the independent test set (n=15) were 100% correctly classified according to its animal origin. Moreover, by using 1 H NMR coupled with chemometrics and several batches of bovine heparins from two producers were differentiated. Thus, NMR spectroscopy combined with chemometrics is an efficient tool for simultaneous identification of animal origin and process based manufacturing difference in heparin products. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Tungsten Deposition on Graphite using Plasma Enhanced Chemical Vapour Deposition.

    NASA Astrophysics Data System (ADS)

    Sharma, Uttam; Chauhan, Sachin S.; Sharma, Jayshree; Sanyasi, A. K.; Ghosh, J.; Choudhary, K. K.; Ghosh, S. K.

    2016-10-01

    The tokamak concept is the frontrunner for achieving controlled thermonuclear reaction on earth, an environment friendly way to solve future energy crisis. Although much progress has been made in controlling the heated fusion plasmas (temperature ∼ 150 million degrees) in tokamaks, technological issues related to plasma wall interaction topic still need focused attention. In future, reactor grade tokamak operational scenarios, the reactor wall and target plates are expected to experience a heat load of 10 MW/m2 and even more during the unfortunate events of ELM's and disruptions. Tungsten remains a suitable choice for the wall and target plates. It can withstand high temperatures, its ductile to brittle temperature is fairly low and it has low sputtering yield and low fuel retention capabilities. However, it is difficult to machine tungsten and hence usages of tungsten coated surfaces are mostly desirable. To produce tungsten coated graphite tiles for the above-mentioned purpose, a coating reactor has been designed, developed and made operational at the SVITS, Indore. Tungsten coating on graphite has been attempted and successfully carried out by using radio frequency induced plasma enhanced chemical vapour deposition (rf -PECVD) for the first time in India. Tungsten hexa-fluoride has been used as a pre-cursor gas. Energy Dispersive X-ray spectroscopy (EDS) clearly showed the presence of tungsten coating on the graphite samples. This paper presents the details of successful operation and achievement of tungsten coating in the reactor at SVITS.

  14. Real-time curling probe monitoring of dielectric layer deposited on plasma chamber wall

    NASA Astrophysics Data System (ADS)

    Hotta, Masaya; Ogawa, Daisuke; Nakamura, Keiji; Sugai, Hideo

    2018-04-01

    A microwave resonator probe called a curling probe (CP) was applied to in situ monitoring of a dielectric layer deposited on a chamber wall during plasma processing. The resonance frequency of the CP was analytically found to shift in proportion to the dielectric layer thickness; the proportionality constant was determined from a comparison with the finite-difference time-domain (FDTD) simulation result. Amorphous carbon layers deposited in acetylene inductively coupled plasma (ICP) discharge were monitored using the CP. The measured resonance frequency shift dictated the carbon layer thickness, which agreed with the results from the surface profiler and ellipsometry.

  15. The properties and performance of moisture/oxygen barrier layers deposited by remote plasma sputtering

    NASA Astrophysics Data System (ADS)

    Brown, Hayley Louise

    The development of flexible lightweight OLED devices requires oxygen/moisture barrier layer thin films with water vapour transmission rates (WVTR) of < 10-6 g/m2/day. This thesis reports on single and multilayer architecture barrier layers (mostly based on SiO2, Al2O3 and TiO2) deposited onto glass, Si and polymeric substrates using remote plasma sputtering. The reactive sputtering depositions were performed on Plasma Quest S500 based sputter systems and the morphology, nanostructure and composition of the coatings have been examined using SEM, EDX, STEM, XPS, XRD and AFM. The WVTR has been determined using industry standard techniques (e.g. MOCON) but, for rapid screening of the deposited layers, an in-house permeation test was also developed. SEM, XRD and STEM results showed that the coatings exhibited a dense, amorphous structure with no evidence of columnar growth. However, all of the single and multilayer coatings exhibited relatively poor WVTRs of > 1 x 10-1 g/m2/day at 38 °C and 85 % RH. Further characterisation indicated that the barrier films were failing due to the presence of substrate asperities and airborne particulates. Different mechanisms were investigated in an attempt to reduce the density of film defects including incorporation of a getter layer, modification of growth kinetics, plasma treatment and polymer planarising, but none were successful in lowering the WVTR. Review of this issue indicated that the achievement of good barrier layers was likely to be problematic in commercial practice due to the cost implications of adequately reducing particulate density and the need to cover deliberately non-planar surfaces and fabricated 3D structures. Conformal coverage would therefore be required to bury surface structures and to mitigate particulate issues. Studies of the remote plasma system showed that it both inherently delivered an ionised physical vapour deposition (IPVD) process and was compatible with bias re-sputtering of substrates

  16. Argon–germane in situ plasma clean for reduced temperature Ge on Si epitaxy by high density plasma chemical vapor deposition

    DOE PAGES

    Douglas, Erica A.; Sheng, Josephine J.; Verley, Jason C.; ...

    2015-06-04

    We found that the demand for integration of near infrared optoelectronic functionality with silicon complementary metal oxide semiconductor (CMOS) technology has for many years motivated the investigation of low temperature germanium on silicon deposition processes. Our work describes the development of a high density plasma chemical vapor deposition process that uses a low temperature (<460 °C) in situ germane/argon plasma surface preparation step for epitaxial growth of germanium on silicon. It is shown that the germane/argon plasma treatment sufficiently removes SiO x and carbon at the surface to enable germanium epitaxy. Finally, the use of this surface preparation step demonstratesmore » an alternative way to produce germanium epitaxy at reduced temperatures, a key enabler for increased flexibility of integration with CMOS back-end-of-line fabrication.« less

  17. Simulation study of depositing the carbon film on nanoparticles in the magnetized methane plasma

    NASA Astrophysics Data System (ADS)

    Mohammadzadeh, Hosein; Pourali, Nima; Ebadi, Zahra

    2018-03-01

    Plasma coating of nanoparticles in low-temperature magnetized methane plasma is studied by a simulation approach. To this end, by using the global model, the electron temperature and concentration of different species considered in this plasma are determined in the center of a capacitively coupled discharge. Then, the plasma-wall transition region in the presence of an oblique magnetic field is simulated by the multi-component fluid description. Nanoparticles with different radii are injected into the transition region and surface deposition and heating models, as well as dynamics and charging models, are employed to examine the coating process. The results of the simulation show that the non-spherical growth of nanoparticles is affected by the presence of the magnetic field, as with passing time, an oscillating increase is seen in the thickness of the film deposited on nanoparticles. Also, it is shown that the uniformity of the deposited film is dependent on the rotation velocity of nanoparticles. Generally, the obtained results imply that the sphericity of nanoparticles and uniformity of the film coated on them are controllable by the magnitude and orientation of the magnetic field.

  18. Friction and wear of plasma-deposited diamond films

    NASA Technical Reports Server (NTRS)

    Miyoshi, Kazuhisa; Wu, Richard L. C.; Garscadden, Alan; Barnes, Paul N.; Jackson, Howard E.

    1993-01-01

    Reciprocating sliding friction experiments in humid air and in dry nitrogen and unidirectional sliding friction experiments in ultrahigh vacuum were conducted with a natural diamond pin in contact with microwave-plasma-deposited diamond films. Diamond films with a surface roughness (R rms) ranging from 15 to 160 nm were produced by microwave-plasma-assisted chemical vapor deposition. In humid air and in dry nitrogen, abrasion occurred when the diamond pin made grooves in the surfaces of diamond films, and thus the initial coefficients of friction increased with increasing initial surface roughness. The equilibrium coefficients of friction were independent of the initial surface roughness of the diamond films. In vacuum the friction for diamond films contacting a diamond pin arose primarily from adhesion between the sliding surfaces. In these cases, the initial and equilibrium coefficients of friction were independent of the initial surface roughness of the diamond films. The equilibrium coefficients of friction were 0.02 to 0.04 in humid air and in dry nitrogen, but 1.5 to 1.8 in vacuum. The wear factor of the diamond films depended on the initial surface roughness, regardless of environment; it increased with increasing initial surface roughness. The wear factors were considerably higher in vacuum than in humid air and in dry nitrogen.

  19. Comparison study of biomimetic strontium-doped calcium phosphate coatings by electrochemical deposition and air plasma spray: morphology, composition and bioactive performance.

    PubMed

    Li, Ling; Lu, Xia; Meng, Yizhi; Weyant, Christopher M

    2012-10-01

    In this study, strontium-doped calcium phosphate coatings were deposited by electrochemical deposition and plasma spray under different process parameters to achieve various coating morphologies. The coating composition was investigated by energy dispersive X-ray spectroscopy and X-ray diffraction. The surface morphologies of the coatings were studied through scanning electron microscopy while the cytocompatibility and bioactivity of the strontium-doped calcium phosphate coatings were evaluated using bone cell culture using MC3T3-E1 osteoblast-like cells. The addition of strontium leads to enhanced proliferation suggesting the possible benefits of strontium incorporation in calcium phosphate coatings. The morphology and composition of deposited coatings showed a strong influence on the growth of cells.

  20. Heparin Reduced Mortality and Sepsis in Severely Burned Children

    PubMed Central

    Zayas, G.J.; Bonilla, A.M.; Saliba, M.J

    2007-01-01

    Summary Objectives. In El Salvador, before 1999, morbidity and mortality in severely burned children were high. In 1998, all children with burns of 40% or larger size died and sepsis was found. With heparin use in 1999, some similarly burned children survived, and sepsis, pain, procedures, and scars were noted to be less. This retrospective study presents the details. Methods. A study was conducted at the National Children's Hospital in El Salvador of all children with burns over 20% size treated in 1998, when no heparin was used, and in 1999, when heparin was added to burns treatment, using an ethics committee approved protocol in use in twelve other countries. Sodium aqueous heparin solution USP from an intestinal source was infused intravenously and applied topically onto burn surfaces and within blisters for the first 1-3 days post-burn. Then heparin, in diminishing doses, was continued only topically until healing. The treatments in 1998 and 1999 were otherwise the same, except that fewer procedures were needed in 1999. Results. There were no significant differences in gender, age, weight, burn aetiology, or burn size between the burned children in 1998 and those in 1999. Burn pain was relieved and pain medicine was not needed in children treated with heparin in 1999. In 1998, one child survived who had a 35% size burn, and the eight children died who had burns of 40% and over. The survival rate was one out of nine (11%). The average burn size was 51.7%. With heparin use in 1999, six of the ten children survived burns of 50.7% average size. The increase in survival with heparin from 11% to 60% and, therefore, the decrease in mortality from 89% to 40% were significant (p < 0.04). Clinical symptoms and positive blood cultures documented bacterial sepsis in the nine children in 1998. In 1999, the blood cultures for sepsis were positive in the four children who died and negative in the six who survived. The nine versus four differences in the incidence of sepsis

  1. ZnO synthesis by high vacuum plasma-assisted chemical vapor deposition using dimethylzinc and atomic oxygen

    NASA Astrophysics Data System (ADS)

    Barnes, Teresa M.; Hand, Steve; Leaf, Jackie; Wolden, Colin A.

    2004-09-01

    Zinc oxide thin films were produced by high vacuum plasma-assisted chemical vapor deposition (HVP-CVD) from dimethylzinc (DMZn) and atomic oxygen. HVP-CVD is differentiated from conventional remote plasma-enhanced CVD in that the operating pressures of the inductively coupled plasma (ICP) source and the deposition chamber are decoupled. Both DMZn and atomic oxygen effuse into the deposition chamber under near collisionless conditions. The deposition rate was measured as a function of DMZn and atomic oxygen flux on glass and silicon substrates. Optical emission spectroscopy and quadrupole mass spectrometry (QMS) were used to provide real time analysis of the ICP source and the deposition chamber. The deposition rate was found to be first order in DMZn pressure and zero order in atomic oxygen density. All films demonstrated excellent transparency and were preferentially orientated along the c-axis. The deposition chemistry occurs exclusively through surface-mediated reactions, since the collisionless transport environment eliminates gas-phase chemistry. QMS analysis revealed that DMZn was almost completely consumed, and desorption of unreacted methyl radicals was greatly accelerated in the presence of atomic oxygen. Negligible zinc was detected in the gas phase, suggesting that Zn was efficiently consumed on the substrate and walls of the reactor.

  2. Diagnostic for Plasma Enhanced Chemical Vapor Deposition and Etch Systems

    NASA Technical Reports Server (NTRS)

    Cappelli, Mark A.

    1999-01-01

    In order to meet NASA's requirements for the rapid development and validation of future generation electronic devices as well as associated materials and processes, enabling technologies ion the processing of semiconductor materials arising from understanding etch chemistries are being developed through a research collaboration between Stanford University and NASA-Ames Research Center, Although a great deal of laboratory-scale research has been performed on many of materials processing plasmas, little is known about the gas-phase and surface chemical reactions that are critical in many etch and deposition processes, and how these reactions are influenced by the variation in operating conditions. In addition, many plasma-based processes suffer from stability and reliability problems leading to a compromise in performance and a potentially increased cost for the semiconductor manufacturing industry. Such a lack of understanding has hindered the development of process models that can aid in the scaling and improvement of plasma etch and deposition systems. The research described involves the study of plasmas used in semiconductor processes. An inductively coupled plasma (ICP) source in place of the standard upper electrode assembly of the Gaseous Electronics Conference (GEC) radio-frequency (RF) Reference Cell is used to investigate the discharge characteristics and chemistries. This ICP source generates plasmas with higher electron densities (approximately 10(exp 12)/cu cm) and lower operating pressures (approximately 7 mTorr) than obtainable with the original parallel-plate version of the GEC Cell. This expanded operating regime is more relevant to new generations of industrial plasma systems being used by the microelectronics industry. The motivation for this study is to develop an understanding of the physical phenomena involved in plasma processing and to measure much needed fundamental parameters, such as gas-phase and surface reaction rates. species

  3. Safety of low dose heparin in elective coronary angioplasty.

    PubMed Central

    Koch, K. T.; Piek, J. J.; de Winter, R. J.; David, G. K.; Mulder, K.; Tijssen, J. G.; Lie, K. I.

    1997-01-01

    OBJECTIVES: To evaluate the safety of a low dose of heparin in consecutive stable patients undergoing elective percutaneous transluminal coronary angioplasty (PTCA). DESIGN: Open prospective study in a single centre. PATIENTS: 1375 consecutive patients had elective PTCA (1952 lesions: type A 11%, B1 34%, B2 36%, and C 19%). There were no angiographic exclusion criteria. INTERVENTIONS: A bolus of 5000 IU heparin was used as the standard anticoagulation regimen during PTCA. The sheaths were removed immediately after successful completion of the procedure. Prolongation of heparin treatment was left to the operator's discretion. MAIN OUTCOME MEASURES: Procedural success was defined as < 50% residual stenosis without death from any cause, acute myocardial infarction, urgent coronary bypass surgery, or repeat angioplasty within 48 hours for acute recurrent ischaemia; the need for prolonged heparinisation; and the occurrence of puncture site complications. RESULTS: Procedural success without clinical events was achieved in 90% of patients. Mortality was 0.3%; coronary bypass surgery was performed in 1.7% of the procedures. The rate of myocardial infarction was 3.3%; repeat angioplasty within 48 hours was carried out in 0.7% of patients. A total of 89.1% of the patients were treated according to the protocol. Prolonged treatment with heparin was considered necessary in 123 patients (8.9%). Repeat angioplasty for abrupt closure was performed in two patients shortly after sheath removal and in two during prolonged heparinisation. Puncture site complications occurred in 2.1% of patients (low dose heparin 1.9% and prolonged heparinisation 4.9%). CONCLUSION: Elective PTCA can be safely performed using a low dose of heparin, with a negligible risk for subacute closure. Low dose heparin may reduce the incidence of puncture site complications, shorten hospitalisation, and enable out-patient angioplasty. PMID:9227294

  4. A photoacoustic tool for therapeutic drug monitoring of heparin (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Wang, Junxin; Hartanto, James; Jokerst, Jesse V.

    2017-03-01

    Heparin is used broadly in cardiac, pulmonary, surgical, and vascular medicine to treat thrombotic disorders with over 500 million doses per year globally. Despite this widespread use, it has a narrow therapeutic window and is one of the top three medication errors. The active partial thromboplastin time (PTT) monitors heparin, but this blood test suffers from long turnaround times, a variable reference range, and limited utility with low molecular weight heparin. Here, we describe an imaging technique that can monitor heparin concentration and activity in real time using photoacoustic spectroscopy via methylene blue as a simple and Federal Drug Agency-approved contrast agent. We found a strong correlation between heparin concentration and photoacoustic signal measured in phosphate buffered saline (PBS) and blood (R2>0.90). Clinically relevant concentrations were detected in blood with a heparin detection limit of 0.28 U/mL and a low molecular weight heparin (enoxaparin) detection limit of 72 μg/mL. We validated this imaging approach by correlation to the PTT (Pearson's r = 0.86; p<0.05) as well as with protamine sulfate treatment. To the best of our knowledge, this is the first report to use imaging data to monitor anticoagulation.

  5. Near room-temperature direct encapsulation of organic photovoltaics by plasma-based deposition techniques

    DOE PAGES

    Perrotta, Alberto; Fuentes-Hernandez, Canek; Khan, Talha M.; ...

    2016-12-02

    Plasma-assisted atomic layer deposition (ALD) is used for the deposition of environmental barriers directly onto organic photovoltaic devices (OPVs) at near room temperature (30 °C). To study the effect of the ALD process on the organic materials forming the device, the precursor diffusion and intermixing at the interface during the growth of different plasma- assisted ALD inorganic barriers (i.e. Al2O3 and TiO2) onto the organic photoactive layer (P3HT:ICBA) was investigated. Depth profile x-ray photoelectron spectroscopy was used to analyze the composition of the organic/inorganic interface to investigate the infiltration of the plasma-assisted ALD precursors into the photoactive layer as amore » function of the precursor dimension, the process temperature, and organic layer morphology. The free volume in the photoactive layer accessible to the ALD precursor was characterized by means of ellipsometric porosimetry (EP) and spectroscopic ellipsometry as a function of temperature. The organic layer is shown to exhibit free volume broadening at high temperatures, increasing the infiltration depth of the ALD precursor into the photoactive layer. Furthermore, based on previous investigations, the intrinsic permeation properties of the inorganic layers deposited by plasma-assisted ALD were predicted from the nano-porosity content as measured by EP and found to be in the 10-6 gm-2 d-1 range. Insight from our studies was used to design and fabricate multilayer barriers synthesized at near-room temperature by plasma-assisted ALD in combination with plasma-enhanced CVD onto organic photovoltaic (OPVs) devices. Encapsulated OPVs displayed shelf-lifetimes up to 1400 h at ambient conditions.« less

  6. Diamond synthesis at atmospheric pressure by microwave capillary plasma chemical vapor deposition

    DOE PAGES

    Gou, Huiyang; Hemley, Russell J.; Hemawan, Kadek W.

    2015-11-02

    Polycrystalline diamond has been successfully synthesized on silicon substrates at atmospheric pressure using a microwave capillary plasma chemical vapor deposition technique. The CH 4/Ar plasma was generated inside of quartz capillary tubes using 2.45 GHz microwave excitation without adding H2 into the deposition gas chemistry. Electronically excited species of CN, C 2, Ar, N 2, CH, H β and H α were observed in emission spectra. Raman measurements of deposited material indicate the formation of well-crystallized diamond, as evidenced by the sharp T 2g phonon at 1333 cm -1 peak relative to the Raman features of graphitic carbon. Furthermore, fieldmore » emission scanning electron microscopy (SEM) images reveal that, depending on the on growth conditions, the carbon microstructures of grown films exhibit “coral” and “cauliflower-like” morphologies or well-facetted diamond crystals with grain sizes ranging from 100 nm to 10 μm.« less

  7. Plasma etching of polymers like SU8 and BCB

    NASA Astrophysics Data System (ADS)

    Mischke, Helge; Gruetzner, Gabi; Shaw, Mark

    2003-01-01

    Polymers with high viscosity, like SU8 and BCB, play a dominant role in MEMS application. Their behavior in a well defined etching plasma environment in a RIE mode was investigated. The 40.68 MHz driven bottom electrode generates higher etch rates combined with much lower bias voltages by a factor of ten or a higher efficiency of the plasma with lower damaging of the probe material. The goal was to obtain a well-defined process for the removal and structuring of SU8 and BCB using fluorine/oxygen chemistry, defined using variables like electron density and collision rate. The plasma parameters are measured and varied using a production proven technology called SEERS (Self Excited Electron Resonance Spectroscopy). Depending on application and on Polymer several metals are possible (e.g., gold, aluminum). The characteristic of SU8 and BCB was examined in the case of patterning by dry etching in a CF4/O2 chemistry. Etch profile and etch rate correlate surprisingly well with plasma parameters like electron density and electron collision rate, thus allowing to define to adjust etch structure in situ with the help of plasma parameters.

  8. The localisation of the heparin binding sites of human and murine interleukin-12 within the carboxyterminal domain of the P40 subunit.

    PubMed

    Garnier, Pascale; Mummery, Rosemary; Forster, Mark J; Mulloy, Barbara; Gibbs, Roslyn V; Rider, Christopher C

    2018-05-09

    We have previously shown that the heterodimeric cytokine interleukin-12, and the homodimer of its larger subunit p40, both bind to heparin and heparan sulfate with relatively high affinity. In the present study we characterised these interactions using a series of chemically modified heparins as competitive inhibitors. Human interleukin-12 and p40 homodimer show indistinguishable binding profiles with a panel of heparin derivatives, but that of murine interleukin-12 is distinct. Heparin markedly protects the human and murine p40 subunits, but not the p35 subunits, from cleavage by the bacterial endoprotease LysC, further implicating the larger subunit as the location of the heparin binding site. Moreover the essential role of the carboxyterminal D3 domain in heparin binding is established by the failure of a truncated construct of the p40 subunit lacking this domain to bind. Predictive docking calculations indicate that a cluster of basic residues at the tip of the exposed C'D' loop within D3 is important in heparin binding. However since the human and murine C'D' loops differ considerably in length, the mode and three dimensional orientation of heparin binding are likely to differ substantially between the human and murine p40s. Thus overall the binding of IL-12 via its p40 subunit to heparin-related polysaccharides of the extracellular matrix appears to be functionally important since it has been conserved across mammalian species despite this structural divergence. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. An enzyme-linked immunosorbent assay for the evaluation of thrombocytopenia induced by heparin.

    PubMed

    Howe, S E; Lynch, D M

    1985-05-01

    Five patients with heparin-associated thrombocytopenia (HAT) were evaluated by platelet aggregation and quantitation of immunoglobulin binding to intact target platelets in both the presence and absence of heparin. These patients developed thrombocytopenia (12,000 to 70,000 platelets/microliter) 7 to 15 days and embolic and hemorrhagic complications 9 to 15 days after the initiation of heparin therapy. Platelet aggregation after the addition of heparin was demonstrated in two of four HAT serum samples, whereas normal serum samples showed no significant platelet aggregation. The five HAT serum samples showed normal to elevated baseline serum platelet-bindable immunoglobulin (SPBIg) with a range of 4.3 to 11.4 fg/platelet (normal less than or equal to 1.0 to 6.5 fg/platelet). When HAT sera were incubated with target platelets and heparin (5 U/ml), the SPBIg increased to 8.5 to 37.5 fg/platelet, a mean increase of 148% in the presence of heparin. Normal and control serum samples (from 10 normal laboratory volunteers, nine patients without thrombocytopenia receiving heparin, nine patients with autoimmune thrombocytopenic purpura, and nine patients with nonimmune thrombocytopenia not receiving heparin) showed only a slight increase in SPBIg of 0 to 2.8 fg/platelet above baseline, a mean increase of 15% after heparin incubation with the serum samples. The measurement of SPBIg of washed platelets incubated with test serum samples in the presence and absence of heparin is potentially a specific and sensitive in vitro test for the diagnosis of HAT and may prove more sensitive than platelet aggregation studies with heparin.

  10. Novel Cyclosilazane-Type Silicon Precursor and Two-Step Plasma for Plasma-Enhanced Atomic Layer Deposition of Silicon Nitride.

