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Sample records for weight heparin dalteparin

  1. In vitro anticoagulation monitoring of low-molecular-weight heparin

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

  2. Characterization of Low-Molecular-Weight Heparins by Strong Anion-Exchange Chromatography.

    Science.gov (United States)

    Sadowski, Radosław; Gadzała-Kopciuch, Renata; Kowalkowski, Tomasz; Widomski, Paweł; Jujeczka, Ludwik; Buszewski, Bogusław

    2017-11-01

    Currently, detailed structural characterization of low-molecular-weight heparin (LMWH) products is an analytical subject of great interest. In this work, we carried out a comprehensive structural analysis of LMWHs and applied a modified pharmacopeial method, as well as methods developed by other researchers, to the analysis of novel biosimilar LMWH products; and, for the first time, compared the qualitative and quantitative composition of commercially available drugs (enoxaparin, nadroparin, and dalteparin). For this purpose, we used strong anion-exchange (SAX) chromatography with spectrophotometric detection because this method is more helpful, easier, and faster than other separation techniques for the detailed disaccharide analysis of new LMWH drugs. In addition, we subjected the obtained results to statistical analysis (factor analysis, t-test, and Newman-Keuls post hoc test).

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

    NARCIS (Netherlands)

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

    1998-01-01

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

  4. Dalteparin versus vitamin K antagonists for the prevention of recurrent venous thromboembolism in patients with cancer and renal impairment: a Canadian pharmacoeconomic analysis

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    Dranitsaris G

    2017-01-01

    Full Text Available George Dranitsaris,1 Lesley G Shane,2 Mark Crowther,3 Guillaume Feugere,4 Seth Woodruff2 1Health Economic and Outcomes Research, Augmentium Pharma Consulting Inc, Toronto, ON, Canada; 2Pfizer Inc, New York, NY, USA; 3McMaster University, Hamilton, ON, 4Pfizer Canada, Montreal, QC, Canada Background: Patients with cancer are at increased risk of venous thromboembolism (VTE and the risk is further elevated after a primary VTE. To reduce the risk of recurrent events, extended prophylaxis with vitamin K antagonists (VKA is available for use. However, in a large randomized trial (Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer [CLOT]; Lee et al, extended duration dalteparin reduced the relative risk of recurrent VTE by 52% compared to VKA (p=0.002. A recent subgroup analysis of patients with moderate-to-severe renal impairment also revealed lower absolute VTE rates with dalteparin (3% vs. 17%; p=0.011. To measure the economic value of dalteparin as an alternative to VKA, a patient-level cost utility analysis was conducted from a Canadian perspective. Methods: Resource use data captured during the CLOT trial were extracted and linked to 2015 Canadian unit cost estimates. Health state utilities were then measured using the Time-Trade-Off technique in 24 randomly selected members of the general Canadian public to estimate the gains in quality-adjusted life years (QALYs. Results: For the entire CLOT trial population (n=676, the dalteparin group had significantly higher mean costs compared to the VKA group ($Can5,771 vs. $Can2,569; p<0.001. However, the utility assessment revealed that 21 of 24 respondents (88% selected dalteparin over VKA, with an associated gain of 0.14 (95% confidence interval [CI]: 0.10–0.18 QALYs. When the incremental cost of dalteparin was combined with the QALY gain, dalteparin had a cost of $Can23,100 (95% CI: $Can19,200

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

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    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

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

    African Journals Online (AJOL)

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

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

    African Journals Online (AJOL)

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

  8. Prophylaxis of postoperative thromboembolism with low molecular weight heparins

    DEFF Research Database (Denmark)

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

    1993-01-01

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

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

    African Journals Online (AJOL)

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

  10. The Effect of Low Molecular Weight Heparins on Fracture Healing.

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

    2015-01-01

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

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

    International Nuclear Information System (INIS)

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

    1987-01-01

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

  12. Intravitreal low molecular weight heparin in PVR surgery.

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    Kumar Atul

    2003-01-01

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

  13. Recent developments in separation of low molecular weight heparin anticoagulants.

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    Sadowski, Radosław; Gadzała-Kopciuch, Renata; Buszewski, Bogusław

    2017-10-05

    The general function of anticoagulants is to prevent blood clotting and growing of the existing clots in blood vessels. In recent years, there has been a significant improvement in developing methods of prevention as well as pharmacologic and surgical treatment of thrombosis. For over the last two decades, low molecular weight heparins (LMWHs) have found their application in the antithrombotic diseases treatment. These types of drugs are widely used in clinical therapy. Despite the biological and medical importance of LMWHs, they have not been completely characterized in terms of their chemical structure. Due to both, the structural complexity of these anticoagulants and the presence of impurities, their structural characterization requires the employment of advanced analytical techniques. Since separation techniques play the key role in these endeavors, this review will focus on the presentation of recent developments in the separation of LMWH anticoagulants. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Obstetric outcome with low molecular weight heparin therapy during pregnancy.

    LENUS (Irish Health Repository)

    Donnelly, J

    2012-01-01

    This was a prospective study of women attending a combined haematology\\/obstetric antenatal clinic in the National Maternity Hospital (2002-2008). Obstetric outcome in mothers treated with low molecular weight heparin (LMWH) was compared to the general obstetric population of 2006. There were 133 pregnancies in 105 women. 85 (63.9%) received prophylactic LMWH and 38 (28.6%) received therapeutic LMWH in pregnancy. 10 (7.5%) received postpartum prophylaxis only. The perinatal mortality rate was 7.6\\/1000 births. 14 (11.3%) women delivered preterm which is significantly higher than the hospital population rate (5.7%, p<