    PubMed

    Park, Jae-Min; Jang, Se Jin; Lee, Sang-Ick; Lee, Won-Jun

    2018-03-14

    We designed cyclosilazane-type silicon precursors and proposed a three-step plasma-enhanced atomic layer deposition (PEALD) process to prepare silicon nitride films with high quality and excellent step coverage. The cyclosilazane-type precursor, 1,3-di-isopropylamino-2,4-dimethylcyclosilazane (CSN-2), has a closed ring structure for good thermal stability and high reactivity. CSN-2 showed thermal stability up to 450 °C and a sufficient vapor pressure of 4 Torr at 60 °C. The energy for the chemisorption of CSN-2 on the undercoordinated silicon nitride surface as calculated by density functional theory method was -7.38 eV. The PEALD process window was between 200 and 500 °C, with a growth rate of 0.43 Å/cycle. The best film quality was obtained at 500 °C, with hydrogen impurity of ∼7 atom %, oxygen impurity less than 2 atom %, low wet etching rate, and excellent step coverage of ∼95%. At 300 °C and lower temperatures, the wet etching rate was high especially at the lower sidewall of the trench pattern. We introduced the three-step PEALD process to improve the film quality and the step coverage on the lower sidewall. The sequence of the three-step PEALD process consists of the CSN-2 feeding step, the NH 3 /N 2 plasma step, and the N 2 plasma step. The H radicals in NH 3 /N 2 plasma efficiently remove the ligands from the precursor, and the N 2 plasma after the NH 3 plasma removes the surface hydrogen atoms to activate the adsorption of the precursor. The films deposited at 300 °C using the novel precursor and the three-step PEALD process showed a significantly improved step coverage of ∼95% and an excellent wet etching resistance at the lower sidewall, which is only twice as high as that of the blanket film prepared by low-pressure chemical vapor deposition.

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

    PubMed

    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.

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

    PubMed

    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 (<14%). The use of the two types of Eudragit in combination with PCL and 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.

  13. Potentiation of C1-esterase inhibitor by heparin and interactions with C1s protease as assessed by surface plasmon resonance.

    PubMed

    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.

  14. On a non-thermal atmospheric pressure plasma jet used for the deposition of silicon-organic films

    NASA Astrophysics Data System (ADS)

    Schäfer, Jan; Sigeneger, Florian; Foest, Rüdiger; Loffhagen, Detlef; Weltmann, Klaus-Dieter

    2018-05-01

    This work represents a concise overview on the results achieved by the authors over the last years on the plasma of a non-thermal reactive plasma jet at atmospheric pressure and of related thin film formation by plasma enhanced chemical vapour deposition (PECVD). The source was developed considering the application of the plasma self-organization for PECVD. The experimental methods comprise spectroscopic measurements of plasma parameters in the active zone, temperature measurements in the active zone and the effluent as well as the analysis of deposited films at the substrate surface. The theoretical investigations are devoted to a single filament in the active zone using a phase-resolved model and to an overall description of the jet including the substrate using a period-averaged model.

  15. Plasma-assisted physical vapor deposition surface treatments for tribological control

    NASA Technical Reports Server (NTRS)

    Spalvins, Talivaldis

    1990-01-01

    In any mechanical or engineering system where contacting surfaces are in relative motion, adhesion, wear, and friction affect reliability and performance. With the advancement of space age transportation systems, the tribological requirements have dramatically increased. This is due to the optimized design, precision tolerance requirements, and high reliability expected for solid lubricating films in order to withstand hostile operating conditions (vacuum, high-low temperatures, high loads, and space radiation). For these problem areas the ion-assisted deposition/modification processes (plasma-based and ion beam techniques) offer the greatest potential for the synthesis of thin films and the tailoring of adherence and chemical and structural properties for optimized tribological performance. The present practices and new approaches of applying soft solid lubricant and hard wear resistant films to engineering substrates are reviewed. The ion bombardment treatments have increased film adherence, lowered friction coefficients, and enhanced wear life of the solid lubricating films such as the dichalcogenides (MoS2) and the soft metals (Au, Ag, Pb). Currently, sputtering is the preferred method of applying MoS2 films; and ion plating, the soft metallic films. Ultralow friction coefficients (less than 0.01) were achieved with sputtered MoS2. Further, new diamond-like carbon and BN lubricating films are being developed by using the ion assisted deposition techniques.

  16. PROFILING GLYCOL-SPLIT HEPARINS BY HPLC/MS ANALYSIS OF THEIR HEPARINASE-GENERATED OLIGOSACCHARIDES1

    PubMed Central

    Alekseeva, Anna; Casu, Benito; Torri, Giangiacomo; Pierro, Sabrina; Naggi, Annamaria

    2012-01-01

    Glycol-split (gs) heparins, obtained by periodate oxidation / borohydride reduction of heparin currently used as anticoagulant and antithrombotic drug, are arousing increasing interest in anti-cancer and anti-inflammation therapies. These new medical uses are favored by the loss of anticoagulant activity associated with glycol-splitting-induced inactivation of the antithrombin III (AT) binding site. The structure of gs-heparins has not been studied yet in detail. In this work, an ion-pair reversed-phase chromatography (IPRP-HPLC) coupled with electrospray ionization mass spectrometry (ESI-MS) widely used for unmodified heparin has been adapted to the analysis of oligosaccharides generated by digestion with heparinases of gs-heparins usually prepared from porcine mucosal heparin. The method has been also found very effective in analyzing glycol-split derivatives obtained from heparins of different animal and tissue origin. Besides the major 2-O-sulfated disaccharides, heparinase digests of gs-heparins mainly contain tetra- and hexasaccharides incorporating one or two gs residues, with distribution patterns typical for individual gs-heparins. A heptasulfated, mono-N-acetylated hexasaccharide with two gs residues has been shown to be a marker of the gs-modified AT binding site within heparin chains. PMID:23201389

  17. Antiangiogenic activity of semisynthetic biotechnological heparins: low-molecular-weight-sulfated Escherichia coli K5 polysaccharide derivatives as fibroblast growth factor antagonists.

    PubMed

    Presta, Marco; Oreste, Pasqua; Zoppetti, Giorgio; Belleri, Mirella; Tanghetti, Elena; Leali, Daria; Urbinati, Chiara; Bugatti, Antonella; Ronca, Roberto; Nicoli, Stefania; Moroni, Emanuela; Stabile, Helena; Camozzi, Maura; Hernandez, German Andrés; Mitola, Stefania; Dell'Era, Patrizia; Rusnati, Marco; Ribatti, Domenico

    2005-01-01

    Low-molecular-weight heparin (LMWH) exerts antitumor activity in clinical trials. The K5 polysaccharide from Escherichia coli has the same structure as the heparin precursor. Chemical and enzymatic modifications of K5 polysaccharide lead to the production of biotechnological heparin-like compounds. We investigated the fibroblast growth factor-2 (FGF2) antagonist and antiangiogenic activity of a series of LMW N,O-sulfated K5 derivatives. Surface plasmon resonance analysis showed that LMW-K5 derivatives bind FGF2, thus inhibiting its interaction with heparin immobilized to a BIAcore sensor chip. Interaction of FGF2 with tyrosine-kinase receptors (FGFRs), heparan sulfate proteoglycans (HSPGs), and alpha(v)beta3 integrin is required for biological response in endothelial cells. Similar to LMWH, LMW-K5 derivatives abrogate the formation of HSPG/FGF2/FGFR ternary complexes by preventing FGF2-mediated attachment of FGFR1-overexpressing cells to HSPG-bearing cells and inhibit FGF2-mediated endothelial cell proliferation. However, LMW-K5 derivatives, but not LMWH, also inhibit FGF2/alpha(v)beta3 integrin interaction and consequent FGF2-mediated endothelial cell sprouting in vitro and angiogenesis in vivo in the chick embryo chorioallantoic membrane. LMW N,O-sulfated K5 derivatives affect both HSPG/FGF2/FGFR and FGF2/alpha(v)beta3 interactions and are endowed with FGF2 antagonist and antiangiogenic activity. These compounds may provide the basis for the design of novel LMW heparin-like angiostatic compounds.

  18. Characterizations of GaN film growth by ECR plasma chemical vapor deposition

    NASA Astrophysics Data System (ADS)

    Fu, Silie; Chen, Junfang; Zhang, Hongbin; Guo, Chaofen; Li, Wei; Zhao, Wenfen

    2009-06-01

    The electron cyclotron resonance plasma-enhanced metalorganic chemical vapor deposition technology (ECR-MOPECVD) is adopted to grow GaN films on (0 0 0 1) α-Al2O3 substrate. The gas sources are pure N2 and trimethylgallium (TMG). Optical emission spectroscopy (OES) and thermodynamic analysis of GaN growth are applied to understand the GaN growth process. The OES of ECR plasma shows that TMG is significantly dissociated in ECR plasma. Reactants N and Ga in the plasma, obtained easily under the self-heating condition, are essential for the GaN growth. They contribute to the realization of GaN film growth at a relatively low temperature. The thermodynamic study shows that the driving force for the GaN growth is high when N2:TMG>1. Furthermore, higher N2:TMG flow ratio makes the GaN growth easier. Finally, X-ray diffraction, photoluminescence, and atomic force microscope are applied to investigate crystal quality, morphology, and roughness of the GaN films. The results demonstrate that the ECR-MOPECVD technology is favorable for depositing GaN films at low temperatures.

  19. Patterned growth of carbon nanotubes obtained by high density plasma chemical vapor deposition

    NASA Astrophysics Data System (ADS)

    Mousinho, A. P.; Mansano, R. D.

    2015-03-01

    Patterned growth of carbon nanotubes by chemical vapor deposition represents an assembly approach to place and orient nanotubes at a stage as early as when they are synthesized. In this work, the carbon nanotubes were obtained at room temperature by High Density Plasmas Chemical Vapor Deposition (HDPCVD) system. This CVD system uses a new concept of plasma generation, where a planar coil coupled to an RF system for plasma generation was used with an electrostatic shield for plasma densification. In this mode, high density plasmas are obtained. We also report the patterned growth of carbon nanotubes on full 4-in Si wafers, using pure methane plasmas and iron as precursor material (seed). Photolithography processes were used to pattern the regions on the silicon wafers. The carbon nanotubes were characterized by micro-Raman spectroscopy, the spectra showed very single-walled carbon nanotubes axial vibration modes around 1590 cm-1 and radial breathing modes (RBM) around 120-400 cm-1, confirming that high quality of the carbon nanotubes obtained in this work. The carbon nanotubes were analyzed by atomic force microscopy and scanning electron microscopy too. The results showed that is possible obtain high-aligned carbon nanotubes with patterned growth on a silicon wafer with high reproducibility and control.

  20. Hydrogen-dominated plasma, due to silane depletion, for microcrystalline silicon deposition

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

    Howling, A. A.; Sobbia, R.; Hollenstein, Ch.

    2010-07-15

    Plasma conditions for microcrystalline silicon deposition generally require a high flux of atomic hydrogen, relative to SiH{sub {alpha}=0{yields}3} radicals, on the growing film. The necessary dominant partial pressure of hydrogen in the plasma is conventionally obtained by hydrogen dilution of silane in the inlet flow. However, a hydrogen-dominated plasma environment can also be obtained due to plasma depletion of the silane in the gas mixture, even up to the limit of pure silane inlet flow, provided that the silane depletion is strong enough. At first sight, it may seem surprising that the composition of a strongly depleted pure silane plasmamore » consists principally of molecular hydrogen, without significant contribution from the partial pressure of silane radicals. The aim here is to bring some physical insight by means of a zero-dimensional, analytical plasma chemistry model. The model is appropriate for uniform large-area showerhead reactors, as shown by comparison with a three-dimensional numerical simulations. The SiH{sub {alpha}} densities remain very low because of their rapid diffusion and surface reactivity, contributing to film growth which is the desired scenario for efficient silane utilization. Significant SiH{sub {alpha}} densities due to poor design of reactor and gas flow, on the other hand, would result in powder formation wasting silane. Conversely, hydrogen atoms are not deposited, but recombine on the film surface and reappear as molecular hydrogen in the plasma. Therefore, in the limit of extremely high silane depletion fraction (>99.9%), the silane density falls below the low SiH{sub {alpha}} densities, but only the H radical can eventually reach significant concentrations in the hydrogen-dominated plasma.« less

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

    PubMed

    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.

  2. Gallium arsenide/gold nanostructures deposited using plasma method

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

    Mangla, O.; Physics Department, Hindu College, University of Delhi, Delhi, 110007; Roy, S.

    2016-05-23

    The fabrication of gallium arsenide (GaAs) nanostructures on gold coated glass, quartz and silicon substrates using the high fluence and highly energetic ions has been reported. The high fluence and highly energetic ions are produced by the hot, dense and extremely non-equilibrium plasma in a modified dense plasma focus device. The nanostructures having mean size about 14 nm, 13 nm and 18 nm are deposited on gold coated glass, quartz and silicon substrates, respectively. The optical properties of nanostructures studied using absorption spectra show surface plasmon resonance peak of gold nanoparticles. In addition, the band-gap of GaAs nanoparticles is more than that ofmore » bulk GaAs suggesting potential applications in the field of optoelectronic and sensor systems.« less

  3. Heparin-induced thrombocytopenia in solid organ transplant recipients: The current scientific knowledge

    PubMed Central

    Assfalg, Volker; Hüser, Norbert

    2016-01-01

    Exposure to heparin is associated with a high incidence of immunization against platelet factor 4 (PF4)/heparin complexes. A subgroup of immunized patients is at risk of developing heparin-induced thrombocytopenia (HIT), an immune mediated prothrombotic adverse drug effect. Transplant recipients are frequently exposed to heparin either due to the underlying end-stage disease, which leads to listing and transplantation or during the transplant procedure and the perioperative period. To review the current scientific knowledge on anti-heparin/PF4 antibodies and HIT in transplant recipients a systematic PubMed literature search on articles in English language was performed. The definition of HIT is inconsistent amongst the publications. Overall, six studies and 15 case reports have been published on HIT before or after heart, liver, kidney, and lung transplantation, respectively. The frequency of seroconversion for anti-PF4/heparin antibodies ranged between 1.9% and 57.9%. However, different methods to detect anti-PF4/heparin antibodies were applied. In none of the studies HIT-associated thromboembolic events or fatalities were observed. More importantly, in patients with a history of HIT, reexposure to heparin during transplantation was not associated with thrombotic complications. Taken together, the overall incidence of HIT after solid organ transplantation seems to be very low. However, according to the current knowledge, cardiac transplant recipients may have the highest risk to develop HIT. Different alternative suggestions for heparin-free anticoagulation have been reported for recipients with suspected HIT albeit no official recommendations on management have been published for this special collective so far. PMID:27011914

  4. Haplotypes of heparin-binding epidermal-growth-factor-like growth factor gene are associated with pre-eclampsia.

    PubMed

    Harendra, Galhenagey Gayani; Jayasekara, Rohan W; Dissanayake, Vajira H W

    2012-01-01

    Heparin-binding epidermal-growth-factor-like growth factor (HBEGF) plays an important role in placentation, including impaired placentation, the primary defect seen in pre-eclampsia. We carried out a case-control disease-association study to examine the association of single nucleotide polymorphisms (SNP) in the HBEGF gene and haplotypes defined by them with pre-eclampsia in a Sinhalese population in Sri Lanka. A total of 175 women with pre-eclampsia and 171 matched normotensive controls were genotyped for six SNP selected in silico as having putative functional effects using mass array Sequenom iplex methodology and a newly designed polymerase chain reaction-restriction fragment length polymorphism assay. The individual SNP were not associated with pre-eclampsia. The haplotypes defined by them, however, showed both predisposing (rs13385T,rs2074613G,rs2237076G,rs2074611C,rs4150196A,rs1862176A; odds ratio,1.65; 95% confidence interval1.04-2.60; P=0.032) and protective (rs13385C,rs2074613G,rs2237076A,rs2074611C,rs4150196A,rs1862176A; odds ratio,0.20; 95% confidence interval, 0.04-0.89; P=0.034) effects. These results confirm that polymorphisms in the HGEGF gene are associated with pre-eclampsia. The haplotypes are likely to exert their effects through the numerous transcription regulation factors binding to the polymorphic sites, namely GATA-1, GATA-3, MZF-1 and AML-1a. © 2011 The Authors. Journal of Obstetrics and Gynaecology Research © 2011 Japan Society of Obstetrics and Gynecology.

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

    PubMed

    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.

  6. PF4/heparin-antibody complex induces monocyte tissue factor expression and release of tissue factor positive microparticles by activation of FcγRI

    PubMed Central

    Glover, Sam L.; Jonas, William; McEachron, Troy; Pawlinski, Rafal; Arepally, Gowthami M.; Key, Nigel S.; Mackman, Nigel

    2012-01-01

    Heparin-induced thrombocytopenia (HIT) is a potentially devastating form of drug-induced thrombocytopenia that occurs in patients receiving heparin for prevention or treatment of thrombosis. Patients with HIT develop autoantibodies to the platelet factor 4 (PF4)/heparin complex, which is termed the HIT Ab complex. Despite a decrease in the platelet count, the most feared complication of HIT is thrombosis. The mechanism of thrombosis in HIT remains poorly understood. We investigated the effects of the HIT Ab complex on tissue factor (TF) expression and release of TF-positive microparticles in peripheral blood mononuclear cells and monocytes. To model these effects ex vivo, we used a murine mAb specific for the PF4/heparin complex (KKO), as well as plasma from patients with HIT. We found that the HIT Ab complex induced TF expression in monocytes and the release of TF-positive microparticles. Further, we found that induction of TF is mediated via engagement of the FcγRI receptor and activation of the MEK1-ERK1/2 signaling pathway. Our data suggest that monocyte TF may contribute to the development of thrombosis in patients with HIT. PMID:22394597

  7. Influence of deposition rate on the structural properties of plasma-enhanced CVD epitaxial silicon

    PubMed Central

    Chen, Wanghua; Cariou, Romain; Hamon, Gwenaëlle; Léal, Ronan; Maurice, Jean-Luc; Cabarrocas, Pere Roca i

    2017-01-01

    Solar cells based on epitaxial silicon layers as the absorber attract increasing attention because of the potential cost reduction. In this work, we studied the influence of the deposition rate on the structural properties of epitaxial silicon layers produced by plasma-enhanced chemical vapor deposition (epi-PECVD) using silane as a precursor and hydrogen as a carrier gas. We found that the crystalline quality of epi-PECVD layers depends on their thickness and deposition rate. Moreover, increasing the deposition rate may lead to epitaxy breakdown. In that case, we observe the formation of embedded amorphous silicon cones in the epi-PECVD layer. To explain this phenomenon, we develop a model based on the coupling of hydrogen and built-in strain. By optimizing the deposition conditions to avoid epitaxy breakdown, including substrate temperatures and plasma potential, we have been able to synthesize epi-PECVD layers up to a deposition rate of 8.3 Å/s. In such case, we found that the incorporation of hydrogen in the hydrogenated crystalline silicon can reach 4 at. % at a substrate temperature of 350 °C. PMID:28262840

  8. Alteration of blood clotting and lung damage by protamine are avoided using the heparin and polyphosphate inhibitor UHRA

    PubMed Central

    Abraham, Libin; Kapopara, Piyushkumar R.; Lai, Benjamin F. L.; Shenoi, Rajesh A.; Rosell, Federico I.; Conway, Edward M.; Pryzdial, Edward L. G.; Haynes, Charles A.

    2017-01-01

    Anticoagulant therapy–associated bleeding and pathological thrombosis pose serious risks to hospitalized patients. Both complications could be mitigated by developing new therapeutics that safely neutralize anticoagulant activity and inhibit activators of the intrinsic blood clotting pathway, such as polyphosphate (polyP) and extracellular nucleic acids. The latter strategy could reduce the use of anticoagulants, potentially decreasing bleeding events. However, previously described cationic inhibitors of polyP and extracellular nucleic acids exhibit both nonspecific binding and adverse effects on blood clotting that limit their use. Indeed, the polycation used to counteract heparin-associated bleeding in surgical settings, protamine, exhibits adverse effects. To address these clinical shortcomings, we developed a synthetic polycation, Universal Heparin Reversal Agent (UHRA), which is nontoxic and can neutralize the anticoagulant activity of heparins and the prothrombotic activity of polyP. Sharply contrasting protamine, we show that UHRA does not interact with fibrinogen, affect fibrin polymerization during clot formation, or abrogate plasma clotting. Using scanning electron microscopy, confocal microscopy, and clot lysis assays, we confirm that UHRA does not incorporate into clots, and that clots are stable with normal fibrin morphology. Conversely, protamine binds to the fibrin clot, which could explain how protamine instigates clot lysis and increases bleeding after surgery. Finally, studies in mice reveal that UHRA reverses heparin anticoagulant activity without the lung injury seen with protamine. The data presented here illustrate that UHRA could be safely used as an antidote during adverse therapeutic modulation of hemostasis. PMID:28034889

  9. Transparent conductive p-type lithium-doped nickel oxide thin films deposited by pulsed plasma deposition

    NASA Astrophysics Data System (ADS)

    Huang, Yanwei; Zhang, Qun; Xi, Junhua; Ji, Zhenguo

    2012-07-01

    Transparent p-type Li0.25Ni0.75O conductive thin films were prepared on conventional glass substrates by pulsed plasma deposition. The effects of substrate temperature and oxygen pressure on structural, electrical and optical properties of the films were investigated. The electrical resistivity decreases initially and increases subsequently as the substrate temperature increases. As the oxygen pressure increases, the electrical resistivity decreases monotonically. The possible physical mechanism was discussed. And a hetero p-n junction of p-Li0.25Ni0.75O/n-SnO2:W was fabricated by depositing n-SnO2:W on top of the p-Li0.25Ni0.75O, which exhibits typical rectifying current-voltage characteristics.

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

    PubMed Central

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

    2012-01-01

    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. PMID:22326251

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

    PubMed

    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.

  12. Deposition kinetics and characterization of stable ionomers from hexamethyldisiloxane and methacrylic acid by plasma enhanced chemical vapor deposition

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

    Urstöger, Georg; Resel, Roland; Coclite, Anna Maria, E-mail: anna.coclite@tugraz.at

    2016-04-07

    A novel ionomer of hexamethyldisiloxane and methacrylic acid was synthesized by plasma enhanced chemical vapor deposition (PECVD). The PECVD process, being solventless, allows mixing of monomers with very different solubilities, and for polymers formed at high deposition rates and with high structural stability (due to the high number of cross-links and covalent bonding to the substrate) to be obtained. A kinetic study over a large set of parameters was run with the aim of determining the optimal conditions for high stability and proton conductivity of the polymer layer. Copolymers with good stability over 6 months' time in air and watermore » were obtained, as demonstrated by ellipsometry, X-Ray reflectivity, and FT-IR spectroscopy. Stable coatings showed also proton conductivity as high as 1.1 ± 0.1 mS cm{sup −1}. Chemical analysis showed that due to the high molecular weight of the chosen precursors, it was possible to keep the plasma energy-input-per-mass low. This allowed limited precursor fragmentation and the functional groups of both monomers to be retained during the plasma polymerization.« less

  13. Heparin/collagen encapsulating nerve growth factor multilayers coated aligned PLLA nanofibrous scaffolds for nerve tissue engineering.

    PubMed

    Zhang, Kuihua; Huang, Dianwu; Yan, Zhiyong; Wang, Chunyang

    2017-07-01

    Biomimicing topological structure of natural nerve tissue to direct axon growth and controlling sustained release of moderate neurotrophic factors are extremely propitious to the functional recovery of damaged nervous systems. In this study, the heparin/collagen encapsulating nerve growth factor (NGF) multilayers were coated onto the aligned poly-L-lactide (PLLA) nanofibrous scaffolds via a layer-by-layer (LbL) self-assembly technique to combine biomolecular signals, and physical guidance cues for peripheral nerve regeneration. Scanning electronic microscopy (SEM) revealed that the surface of aligned PLLA nanofibrous scaffolds coated with heparin/collagen multilayers became rougher and appeared some net-like filaments and protuberances in comparison with PLLA nanofibrous scaffolds. The heparin/collagen multilayers did not destroy the alignment of nanofibers. X-ray photoelectron spectroscopy and water contact angles displayed that heparin and collagen were successfully coated onto the aligned PLLA nanofibrous scaffolds and improved its hydrophilicity. Three-dimensional (3 D) confocal microscopy images further demonstrated that collagen, heparin, and NGF were not only coated onto the surface of aligned PLLA nanofibrous scaffolds but also permeated into the inner of scaffolds. Moreover, NGF presented a sustained release for 2 weeks from aligned nanofibrous scaffolds coated with 5.5 bilayers or above and remained good bioactivity. The heparin/collagen encapsulating NGF multilayers coated aligned nanofibrous scaffolds, in particular 5.5 bilayers or above, was more beneficial to Schwann cells (SCs) proliferation and PC12 cells differentiation as well as the SC cytoskeleton and neurite growth along the direction of nanofibrous alignment compared to the aligned PLLA nanofibrous scaffolds. This novel scaffolds combining sustained release of bioactive NGF and aligned nanofibrous topography presented an excellent potential in peripheral nerve regeneration. © 2016 Wiley

  14. Analysis of heparin oligosaccharides by capillary electrophoresis-negative-ion electrospray ionization mass spectrometry.

    PubMed

    Lin, Lei; Liu, Xinyue; Zhang, Fuming; Chi, Lianli; Amster, I Jonathan; Leach, Franklyn E; Xia, Qiangwei; Linhardt, Robert J

    2017-01-01

    Most hyphenated analytical approaches that rely on liquid chromatography-MS require relatively long separation times, produce incomplete resolution of oligosaccharide mixtures, use eluents that are incompatible with electrospray ionization, or require oligosaccharide derivatization. Here we demonstrate the analysis of heparin oligosaccharides, including disaccharides, ultralow molecular weight heparin, and a low molecular weight heparin, using a novel electrokinetic pump-based CE-MS coupling eletrospray ion source. Reverse polarity CE separation and negative-mode electrospray ionization were optimized using a volatile methanolic ammonium acetate electrolyte and sheath fluid. The online CE hyphenated negative-ion electrospray ionization MS on an LTQ Orbitrap mass spectrometer was useful in disaccharide compositional analysis and bottom-up and top-down analysis of low molecular weight heparin. The application of this CE-MS method to ultralow molecular heparin suggests that a charge state distribution and the low level of sulfate group loss that is achieved make this method useful for online tandem MS analysis of heparins. Graphical abstract Most hyphenated analytical approaches that rely on liquid chromatography-MS require relatively long separation times, produce incomplete resolution of oligosaccharide mixtures, use eluents that are incompatible with electrospray ionization, or require oligosaccharide derivatization. Here we demonstrate the analysis of heparin oligosaccharides, including disaccharides, ultralow molecular weight heparin, and a low molecular weight heparin, using a novel electrokinetic pump-based CE-MS coupling eletrospray ion source. Reverse polarity CE separation and negative-mode electrospray ionization were optimized using a volatile methanolic ammonium acetate electrolyte and sheath fluid. The online CE hyphenated negative-ion electrospray ionization MS on an LTQ Orbitrap mass spectrometer was useful in disaccharide compositional analysis and

  15. Semiconductor gas sensor based on tin oxide nanorods prepared by plasma-enhanced chemical vapor deposition with postplasma treatment

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

    Huang Hui; Tan, O.K.; Lee, Y.C.

    2005-10-17

    SnO{sub 2} thin films were deposited by radio-frequency inductively coupled plasma-enhanced chemical vapor deposition. Postplasma treatments were used to modify the microstructure of the as-deposited SnO{sub 2} thin films. Uniform nanorods with dimension of null-set 7x100 nm were observed in the plasma-treated films. After plasma treatments, the optimal operating temperature of the plasma-treated SnO{sub 2} thin films decreased by 80 deg. C, while the gas sensitivity increased eightfold. The enhanced gas sensing properties of the plasma-treated SnO{sub 2} thin film were believed to result from the large surface-to-volume ratio of the nanorods' tiny grain size in the scale comparable tomore » the space-charge length and its unique microstructure of SnO{sub 2} nanorods rooted in SnO{sub 2} thin films.« less

  16. Generalized Keller-Simmons formula for nonisothermal plasma-assisted sputtering depositions

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

    Palmero, A.; Rudolph, H.; Habraken, F. H. P. M.

    2006-11-20

    A general description of the relation between the sputtering rate and the deposition rate in plasma-assisted sputtering deposition has been developed. The equation derived yields the so-called Keller-Simmons [IBM J. Res. Dev. 23, 24 (1979)] formula in the limit of zero thermal gradients in the deposition system. It is shown that the Keller-Simmons formula can still be applied to fit the experimental results if the characteristic pressure-distance product, p{sub 0}L{sub 0}, is related to the temperature of the sputter cathode and the growing film. Using this relation, it is found that the variations in the values for p{sub 0}L{sub 0}more » for different experimental conditions agree with the thus far not well understood experimental trends reported in the literature.« less

  17. Caracterisation of Titanium Nitride Layers Deposited by Reactive Plasma Spraying

    NASA Astrophysics Data System (ADS)

    Roşu, Radu Alexandru; Şerban, Viorel-Aurel; Bucur, Alexandra Ioana; Popescu, Mihaela; Uţu, Dragoş

    2011-01-01

    Forming and cutting tools are subjected to the intense wear solicitations. Usually, they are either subject to superficial heat treatments or are covered with various materials with high mechanical properties. In recent years, thermal spraying is used increasingly in engineering area because of the large range of materials that can be used for the coatings. Titanium nitride is a ceramic material with high hardness which is used to cover the cutting tools increasing their lifetime. The paper presents the results obtained after deposition of titanium nitride layers by reactive plasma spraying (RPS). As deposition material was used titanium powder and as substratum was used titanium alloy (Ti6Al4V). Macroscopic and microscopic (scanning electron microscopy) images of the deposited layers and the X ray diffraction of the coatings are presented. Demonstration program with layers deposited with thickness between 68,5 and 81,4 μm has been achieved and presented.

  18. CXCL4-platelet factor 4, heparin-induced thrombocytopenia and cancer.

    PubMed

    Sandset, Per Morten

    2012-04-01

    Platelet factor 4 (CXCL4-PF4) is a chemokine that binds to and neutralizes heparin and other negatively charged proteoglycans, but is also involved in angiogenesis and cancer development. In some patients exposed to heparin, antibodies are generated against the CXCL-PF4/heparin complex that may activate platelets and coagulation and lead to thrombocytopenia and arterial or venous thrombosis, a condition commonly named heparin induced thrombocytopenia (HIT). HIT has been investigated in numerous clinical settings, but there is limited data on the epidemiology and phenotype of HIT in cancer patients. The present review describes the role of CXCL4-PF4 in cancer, the immunobiology, clinical presentation and diagnosis of HIT, and the specific problems faced in cancer patients. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Topographic, optical and chemical properties of zinc particle coatings deposited by means of atmospheric pressure plasma

    NASA Astrophysics Data System (ADS)

    Wallenhorst, L. M.; Loewenthal, L.; Avramidis, G.; Gerhard, C.; Militz, H.; Ohms, G.; Viöl, W.

    2017-07-01

    In this research, topographic, optical and chemical properties of zinc oxide layers deposited by a cold plasma-spray process were measured. Here, zinc micro particles were fed to the afterglow of a plasma spark discharge whereas the substrates were placed in a quite cold zone of the effluent plasma jet. In this vein, almost closed layers were realised on different samples. As ascertained by laser scanning and atomic force microscopic measurements the particle size of the basic layer is in the nanometre scale. Additionally, larger particles and agglomerates were found on its top. The results indicate a partial plasma-induced diminishment of the initial particles, most probably due to melting or vaporisation. It is further shown that the plasma gives rise to an increased oxidation of such particles as confirmed by X-ray photoelectron spectroscopy. Quantitative analysis of the resulting mixed layer was performed. It is shown that the deposited layers consist of zinc oxide and elemental zinc in approximately equal shares. In addition, the layer's band gap energy was determined by spectroscopic analysis. Here, considerable UV blocking properties of the deposited layers were observed. Possible underlying effects as well as potential applications are presented.

  20. Deposition of Composite LSCF-SDC and SSC-SDC Cathodes by Axial-Injection Plasma Spraying

    NASA Astrophysics Data System (ADS)

    Harris, Jeffrey; Qureshi, Musab; Kesler, Olivera

    2012-06-01

    The performance of solid oxide fuel cell cathodes can be improved by increasing the number of electrochemical reaction sites, by controlling microstructures, or by using composite materials that consist of an ionic conductor and a mixed ionic and electronic conductor. LSCF (La0.6Sr0.4Co0.2Fe0.8O3-δ) and SSC (Sm0.5Sr0.5CoO3) cathodes were manufactured by axial-injection atmospheric plasma spraying, and composite cathodes were fabricated by mixing SDC (Ce0.8Sm0.2O1.9) into the feedstock powders. The plasma power was varied by changing the proportion of nitrogen in the plasma gas. The microstructures of cathodes produced with different plasma powers were characterized by scanning electron microscopy and gas permeation measurements. The deposition efficiencies of these cathodes were calculated based on the mass of the sprayed cathode. Particle surface temperatures were measured in-flight to enhance understanding of the relationship between spray parameters, microstructure, and deposition efficiency.

  1. Heparin at low concentration acts as antivenom against Bothrops jararacussu venom and bothropstoxin-I neurotoxic and myotoxic actions

    PubMed Central

    Rostelato-Ferreira, Sandro; Leite, Gildo Bernardo; Cintra, Adélia Cristina Oliveira; da Cruz-Höfling, Maria Alice; Rodrigues-Simioni, Léa; Oshima-Franco, Yoko

    2010-01-01

    Heparin has been shown to antagonize myotoxic effects of crotaline venoms. Here a very low heparin concentration (LHC) was examined in its ability to antagonize the neurotoxic/myotoxic effects of Bothrops jararacussu venom and its phospholipase A2 myotoxin, bothropstoxin-I (BthTX-I), in an in vitroz nerve-muscle preparation and in mice gastrocnemius. Normalization of results was done by assays with commercial antibothropic antivenom (CBA). LHC (1IU/ml) added to the incubation bath reduced by 4- and 4.5-fold (vs 2.8- and 2.5-fold by CBA) the neuromuscular paralysis, by 5.4 and 4.4-fold (vs 2.5- and 13.3-fold by CBA) the percentage of fibers damaged and by 6- and 1.7-fold (vs 30- and 1.6-fold by CBA) the CK activity induced by B. jararacussu and BthTX-I, respectively. Protamine sulphate added 15min after the incubation of the preparation with LHC+venom, avoided the LHC neutralizing effect against venom neurotoxicity. This strongly attests that given the polycationic nature of protamine, it probably complexed with the polyanionic heparin making it unattainable for binding to basic components of venom, reducing toxicity. Since heparin antagonism is generally stronger against venom effects than is myotoxin we discuss that other venom components than the BthTX-I are likely target for the antagonism promoted by the polyanionic heparin. PMID:21544183

  2. Comparison of cryogenic (hydrogen) and TESPEL (polystyrene) pellet particle deposition in a magnetically confined plasma

    NASA Astrophysics Data System (ADS)

    McCarthy, K. J.; Tamura, N.; Combs, S. K.; Panadero, N.; Ascabíbar, E.; Estrada, T.; García, R.; Hernández Sánchez, J.; López Fraguas, A.; Navarro, M.; Pastor, I.; Soleto, A.; TJ-II Team

    2017-10-01

    A cryogenic pellet injector (PI) and tracer encapsulated solid pellet (TESPEL) injector system has been operated in combination on the stellarator TJ-II. This unique arrangement has been created by piggy-backing a TESPEL injector onto the backend of a pipe-gun-type PI. The combined injector provides a powerful new tool for comparing ablation and penetration of polystyrene TESPEL pellets and solid hydrogen pellets, as well as for contrasting subsequent pellet particle deposition and plasma perturbation under analogous plasma conditions. For instance, a significantly larger increase in plasma line-averaged electron density, and electron content, is observed after a TESPEL pellet injection compared with an equivalent cryogenic pellet injection. Moreover, for these injections from the low-magnetic-field side of the plasma cross-section, TESPEL pellets deposit electrons deeper into the plasma core than cryogenic pellets. Finally, the physics behind these observations and possible implications for pellet injection studies are discussed.

  3. Comparison of cryogenic (hydrogen) and TESPEL (polystyrene) pellet particle deposition in a magnetically confined plasma

    DOE PAGES

    McCarthy, K. J.; Tamura, N.; Combs, S. K.; ...

    2018-01-05

    Here, a cryogenic pellet injector (PI) and tracer encapsulated solid pellet (TESPEL) injector system has been operated in combination on the stellarator TJ-II. This unique arrangement has been created by piggy-backing a TESPEL injector onto the backend of a pipe-gun–type PI. The combined injector provides a powerful new tool for comparing ablation and penetration of polystyrene TESPEL pellets and solid hydrogen pellets, as well as for contrasting subsequent pellet particle deposition and plasma perturbation under analogous plasma conditions. For instance, a significantly larger increase in plasma line-averaged electron density, and electron content, is observed after a TESPEL pellet injection comparedmore » with an equivalent cryogenic pellet injection. Moreover, for these injections from the low-magnetic-field side of the plasma cross-section, TESPEL pellets deposit electrons deeper into the plasma core than cryogenic pellets. Finally, the physics behind these observations and possible implications for pellet injection studies are discussed.« less

  4. Comparison of cryogenic (hydrogen) and TESPEL (polystyrene) pellet particle deposition in a magnetically confined plasma

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

    McCarthy, K. J.; Tamura, N.; Combs, S. K.

    Here, a cryogenic pellet injector (PI) and tracer encapsulated solid pellet (TESPEL) injector system has been operated in combination on the stellarator TJ-II. This unique arrangement has been created by piggy-backing a TESPEL injector onto the backend of a pipe-gun–type PI. The combined injector provides a powerful new tool for comparing ablation and penetration of polystyrene TESPEL pellets and solid hydrogen pellets, as well as for contrasting subsequent pellet particle deposition and plasma perturbation under analogous plasma conditions. For instance, a significantly larger increase in plasma line-averaged electron density, and electron content, is observed after a TESPEL pellet injection comparedmore » with an equivalent cryogenic pellet injection. Moreover, for these injections from the low-magnetic-field side of the plasma cross-section, TESPEL pellets deposit electrons deeper into the plasma core than cryogenic pellets. Finally, the physics behind these observations and possible implications for pellet injection studies are discussed.« less

  5. Low-Temperature Silicon Epitaxy by Remote, Plasma - Chemical Vapor Deposition

    NASA Astrophysics Data System (ADS)

    Habermehl, Scott Dwight

    The dynamics of low temperature Si homoepitaxial and heteroepitaxial growth, by remote plasma enhanced chemical vapor deposition, RPECVD, have been investigated. For the critical step of pre-deposition surface preparation of Si(100) surfaces, the attributes of remote plasma generated atomic H are compared to results obtained with a rapid thermal desorption, RTD, technique and a hybrid H-plasma/RTD technique. Auger electron spectroscopy, AES, and electron diffraction analysis indicate the hybrid technique to be very effective at surface passivation, while the RTD process promotes the formation of SiC precipitates, which induce defective epitaxial growth. For GaP and GaAs substrates, the use of atomic H exposure is investigated as a surface passivation technique. AES shows this technique to be effective at producing atomically clean surfaces. For processing at 400^circrm C, the GaAs(100) surface is observed to reconstruct to a c(8 x 2)Ga symmetry while, at 530^ circrm C the vicinal GaP(100) surface, miscut 10^circ , is observed to reconstruct to a (1 x n) type symmetry; an unreconstructed (1 x 1) symmetry is observed for GaP(111). Differences in the efficiency with which native oxides are removed from the surface are attributed to variations in the local atomic bonding order of group V oxides. The microstructure of homoepitaxial Si films, deposited at temperatures of 25-450^circ rm C and pressures of 50-500 mTorr, is catalogued. Optimized conditions for the deposition of low defect, single crystal films are identified. The existence of two pressure dependent regimes for process activation are observed. In-situ mass spectral analysis indicates that the plasma afterglow is dominated by monosilane ions below 200 mTorr, while above 200 mTorr, low mass rm H_{x} ^+ (x = 1,2,3) and rm HHe^+ ions dominate. Consideration of the growth rate data indicates that downstream dissociative silane ionization, in the lower pressure regime, is responsible for an enhanced surface H

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

    PubMed

    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.

  7. No calcium-fluoride-like deposits detected in plaque shortly after a sodium fluoride mouthrinse.

    PubMed

    Vogel, G L; Tenuta, L M A; Schumacher, G E; Chow, L C

    2010-01-01

    Plaque 'calcium-fluoride-like' (CaF(2)-like) and fluoride deposits held by biological/bacterial calcium fluoride (Ca-F) bonds appear to be the source of cariostatic concentrations of fluoride in plaque fluid. The aim of this study was to quantify the amounts of plaque fluoride held in these reservoirs after a sodium fluoride rinse. 30 and 60 min after a 228 microg/g fluoride rinse, plaque samples were collected from 11 volunteers. Each sample was homogenized, split into 2 aliquots (aliquots 1 and 2), centrifuged, and the recovered plaque fluid combined and analyzed using microelectrodes. The plaque mass from aliquot 1 was retained. The plaque mass from aliquot 2 was extracted several times with a solution having the same fluoride, calcium and pH as the plaque fluid in order to extract the plaque CaF(2)-like deposits. The total fluoride in both aliquots was then determined. In a second experiment, the extraction completeness was examined by applying the above procedure to in vitro precipitates containing known amounts of CaF(2)-like deposits. Nearly identical fluoride concentrations were found in both plaque aliquots. The extraction of the CaF(2)-like precipitates formed in vitro removed more than 80% of these deposits. The results suggest that either CaF(2)-like deposits were not formed in plaque or, if these deposits had been formed, they were rapidly lost. The inability to form persistent amounts of CaF(2)-like deposits in plaque may account for the relatively rapid loss of plaque fluid fluoride after the use of conventional fluoride dentifrices or rinses. (c) 2010 S. Karger AG, Basel.

  8. Synthesis and characterization of Poloxamer 188-grafted heparin copolymer.

    PubMed

    Tian, Ji-Lai; Zhao, Ying-Zheng; Jin, Zhuo; Lu, Cui-Tao; Tang, Qin-Qin; Xiang, Qi; Sun, Chang-Zheng; Zhang, Lu; Xu, Yan-Yan; Gao, Hui-Sheng; Zhou, Zhi-Cai; Li, Xiao-Kun; Zhang, Ying

    2010-07-01

    Poloxamer 188 is a safe biocompatible polymer that can be used in protein drug delivery system. In this study, a new heparin-poloxamer 188 conjugate (HP) was synthesized and its physicochemical properties were investigated. HP structure was confirmed by Fourier transform infrared spectroscopy (FTIR) and Hydrogen-1 nuclear magnetic resonance spectroscopy ((1)H-NMR). Content of the conjugated heparin was analyzed using Toluidine Blue. The critical micelle concentration (CMC) of the copolymer was determined by a fluorescence probe technique. The effect of HP on the gelation of poloxamer 188 was characterized by the rheological properties of the HP-poloxamer hydrogels. Solubility and viscosity of HP were also evaluated compared with poloxamer 188. From the results, the solubility of the conjugated heparin was increased compared with free heparin. The content of heparin in HP copolymer was 62.9%. The CMC of HP and poloxamer 188 were 0.483 and 0.743 mg/mL, respectively. The gelation temperature of 0.4 g/mL HP was 43.5 degrees C, whereas that of the same concentration of poloxamer 188 was 37.3 degrees C. With HP content in poloxamer 188 solution increasing, a V-shape change of gelation temperature was observed. Considering the importance of poloxamer 188 in functional material, HP may prove to be a facile temperature-sensitive material for protein drug-targeted therapy.

  9. Plasma-deposited tetraglyme surfaces greatly reduce total blood protein adsorption, contact activation, platelet adhesion, platelet procoagulant activity, and in vitro thrombus deposition.

    PubMed

    Cao, Lan; Chang, Mark; Lee, Chi-Ying; Castner, David G; Sukavaneshvar, Sivaprasad; Ratner, Buddy D; Horbett, Thomas A

    2007-06-15

    The ability of tetraethylene glycol dimethyl ether (tetraglyme) plasma deposited coatings exhibiting ultralow fibrinogen adsorption to reduce blood activation was studied with six in vitro methods, namely fibrinogen and von Willebrand's factor adsorption, total protein adsorption, clotting time in recalcified plasma, platelet adhesion and procoagulant activity, and whole blood thrombosis in a disturbed flow catheter model. Surface plasmon resonance results showed that tetraglyme surfaces strongly resisted the adsorption of all proteins from human plasma. The clotting time in the presence of tetraglyme surfaces was lengthened compared with controls, indicating a lower activation of the intrinsic coagulation cascade. Platelet adhesion and thrombin generation by adherent platelets were greatly reduced on tetraglyme-coated materials, compared with uncoated and Biospan-coated glass slides. In the in vitro disturbed blood flow model, tetraglyme plasma coated catheters had 50% less thrombus than did the uncoated catheters. Tetraglyme-coated materials thus had greatly reduced blood interactions as measured with all six methods. The improved blood compatibility of plasma-deposited tetraglyme is thus not only due to their reduced platelet adhesion and activation, but also to a generalized reduction in blood interactions. (c) 2007 Wiley Periodicals, Inc.

  10. On the energy deposition into the plasma for an inverted fireball geometry

    NASA Astrophysics Data System (ADS)

    Levko, Dmitry; Gruenwald, Johannes

    2017-10-01

    Energy deposition into a plasma for an inverted fireball geometry is studied using a self-consistent two-dimensional Particle-in-Cell Monte Carlo collision model. In this model, the cathode is a pin which injects the fixed electron current and the anode is a hollow metal tube covered with the metal grid. We obtain an almost constant ratio between the densities of plasmas generated in the cathode-grid gap and inside the hollow anode. The results of the simulations show that there is no energy exchange between the beam and plasma electrons at low emission currents. For increasing current, however, we observe the increasing coupling between the electron beam and the thermal plasma electrons. This leads to the heating of plasma electrons and the generation of the so-called supra-thermal electrons.

  11. Deposition and composition-control of Mn-doped ZnO thin films by combinatorial pulsed laser deposition using two delayed plasma plumes

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

    Sanchez-Ake, C.; Camacho, R.; Moreno, L.

    2012-08-15

    Thin films of ZnO doped with manganese were deposited by double-beam, combinatorial pulsed laser deposition. The laser-induced plasmas were studied by means of fast photography and using a Langmuir probe, whereas the films were analyzed by x-ray-diffraction and energy-dispersive x-ray spectroscopy. The effect of the relative delay between plasma plumes on the characteristics of the films was analyzed. It was found that using this parameter, it is possible to control the dopant content keeping the oriented wurtzite structure of the films. The minimum content of Mn was found for plume delays between 0 and 10 {mu}s as the interaction betweenmore » plasmas scatters the dopant species away from the substrate, thus reducing the incorporation of Mn into the films. Results suggest that for delays shorter than {approx}100 {mu}s, the expansion of the second plume through the region behind the first plume affects the composition of the film.« less

  12. The risk for cross-reactions after a cutaneous delayed-type hypersensitivity reaction to heparin preparations is independent of their molecular weight: a systematic review.

    PubMed

    Weberschock, Tobias; Meister, Anna Christina; Bohrt, Kevin; Schmitt, Jochen; Boehncke, Wolf-Henning; Ludwig, Ralf J

    2011-10-01

    Heparins are a widely used class of drugs known to cause delayed-type hypersensitivity (DTH) reactions. Recent publications indicate that the incidence of these may be higher than previously thought. To date, patient-related but no drug-related risk factors for the development of DTH reactions to heparins have been identified, although molecular weight is discussed as a potentially relevant parameter. To address this, a systematic review was conducted on the frequency of cross-reactions after DTH reactions to heparin preparations. We electronically searched MEDLINE and EMBASE, hand-searched selected journals and references, and contacted experts for unpublished data. Sixty-six publications and unpublished data of 14 patients resulted in 198 patients with 1084 tests for cross-reactivity. The primary causative agents were mostly unfractionated heparin (50%) and low molecular weight heparins (49.5%). Cross-reactions were more likely after an initial DTH reaction to unfractionated heparin than after an initial DTH reaction to low molecular weight heparin. Our findings also indicate that molecular weight does not correlate with the risk for cross-reactivity, which is in line with recent observations, indicating that different heparins have to be individually considered. The available data demonstrated the lowest overall risk for cross-reactions for pentosan polysulfate (36.4%) and fondaparinux (10.4%). In the clinical context, fondaparinux is recommended as the current best alternative when a DTH reaction occurs. © 2011 John Wiley & Sons A/S.

  13. Tungsten dust impact on ITER-like plasma edge

    DOE PAGES

    Smirnov, R. D.; Krasheninnikov, S. I.; Pigarov, A. Yu.; ...

    2015-01-12

    The impact of tungsten dust originating from divertor plates on the performance of edge plasma in ITER-like discharge is evaluated using computer modeling with the coupled dust-plasma transport code DUSTT-UEDGE. Different dust injection parameters, including dust size and mass injection rates, are surveyed. It is found that tungsten dust injection with rates as low as a few mg/s can lead to dangerously high tungsten impurity concentrations in the plasma core. Dust injections with rates of a few tens of mg/s are shown to have a significant effect on edge plasma parameters and dynamics in ITER scale tokamaks. The large impactmore » of certain phenomena, such as dust shielding by an ablation cloud and the thermal force on tungsten ions, on dust/impurity transport in edge plasma and consequently on core tungsten contamination level is demonstrated. Lastly, it is also found that high-Z impurities provided by dust can induce macroscopic self-sustained plasma oscillations in plasma edge leading to large temporal variations of edge plasma parameters and heat load to divertor target plates.« less

  14. Angiogenic Factor Profiles in Pregnant Women With a History of Early-Onset Severe Preeclampsia Receiving Low-Molecular-Weight Heparin Prophylaxis.

    PubMed

    Lecarpentier, Edouard; Gris, Jean Christophe; Cochery-Nouvellon, Eva; Mercier, Erick; Touboul, Cyril; Thadhani, Ravi; Karumanchi, S Ananth; Haddad, Bassam

    2018-01-01

    To evaluate whether daily low-molecular-weight (LMW) heparin prophylaxis during pregnancy alters profile of circulating angiogenic factors that have been linked with the pathogenesis of preeclampsia and fetal growth restriction. This is a planned ancillary study of the Heparin-Preeclampsia trial, a randomized trial in pregnant women with a history of severe early-onset preeclampsia (less than 34 weeks of gestation). In the parent study, all women were treated with aspirin and then randomized to receive LMW heparin or aspirin alone. In this study, we measured serum levels of circulating angiogenic factors (soluble fms-like tyrosine kinase-1, placental growth factor, and soluble endoglin by immunoassay) at the following gestational windows: 10-13 6/7 weeks, 14-17 6/7 weeks, 18-21 6/7 weeks, 22-25 6/7 weeks, 26-29 6/7 weeks, 30-33 6/7 weeks, and 34-37 6/7 weeks. Samples were available from 185 patients: LMW heparin+aspirin (n=92) and aspirin alone (n=93). The two groups had comparable baseline characteristics and had similar adverse composite outcomes (35/92 [38.0%] compared with 36/93 [38.7%]; P=.92). There were no significant differences in serum levels of soluble fms-like tyrosine kinase-1, placental growth factor, and soluble endoglin in the participants who received LMW heparin and aspirin compared with those who received aspirin alone regardless of gestational age period. Finally, women who developed an adverse composite outcome at less than 34 weeks of gestation demonstrated significant alterations in serum angiogenic profile as early as 10-13 6/7 weeks that was most dramatic 6-8 weeks preceding delivery. Prophylactic LMW heparin therapy when beginning from before 14 weeks of gestation with aspirin during pregnancy is not associated with an improved angiogenic profile. This may provide a molecular explanation for the lack of clinical benefit noted in recent trials. ClinicalTrials.gov, NCT00986765.

  15. Quantitation of heparosan with heparin lyase III and spectrophotometry.

    PubMed

    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.

  16. No Calcium-Fluoride-Like Deposits Detected in Plaque Shortly after a Sodium Fluoride Mouthrinse

    PubMed Central

    Vogel, G.L.; Tenuta, L.M.A.; Schumacher, G.E.; Chow, L.C.

    2010-01-01

    Plaque ‘calcium-fluoride-like’ (CaF2-like) and fluoride deposits held by biological/bacterial calcium fluoride (Ca-F) bonds appear to be the source of cariostatic concentrations of fluoride in plaque fluid. The aim of this study was to quantify the amounts of plaque fluoride held in these reservoirs after a sodium fluoride rinse. 30 and 60 min after a 228 μg/g fluoride rinse, plaque samples were collected from 11 volunteers. Each sample was homogenized, split into 2 aliquots (aliquots 1 and 2), centrifuged, and the recovered plaque fluid combined and analyzed using microelectrodes. The plaque mass from aliquot 1 was retained. The plaque mass from aliquot 2 was extracted several times with a solution having the same fluoride, calcium and pH as the plaque fluid in order to extract the plaque CaF2-like deposits. The total fluoride in both aliquots was then determined. In a second experiment, the extraction completeness was examined by applying the above procedure to in vitro precipitates containing known amounts of CaF2-like deposits. Nearly identical fluoride concentrations were found in both plaque aliquots. The extraction of the CaF2-like precipitates formed in vitro removed more than 80% of these deposits. The results suggest that either CaF2-like deposits were not formed in plaque or, if these deposits had been formed, they were rapidly lost. The inability to form persistent amounts of CaF2-like deposits in plaque may account for the relatively rapid loss of plaque fluid fluoride after the use of conventional fluoride dentifrices or rinses. PMID:20185917

  17. Haemostatic agent etamsylate in vitro and in vivo antagonizes anti-coagulant activity of heparin.

    PubMed

    Cobo-Nuñez, M Yolanda; El Assar, Mariam; Cuevas, Pedro; Sánchez-Ferrer, Alberto; Martínez-González, Jennifer; Rodríguez-Mañas, Leocadio; Angulo, Javier

    2018-05-15

    Etamsylate is indicated for several anti-hemorrhagic indications in human and veterinary medicine. However, etamsylate has been shown to be effective only in specific hemorrhagic situations. Furthermore, mechanism of action of etamsylate is not known but recent research has shown its ability to inhibit heparin binding to several growth factors. We have evaluated the ability of etamsylate to interfere with the activities of heparin. Effects of etamsylate on vasodilatory activity of heparin were evaluated in rat aortic segments. Influence of etamsylate on anticoagulant activity of heparin was evaluated in vitro by determining prothrombin (PT) time and activated partial thromboplastin time (aPTT) in dog blood and in vivo by determining the interference of systemic and topical etamsylate on heparin-induced extension in bleeding time (BT) in rats. Despite failing to inhibit heparin-induced vasodilation of rat aorta, etamsylate significantly reduced the increase in aPTT caused by heparin (+30.4 ± 6.7% vs. +15.0 ± 2.8% for etamsylate at 100 µM, P < 0.05). Etamsylate also antagonized the anticoagulant effects driven by heparin in vivo since prevented the heparin-induced increase in BT when systemically (i.p.) administered (+94.6 ± 7.5% vs. +57.9 ± 9.2% at 10 mg/kg, P < 0.05, vs. +22.2 ± 16.8% at 30 mg/kg, P < 0.01). Additionally, topically applied etamsylate (125 mg/ml) significantly reduced heparin-induced BT increase (+102.5 ± 3.2% vs. +54.0 ± 5.8%, P < 0.01). These evidences show a pharmacological interference by etamsylate on heparin activities antagonizing pro-hemorrhagic effects of heparin in vitro and in vivo without inhibiting its vasodilatory properties. This ability could help to explain pharmacological effects of etamsylate and proposes its role for reversing pro-hemorrhagic states. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Effect of tetramethylsilane flow on the deposition and tribological behaviors of silicon doped diamond-like carbon rubbed against poly(oxymethylene)

    NASA Astrophysics Data System (ADS)

    Deng, Xingrui; Lim, Yankuang; Kousaka, Hiroyuki; Tokoroyama, Takayuki; Umehara, Noritsugu

    2014-11-01

    In this study, silicon doped diamond-like carbon (Si-DLC) was deposited on stainless steel (JIS SUS304) by using surface wave-excited plasma (SWP). The effects of tetramethylsilane (TMS) flow on the composition, topography, mechanical properties and tribological behavior were investigated. Pin-on-disc tribo-meter was used to investigate the tribological behavior of the Si-DLC coating rubbed against poly(oxymethylene) (POM). The results show that the deposition rate, roughness of Si-DLC increased and the hardness of Si-DLC decreased with the increase of TMS flow rate from 2 to 4 sccm; the roughness increase therein led to the increase of ploughing term of friction. The increase of adhesion term was also seen with the increase of TMS flow rate, being attributed to the decrease of hydrogen concentration in the coating. It was considered that more POM transferred onto the Si-DLC deposited at higher TMS flow rate due to larger heat generation by friction.

  19. Immobilization of heparin/poly-(L)-lysine nanoparticles on dopamine-coated surface to create a heparin density gradient for selective direction of platelet and vascular cells behavior.

    PubMed

    Liu, Tao; Liu, Yang; Chen, Yuan; Liu, Shihui; Maitz, Manfred F; Wang, Xue; Zhang, Kun; Wang, Jian; Wang, Yuan; Chen, Junying; Huang, Nan

    2014-05-01

    Restenosis, thrombosis formation and delayed endothelium regeneration continue to be problematic for coronary artery stent therapy. To improve the hemocompatibility of the cardiovascular implants and selectively direct vascular cell behavior, a novel kind of heparin/poly-l-lysine (Hep/PLL) nanoparticle was developed and immobilized on a dopamine-coated surface. The stability and structural characteristics of the nanoparticles changed with the Hep:PLL concentration ratio. A Hep density gradient was created on a surface by immobilizing nanoparticles with various Hep:PLL ratios on a dopamine-coated surface. Antithrombin III binding quantity was significantly enhanced, and in plasma the APTT and TT times as coagulation tests were prolonged, depending on the Hep density. A low Hep density is sufficient to prevent platelet adhesion and activation. The sensitivity of vascular cells to the Hep density is very different: high Hep density inhibits the growth of all vascular cells, while low Hep density could selectively inhibit smooth muscle cell hyperplasia but promote endothelial progenitor cells and endothelial cell proliferation. These observations provide important guidance for modification of surface heparinization. We suggest that this method will provide a potential means to construct a suitable platform on a stent surface for selective direction of vascular cell behavior with low side effects. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  20. Redeposition in plasma-assisted atomic layer deposition: Silicon nitride film quality ruled by the gas residence time

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

    Knoops, Harm C. M., E-mail: h.c.m.knoops@tue.nl, E-mail: w.m.m.kessels@tue.nl; Oxford Instruments Plasma Technology, North End, Bristol BS49 4AP; Peuter, K. de

    2015-07-06

    The requirements on the material properties and growth control of silicon nitride (SiN{sub x}) spacer films in transistors are becoming ever more stringent as scaling of transistor structures continues. One method to deposit high-quality films with excellent control is atomic layer deposition (ALD). However, depositing SiN{sub x} by ALD has turned out to be very challenging. In this work, it is shown that the plasma gas residence time τ is a key parameter for the deposition of SiN{sub x} by plasma-assisted ALD and that this parameter can be linked to a so-called “redeposition effect”. This previously ignored effect, which takesmore » place during the plasma step, is the dissociation of reaction products in the plasma and the subsequent redeposition of reaction-product fragments on the surface. For SiN{sub x} ALD using SiH{sub 2}(NH{sup t}Bu){sub 2} as precursor and N{sub 2} plasma as reactant, the gas residence time τ was found to determine both SiN{sub x} film quality and the resulting growth per cycle. It is shown that redeposition can be minimized by using a short residence time resulting in high-quality films with a high wet-etch resistance (i.e., a wet-etch rate of 0.5 nm/min in buffered HF solution). Due to the fundamental nature of the redeposition effect, it is expected to play a role in many more plasma-assisted ALD processes.« less

  1. Optical study of plasma sprayed hydroxyapatite coatings deposited at different spray distance

    NASA Astrophysics Data System (ADS)

    Belka, R.; Kowalski, S.; Żórawski, W.

    2017-08-01

    Series of hydroxyapatite (HA) coatings deposited on titanium substrate at different spray (plasma gun to workpiece) distance were investigated. The optical methods as dark field confocal microscopy, Raman/PL and UV-VIS spectroscopy were used for study the influence of deposition process on structural degradation of HA precursor. The hydroxyl group concentration was investigated by study the OH mode intensity in the Raman spectra. Optical absorption coefficients at near UV region were analyzed by Diffuse Reflectance Spectroscopy. PL intensity observed during Raman measurement was also considered as relation to defects concentration and degradation level. It was confirmed the different gunsubstrate distance has a great impact on structure of deposited HA ceramics.

  2. Low-Temperature Plasma-Assisted Atomic Layer Deposition of Silicon Nitride Moisture Permeation Barrier Layers.

    PubMed

    Andringa, Anne-Marije; Perrotta, Alberto; de Peuter, Koen; Knoops, Harm C M; Kessels, Wilhelmus M M; Creatore, Mariadriana

    2015-10-14

    Encapsulation of organic (opto-)electronic devices, such as organic light-emitting diodes (OLEDs), photovoltaic cells, and field-effect transistors, is required to minimize device degradation induced by moisture and oxygen ingress. SiNx moisture permeation barriers have been fabricated using a very recently developed low-temperature plasma-assisted atomic layer deposition (ALD) approach, consisting of half-reactions of the substrate with the precursor SiH2(NH(t)Bu)2 and with N2-fed plasma. The deposited films have been characterized in terms of their refractive index and chemical composition by spectroscopic ellipsometry (SE), X-ray photoelectron spectroscopy (XPS), and Fourier-transform infrared spectroscopy (FTIR). The SiNx thin-film refractive index ranges from 1.80 to 1.90 for films deposited at 80 °C up to 200 °C, respectively, and the C, O, and H impurity levels decrease when the deposition temperature increases. The relative open porosity content of the layers has been studied by means of multisolvent ellipsometric porosimetry (EP), adopting three solvents with different kinetic diameters: water (∼0.3 nm), ethanol (∼0.4 nm), and toluene (∼0.6 nm). Irrespective of the deposition temperature, and hence the impurity content in the SiNx films, no uptake of any adsorptive has been observed, pointing to the absence of open pores larger than 0.3 nm in diameter. Instead, multilayer development has been observed, leading to type II isotherms that, according to the IUPAC classification, are characteristic of nonporous layers. The calcium test has been performed in a climate chamber at 20 °C and 50% relative humidity to determine the intrinsic water vapor transmission rate (WVTR) of SiNx barriers deposited at 120 °C. Intrinsic WVTR values in the range of 10(-6) g/m2/day indicate excellent barrier properties for ALD SiNx layers as thin as 10 nm, competing with that of state-of-the-art plasma-enhanced chemical vapor-deposited SiNx layers of a few hundred

  3. Human trophoblast survival at low oxygen concentrations requires metalloproteinase-mediated shedding of heparin-binding EGF-like growth factor

    PubMed Central

    Armant, D. Randall; Kilburn, Brian A.; Petkova, Anelia; Edwin, Samuel S.; Duniec-Dmuchowski, Zophia M.; Edwards, Holly J.; Romero, Roberto; Leach, Richard E.

    2006-01-01

    Heparin-binding EGF-like growth factor (HBEGF), which is expressed in the placenta during normal pregnancy, is downregulated in pre-eclampsia, a human pregnancy disorder associated with poor trophoblast differentiation and survival. This growth factor protects against apoptosis during stress, suggesting a role in trophoblast survival in the relatively low O2 (∼2%) environment of the first trimester conceptus. Using a well-characterized human first trimester cytotrophoblast cell line, we found that a 4-hour exposure to 2% O2 upregulates HBEGF synthesis and secretion independently of an increase in its mRNA. Five other expressed members of the EGF family are largely unaffected. At 2% O2, signaling via HER1 or HER4, known HBEGF receptors, is required for both HBEGF upregulation and protection against apoptosis. This positive-feedback loop is dependent on metalloproteinase-mediated cleavage and shedding of the HBEGF ectodomain. The restoration of trophoblast survival by the addition of soluble HBEGF in cultures exposed to low O2 and metalloproteinase inhibitor suggests that the effects of HBEGF are mediated by autocrine/paracrine, rather than juxtacrine, signaling. Our results provide evidence that a post-transcriptional mechanism induced in trophoblasts by low O2 rapidly amplifies HBEGF signaling to inhibit apoptosis. These findings have a high clinical significance, as the downregulation of HBEGF in pre-eclampsia is likely to be a contributing factor leading to the demise of trophoblasts. PMID:16407398

  4. Human trophoblast survival at low oxygen concentrations requires metalloproteinase-mediated shedding of heparin-binding EGF-like growth factor.

    PubMed

    Armant, D Randall; Kilburn, Brian A; Petkova, Anelia; Edwin, Samuel S; Duniec-Dmuchowski, Zophia M; Edwards, Holly J; Romero, Roberto; Leach, Richard E

    2006-02-01

    Heparin-binding EGF-like growth factor (HBEGF), which is expressed in the placenta during normal pregnancy, is down regulated in pre-eclampsia, a human pregnancy disorder associated with poor trophoblast differentiation and survival. This growth factor protects against apoptosis during stress, suggesting a role in trophoblast survival in the relatively low O(2) ( approximately 2%) environment of the first trimester conceptus. Using a well-characterized human first trimester cytotrophoblast cell line, we found that a 4-hour exposure to 2% O(2) upregulates HBEGF synthesis and secretion independently of an increase in its mRNA. Five other expressed members of the EGF family are largely unaffected. At 2% O(2), signaling via HER1 or HER4, known HBEGF receptors, is required for both HBEGF upregulation and protection against apoptosis. This positive-feedback loop is dependent on metalloproteinase-mediated cleavage and shedding of the HBEGF ectodomain. The restoration of trophoblast survival by the addition of soluble HBEGF in cultures exposed to low O(2) and metalloproteinase inhibitor suggests that the effects of HBEGF are mediated by autocrine/paracrine, rather than juxtacrine, signaling. Our results provide evidence that a post-transcriptional mechanism induced in trophoblasts by low O(2) rapidly amplifies HBEGF signaling to inhibit apoptosis. These findings have a high clinical significance, as the downregulation of HBEGF in pre-eclampsia is likely to be a contributing factor leading to the demise of trophoblasts.

  5. Characteristics of Ge-Sb-Te films prepared by cyclic pulsed plasma-enhanced chemical vapor deposition.

    PubMed

    Suk, Kyung-Suk; Jung, Ha-Na; Woo, Hee-Gweon; Park, Don-Hee; Kim, Do-Heyoung

    2010-05-01

    Ge-Sb-Te (GST) thin films were deposited on TiN, SiO2, and Si substrates by cyclic-pulsed plasma-enhanced chemical vapor deposition (PECVD) using Ge{N(CH3)(C2H5)}, Sb(C3H7)3, Te(C3H7)3 as precursors in a vertical flow reactor. Plasma activated H2 was used as the reducing agent. The growth behavior was strongly dependent on the type of substrate. GST grew as a continuous film on TiN regardless of the substrate temperature. However, GST formed only small crystalline aggregates on Si and SiO2 substrates, not a continuous film, at substrate temperatures > or = 200 degrees C. The effects of the deposition temperature on the surface morphology, roughness, resistivity, crystallinity, and composition of the GST films were examined.

  6. Adequacy of Fixed-Dose Heparin Infusions for Venous Thromboembolism Prevention after Microsurgical Procedures.

    PubMed

    Bertolaccini, Corinne M; Prazak, Ann Marie B; Agarwal, Jayant; Goodwin, Isak A; Rockwell, W Bradford; Pannucci, Christopher J

    2018-05-22

     In microvascular surgery, patients often receive unfractionated heparin infusions to minimize risk for microvascular thrombosis. Patients who receive intravenous (IV) heparin are believed to have adequate prophylaxis against venous thromboembolism (VTE). Whether a fixed dose of IV heparin provides detectable levels of anticoagulation, or whether the "one size fits all" approach provides adequate prophylaxis against VTE remains unknown. This study examined the pharmacodynamics of fixed-dose heparin infusions and the effects of real-time, anti-factor Xa (aFXa) level driven heparin dose adjustments.  This prospective clinical trial recruited adult microvascular surgery patients placed on a fixed-dose (500 units/h) unfractionated heparin infusion during their initial microsurgical procedure. Steady-state aFXa levels, a marker of unfractionated heparin efficacy and safety, were monitored. Patients with out-of-range aFXa levels received protocol-driven real-time dose adjustments. Outcomes of interest included aFXa levels in response to heparin 500 units/h, number of dose adjustments required to achieve goal aFXa levels, time to reach goal aFXa level, and 90-day clinically relevant bleeding and VTE.  Twenty patients were recruited prospectively. None of 20 patients had any detectable level of anticoagulation in response to heparin infusions at 500 units/h. The median number of dose adjustments required to reach goal level was five, and median weight-based dose to reach goal level was 11.8 units/kg/h. Real-time dose adjustments significantly increased the proportion of patients with in-range levels (60 vs. 0%, p  = 0.0001). The 90-day VTE rate was 5% and 90-day clinically relevant bleeding rate was 5%.  Fixed-dose heparin infusions at a rate of 500 units/h do not provide a detectable level of anticoagulation after microsurgical procedures and are insufficient for the majority of patients who require VTE prophylaxis. Weight-based heparin infusions at 10 to 12

  7. Simultaneous Power Deposition Detection of Two EC Beams with the BIS Analysis in Moving TCV Plasmas

    NASA Astrophysics Data System (ADS)

    Curchod, L.; Pochelon, A.; Decker, J.; Felici, F.; Goodman, T. P.; Moret, J.-M.; Paley, J. I.

    2009-11-01

    Modulation of power amplitude is a widespread to determine the radial absorption profile of externally launched power in fusion plasmas. There are many techniques to analyze the plasma response to such a modulation. The break-in-slope (BIS) analysis can draw an estimated power deposition profile for each power step up. In this paper, the BIS analysis is used to monitor the power deposition location of one or two EC power beams simultaneously in a non-stationary plasma being displaced vertically in the TCV tokamak vessel. Except from radial discrepancies, the results have high time resolution and compare well with simulations from the R2D2-C3PO-LUKE ray-tracing and Fokker-Planck code suite.

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

    PubMed

    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.

  9. Photoactive chitosan switching on bone-like apatite deposition.

    PubMed

    Chiono, Valeria; Gentile, Piergiorgio; Boccafoschi, Francesca; Carmagnola, Irene; Ninov, Momchil; Georgieva, Ventsislava; Georgiev, George; Ciardelli, Gianluca

    2010-02-08

    The work was focused on the synthesis and characterization of the chitosan-g-fluorescein (CHFL) conjugate polymer as a biocompatible amphiphilic water-soluble photosensitizer, able to stimulate hydroxyapatite deposition upon visible light irradiation. Fluorescein (FL) grafting to chitosan (CH) chains was confirmed by UV-vis analysis of water solutions of FL and CHFL and by Fourier transform infrared spectroscopy (FTIR-ATR) analysis of CHFL and CH. Smooth CHFL cast films with 4 microm thickness were obtained by solvent casting. Continuous exposure to visible light for 7 days was found to activate the deposition of calcium phosphate crystals from a conventional simulated body fluid (SBF 1.0x) on the surface of CHFL cast films. EDX and FTIR-ATR analyses confirmed the apatite nature of the deposited calcium phosphate crystals. CHFL films preincubated in SBF (1.0x) solution under visible light irradiation and in the dark for 7 days were found to support the in vitro adhesion and proliferation of MG63 osteoblast-like cells (MTT viability test; 1-3 days culture time). On the other hand, the mineralization ability of MG63 osteoblast-like cells was significantly improved on CHFL films preincubated under visible light exposure (alkaline phosphatase activity (ALP) test for 1, 3, 7, and 14 days). The use of photoactive biocompatible conjugate polymer, such as CHFL, may lead to new therapeutic options in the field of bone/dental repair, exploiting the photoexcitation mechanism as a tool for biomineralization.

  10. Solid oxide fuel cell electrolytes produced via very low pressure suspension plasma spray and electrophoretic deposition

    NASA Astrophysics Data System (ADS)

    Fleetwood, James D.

    Solid oxide fuel cells (SOFCs) are a promising element of comprehensive energy policies due to their direct mechanism for converting the oxidization of fuel, such as hydrogen, into electrical energy. Both very low pressure plasma spray and electrophoretic deposition allow working with high melting temperature SOFC suspension based feedstock on complex surfaces, such as in non-planar SOFC designs. Dense, thin electrolytes of ideal composition for SOFCs can be fabricated with each of these processes, while compositional control is achieved with dissolved dopant compounds that are incorporated into the coating during deposition. In the work reported, sub-micron 8 mole % Y2O3-ZrO2 (YSZ) and gadolinia-doped ceria (GDC), powders, including those in suspension with scandium-nitrate dopants, were deposited on NiO-YSZ anodes, via very low pressure suspension plasma spray (VLPSPS) at Sandia National Laboratories' Thermal Spray Research Laboratory and electrophoretic deposition (EPD) at Purdue University. Plasma spray was carried out in a chamber held at 320 - 1300 Pa, with the plasma composed of argon, hydrogen, and helium. EPD was characterized utilizing constant current deposition at 10 mm electrode separation, with deposits sintered from 1300 -- 1500 °C for 2 hours. The role of suspension constituents in EPD was analyzed based on a parametric study of powder loading, powder specific surface area, polyvinyl butyral (PVB) content, polyethyleneimine (PEI) content, and acetic acid content. Increasing PVB content and reduction of particle specific surface area were found to eliminate the formation of cracks when drying. PEI and acetic acid content were used to control suspension stability and the adhesion of deposits. Additionally, EPD was used to fabricate YSZ/GDC bilayer electrolyte systems. The resultant YSZ electrolytes were 2-27 microns thick and up to 97% dense. Electrolyte performance as part of a SOFC system with screen printed LSCF cathodes was evaluated with peak

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

    PubMed

    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

  12. Influence of the normalized ion flux on the constitution of alumina films deposited by plasma-assisted chemical vapor deposition

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

    Kurapov, Denis; Reiss, Jennifer; Trinh, David H.

    2007-07-15

    Alumina thin films were deposited onto tempered hot working steel substrates from an AlCl{sub 3}-O{sub 2}-Ar-H{sub 2} gas mixture by plasma-assisted chemical vapor deposition. The normalized ion flux was varied during deposition through changes in precursor content while keeping the cathode voltage and the total pressure constant. As the precursor content in the total gas mixture was increased from 0.8% to 5.8%, the deposition rate increased 12-fold, while the normalized ion flux decreased by approximately 90%. The constitution, morphology, impurity incorporation, and the elastic properties of the alumina thin films were found to depend on the normalized ion flux. Thesemore » changes in structure, composition, and properties induced by normalized ion flux may be understood by considering mechanisms related to surface and bulk diffusion.« less

  13. Heparin-Based Coacervate of FGF2 Improves Dermal Regeneration by Asserting a Synergistic Role with Cell Proliferation and Endogenous Facilitated VEGF for Cutaneous Wound Healing.

    PubMed

    Wu, Jiang; Ye, Jingjing; Zhu, Jingjing; Xiao, Zecong; He, Chaochao; Shi, Hongxue; Wang, Yadong; Lin, Cai; Zhang, Hongyu; Zhao, Yingzheng; Fu, Xiaobing; Chen, Hong; Li, Xiaokun; Li, Lin; Zheng, Jie; Xiao, Jian

    2016-06-13

    Effective wound healing requires complicated, coordinated interactions and responses at protein, cellular, and tissue levels involving growth factor expression, cell proliferation, wound closure, granulation tissue formation, and vascularization. In this study, we develop a heparin-based coacervate consisting of poly(ethylene argininylaspartate digylceride) (PEAD) as a storage matrix, heparin as a bridge, and fibroblast growth factor-2 (FGF2) as a cargo (namely heparin-FGF2@PEAD) for wound healing. First, in vitro characterization demonstrates the loading efficiency and control release of FGF2 from the heparin-FGF2@PEAD coacervate. The following in vivo studies examine the wound healing efficiency of the heparin-FGF2@PEAD coacervate upon delivering FGF2 to full-thickness excisional skin wounds in vivo, in comparison with the other three control groups with saline, heparin@PEAD as vehicle, and free FGF2. Collective in vivo data show that controlled release of FGF2 to the wounds by the coacervate significantly accelerates the wound healing by promoting cell proliferation, stimulating the secretion of vascular endothelial growth factor (VEGF) for re-epithelization, collagen deposition, and granulation tissue formation, and enhancing the expression of platelet endothelial cell adhesion molecule (CD31) and alpha-smooth muscle actin (α-SMA) for blood vessel maturation. In parallel, no obvious wound healing effect is found for the control, vehicle, and free FGF2 groups, indicating the important role of the coavervate in the wound healing process. This work designs a suitable delivery system that can protect and release FGF2 in a sustained and controlled manner, which provides a promising therapeutic potential for topical treatment of wounds.

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

    PubMed

    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.

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

    PubMed

    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.

  16. High Sulfation and a High Molecular Weight Are Important for Anti-hepcidin Activity of Heparin

    PubMed Central

    Asperti, Michela; Naggi, Annamaria; Esposito, Emiliano; Ruzzenenti, Paola; Di Somma, Margherita; Gryzik, Magdalena; Arosio, Paolo; Poli, Maura

    2016-01-01

    Heparins are efficient inhibitors of hepcidin expression even in vivo, where they induce an increase of systemic iron availability. Heparins seem to act by interfering with BMP6 signaling pathways that control the expression of liver hepcidin, causing the suppression of SMAD1/5/8 phosphorylation. The anti-hepcidin activity persists also when the heparin anticoagulant property is abolished or reduced by chemical reactions of oxidation/reduction (glycol-split, Gs-Heparins) or by high sulfation (SS-Heparins), but the structural characteristics needed to optimize this inhibitory activity have not been studied in detail. To this aim we analyzed three different heparins (Mucosal Heparin, the Glycol split RO-82, the partially desulfated glycol-split RO-68 and the oversulfated SSLMWH) and separated them in fractions of molecular weight in the range 4–16 kD. Since the distribution of the negative charges in heparins contributes to the activity, we produced 2-O- and 6-O-desulfated heparins. These derivatives were analyzed for the capacity to inhibit hepcidin expression in hepatic HepG2 cells and in mice. The two approaches produced consistent results and showed that the anti-hepcidin activity strongly decreases with molecular weight below 7 kD, with high N-acetylation and after 2-O and 6-O desulfation. The high sulfation and high molecular weight properties for efficient anti-hepcidin activity suggest that heparin is involved in multiple binding sites. PMID:26955355

  17. Towards plasma cleaning of ITER first mirrors

    NASA Astrophysics Data System (ADS)

    Moser, L.; Marot, L.; Eren, B.; Steiner, R.; Mathys, D.; Leipold, F.; Reichle, R.; Meyer, E.

    2015-06-01

    To avoid reflectivity losses in ITER's optical diagnostic systems, on-site cleaning of metallic first mirrors via plasma sputtering is foreseen to remove deposit build-ups migrating from the main wall. In this work, the influence of aluminium and tungsten deposits on the reflectivity of molybdenum mirrors as well as the possibility to clean them with plasma exposure is investigated. Porous ITER-like deposits are grown to mimic the edge conditions expected in ITER, and a severe degradation in the specular reflectivity is observed as these deposits build up on the mirror surface. In addition, dense oxide films are produced for comparisons with porous films. The composition, morphology and crystal structure of several films were characterized by means of scanning electron microscopy, x-ray photoelectron spectroscopy, x-ray diffraction and secondary ion mass spectrometry. The cleaning of the deposits and the restoration of the mirrors' optical properties are possible either with a Kaufman source or radio frequency directly applied to the mirror (or radio frequency plasma generated directly around the mirror surface). Accelerating ions of an external plasma source through a direct current applied onto the mirror does not remove deposits composed of oxides. A possible implementation of plasma cleaning in ITER is addressed.

  18. Atomic description of the immune complex involved in heparin-induced thrombocytopenia

    DOE PAGES

    Cai, Zheng; Yarovoi, Serge V.; Zhu, Zhiqiang; ...

    2015-09-22

    Heparin-induced thrombocytopenia (HIT) is an autoimmune thrombotic disorder caused by immune complexes containing platelet factor 4 (PF4), antibodies to PF4 and heparin or cellular glycosaminoglycans (GAGs). Here we solve the crystal structures of the: (1) PF4 tetramer/fondaparinux complex, (2) PF4 tetramer/KKO-Fab complex (a murine monoclonal HIT-like antibody) and (3) PF4 monomer/RTO-Fab complex (a non-HIT anti-PF4 monoclonal antibody). Fondaparinux binds to the ‘closed’ end of the PF4 tetramer and stabilizes its conformation. This interaction in turn stabilizes the epitope for KKO on the ‘open’ end of the tetramer. Fondaparinux and KKO thereby collaborate to ‘stabilize’ the ternary pathogenic immune complex. Bindingmore » of RTO to PF4 monomers prevents PF4 tetramerization and inhibits KKO and human HIT IgG-induced platelet activation and platelet aggregation in vitro, and thrombus progression in vivo. Lastly, the atomic structures provide a basis to develop new diagnostics and non-anticoagulant therapeutics for HIT.« less

  19. [Outpatient use of heparin: data from the Midi-Pyrenes Health Fund].

    PubMed

    Berchery, Delphine; Roussel, Henri; Bourrel, Robert; Sciortino, Vincent

    2003-01-01

    The risk of haemorrhagic complications associated with heparin therapy can be reduced by good clinical practice. The aim of this study was to describe outpatient heparin therapy by using the database of the National Health Fund. The study population consisted of affiliates of the salaried employees insured by the health fund branch of the Midi-Pyrénées region, and corresponded to 62% of the residents of that region. Analysis of treatments and biological monitoring was carried out on a 1-year period. During this period, 16,462 patients started a treatment with heparin, 92% for a single treatment. The mean age of the patients was 55 years (SD = 19.8) and the majority were women (53%). Nine percent of these patients were switched to oral anticoagulant therapy. Of the other patients, 52% received heparin for less than 10 days, 36% for between 10 days and 5 weeks, and 12% for more than 5 weeks; 33% of the last group where heparin was prescribed for more than 5 weeks corresponds to a prescription of more than 3 months. Seventy-three percent of the heparin treatment durations complied with the authorities' (l'Agence française de sécurité sanitaire des produits de santé [AFSSAPS]) recommendations. Biological monitoring comprised a platelet count, an APTT (activated partial thromboplastin time) or an anti-Xa check in 41.9%, 27.8% and 3.1% of treated patients, respectively. Creatininaemia was measured in 27% of patients aged > 75 years (a group at increased risk of adverse drug reactions). Even considering some of the differences noted between the medical prescriptions and the reimbursement data of the health fund, results from this study allowed an evaluation of medical practices and suggests that monitoring of patients receiving heparin treatments remains insufficient, thus decreasing the benefit/risk ratio of such therapies.

  20. Plasma enhanced chemical vapor deposition (PECVD) method of forming vanadium oxide films and vanadium oxide thin-films prepared thereby

    DOEpatents

    Zhang, Ji-Guang; Tracy, C. Edwin; Benson, David K.; Turner, John A.; Liu, Ping

    2000-01-01

    A method is disclosed of forming a vanadium oxide film on a substrate utilizing plasma enhanced chemical vapor deposition. The method includes positioning a substrate within a plasma reaction chamber and then forming a precursor gas comprised of a vanadium-containing chloride gas in an inert carrier gas. This precursor gas is then mixed with selected amounts of hydrogen and oxygen and directed into the reaction chamber. The amounts of precursor gas, oxygen and hydrogen are selected to optimize the final properties of the vanadium oxide film An rf plasma is generated within the reaction chamber to chemically react the precursor gas with the hydrogen and the oxygen to cause deposition of a vanadium oxide film on the substrate while the chamber deposition pressure is maintained at about one torr or less. Finally, the byproduct gases are removed from the plasma reaction chamber.

  1. Plasma-Enhanced Deposition and Processing of Transition Metals and Transition Metal Silicides for VLSI.

    DTIC Science & Technology

    1986-05-20

    molybdenum trifluoride in the deposited material. Titanium silicide films formed from a discharge of titanium tetrachlotide, silane, and hydrogen...displayed resistivities of -150 /4-cm, due to small amounts of oxygen and chlorine incorporated during deposition. Plasma etching studies of tungsten films...material, thereby reducing speed, and aluminum is a low melting material, thereby limiting processing latitude. As a result, mmition metals and

  2. Optical emission diagnostics of plasmas in chemical vapor deposition of single-crystal diamond

    DOE PAGES

    Hemawan, Kadek W.; Hemley, Russell J.

    2015-08-03

    Here, a key aspect of single crystal diamond growth via microwave plasma chemical vapor deposition is in-process control of the local plasma-substrate environment, that is, plasma gas phase concentrations of activated species at the plasma boundary layer near the substrate surface. Emission spectra of the plasma relative to the diamond substrate inside the microwave plasma reactor chamber have been analyzed via optical emission spectroscopy. The spectra of radical species such as CH, C 2, and H (Balmer series) important for diamond growth were found to be more depndent on operating pressure than on microwave power. Plasma gas temperatures were calculatedmore » from measurements of the C 2 Swan band (d 3Π → a 3Π transition) system. The plasma gas temperature ranges from 2800 to 3400 K depending on the spatial location of the plasma ball, microwave power and operating pressure. Addition of Ar into CH 4 + H 2 plasma input gas mixture has little influence on the Hα, Hβ, and Hγ intensities and single-crystal diamond growth rates.« less

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

    PubMed Central

    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

  4. Atomic features of an autoantigen in heparin-induced thrombocytopenia (HIT).

    PubMed

    Cai, Zheng; Zhu, Zhiqiang; Greene, Mark I; Cines, Douglas B

    2016-07-01

    Autoantigen development is poorly understood at the atomic level. Heparin-induced thrombocytopenia (HIT) is an autoimmune thrombotic disorder caused by antibodies to an antigen composed of platelet factor 4 (PF4) and heparin or cellular glycosaminoglycans (GAGs). In solution, PF4 exists as an equilibrium among monomers, dimers and tetramers. Structural studies of these interacting components helped delineate a multi-step process involved in the pathogenesis of HIT. First, heparin binds to the 'closed' end of the PF4 tetramer and stabilizes its conformation; exposing the 'open' end. Second, PF4 arrays along heparin/GAG chains, which approximate tetramers, form large antigenic complexes that enhance antibody avidity. Third, pathogenic HIT antibodies bind to the 'open' end of stabilized PF4 tetramers to form an IgG/PF4/heparin ternary immune complex and also to propagate the formation of 'ultralarge immune complexes' (ULCs) that contain multiple IgG antibodies. Fourth, ULCs signal through FcγRIIA receptors, activating platelets and monocytes directly and generating thrombin, which transactivates hematopoietic and endothelial cells. A non-pathogenic anti-PF4 antibody prevents tetramer formation, binding of pathogenic antibody, platelet activation and thrombosis, providing a new approach to manage HIT. An improved understanding of the pathogenesis of HIT may lead to novel diagnostics and therapeutics for this autoimmune disease. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Biologically Derived Soft Conducting Hydrogels Using Heparin-Doped Polymer Networks

    PubMed Central

    2015-01-01

    The emergence of flexible and stretchable electronic components expands the range of applications of electronic devices. Flexible devices are ideally suited for electronic biointerfaces because of mechanically permissive structures that conform to curvilinear structures found in native tissue. Most electronic materials used in these applications exhibit elastic moduli on the order of 0.1–1 MPa. However, many electronically excitable tissues exhibit elasticities in the range of 1–10 kPa, several orders of magnitude smaller than existing components used in flexible devices. This work describes the use of biologically derived heparins as scaffold materials for fabricating networks with hybrid electronic/ionic conductivity and ultracompliant mechanical properties. Photo-cross-linkable heparin–methacrylate hydrogels serve as templates to control the microstructure and doping of in situ polymerized polyaniline structures. Macroscopic heparin-doped polyaniline hydrogel dual networks exhibit impedances as low as Z = 4.17 Ω at 1 kHz and storage moduli of G′ = 900 ± 100 Pa. The conductivity of heparin/polyaniline networks depends on the oxidation state and microstructure of secondary polyaniline networks. Furthermore, heparin/polyaniline networks support the attachment, proliferation, and differentiation of murine myoblasts without any surface treatments. Taken together, these results suggest that heparin/polyaniline hydrogel networks exhibit suitable physical properties as an electronically active biointerface material that can match the mechanical properties of soft tissues composed of excitable cells. PMID:24738911

  6. Serum and plasma for total and free anticonvulsant drug analyses: effects on EMIT assays and ultrafiltration devices.

    PubMed

    Godolphin, W; Trepanier, J; Farrell, K

    1983-01-01

    The suitability of serum and plasma anticoagulated with heparin, EDTA, citrate, or oxalate was assessed for analysis of free and total phenytoin, carbamazepine, and valproic acid. The free fraction was isolated by ultrafiltration through FreeLevel devices (Syva, Palo Alto, CA). Serum, heparin, and EDTA plasma were satisfactory for both free and total phenytoin and carbamazepine. EDTA could not be used for EMIT (Syva) analysis of valproate. Citrate and, to a lesser degree, oxalate cause a significant negative interference in the concentration of these three drugs as measured both by EMIT and gas-liquid chromatography.

  7. Highly sensitive ratiometric detection of heparin and its oversulfated chondroitin sulfate contaminant by fluorescent peptidyl probe.

    PubMed

    Mehta, Pramod Kumar; Lee, Hyeri; Lee, Keun-Hyeung

    2017-05-15

    The selective and sensitive detection of heparin, an anticoagulant in clinics as well as its contaminant oversulfated chondroitin sulfate (OSCS) is of great importance. We first reported a ratiometric sensing method for heparin as well as OSCS contaminants in heparin using a fluorescent peptidyl probe (Pep1, pyrene-GSRKR) and heparin-digestive enzyme. Pep1 exhibited a highly sensitive ratiometric response to nanomolar concentration of heparin in aqueous solution over a wide pH range (2~11) and showed highly selective ratiometric response to heparin among biological competitors such as hyaluronic acid and chondroitin sulfate. Pep1 showed a linear ratiometric response to nanomolar concentrations of heparin in aqueous solutions and in human serum samples. The detection limit for heparin was calculated to be 2.46nM (R 2 =0.99) in aqueous solutions, 2.98nM (R 2 =0.98) in 1% serum samples, and 3.43nM (R 2 =0.99) in 5% serum samples. Pep1 was applied to detect the contaminated OSCS in heparin with heparinase I, II, and III, respectively. The ratiometric sensing method using Pep1 and heparinase II was highly sensitive, fast, and efficient for the detection of OSCS contaminant in heparin. Pep1 with heparinase II could detect as low as 0.0001% (w/w) of OSCS in heparin by a ratiometric response. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Modelling of low-temperature/large-area distributed antenna array microwave-plasma reactor used for nanocrystalline diamond deposition

    NASA Astrophysics Data System (ADS)

    Bénédic, Fabien; Baudrillart, Benoit; Achard, Jocelyn

    2018-02-01

    In this paper we investigate a distributed antenna array Plasma Enhanced Chemical Vapor Deposition system, composed of 16 microwave plasma sources arranged in a 2D matrix, which enables the growth of 4-in. diamond films at low pressure and low substrate temperature by using H2/CH4/CO2 gas chemistry. A self-consistent two-dimensional plasma model developed for hydrogen discharges is used to study the discharge behavior. Especially, the gas temperature is estimated close to 350 K at a position corresponding to the substrate location during the growth, which is suitable for low temperature deposition. Multi-source discharge modeling evidences that the uniformity of the plasma sheet formed by the individual plasmas ignited around each elementary microwave source strongly depends on the distance to the antennas. The radial profile of the film thickness homogeneity may be thus linked to the local variations of species density. Contribution to the topical issue "Plasma Sources and Plasma Processes (PSPP)", edited by Luis Lemos Alves, Thierry Belmonte and Tibeinea Minea.

  9. Membrane type 1-matrix metalloproteinase cleaves off the NH2-terminal portion of heparin-binding epidermal growth factor and converts it into a heparin-independent growth factor.

    PubMed

    Koshikawa, Naohiko; Mizushima, Hiroto; Minegishi, Tomoko; Iwamoto, Ryo; Mekada, Eisuke; Seiki, Motoharu

    2010-07-15

    Epidermal growth factor (EGF) receptors (ErbB) and EGF family members represent promising targets for cancer therapy. Heparin-binding EGF (HB-EGF) is a member of the EGF family and is an important target for therapy in some types of human cancers. Processing of HB-EGF by proprotein convertases, and successively, by ADAM family proteases, generates a soluble growth factor that requires heparin as a cofactor. Although heparin potentiates HB-EGF activity in vitro, it is not clear how the heparin-binding activity of HB-EGF is regulated. Here, we show that membrane type 1-matrix metalloproteinase (MT1-MMP; MMP14), a potent invasion-promoting protease, markedly enhances HB-EGF-dependent tumor formation in mice. MT1-MMP additionally cleaves HB-EGF and removes the NH(2)-terminal 20 amino acids that are important for binding heparin. Consequently, the processing of HB-EGF by MT1-MMP converts HB-EGF into a heparin-independent growth factor with enhanced mitogenic activity, and thereby, expression of both proteins costimulates tumor cell growth in vitro and in vivo. The ErbB family of receptors expressed in human gastric carcinoma cells play a role in mediating enhanced HB-EGF activity by MT1-MMP during invasive cell growth in collagen. Thus, we shed light on a new mechanism whereby HB-EGF activity is regulated that should be considered when designing HB-EGF-targeted cancer therapy. (c)2010 AACR.

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

    PubMed

    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.

  11. Photoluminescence from PP-HMDSO thin films deposited using a remote plasma of 13.56 MHz hollow cathode discharge

    NASA Astrophysics Data System (ADS)

    Naddaf, M.; Saloum, S.; Hamadeh, H.

    2007-07-01

    Room temperature photoluminescence (PL) from plasma-polymerized hexamethyldisiloxane (PP-HMDSO) thin films deposited on silicon wafers has been investigated as a function of both the applied RF power and the monomer flow rate. Films were deposited in a low pressure-low temperature remote plasma ignited in a 13.56 MHz hollow cathode discharge reactor, using pure HMDSO as a monomer and Ar as a feed gas. The substrate temperature during the deposition was as low as 40 °C and the total pressure was about 0.03 mbar. Optical emission spectroscopy (OES) has been used as in situ tool for monitoring the different chemical species present in the plasma during deposition processes. The deposited PP-HMDSO films showed a strong, broad 'green/yellow' PL band. The RF power and the flow rate of the HMDSO monomer are found to have a significant impact on the PL intensity of the deposited film. The changes in the chemical bonding of the film as a function of deposition parameters have been investigated by using the Fourier transform infrared (FTIR) spectroscopic analysis and are related to PL and OES results. The 'green/yellow' PL band is ascribed to chemical groups and bonds of silicon, hydrogen and/or oxygen constituting the films, in particular, SiH, SiO bonds and silanol Si-O-H groups.

  12. Plasma interactions determine the composition in pulsed laser deposited thin films

    NASA Astrophysics Data System (ADS)

    Chen, Jikun; Döbeli, Max; Stender, Dieter; Conder, Kazimierz; Wokaun, Alexander; Schneider, Christof W.; Lippert, Thomas

    2014-09-01

    Plasma chemistry and scattering strongly affect the congruent, elemental transfer during pulsed laser deposition of target metal species in an oxygen atmosphere. Studying the plasma properties of La0.6Sr0.4MnO3, we demonstrate for as grown La0.6Sr0.4MnO3-δ films that a congruent transfer of metallic species is achieved in two pressure windows: ˜10-3 mbar and ˜2 × 10-1 mbar. In the intermediate pressure range, La0.6Sr0.4MnO3-δ becomes cation deficient and simultaneously almost fully stoichiometric in oxygen. Important for thin film growth is the presence of negative atomic oxygen and under which conditions positive metal-oxygen ions are created in the plasma. This insight into the plasma chemistry shows why the pressure window to obtain films with a desired composition and crystalline structure is narrow and requires a careful adjustment of the process parameters.

  13. Perioperative use of iloprost in cardiac surgery patients diagnosed with heparin-induced thrombocytopenia-reactive antibodies or with true HIT (HIT-reactive antibodies plus thrombocytopenia): An 11-year experience.

    PubMed

    Palatianos, George; Michalis, Alkiviadis; Alivizatos, Petros; Lacoumenda, Stavroula; Geroulanos, Stefanos; Karabinis, Andreas; Iliopoulou, Eugenia; Soufla, Giannoula; Kanthou, Chryso; Khoury, Mazen; Sfyrakis, Petros; Stavridis, George; Astras, George; Vassili, Maria; Antzaka, Christina; Marathias, Katerina; Kriaras, Ioannis; Tasouli, Androniki; Papadopoulos, Kyrillos; Katafygioti, Marina; Matoula, Nikoletta; Angelidis, Antonios; Melissari, Euthemia

    2015-07-01

    Thrombocytopenia and thromboembolism(s) may develop in heparin immune-mediated thrombocytopenia (HIT) patients after reexposure to heparin. At the Onassis Cardiac Surgery Center, 530 out of 17,000 patients requiring heart surgery over an 11-year period underwent preoperative HIT assessment by ELISA and a three-point heparin-induced platelet aggregation assay (HIPAG). The screening identified 110 patients with HIT-reactive antibodies, out of which 46 were also thrombocytopenic (true HIT). Cardiac surgery was performed in HIT-positive patients under heparin anticoagulation and iloprost infusion. A control group of 118 HIT-negative patients received heparin but no iloprost during surgery. For the first 20 patients, the dose of iloprost diminishing the HIPAG test to ≤5% was determined prior to surgery by in vitro titration using the patients' own plasma and donor platelets. In parallel, the iloprost "target dose" was also established for each patient intraoperatively, but before heparin administration. Iloprost was infused initially at 3 ng/kg/mL and further adjusted intraoperatively, until ex vivo aggregation reached ≤5%. As a close correlation was observed between the "target dose" identified before surgery and that established intraoperatively, the remaining 90 patients were administered iloprost starting at the presurgery identified "target dose." This process significantly reduced the number of intraoperative HIPAG reassessments needed to determine the iloprost target dose, and reduced surgical time, while maintaining similar primary clinical outcomes to controls. Therefore, infusion of iloprost throughout surgery, under continuous titration, allows cardiac surgery to be undertaken safely using heparin, while avoiding life-threatening iloprost-induced hypotension in patients diagnosed with HIT-reactive antibodies or true HIT. © 2015 Wiley Periodicals, Inc.

  14. Fabrication and Characterization of Thermoresponsive Films Deposited by an RF Plasma Reactor

    PubMed Central

    Lucero, Adrianne E.; Reed, Jamie A.; Wu, Xiaomei; Canavan, Heather E.

    2014-01-01

    Summary Poly(N-isopropyl acrylamide) (pNIPAM) undergoes a sharp property change in response to a moderate thermal stimulus at physiological temperatures. In this work, we constructed a radio frequency (RF) plasma reactor for the plasma polymerization of pNIPAM. RF deposition is a method that coats surfaces of any geometry producing surfaces that are sterile and uniform, making this technique useful for forming biocompatible films. The films generated are characterized using X-ray photoelectron spectroscopy (XPS), contact angles, cell culture, and interferometry. We find that a plasma with a decreasing series of power settings (i.e., from 100W to 1W) at a pressure of 140 millitorr yields the most favorable results. PMID:24634643

  15. Controllable production of low molecular weight heparins by combinations of heparinase I/II/III.

    PubMed

    Wu, Jingjun; Zhang, Chong; Mei, Xiang; Li, Ye; Xing, Xin-Hui

    2014-01-30

    Enzymatic depolymerization of heparin by heparinases is promising for production of low molecular weight heparins (LMWHs) as anticoagulants, due to its mild reaction conditions and high selectivity. Here, different heparinase combinations were used to depolymerize heparin. Heparinase I and heparinase II can depolymerize heparin more efficiently than heparinase III, respectively, but heparinase III was the best able to protect the anticoagulant activities of LMWHs. Heparinase III and heparinase I/II combinations were able to efficiently depolymerize heparin to LMWHs with higher anticoagulant activity than the LMWHs produced by the respective heparinase I and heparinase II. HepIII and HepI is the best combination for maintaining high anti-IIa activity (75.7 ± 4.21 IU/mg) at the same Mw value. Furthermore, considering both the changes in molecular weight and anticoagulant activity, the action patterns of heparinase I and heparinase II were found not to follow the exolytic and processive depolymerizing mechanism from the reducing end of heparin. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Establishment of replacement batches for heparin low-molecular-mass for calibration CRS, and the International Standard Low Molecular Weight Heparin for Calibration.

    PubMed

    Mulloy, B; Heath, A; Behr-Gross, M-E

    2007-12-01

    An international collaborative study involving fourteen laboratories has taken place, organised by the European Directorate for the Quality of Medicines & HealthCare (EDQM) with National Institute for Biological Standards & Control (NIBSC) (in its capacity as a World Health Organisation (WHO) Laboratory for Biological Standardisation) to provide supporting data for the establishment of replacement batches of Heparin Low-Molecular-Mass (LMM) for Calibration Chemical Reference Substance (CRS), and of the International Reference Reagent (IRR) Low Molecular Weight Heparin for Molecular Weight Calibration. A batch of low-molecular-mass heparin was donated to the organisers and candidate preparations of freeze-dried heparin were produced at NIBSC and EDQM. The establishment study was organised in two phases: a prequalification (phase 1, performed in 3 laboratories in 2005) followed by an international collaborative study (phase 2). In phase 2, started in March 2006, molecular mass parameters were determined for seven different LMM heparin samples using the current CRS batch and two batches of candidate replacement material with a defined number average relative molecular mass (Mn) of 3,700, determined in phase 1. The values calculated using the candidates as standard were systematically different from values calculated using the current batch with its assigned number-average molecular mass (Mna) of 3,700. Using raw data supplied by participants, molecular mass parameters were recalculated using the candidates as standard with values for Mna of 3,800 and 3,900. Values for these parameters agreed more closely with those calculated using the current batch supporting the fact that the candidates, though similar to batch 1 in view of the production processes used, differ slightly in terms of molecular mass distribution. Therefore establishment of the candidates was recommended with an assigned Mna value of 3,800 that is both consistent with phase 1 results and guarantees

  17. Low-temperature plasma-deposited silicon epitaxial films: Growth and properties

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

    Demaurex, Bénédicte, E-mail: benedicte.demaurex@epfl.ch; Bartlome, Richard; Seif, Johannes P.

    2014-08-07

    Low-temperature (≤200 °C) epitaxial growth yields precise thickness, doping, and thermal-budget control, which enables advanced-design semiconductor devices. In this paper, we use plasma-enhanced chemical vapor deposition to grow homo-epitaxial layers and study the different growth modes on crystalline silicon substrates. In particular, we determine the conditions leading to epitaxial growth in light of a model that depends only on the silane concentration in the plasma and the mean free path length of surface adatoms. For such growth, we show that the presence of a persistent defective interface layer between the crystalline silicon substrate and the epitaxial layer stems not only frommore » the growth conditions but also from unintentional contamination of the reactor. Based on our findings, we determine the plasma conditions to grow high-quality bulk epitaxial films and propose a two-step growth process to obtain device-grade material.« less

  18. Low-temperature plasma-deposited silicon epitaxial films: Growth and properties

    DOE PAGES

    Demaurex, Bénédicte; Bartlome, Richard; Seif, Johannes P.; ...

    2014-08-05

    Low-temperature (≤ 180 °C) epitaxial growth yields precise thickness, doping, and thermal-budget control, which enables advanced-design semiconductor devices. In this paper, we use plasma-ehanced chemical vapor deposition to grow homo-epitaxial layers and study the different growth modes on crystalline silicon substrates. In particular, we determine the conditions leading to epitaxial growth in light of a model that depends only on the silane concentration in the plasma and the mean free path length of surface adatoms. For such growth, we show that the presence of a persistent defective interface layer between the crystalline silicon substrate and the epitaxial layer stems notmore » only from the growth conditions but also from unintentional contamination of the reactor. As a result of our findings, we determine the plasma conditions to grow high-quality bulk epitaxial films and propose a two-step growth process to obtain device-grade material.« less

  19. Optimizing Thermoelectric Properties of In Situ Plasma-Spray-Synthesized Sub-stoichiometric TiO2-x Deposits

    NASA Astrophysics Data System (ADS)

    Lee, Hwasoo; Seshadri, Ramachandran Chidambaram; Pala, Zdenek; Sampath, Sanjay

    2018-06-01

    In this article, an attempt has been made to relate the thermoelectric properties of thermal spray deposits of sub-stoichiometric titania to process-induced phase and microstructural variances. The TiO2-x deposits were formed through the in situ reaction of the TiO1.9 or TiO1.7 feedstock within the high-temperature plasma flame and manipulated via varying the amounts of hydrogen fed into in the thermal plasma. Changes in the flow rates of H2 in the plasma plume greatly affected the in-flight particle behavior and composition of the deposits. For reference, a high-velocity oxy-fuel spray torch was also used to deposit the two varieties of feedstocks. Refinements to the representation of the in-flight particle characteristics derived via single particle and ensemble diagnostic methods are proposed using the group parameters (melting index and kinetic energy). The results show that depending on the value of the melting index, there is an inverse proportional relationship between electrical conductivity and Seebeck coefficient, whereas thermal conductivity has a directly proportional relationship with the electrical conductivity. Retention of the original phase and reduced decomposition is beneficial to retain the high Seebeck coefficient or the high electrical conductivity in the TiO2 system.

  20. Major proteins of boar seminal plasma as a tool for biotechnological preservation of spermatozoa.

    PubMed

    Caballero, I; Vazquez, J M; García, E M; Parrilla, I; Roca, J; Calvete, J J; Sanz, L; Martínez, E A

    2008-11-01

    Boar seminal plasma is a complex mixture of secretions from the testes, epididymides, and the male accessory reproductive organs which bathe the spermatozoa at ejaculation. The seminal plasma contains factors, mostly proteins, which influence the spermatozoa, the female genital tract, and the ovum. In boars, most of the proteins belong to the spermadhesin family and bind to the sperm surface. Spermadhesins are multifunctional proteins with a wide range of ligand-binding abilities to heparin, phospholipids, protease inhibitors and carbohydrates; the family can be roughly divided into heparin-binding (AQN-1, AQN-3, AWN) and non-heparin-binding spermadhesins (PSP-I/PSP-II heterodimer). These proteins have various effects promoting or inhibiting sperm functions including motility, oviduct binding, zona binding/penetration, and ultimately fertilization. The complexity of the environmental signals that influence these actions have implications for the uses of these proteins in vivo and in vitro, and may lead to uses in improving sperm storage.

  1. Increasing Stabilized Performance Of Amorphous Silicon Based Devices Produced By Highly Hydrogen Diluted Lower Temperature Plasma Deposition.

    DOEpatents

    Li, Yaun-Min; Bennett, Murray S.; Yang, Liyou

    1999-08-24

    High quality, stable photovoltaic and electronic amorphous silicon devices which effectively resist light-induced degradation and current-induced degradation, are produced by a special plasma deposition process. Powerful, efficient single and multi-junction solar cells with high open circuit voltages and fill factors and with wider bandgaps, can be economically fabricated by the special plasma deposition process. The preferred process includes relatively low temperature, high pressure, glow discharge of silane in the presence of a high concentration of hydrogen gas.

  2. Increased Stabilized Performance Of Amorphous Silicon Based Devices Produced By Highly Hydrogen Diluted Lower Temperature Plasma Deposition.

    DOEpatents

    Li, Yaun-Min; Bennett, Murray S.; Yang, Liyou

    1997-07-08

    High quality, stable photovoltaic and electronic amorphous silicon devices which effectively resist light-induced degradation and current-induced degradation, are produced by a special plasma deposition process. Powerful, efficient single and multi-junction solar cells with high open circuit voltages and fill factors and with wider bandgaps, can be economically fabricated by the special plasma deposition process. The preferred process includes relatively low temperature, high pressure, glow discharge of silane in the presence of a high concentration of hydrogen gas.

  3. Chromatographic molecular weight measurements for heparin, its fragments and fractions, and other glycosaminoglycans.

    PubMed

    Mulloy, Barbara; Hogwood, John

    2015-01-01

    Glycosaminoglycan samples are usually polydisperse, consisting of molecules with differing length and differing sequence. Methods for measuring the molecular weight of heparin have been developed to assure the quality and consistency of heparin products for medicinal use, and these methods can be applied in other laboratory contexts. In the method described here, high-performance gel permeation chromatography is calibrated using appropriate heparin molecular weight markers or a single broad standard calibrant, and used to characterize the molecular weight distribution of polydisperse samples or the peak molecular weight of monodisperse, or approximately monodisperse, heparin fractions. The same technology can be adapted for use with other glycosaminoglycans.

  4. Heparin-binding growth factor isolated from human prostatic extracts.

    PubMed

    Mydlo, J H; Bulbul, M A; Richon, V M; Heston, W D; Fair, W R

    1988-01-01

    Prostatic tissue extracts from patients with benign prostatic hyperplasia (BPH) and prostatic carcinoma were fractionated using heparin-Sepharose chromatography. The mitogenic activity of eluted fractions on quiescent subconfluent Swiss Albino 3T3 fibroblasts was tested employing a tritiated-thymidine-incorporation assay. Two peaks of activity were consistently noted--one in the void volume and a second fraction which eluted with 1.3-1.6 M NaCl and contained the majority of the mitogenic activity. Both non-heparin- and heparin-binding fractions increased tritiated incorporation into a mouse osteoblast cell line (MC3T3), while only the heparin-binding fractions stimulated a human umbilical vein endothelial cell line (HUV). No increased uptake of thymidine was seen using a human prostatic carcinoma cell line (PC-3). Sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS/PAGE) of lyophilized active fractions showed a persistent band at 17,500 daltons. The purified protein demonstrated angiogenic properties using the chick embryo chorioallantoic membrane (CAM) assay. Western blot analysis using antibodies specific to basic fibroblast growth factor (bFGF) or acidic FGF (aFGF) demonstrated that the former, but not the latter, bound to prostatic growth factor (PrGF), and inhibited its mitogenic activity as well. It appears that PrGF shares homology with basic fibroblast growth factors.

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

    PubMed

    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.

  6. An international survey of current practice in the laboratory assessment of anticoagulant therapy with heparin.

    PubMed

    Favaloro, Emmanuel J; Bonar, Roslyn; Sioufi, John; Wheeler, Michael; Low, Joyce; Aboud, Margaret; Lloyd, John; Street, Alison; Marsden, Katherine

    2005-06-01

    We conducted a survey of laboratory practice for assessment of heparin anticoagulant therapy by participants of the Royal College of Pathologists of Australasia Quality Assurance Program (RCPA QAP). A questionnaire was sent to 646 laboratories enrolled in the Haematology component of the QAP, requesting details of tests used for monitoring heparin therapy. Seventy laboratories (10.8%) returned results that indicated that they performed laboratory monitoring of heparin therapy. Most laboratories (69/70 = 98.6%) use the activated partial thromboplastin time (APTT) to monitor unfractionated heparin, with eight (11.4%) also using the APTT for monitoring low molecular weight (LMW) heparin. Five (7.1%) laboratories use the thrombin time (TT) test to help monitor heparin therapy and 37 (52.9%) laboratories use an anti-Xa assay to monitor heparin (either LMW or unfractionated). Normal reference ranges (NRR) for APTT differed considerably between laboratories, even those using the same reagent. Therapeutic ranges (TR) also differed considerably between laboratories, for both APTT and the anti-Xa assay. Laboratory differences in NRR and TR using the same reagents could only be partly explained by the use of different instrumentation. There is a large variation in current laboratory practice relating to monitoring of heparin anticoagulant therapy. This finding is similar to that of a similar survey conducted by the RCPA QAP almost a decade ago. This study suggests that better standardisation is still required for laboratory monitoring of heparin therapy.

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

    PubMed

    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.

  8. Deposition and re-erosion studies by means of local impurity injection in TEXTOR

    NASA Astrophysics Data System (ADS)

    Textor Team Kirschner, A.; Kreter, A.; Wienhold, P.; Brezinsek, S.; Coenen, J. W.; Esser, H. G.; Pospieszczyk, A.; Schulz, Ch.; Breuer, U.; Borodin, D.; Clever, M.; Ding, R.; Galonska, A.; Huber, A.; Litnovsky, A.; Matveev, D.; Ohya, K.; Philipps, V.; Samm, U.; Schmitz, O.; Schweer, B.; Stoschus, H.

    2011-08-01

    Pioneering experiments to study local erosion and deposition processes have been carried out in TEXTOR by injecting 13C marked hydrocarbons (CH4 and C2H4) as well as silane (SiD4) and tungsten-hexafluoride (WF6) through test limiters exposed to the edge plasma. The influence of various limiter materials (C, W, Mo) and surface roughness, different geometries (spherical or roof-like) and local plasma parameters has been studied. Depending on these conditions the local deposition efficiency of injected species varies between 0.1% and 9% - the largest deposition has been found for 13CH4 injection through unpolished, spherical C test limiter and ohmic plasma conditions. The most striking result is that ERO modelling cannot reproduce these low deposition efficiencies using the common assumptions on sticking probabilities and physical and chemical re-erosion yields. As an explanation large re-erosion due to background plasma and possibly low "effective sticking" of returning species is applied. This has been interpreted as enhanced re-erosion of re-deposits under simultaneous impact of high ion fluxes from plasma background.

  9. Plasma-enhanced chemical vapor deposition of multiwalled carbon nanofibers.

    PubMed

    Matthews, Kristopher; Cruden, Brett A; Chen, Bin; Meyyappan, M; Delzeit, Lance

    2002-10-01

    Plasma-enhanced chemical vapor deposition is used to grow vertically aligned multiwalled carbon nanofibers (MWNFs). The graphite basal planes in these nanofibers are not parallel as in nanotubes; instead they exhibit a small angle resembling a stacked cone arrangement. A parametric study with varying process parameters such as growth temperature, feedstock composition, and substrate power has been conducted, and these parameters are found to influence the growth rate, diameter, and morphology. The well-aligned MWNFs are suitable for fabricating electrode systems in sensor and device development.

  10. Plasma-enhanced chemical vapor deposition of multiwalled carbon nanofibers

    NASA Technical Reports Server (NTRS)

    Matthews, Kristopher; Cruden, Brett A.; Chen, Bin; Meyyappan, M.; Delzeit, Lance

    2002-01-01

    Plasma-enhanced chemical vapor deposition is used to grow vertically aligned multiwalled carbon nanofibers (MWNFs). The graphite basal planes in these nanofibers are not parallel as in nanotubes; instead they exhibit a small angle resembling a stacked cone arrangement. A parametric study with varying process parameters such as growth temperature, feedstock composition, and substrate power has been conducted, and these parameters are found to influence the growth rate, diameter, and morphology. The well-aligned MWNFs are suitable for fabricating electrode systems in sensor and device development.

  11. Super-Anticoagulant Heparin-Mimicking Hydrogel Thin Film Attached Substrate Surfaces to Improve Hemocompatibility.

    PubMed

    He, Min; Cui, Xiaofei; Jiang, Huiyi; Huang, Xuelian; Zhao, Weifeng; Zhao, Changsheng

    2017-02-01

    In this study, heparin-mimicking hydrogel thin films are covalently attached onto poly(ether sulfone) membrane surfaces to improve anticoagulant property. The hydrogel films display honeycomb-like porous structure with well controlled thickness and show long-term stability. After immobilizing the hydrogel films, the membranes show excellent anticoagulant property confirmed by the activated partial thromboplastin time values exceeding 600 s. Meanwhile, the thrombin time values increase from 20 to 61 s as the sodium allysulfonate proportions increase from 0 to 80 mol%. In vitro investigations of protein adsorption and blood-related complement activation also confirm that the membranes exhibit super-anticoagulant property. Furthermore, gentamycin sulfate is loaded into the hydrogel films, and the released drug shows significant inhibition toward E. coli bacteria. It is believed that the surface attached heparin-mimicking hydrogel thin films may show high potential for the applications in various biological fields, such as blood contacting materials and drug loading materials. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Selective Plasma Deposition of Fluorocarbon Films on SAMs

    NASA Technical Reports Server (NTRS)

    Crain, Mark M., III; Walsh, Kevin M.; Cohn, Robert W.

    2006-01-01

    A dry plasma process has been demonstrated to be useful for the selective modification of self-assembled monolayers (SAMs) of alkanethiolates. These SAMs are used, during the fabrication of semiconductor electronic devices, as etch masks on gold layers that are destined to be patterned and incorporated into the devices. The selective modification involves the formation of fluorocarbon films that render the SAMs more effective in protecting the masked areas of the gold against etching by a potassium iodide (KI) solution. This modification can be utilized, not only in the fabrication of single electronic devices but also in the fabrication of integrated circuits, microelectromechanical systems, and circuit boards. In the steps that precede the dry plasma process, a silicon mold in the desired pattern is fabricated by standard photolithographic techniques. A stamp is then made by casting polydimethylsiloxane (commonly known as silicone rubber) in the mold. The stamp is coated with an alkanethiol solution, then the stamp is pressed on the gold layer of a device to be fabricated in order to deposit the alkanethiol to form an alkanethiolate SAM in the desired pattern (see figure). Next, the workpiece is exposed to a radio-frequency plasma generated from a mixture of CF4 and H2 gases. After this plasma treatment, the SAM is found to be modified, while the exposed areas of gold remain unchanged. This dry plasma process offers the potential for forming masks superior to those formed in a prior wet etching process. Among the advantages over the wet etching process are greater selectivity, fewer pin holes in the masks, and less nonuniformity of the masks. The fluorocarbon films formed in this way may also be useful as intermediate layers for subsequent fabrication steps and as dielectric layers to be incorporated into finished products.

  13. Sulfated Low Molecular Weight Lignins, Allosteric Inhibitors of Coagulation Proteinases via the Heparin Binding Site, Significantly Alter the Active Site of Thrombin and Factor Xa Compared to Heparin

    PubMed Central

    Henry, Brian L.; Desai, Umesh R.

    2014-01-01

    Sulfated low molecular weight lignins (LMWLs) have been found to bind in the heparin binding sites of coagulation proteinases. LMWLs represent a library of diverse non-carbohydrate, aromatic molecules which are structures different from heparin, but still potently inhibit thrombin and factor Xa. To better understand their mechanism of action, we studied the effects of three sulfated LMWLs (CDSO3, FDSO3, and SDSO3) on the active sites of thrombin and factor Xa. LMWLs were found to uniformly inhibit the catalytic activity of thrombin and factor Xa, regardless of the substrate used. Michaelis-Menten kinetic studies indicate that maximal velocity of hydrolysis of each chromogenic substrate decreases significantly in the presence of sulfated LMWLs, while the effect on Michaelis constant is dependent on the nature of the substrate. These studies indicate that LMWLs inhibit thrombin and factor Xa through allosteric disruption of the catalytic apparatus, specifically through the catalytic step. As opposed to heparin, LMWLs significantly alter the binding of the active site fluorescent ligand p-aminobenzamidine. LMWLs also had a greater effect on the molecular orientation of fluorescein-labeled His 57 than heparin. The molecular geometry surrounding the most important catalytic amino acid, Ser 195, was significantly altered by the binding of LMWLs while heparin had no measurable effect on Ser 195. These results further advance the concept of sulfated LMWLs as heparin mimics and will aid the design of anticoagulants based on their novel scaffold. PMID:25242245

  14. Sulfated low molecular weight lignins, allosteric inhibitors of coagulation proteinases via the heparin binding site, significantly alter the active site of thrombin and factor xa compared to heparin.

    PubMed

    Henry, Brian L; Desai, Umesh R

    2014-11-01

    Sulfated low molecular weight lignins (LMWLs) have been found to bind in the heparin binding sites of coagulation proteinases. LMWLs represent a library of diverse non-carbohydrate, aromatic molecules which are structures different from heparin, but still potently inhibit thrombin and factor Xa. To better understand their mechanism of action, we studied the effects of three sulfated LMWLs (CDSO3, FDSO3, and SDSO3) on the active sites of thrombin and factor Xa. LMWLs were found to uniformly inhibit the catalytic activity of thrombin and factor Xa, regardless of the substrate used. Michaelis-Menten kinetic studies indicate that maximal velocity of hydrolysis of each chromogenic substrate decreases significantly in the presence of sulfated LMWLs, while the effect on Michaelis constant is dependent on the nature of the substrate. These studies indicate that LMWLs inhibit thrombin and factor Xa through allosteric disruption of the catalytic apparatus, specifically through the catalytic step. As opposed to heparin, LMWLs significantly alter the binding of the active site fluorescent ligand p-aminobenzamidine. LMWLs also had a greater effect on the molecular orientation of fluorescein-labeled His 57 than heparin. The molecular geometry surrounding the most important catalytic amino acid, Ser 195, was significantly altered by the binding of LMWLs while heparin had no measurable effect on Ser 195. These results further advance the concept of sulfated LMWLs as heparin mimics and will aid the design of anticoagulants based on their novel scaffold. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Heparin-induced thrombocytopenia and heart operation: management with tedelparin.

    PubMed

    Altés, A; Martino, R; Gari, M; Cámara, M L; Garín, R; Casas, J I; Fontcuberta, J

    1995-02-01

    Anticoagulation for cardiopulmonary bypass in the infrequent clinical setting of thrombocytopenia associated with the use of unfractionated heparin is a very serious problem. We describe a case in which a low-molecular-weight heparin (tedelparin) was selected for this purpose based on a platelet aggregation test, permitting adequate anticoagulation during cardiopulmonary bypass for valve replacement. This case report might help establish an adequate anticoagulation protocol when faced with a patient suffering from this condition.

  16. Deposition of magnesium nitride thin films on stainless steel-304 substrates by using a plasma focus device

    NASA Astrophysics Data System (ADS)

    Ramezani, Amir Hoshang; Habibi, Maryam; Ghoranneviss, Mahmood

    2014-08-01

    In this research, for the first time, we synthesize magnesium nitride thin films on 304-type stainless steel substrates using a Mather-type (2 kJ) plasma focus (PF) device. The films of magnesium nitride are coated with different number of focus shots (like 15, 25 and 35) at a distance of 8 cm from the anode tip and at 0° angular position with respect to the anode axis. For investigation of the structural properties and surface morphology of magnesium nitride films, we utilized the X-ray diffractometer (XRD), atomic force microscopy (AFM) and scanning electron microscopy (SEM) analysis, respectively. Also, the elemental composition is characterized by energy-dispersive X-ray (EDX) analysis. Furthermore, Vicker's microhardness is used to study the mechanical properties of the deposited films. The results show that the degree of crystallinity of deposited thin films (from XRD), the average size of particles and surface roughness (from AFM), crystalline growth of structures (from SEM) and the hardness values of the films depend on the number of focus shots. The EDX analysis demonstrates the existence of the elemental composition of magnesium in the deposited samples.

  17. Overexpression of Heparin-Binding Epidermal Growth Factor-Like Growth Factor Mediates Liver Fibrosis in Transgenic Mice.

    PubMed

    Guo, Yongze; Ding, Qian; Chen, Lei; Ji, Chenguang; Hao, Huiyao; Wang, Jia; Qi, Wei; Xie, Xiaoli; Ma, Junji; Li, Aidi; Jiang, Xiaoyu; Li, Xiaotian; Jiang, Huiqing

    2017-08-01

    The role of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in liver fibrosis is not clear and is sometimes even contradictory. To clarify this role, a HB-EGF transgenic (Tg) mouse model was, for the first time, used to evaluate the functions of HB-EGF in liver fibrosis. For the in vivo study, carbon tetrachloride injection and bile duct ligation treatment were used to induce liver fibrosis in HB-EGF Tg mice and wild-type (WT) mice, respectively. Primary hepatic satellite cells (HSCs) were isolated from HB-EGF Tg and WT mice for the in vitro study. Compared with the WT mice, HB-EGF Tg mice were shown to develop more severe liver fibrosis when treated with carbon tetrachloride or bile duct ligation, with increased matrix metalloproteinases 13 activity and enhanced expression of fibrogenic genes including α-smooth muscle actin and collagen I. HB-EGF gene transfer led to an increase in proliferation and a decrease in apoptosis in primary HSCs. The ERK signaling pathway was more highly activated in primary HSCs from HB-EGF Tg mice than in those from WT mice. Our investigation confirmed the profibrotic effect of HB-EGF on the liver using a Tg mouse model. This result may contribute to the elucidation of HB-EGF as a therapeutic target in liver fibrosis. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  18. Plasma deposited stability enhancement coating for amorphous ketoprofen.

    PubMed

    Bosselmann, Stephanie; Owens, Donald E; Kennedy, Rachel L; Herpin, Matthew J; Williams, Robert O

    2011-05-01

    A hydrophobic fluorocarbon coating deposited onto amorphous ketoprofen via pulsed plasma-enhanced chemical vapor deposition (PPECVD) significantly prolonged the onset of recrystallization compared to uncoated drug. Rapid freezing (RF) employed to produce amorphous ketoprofen was followed by PPECVD of perfluorohexane. The effect of coating thickness on the recrystallization and dissolution behavior of ketoprofen was investigated. Samples were stored in open containers at 40°C and 75% relative humidity, and the onset of recrystallization was monitored by DSC. An increase in coating thickness provided enhanced stability against recrystallization for up to 6 months at accelerated storage conditions (longest time of observation) when compared to three days for uncoated ketoprofen. Results from XPS analysis demonstrated that an increase in coating thickness was associated with improved surface coverage thus enabling superior protection. Dissolution testing showed that at least 80% of ketoprofen was released in buffer pH 6.8 from all coated samples. Overall, an increase in coating thickness resulted in a more complete drug release due to decreased adhesion of the coating to the substrate. Copyright © 2010 Elsevier B.V. All rights reserved.

  19. Performance improvements of the BNC tubes from unique double-silicone-tube bioreactors by introducing chitosan and heparin for application as small-diameter artificial blood vessels.

    PubMed

    Li, Xue; Tang, Jingyu; Bao, Luhan; Chen, Lin; Hong, Feng F

    2017-12-15

    In order to improve property of bacterial nano-cellulose (BNC) to achieve the requirements of clinical application as small caliber vascular grafts, chitosan (CH) was deposited into the fibril network of the BNC tubes fabricated in unique Double-Silicone-Tube bioreactors. Heparin (Hep) was then chemically grafted into the BNC-based tubes using EDC/NHS crosslinking to improve performance of anticoagulation and endothelialization. Physicochemical and mechanical property, blood compatibility, and cytocompatibility were compared before and after compositing. The results indicated that strength at break was increased but burst pressure decreased slightly after compositing. Performance of the BNC tubes was improved remarkably after introducing chitosan and heparin. The EDC/NHS crosslinking catalyzed both amide bonds and ester bonds formation in the BNC/CH-Hep composites. Three-dimensional surface structure and roughness were firstly obtained and discussed in relation to the hemocompatibility of BNC-based tubes. This work demonstrates the heparinized BNC-based tubes have great potential in application as small-diameter vascular prosthesis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Dielectric properties of Ba0.6Sr0.4TiO3 thin films deposited by mist plasma evaporation using aqueous solution precursor

    NASA Astrophysics Data System (ADS)

    Huang, Hui; Shi, Peng; Wang, Minqiang; Yao, Xi; Tan, O. K.

    2006-06-01

    Mist plasma evaporation (MPE) technique has been developed to deposit Ba0.6Sr0.4TiO3 (BST) thin films on SiO2/Si and Pt/Ti/SiO2/Si substrates at atmospheric pressure using metal nitrate aqueous solution as precursor. MPE is characterized by the injection of liquid reactants into thermal plasma where the source materials in the droplets are evaporated by the high temperature of the thermal plasma. Nanometer-scale clusters are formed in the tail flame of the plasma, and then deposited and rearranged on the substrate at a lower temperature. Due to the high temperature annealing process of the thermal plasma before deposition, well-crystallized BST films were deposited at substrate temperature of 630 °C. The dielectric constant and dielectric loss of the film at 100 kHz are 715 and 0.24, respectively. Due to the good crystallinity of the BST films deposited by MPE, high dielectric tunability up to 39.3% is achieved at low applied electric field of 100 kV cm-1.

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

    PubMed

    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.

  2. Optically transparent, scratch-resistant, diamond-like carbon coatings

    DOEpatents

    He, Xiao-Ming; Lee, Deok-Hyung; Nastasi, Michael A.; Walter, Kevin C.; Tuszewski, Michel G.

    2003-06-03

    A plasma-based method for the deposition of diamond-like carbon (DLC) coatings is described. The process uses a radio-frequency inductively coupled discharge to generate a plasma at relatively low gas pressures. The deposition process is environmentally friendly and scaleable to large areas, and components that have geometrically complicated surfaces can be processed. The method has been used to deposit adherent 100-400 nm thick DLC coatings on metals, glass, and polymers. These coatings are between three and four times harder than steel and are therefore scratch resistant, and transparent to visible light. Boron and silicon doping of the DLC coatings have produced coatings having improved optical properties and lower coating stress levels, but with slightly lower hardness.

  3. Targeted use of heparin, heparinoids, or low-molecular-weight heparin to improve outcome after acute ischaemic stroke: an individual patient data meta-analysis of randomised controlled trials

    PubMed Central

    Whiteley, William N; Adams, Harold P; Bath, Philip MW; Berge, Eivind; Sandset, Per Morten; Dennis, Martin; Murray, Gordon D; Wong, Ka-Sing Lawrence; Sandercock, Peter AG

    2013-01-01

    Summary Background Many international guidelines on the prevention of venous thromboembolism recommend targeting heparin treatment at patients with stroke who have a high risk of venous thrombotic events or a low risk of haemorrhagic events. We sought to identify reliable methods to target anticoagulant treatment and so improve the chance of avoiding death or dependence after stroke. Methods We obtained individual patient data from the five largest randomised controlled trials in acute ischaemic stroke that compared heparins (unfractionated heparin, heparinoids, or low-molecular-weight heparin) with aspirin or placebo. We developed and evaluated statistical models for the prediction of thrombotic events (myocardial infarction, stroke, deep vein thrombosis, or pulmonary embolism) and haemorrhagic events (symptomatic intracranial or significant extracranial) in the first 14 days after stroke. We calculated the absolute risk difference for the outcome “dead or dependent” in patients grouped by quartiles of predicted risk of thrombotic and haemorrhagic events with random effect meta-analysis. Findings Patients with ischaemic stroke who were of advanced age, had increased neurological impairment, or had atrial fibrillation had a high risk of both thrombotic and haemorrhagic events after stroke. Additionally, patients with CT-visible evidence of recent cerebral ischaemia were at increased risk of thrombotic events. In evaluation datasets, the area under a receiver operating curve for prediction models for thrombotic events was 0·63 (95% CI 0·59–0·67) and for haemorrhagic events was 0·60 (0·55–0·64). We found no evidence that the net benefit from heparins increased with either increasing risk of thrombotic events or decreasing risk of haemorrhagic events. Interpretation There was no evidence that patients with ischaemic stroke who were at higher risk of thrombotic events or lower risk of haemorrhagic events benefited from heparins. We were therefore unable

  4. Targeted use of heparin, heparinoids, or low-molecular-weight heparin to improve outcome after acute ischaemic stroke: an individual patient data meta-analysis of randomised controlled trials.

    PubMed

    Whiteley, William N; Adams, Harold P; Bath, Philip M W; Berge, Eivind; Sandset, Per Morten; Dennis, Martin; Murray, Gordon D; Wong, Ka-Sing Lawrence; Sandercock, Peter A G

    2013-06-01

    Many international guidelines on the prevention of venous thromboembolism recommend targeting heparin treatment at patients with stroke who have a high risk of venous thrombotic events or a low risk of haemorrhagic events. We sought to identify reliable methods to target anticoagulant treatment and so improve the chance of avoiding death or dependence after stroke. We obtained individual patient data from the five largest randomised controlled trials in acute ischaemic stroke that compared heparins (unfractionated heparin, heparinoids, or low-molecular-weight heparin) with aspirin or placebo. We developed and evaluated statistical models for the prediction of thrombotic events (myocardial infarction, stroke, deep vein thrombosis, or pulmonary embolism) and haemorrhagic events (symptomatic intracranial or significant extracranial) in the first 14 days after stroke. We calculated the absolute risk difference for the outcome "dead or dependent" in patients grouped by quartiles of predicted risk of thrombotic and haemorrhagic events with random effect meta-analysis. Patients with ischaemic stroke who were of advanced age, had increased neurological impairment, or had atrial fibrillation had a high risk of both thrombotic and haemorrhagic events after stroke. Additionally, patients with CT-visible evidence of recent cerebral ischaemia were at increased risk of thrombotic events. In evaluation datasets, the area under a receiver operating curve for prediction models for thrombotic events was 0·63 (95% CI 0·59-0·67) and for haemorrhagic events was 0·60 (0·55-0·64). We found no evidence that the net benefit from heparins increased with either increasing risk of thrombotic events or decreasing risk of haemorrhagic events. There was no evidence that patients with ischaemic stroke who were at higher risk of thrombotic events or lower risk of haemorrhagic events benefited from heparins. We were therefore unable to define a targeted approach to select the patients who

  5. Recent advances in the diagnosis and treatment of heparin-induced thrombocytopenia

    PubMed Central

    Bakchoul, Tamam

    2012-01-01

    Heparin-induced thrombocytopenia (HIT) is a drug-mediated, prothrombotic disorder caused by immunization against platelet factor 4 (PF4) after complex formation with heparin or other polyanions. After their binding to PF4/heparin complexes on the platelet surface, HIT antibodies are capable of intravascular platelet activation by cross-linking Fcγ receptor IIA leading to a platelet count decrease and/or thrombosis. Diagnosis of HIT is often difficult. This, and the low specificity of the commercially available immunoassays, leads currently to substantial overdiagnosis of HIT. Timing of onset, the moderate nature of thrombocytopenia, and the common concurrence of thrombosis are very important factors, which help to differentiate HIT from other potential causes of thrombocytopenia. A combination of a clinical pretest scoring system and laboratory investigation is usually necessary to diagnose HIT. Although HIT is considered to be a rare complication of heparin treatment, the very high number of hospital inpatients, and increasingly also hospital outpatients receiving heparin, still result in a considerable number of patients developing HIT. If HIT occurs, potentially devastating complications such as life-threatening thrombosis make it one of the most serious adverse drug reactions. If HIT is strongly suspected, all heparin must be stopped and an alternative nonheparin anticoagulant started at a therapeutic dose to prevent thromboembolic complications. However, the nonheparin alternative anticoagulants bear a considerable bleeding risk, especially if given to patients with thrombocytopenia due to other reasons than HIT. While established drugs for HIT are disappearing from the market (lepirudin, danaparoid), bivalirudin, fondaparinux and potentially the new anticoagulants such as dabigatran, rivaroxaban and apixaban provide new treatment options. PMID:23606934

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

    PubMed

    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.

  7. Initial deposition of calcium phosphate ceramic on polystyrene and polytetrafluoroethylene by rf magnetron sputtering deposition

    NASA Astrophysics Data System (ADS)

    Feddes, B.; Wolke, J. G. C.; Jansen, J. A.; Vredenberg, A. M.

    2003-03-01

    Calcium phosphate (CaP) coatings can be applied to improve the biological performance of polymeric medical implants. A strong interfacial bond between ceramic and polymer is required for clinical applications. Because the chemical structure of an interface plays an important role in the adhesion of a coating, we studied the formation of the interface between CaP and polystyrene (PS) and polytetrafluoroethylene (PTFE). The coating was deposited in a radio frequency (rf) magnetron sputtering deposition system. Prior to the deposition, some samples received an oxygen plasma pretreatment. We found that the two substrates show a strongly different reactivity towards CaP. On PS a phosphorus and oxygen enrichment is present at the interface. This is understood from POx complexes that are able to bind to the PS. The effects of the plasma pretreatment are overruled by the deposition process itself. On PTFE, a calcium enrichment and an absence of phosphorus is found at the interface. The former is the result of CaF2-like material being formed at the interface. The latter may be the result of phosphorus reacting with escaping fluorine to a PF3 molecule, which than escapes from the material as a gas molecule. We found that the final structure of the interface is mostly controlled by the bombardment of energetic particles escaping either from the plasma or from the sputtering target. The work described here can be used to understand and improve the adhesion of CaP coatings deposited on medical substrates.

  8. Heparin Oligosaccharides as Potential Therapeutic Agents in Senile Dementia

    PubMed Central

    Ma, Qing; Cornelli, Umberto; Hanin, Israel; Jeske, Walter P.; Linhardt, Robert J.; Walenga, Jeanine M.; Fareed, Jawed; Lee, John M.

    2014-01-01

    Heparin is a glycosaminoglycan mixture currently used in prophylaxis and treatment of thrombosis. Heparin possesses non-anticoagulant properties, including modulation of various proteases, interactions with fibroblast growth factors, and anti-inflammatory actions. Senile dementia of Alzheimer’s type is accompanied by inflammatory responses contributing to irreversible changes in neuronal viability and brain function. Vascular factors are also involved in the pathogenesis of senile dementia. Inflammation, endogenous proteoglycans, and assembly of senile plagues and neurofibrillary tangles contribute directly and indirectly to further neuronal damage. Neuron salvage can be achieved by anti-inflammation and the competitive inhibition of proteoglycans accumulation. The complexity of the pathology of senile dementia provides numerous potential targets for therapeutic interventions designed to modulate inflammation and proteoglycan assembly. Heparin and related oligosaccharides are known to exhibit anti-inflammatory effects as well as inhibitory effects on proteoglycan assembly and may prove useful as neuroprotective agents. PMID:17504153

  9. Modulation of human endothelial cell proliferation and migration by fucoidan and heparin.

    PubMed

    Giraux, J L; Matou, S; Bros, A; Tapon-Bretaudière, J; Letourneur, D; Fischer, A M

    1998-12-01

    Fucoidan is a sulfated polysaccharide extracted from brown seaweeds. It has anticoagulant and antithrombotic properties and inhibits, as well as heparin, vascular smooth muscle cell growth. In this study, we investigated, in the presence of serum and human recombinant growth factors, the effects of fucoidan and heparin on the growth and migration of human umbilical vein endothelial cells (HUVEC) in culture. We found that fucoidan stimulated fetal bovine serum-induced HUVEC proliferation, whereas heparin inhibited it. In the presence of fibroblast growth factor-1 (FGF-1), both fucoidan and heparin potentiated HUVEC growth. In contrast, fucoidan and heparin inhibited HUVEC proliferation induced by FGF-2, but did not influence the mitogenic activity of vascular endothelial growth factor (VEGF). In the in vitro migration assay from a denuded area of confluent cells, the two sulfated polysaccharides markedly enhanced the migration of endothelial cells in the presence of FGF-1. Finally, a weak inhibitory effect on cell migration was found only with the two polysaccharides at high concentrations (> or = 100 micro/ml) in presence of serum or combined with FGF-2. All together, the results indicated that heparin and fucoidan can be used as tools to further investigate the cellular mechanisms regulating the proliferation and migration of human vascular cells. Moreover, the data already suggest a potential role of fucoidan as a new therapeutic agent of vegetal origin in the vascular endothelium wound repair.

  10. Sodium citrate 4% versus heparin as a lock solution in hemodialysis patients with central venous catheters.

    PubMed

    Yon, Calantha K; Low, Chai L

    2013-01-15

    The effects of heparin versus sodium citrate 4% as a lock solution on catheter-related infections (CRIs), catheter patency, and hospitalizations in long-term hemodialysis patients with central venous catheters (CVCs) were compared. Data for patients receiving heparin lock solutions were collected from July 2008 to July 2009. Data on patients receiving sodium citrate 4% lock solution were collected from September 2009 through December 2010. Patients who were receiving the heparin lock solution who continued to have a CVC in September 2009 were transitioned from heparin to sodium citrate catheter 4% lock solution. New patients with CVCs placed after September 2009 received sodium citrate 4% without a period of using heparin lock solution. Pertinent information on patient medical history, bleeding or clotting events, infections, and hospitalization was collected. Data were collected retrospectively for the heparin group and prospectively for the sodium citrate group. Data were collected from 360 patient-months among 60 patients during the heparin treatment period and from 451 patient-months among 58 patients during the sodium citrate period. Thirty-three patients were common to both study groups. There were significantly more CRIs and CRIs per 1000 catheter-days in the heparin than the sodium citrate treatment group. Secondary outcomes of hospitalizations and catheter thrombosis were comparable. CRIs and thrombosis led to significantly more catheter exchanges or removals in the heparin group than the sodium citrate group. In patients with long-term hemodialysis catheters, a lock solution of sodium citrate 4% was associated with fewer CRIs and similar effectiveness when compared with heparin 5000 units/mL.

  11. Study of supersonic plasma technology jets

    NASA Astrophysics Data System (ADS)

    Selezneva, Svetlana; Gravelle, Denis; Boulos, Maher; van de Sanden, Richard; Schram, Dc

    2001-10-01

    Recently some new techniques using remote thermal plasma for thin film deposition and plasma chemistry processes were developed. These techniques include PECVD of diamonds, diamond-like and polymer films; a-C:H and a-Si:H films. The latter are of especial interest because of their applications for solar cell production industry. In remote plasma deposition, thermal plasma is formed by means of one of traditional plasma sources. The chamber pressure is reduced with the help of continuous pumping. In that way the flow is accelerated up to the supersonic speed. The plasma expansion is controlled using a specific torch nozzle design. To optimize the deposition process detailed knowledge about the gas dynamic structure of the jet and chemical kinetics mechanisms is required. In the paper, we show how the flow pattern and the character of the deviations from local thermodynamic equilibrium differs in plasmas generated by different plasma sources, such as induction plasma torch, traditional direct current arc and cascaded arc. We study the effects of the chamber pressure, nozzle design and carrier gas on the resulting plasma properties. The analysis is performed by means of numerical modeling using commercially available FLUENT program with incorporated user-defined subroutines for two-temperature model. The results of continuum mechanics approach are compared with that of the kinetic Monte Carlo method and with the experimental data.

  12. [Intraoperative administration of low-molecular-weight heparins in reconstructive vascular operations].

    PubMed

    Pokrovskiĭ, A V; Demidova, V S; Titova, M I; Gontarenko, V N; Burtseva, E A

    2008-01-01

    The article deals with analysing the outcomes of administering low-molecular-weight heparins (LMWH) by the example of nadroparin ("Fraxiparin") during the intraoperative period in patients diagnosed with atherosclerotic lesions of femoropoplietal-crural segment of the lower-limb arteries as compared with non-fractionated heparin (NFH). Studied were the alterations in the parameters of the plasmatic and thrombocytic links of haemostasis on the background of administering various molecular-weight fractions of heparin. A conclusion was drawn on advantageous use of LMWH in the cohort of the patients involved. Also presented herein is an analysis of the literature data concerning appropriate usage of LMWH during the intraoperative period.

  13. Nanostructured Photocatalytic TiO2 Coating Deposited by Suspension Plasma Spraying with Different Injection Positions

    NASA Astrophysics Data System (ADS)

    Liu, Xuezhang; Wen, Kui; Deng, Chunming; Yang, Kun; Deng, Changguang; Liu, Min; Zhou, Kesong

    2018-02-01

    High plasma power is beneficial for the deposition efficiency and adhesive strength of suspension-sprayed photocatalytic TiO2 coatings, but it confronts two challenges: one is the reduced activity due to the critical phase transformation of anatase into rutile, and the other is fragmented droplets which cannot be easily injected into the plasma core. Here, TiO2 coatings were deposited at high plasma power and the position of suspension injection was varied with the guidance of numerical simulation. The simulation was based on a realistic three-dimensional time-dependent numerical model that included the inside and outside of torch regions. Scanning electron microscopy was performed to study the microstructure of the TiO2 coatings, whereas x-ray diffraction was adopted to analyze phase composition. Meanwhile, photocatalytic activities of the manufactured TiO2 coatings were evaluated by the degradation of an aqueous solution of methylene blue dye. Fragmented droplets were uniformly injected into the plasma jet, and the solidification pathway of melting particles was modified by varying the position of suspension injection. A nanostructured TiO2 coating with 93.9% anatase content was obtained at high plasma power (48.1 kW), and the adhesive coating bonding to stainless steel exhibited the desired photocatalytic activity.

  14. Sequencing the oligosaccharide pool in the low molecular weight heparin dalteparin with offline HPLC and ESI-MS/MS.

    PubMed

    Wang, Zhangjie; Zhang, Tianji; Xie, Shaoshuai; Liu, Xinyue; Li, Hongmei; Linhardt, Robert J; Chi, Lianli

    2018-03-01

    Low molecular weight heparins (LMWHs) are widely used anticoagulant drugs. The composition and sequence of LMWH oligosaccharides determine their safety and efficacy. The short oligosaccharide pool in LMWHs undergoes more depolymerization reactions than the longer chains and is the most sensitive indicator of the manufacturing process. Electrospray ionization tandem mass spectrometry (ESI-MS/MS) has been demonstrated as a powerful tool to sequence synthetic heparin oligosaccharide but never been applied to analyze complicated mixture like LMWHs. We established an offline strong anion exchange (SAX)-high performance liquid chromatography (HPLC) and ESI-MS/MS approach to sequence the short oligosaccharides of dalteparin sodium. With the help of in-house developed MS/MS interpretation software, the sequences of 18 representative species ranging from tetrasaccharide to octasaccharide were obtained. Interestingly, we found a novel 2,3-disulfated hexauronic acid structure and reconfirmed it by complementary heparinase digestion and LC-MS/MS analysis. This approach provides straightforward and in-depth insight to the structure of LMWHs and the reaction mechanism of heparin depolymerization. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Nanostructured bioactive glass-ceramic coatings deposited by the liquid precursor plasma spraying process

    NASA Astrophysics Data System (ADS)

    Xiao, Yanfeng; Song, Lei; Liu, Xiaoguang; Huang, Yi; Huang, Tao; Wu, Yao; Chen, Jiyong; Wu, Fang

    2011-01-01

    Bioactive glass-ceramic coatings have great potential in dental and orthopedic medical implant applications, due to its excellent bioactivity, biocompatibility and osteoinductivity. However, most of the coating preparation techniques either produce only thin thickness coatings or require tedious preparation steps. In this study, a new attempt was made to deposit bioactive glass-ceramic coatings on titanium substrates by the liquid precursor plasma spraying (LPPS) process. Tetraethyl orthosilicate, triethyl phosphate, calcium nitrate and sodium nitrate solutions were mixed together to form a suspension after hydrolysis, and the liquid suspension was used as the feedstock for plasma spraying of P 2O 5-Na 2O-CaO-SiO 2 bioactive glass-ceramic coatings. The in vitro bioactivities of the as-deposited coatings were evaluated by soaking the samples in simulated body fluid (SBF) for 4 h, 1, 2, 4, 7, 14, and 21 days, respectively. The as-deposited coating and its microstructure evolution behavior under SBF soaking were systematically analyzed by scanning electron microscopy (SEM), X-ray diffraction (XRD), inductively coupled plasma (ICP), and Fourier transform infrared (FTIR) spectroscopy. The results showed that P 2O 5-Na 2O-CaO-SiO 2 bioactive glass-ceramic coatings with nanostructure had been successfully synthesized by the LPPS technique and the synthesized coatings showed quick formation of a nanostructured HCA layer after being soaked in SBF. Overall, our results indicate that the LPPS process is an effective and simple method to synthesize nanostructured bioactive glass-ceramic coatings with good in vitro bioactivity.

  16. Effect of argon and hydrogen on deposition of silicon from tetrochlrosilane in cold plasmas

    NASA Technical Reports Server (NTRS)

    Manory, R. R.; d.

    1985-01-01

    The roles of Ar and H2 on the decomposition of SiCl4 in cold plasma were investigated by Langmuir probes and mass spectrometry. Decomposition of the reactant by Ar only has been found to be very slow. In presence of H2 in the plasma SiCl4 is decomposed by fast radical-molecule reactions which are further enhanced by Ar due to additional ion-molecule reactions in which more H radicals are produced. A model for the plasma-surface interactions during deposition of mu-Si in the Ar + H2 + SiCl4 system is presented.

  17. The role of novel chitin-like polysaccharides in Alzheimer disease.

    PubMed

    Castellani, Rudy J; Perry, George; Smith, Mark A

    2007-12-01

    While controversy over the role of carbohydrates in amyloidosis has existed since the initial recognition of amyloid, current understanding of the role of polysaccharides in the pathogenesis of amyloid deposition of Alzheimer disease and other amyloidoses is limited to studies of glyco-conjugates such as heparin sulfate proteoglycan. We hypothesized that polysaccharides may play a broader role in light of 1) the impaired glucose utilization in Alzheimer disease; 2) the demonstration of amylose in the Alzheimer disease brain; 3) the role of amyloid in Alzheimer disease pathogenesis. Specifically, as with glucose polymers (amyloid), we wanted to explore whether glucosamine polymers such as chitin were being synthesized and deposited as a result of impaired glucose utilization and aberrant hexosamine pathway activation. To this end, using calcofluor histochemistry, we recently demonstrated that amyloid plaques and blood vessels affected by amyloid angiopathy in subjects with sporadic and familial Alzheimer disease elicit chitin-type characteristics. Since chitin is a highly insoluble molecule and a substrate for glycan-protein interactions, chitin-like polysaccharides within the Alzheimer disease brain could provide a scaffolding for amyloid-beta deposition. As such, glucosamine may facilitate the process of amyloidosis, and /or provide neuroprotection in the Alzheimer disease brain.

  18. Structure and activity of a new low-molecular-weight heparin produced by enzymatic ultrafiltration.

    PubMed

    Fu, Li; Zhang, Fuming; Li, Guoyun; Onishi, Akihiro; Bhaskar, Ujjwal; Sun, Peilong; Linhardt, Robert J

    2014-05-01

    The standard process for preparing the low-molecular-weight heparin (LMWH) tinzaparin, through the partial enzymatic depolymerization of heparin, results in a reduced yield because of the formation of a high content of undesired disaccharides and tetrasaccharides. An enzymatic ultrafiltration reactor for LMWH preparation was developed to overcome this problem. The behavior, of the heparin oligosaccharides and polysaccharides using various membranes and conditions, was investigated to optimize this reactor. A novel product, LMWH-II, was produced from the controlled depolymerization of heparin using heparin lyase II in this optimized ultrafiltration reactor. Enzymatic ultrafiltration provides easy control and high yields (>80%) of LMWH-II. The molecular weight properties of LMWH-II were similar to other commercial LMWHs. The structure of LMWH-II closely matched heparin's core structural features. Most of the common process artifacts, present in many commercial LWMHs, were eliminated as demonstrated by 1D and 2D nuclear magnetic resonance spectroscopy. The antithrombin III and platelet factor-4 binding affinity of LMWH-II were comparable to commercial LMWHs, as was its in vitro anticoagulant activity. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  19. Surface Passivation of ZrO2 Artificial Dentures by Magnetized Coaxial Plasma deposition

    NASA Astrophysics Data System (ADS)

    Arai, Soya; Kurumi, Satoshi; Matsuda, Ken-Ichi; Suzuki, Kaoru; Hara, Katsuya; Kato, Tatsuya; Asai, Tomohiko; Hirose, Hideharu; Masutani, Shigeyuki; Nihon University Team

    2015-09-01

    Recent growth and fabrication technologies for functional materials have been greatly contributed to drastic development of oral surgery field. Zirconia based ceramics is expected to utilize artificial dentures because these ceramics have good biocompatibility, high hardness and aesthetic attractively. However, to apply these ceramics to artificial dentures, this denture is removed from a dental plate because of weakly bond. For improving this problem, synthesis an Al passivation-layer on the ceramics for bonding with these dental items is suitable. In order to deposit the passivation layer, we focused on a magnetized coaxial plasma deposition (MCPD). The greatest characteristic of MCPD is that high-melting point metal can be deposited on various substrates. Additionally, adhesion force between substrate and films deposited by the MCPD is superior to it of general deposition methods. In this study, we have reported on the growth techniques of Al films on ZrO2 for contributing to oral surgery by the MCPD. Surface of deposited films shows there were some droplets and thickness of it is about 200 nm. Thickness is increased to 500 nm with increasing applied voltage.

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

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

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

    1985-08-01

    The binding of the glycosaminoglycan (3H) 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 (TH) heparin were performed to quantitate the binding characteristics of each sample. Scatchard plot analyses indicated a significant difference in the binding affinity for (TH) heparin between bulls of high and low fertility. Dissociation constants were 69.0 and 119.3 pmol for bullsmore » of high and low fertility, respectively. In contrast, the number of binding sites for (TH) heparin did not differ significantly among bulls. Differences in binding affinity of (TH) heparin to bull sperm might be used to predict relative fertility of dairy bulls.« less

  1. Energy deposition into heavy gas plasma via pulsed inductive theta-pinch

    NASA Astrophysics Data System (ADS)

    Pahl, Ryan Alan

    The objective of this research is to study the formation processes of a pulsed inductive plasma using heavy gases, specifically the coupling of stored capacitive energy into plasma via formation in a theta pinch coil. To aid in this research, the Missouri Plasmoid Experiment Mk. I (and later Mk. II) was created. In the first paper, the construction of differential magnetic field probes are discussed. The effects of calibration setup on B-dot probes is studied using a Helmholtz coil driven by a vector network analyzer and a pulsed-power system. Calibration in a pulsed-power environment yielded calibration factors at least 9.7% less than the vector network analyzer. In the second paper, energy deposition into various gases using a pulsed inductive test article is investigated. Experimental data are combined with a series RLC model to quantify the energy loss associated with plasma formation in Argon, Hydrogen, and Xenon at pressures from 10-100 mTorr. Plasma resistance is found to vary from 25.8-51.6 mΩ and plasma inductance varies from 41.3--47.0 nH. The greatest amount of initial capacitively stored energy that could be transferred to the plasma was 6.4 J (8.1%) of the initial 79.2 +/- 0.1 J. In the third paper, the effects of a DC preionization source on plasma formation energy is studied. The preionization source radial location is found to have negligible impact on plasma formation repeatability while voltage is found to be critical at low pressures. Without preionization, plasma formation was not possible. At 20 mTorr, 0.20 W of power was sufficient to stabilize plasma formation about the first zero-crossing of the discharge current. Increasing power to 1.49 W increased inductively coupled energy by 39%. At 200 mTorr, 4.3 mW was sufficient to produce repeatable plasma properties.

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

    PubMed

    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.

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

    PubMed

    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.

  4. Bivalirudin versus heparin in primary PCI: clinical outcomes and cost analysis

    PubMed Central

    Deharo, Pierre; Johnson, Thomas W; Rahbi, Hazim; Kandan, Raveen; Bowles, Ruth; Mozid, Abdul; Dorman, Stephen; Strange, Julian W; Baumbach, Andreas

    2018-01-01

    Background The evidence for benefits of bivalirudin over heparin has recently been challenged. We aimed to analyse the safety and cost-effectiveness following reintroduction of heparin instead of bivalirudin as the standard anticoagulation for primary percutaneous coronary intervention (PPCI) in a high-volume centre. Methods and results This analysis was an open-label, prospective registry including all patients admitted to our centre for PPCI from April 2014 to April 2016. Heparin was reintroduced as standard anticoagulant in April 2015. During the 2 years, 1291 patients underwent a PPCI, 662 in the Bivalirudin protocol period (Cohort B) and 629 in the Heparin protocol period (Cohort H). Baseline and procedural characteristics were not significantly different, except for a higher use of thromboaspiration and femoral access in the earlier Cohort B. Glycoprotein 2b3a (Gp2b3a) antagonists were used in 24% of the patients in Cohort B versus 28% in Cohort H (P<0.01). We did not observe any differences in death at 180 days (11.03% in Cohort B vs 11.29% in Cohort H)(HR 95% CI 0.98 (0.72 to 1.33), P=0.88). The incidence of any bleeding complications at 30 days did not differ between the two periods (21.9% vs 21.9%, P=0.99). The cost related to the anticoagulants amounted to £246 236 in Cohort B versus £4483 in Cohort H (£324 406 vs £102 347 when adding Gp2b3a antagonists). Conclusion We did not find clinically relevant changes in patient outcomes, including bleeding complications with reintroduction of heparin in our PPCI protocol. However, the use of heparin was associated with a major reduction in treatment costs. PMID:29765614

  5. Molecular dynamics simulations on networks of heparin and collagen.

    PubMed

    Kulke, Martin; Geist, Norman; Friedrichs, Wenke; Langel, Walter

    2017-06-01

    Synthetic scaffolds containing collagen (Type I) are of increasing interest for bone tissue engineering, especially for highly porous biomaterials in combination with glycosaminoglycans. In experiments the integration of heparin during the fibrillogenesis resulted in different types of collagen fibrils, but models for this aggregation on a molecular scale were only tentative. We conducted molecular dynamic simulations investigating the binding of heparin to collagen and the influence of the telopeptides during collagen aggregation. This aims at explaining experimental findings on a molecular level. Novel structures for N- and C-telopeptides were developed with the TIGER2 replica exchange algorithm and dihedral principle component analysis. We present an extended statistical analysis of the mainly electrostatic interaction between heparin and collagen and identify several binding sites. Finally, we propose a molecular mechanism for the influence of glycosaminoglycans on the morphology of collagen fibrils. Proteins 2017; 85:1119-1130. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  6. Preparation of erosion and deposition investigations on plasma facing components in Wendelstein 7-X

    NASA Astrophysics Data System (ADS)

    Dhard, C. P.; Balden, M.; Braeuer, T.; Brezinsek, S.; Coenen, J. W.; Dudek, A.; Ehrke, G.; Hathiramani, D.; Klose, S.; König, R.; Laux, M.; Linsmeier, Ch; Manhard, A.; Masuzaki, S.; Mayer, M.; Motojima, G.; Naujoks, D.; Neu, R.; Neubauer, O.; Rack, M.; Ruset, C.; Schwarz-Selinger, T.; Pedersen, T. Sunn; Tokitani, M.; Unterberg, B.; Yajima, M.; W7-X Team1, The

    2017-12-01

    In the Wendelstein 7-X stellarator with its twisted magnetic geometry the investigation of plasma wall interaction processes in 3D plasma configurations is an important research subject. For the upcoming operation phase i.e. OP1.2, three different types of material probes have been installed within the plasma vessel for the erosion/deposition investigations in selected areas with largely different expected heat load levels, namely, ≤10 MW m-2 at the test divertor units (TDU), ≤500 kW m-2 at the baffles, heat shields and toroidal closures and ≤100 kW m-2 at the stainless steel wall panels. These include 18 exchangeable target elements at TDU, about 30 000 screw heads at graphite tiles and 44 wafer probes on wall panels, coated with marker layers. The layer thicknesses, surface morphologies and the impurity contents were pre-characterized by different techniques and subjected to various qualification tests. The positions of these probes were fixed based on the strike line locations on the divertor predicted by field line diffusion and EMC3/EIRENE modeling calculations for the OP1.2 plasma configurations and availability of locations on panels in direct view of the plasma. After the first half of the operation phase i.e. OP1.2a the probes will be removed to determine the erosion/deposition pattern by post-mortem analysis and replaced by a new set for the second half of the operation phase, OP1.2b.

  7. Low molecular weight heparin restores antithrombin III activity from hyperglycemia induced alterations.

    PubMed

    Ceriello, A; Marchi, E; Palazzni, E; Quatraro, A; Giugliano, D

    1990-01-01

    Alteration of antithrombin III (ATIII) activity, glycemia level dependent, exists in diabetes mellitus. In this study the ability of a low molecular weight heparin (LMWH) (Fluxum, Alfa-Wassermann S.p.A., Bologna, Italy), as well as unfractioned héparin, to preserve ATIII activity from glucose-induced alterations, both in vitro and in vivo, is reported. The subcutaneous and intravenous LMWH and heparin administration increases basal depressed ATIII activity in diabetic patients. Heparin shows an equivalent effect on both anti-IIa and anti-Xa activity of ATIII, while LMWH is more effective in preserving the anti-Xa activity. Similarity, heparin preserves ATIII activity from hyperglycemia-induced alterations, during hyperglycemic clamp, and LMWH infusion is able to preserve a significant amount of anti-Xa activity from glucose-induced alterations. Since diabetic patients show a high incidence of thrombotic accidents, LMWH appears to be a promising innovation for the prevention of diabetic thrombophylia.

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

    PubMed

    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.

  9. Characterization of plasma-enhanced atomic layer deposition of Al{sub 2}O{sub 3} using dimethylaluminum isopropoxide

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

    Yang, Jialing; Eller, Brianna S.; Nemanich, Robert J.

    2014-03-15

    In this research, Al{sub 2}O{sub 3} films were grown by remote plasma-enhanced atomic layer deposition using a nonpyrophoric precursor, dimethylaluminum isopropoxide (DMAI), and oxygen plasma. After optimization, the growth rate was determined to be ∼1.5 Å/cycle within a growth window of 25–220 °C; the higher growth rate than reported for thermal atomic layer deposition was ascribed to the higher reactivity of the plasma species compared with H{sub 2}O and the adsorption of active oxygen at the surface, which was residual from the oxygen plasma exposure. Both effects enhance DMAI chemisorption and increase the saturation density. In addition, a longer oxygen plasma timemore » was required at room temperature to complete the reaction and decrease the carbon contamination below the detection limit of x-ray photoemission spectroscopy. The properties of the subsequent Al{sub 2}O{sub 3} films were measured for different temperatures. When deposited at 25 °C and 200 °C, the Al{sub 2}O{sub 3} films demonstrated a single Al-O bonding state as measured by x-ray photoemission spectroscopy, a similar band gap of 6.8±0.2 eV as determined by energy loss spectroscopy, a similar index of refraction of 1.62±0.02 as determined by spectroscopic ellipsometry, and uniform growth with a similar surface roughness before and after growth as confirmed by atomic force microscopy. However, the room temperature deposited Al{sub 2}O{sub 3} films had a lower mass density (2.7 g/cm{sup 3} compared with 3.0 g/cm{sup 3}) and a higher atomic ratio of O to Al (2.1 compared with 1.6) as indicated by x-ray reflectivity and Rutherford backscattering spectroscopy, respectively.« less

  10. Necessity of heparin for maintaining peripheral venous catheters: A systematic review and meta-analysis

    PubMed Central

    You, Tao; Jiang, Jianliang; Chen, Jianchang; Xu, Weiting; Xiang, Li; Jiao, Yang

    2017-01-01

    Heparin has typically been used as a flushing or infusion solution for vascular lines in daily practice. However, several clinical trials have yielded controversial results about the benefits of heparin in maintaining peripheral venous catheters. The present meta-analysis was conducted to evaluate the efficacy of heparin on the patency profiles and complications in peripheral intravenous catheters. PubMed, Embase and Cochrane Central Register of Controlled Trials were searched up to February 2016 for randomized controlled trials comparing heparin with placebo in maintaining peripheral intravenous catheters. Additional studies were retrieved from the reference lists of identified articles. In total 32 eligible studies were included, from which the pooled standard mean difference (SMD), relative risk (RR) and corresponding 95% confidence interval (CI) were calculated. The use of heparin as a continuous infusion significantly prolonged the duration of patency (SMD, 0.90; 95% CI, 0.48–1.32; P<0.001), reduced rates of infusion failure (RR, 0.83; 95% CI, 0.76–0.92; P<0.001) and occlusion (RR, 0.82; 95% CI, 0.69–0.98; P<0.05) in a peripheral intravenous catheter. However, there were no significant changes in the duration of patency and infusion failure when heparin was used intermittently as a flushing solution, although a significantly decreased risk of occlusion was observed in this setting (RR, 0.80; 95% CI, 0.66–0.98; P<0.05). Furthermore, the risk of phlebitis was significantly decreased by both continuous infusion (RR, 0.66; 95% CI, 0.58–0.75; P<0.01) and intermittent flushing (RR, 0.70; 95% CI, 0.56–0.86; P<0.01) of heparin in peripheral venous catheters. In conclusion, the use of heparin as continuous infusion in peripheral intravenous catheters improved the duration of patency, reduced infusion failure and phlebitis, whereas heparin as intermittent flushing showed more benefits in ameliorating phlebitis rather than in patency profiles. PMID:28810636

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

    PubMed

    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.

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

    PubMed Central

    Nicholson, Tricia; McGuire, Alistair; Milne, Ruairidh

    2001-01-01

    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. PMID:11701090

  13. Improving Erosion Resistance of Plasma-Sprayed Ceramic Coatings by Elevating the Deposition Temperature Based on the Critical Bonding Temperature

    NASA Astrophysics Data System (ADS)

    Yao, Shu-Wei; Yang, Guan-Jun; Li, Cheng-Xin; Li, Chang-Jiu

    2018-01-01

    Interlamellar bonding within plasma-sprayed coatings is one of the most important factors dominating the properties and performance of coatings. The interface bonding between lamellae significantly influences the erosion behavior of plasma-sprayed ceramic coatings. In this study, TiO2 and Al2O3 coatings with different microstructures were deposited at different deposition temperatures based on the critical bonding temperature concept. The erosion behavior of ceramic coatings was investigated. It was revealed that the coatings prepared at room temperature exhibit a typical lamellar structure with numerous unbonded interfaces, whereas the coatings deposited at the temperature above the critical bonding temperature present a dense structure with well-bonded interfaces. The erosion rate decreases sharply with the improvement of interlamellar bonding when the deposition temperature increases to the critical bonding temperature. In addition, the erosion mechanisms of ceramic coatings were examined. The unbonded interfaces in the conventional coatings act as pre-cracks accelerating the erosion of coatings. Thus, controlling interlamellar bonding formation based on the critical bonding temperature is an effective approach to improve the erosion resistance of plasma-sprayed ceramic coatings.

  14. Thermal and Kerr nonlinear properties of plasma-deposited silicon nitride/ silicon dioxide waveguides.

    PubMed

    Ikeda, Kazuhiro; Saperstein, Robert E; Alic, Nikola; Fainman, Yeshaiahu

    2008-08-18

    We introduce and present experimental evaluations of loss and nonlinear optical response in a waveguide and an optical resonator, both implemented with a silicon nitride/ silicon dioxide material platform prepared by plasma-enhanced chemical vapor deposition with dual frequency reactors that significantly reduce the stress and the consequent loss of the devices. We measure a relatively small loss of approximately 4dB/cm in the waveguides. The fabricated ring resonators in add-drop and all-pass arrangements demonstrate quality factors of Q=12,900 and 35,600. The resonators are used to measure both the thermal and ultrafast Kerr nonlinearities. The measured thermal nonlinearity is larger than expected, which is attributed to slower heat dissipation in the plasma-deposited silicon dioxide film. The n2 for silicon nitride that is unknown in the literature is measured, for the first time, as 2.4 x 10(-15)cm(2)/W, which is 10 times larger than that for silicon dioxide.

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

    PubMed

    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.

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

    PubMed

    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.

  17. Controlled surface diffusion in plasma-enhanced chemical vapor deposition of GaN nanowires.

    PubMed

    Hou, Wen Chi; Hong, Franklin Chau-Nan

    2009-02-04

    This study investigates the growth of GaN nanowires by controlling the surface diffusion of Ga species on sapphire in a plasma-enhanced chemical vapor deposition (CVD) system. Under nitrogen-rich growth conditions, Ga has a tendency to adsorb on the substrate surface diffusing to nanowires to contribute to their growth. The significance of surface diffusion on the growth of nanowires is dependent on the environment of the nanowire on the substrate surface as well as the gas phase species and compositions. Under nitrogen-rich growth conditions, the growth rate is strongly dependent on the surface diffusion of gallium, but the addition of 5% hydrogen in nitrogen plasma instantly diminishes the surface diffusion effect. Gallium desorbs easily from the surface by reaction with hydrogen. On the other hand, under gallium-rich growth conditions, nanowire growth is shown to be dominated by the gas phase deposition, with negligible contribution from surface diffusion. This is the first study reporting the inhibition of surface diffusion effects by hydrogen addition, which can be useful in tailoring the growth and characteristics of nanowires. Without any evidence of direct deposition on the nanowire surface, gallium and nitrogen are shown to dissolve into the catalyst for growing the nanowires at 900 degrees C.

  18. Uniformity and passivation research of Al2O3 film on silicon substrate prepared by plasma-enhanced atom layer deposition.

    PubMed

    Jia, Endong; Zhou, Chunlan; Wang, Wenjing

    2015-01-01

    Plasma-enhanced atom layer deposition (PEALD) can deposit denser films than those prepared by thermal ALD. But the improvement on thickness uniformity and the decrease of defect density of the films deposited by PEALD need further research. A PEALD process from trimethyl-aluminum (TMA) and oxygen plasma was investigated to study the influence of the conditions with different plasma powers and deposition temperatures on uniformity and growth rate. The thickness and refractive index of films were measured by ellipsometry, and the passivation effect of alumina on n-type silicon before and after annealing was measured by microwave photoconductivity decay method. Also, the effects of deposition temperature and annealing temperature on effective minority carrier lifetime were investigated. Capacitance-voltage and conductance-voltage measurements were used to investigate the interface defect density of state (D it) of Al2O3/Si. Finally, Al diffusion P(+) emitter on n-type silicon was passivated by PEALD Al2O3 films. The conclusion is that the condition of lower substrate temperature accelerates the growth of films and that the condition of lower plasma power controls the films' uniformity. The annealing temperature is higher for samples prepared at lower substrate temperature in order to get the better surface passivation effects. Heavier doping concentration of Al increased passivation quality after annealing by the effective minority carrier lifetime up to 100 μs.

  19. RF plasma MOCVD of Y2O3 thin films: Effect of RF self-bias on the substrates during deposition

    NASA Astrophysics Data System (ADS)

    Chopade, S. S.; Barve, S. A.; Thulasi Raman, K. H.; Chand, N.; Deo, M. N.; Biswas, A.; Rai, Sanjay; Lodha, G. S.; Rao, G. M.; Patil, D. S.

    2013-11-01

    Yttrium oxide (Y2O3) thin films have been deposited by radio frequency plasma assisted metal organic chemical vapor deposition (MOCVD) process using (2,2,6,6-tetramethyl-3,5-heptanedionate) yttrium (commonly known as Y(thd)3) precursor in a plasma of argon and oxygen gases at a substrate temperature of 350 °C. The films have been deposited under influence of varying RF self-bias (-50 V to -175 V) on silicon, quartz, stainless steel and tantalum substrates. The deposited coatings are characterized by glancing angle X-ray diffraction (GIXRD), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), spectroscopic ellipsometry and scanning electron microscopy (SEM). GIXRD and FTIR results indicate deposition of Y2O3 (BCC structure) in all cases. However, XPS results indicate nonstoichiometric cubic phase deposition on the surface of deposited films. The degree of nonstoichiometry varies with bias during deposition. Ellipsometry results indicate that the refractive index for the deposited films is varying from 1.70 to 1.83 that is typical for Y2O3. All films are transparent in the investigated wavelength range 300-1200 nm. SEM results indicate that the microstructure of the films is changing with applied bias. Results indicate that it is possible to deposit single phase cubic Y2O3 thin films at low substrate temperature by RF plasma MOCVD process. RF self-bias that decides about the energy of impinging ions on the substrates plays an important role in controlling the texture of deposited Y2O3 films on the substrates. Results indicate that to control the structure of films and its texture, it is important to control the bias on the substrate during deposition. The films deposited at high bias level show degradation in the crystallinity and reduction of thickness.

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

    Wall, Jonathan; Martin, Emily B.; Richey, Tina

    Amyloid is a complex pathologic matrix comprised principally of para-crystalline protein fibrils and heparan sulfate proteoglycans. Systemic amyloidoses are rare (~3500 new cases per year in the US); thus, routine diagnosis is often challenging, and effective treatment options are limited, resulting in high morbidity and mortality rates. Glycosaminoglycans contribute inextricably to the formation of amyloid fibrils and foster the deposition of amyloid in tissues. Those present in amyloid deposits are biochemically and electrochemically distinct from glycosaminoglycans found in the plasma membrane and extracellular matrices of healthy tissues due to the presence of a high degree of heparin-like hypersulfation. We havemore » exploited this unique property and evaluated heparin-reactive peptides, such as p5+14. Herein we show efficacious detection of murine systemic amyloid in vivo by using molecular imaging, and the specific targeting of the peptide to major forms of human amyloid in tissue sections. Furthermore, we have demonstrated that the peptide also binds synthetic amyloid fibrils that lack glycosaminoglycans implying that the dense anionic motif present on heparin is mimicked by the amyloid protein fibril itself. These biochemical and functional data support the translation of radiolabeled peptide p5+14 for the clinical imaging of amyloid in patients; thus, providing a novel technique for prognostication, patient stratification, and monitoring response to therapy.« less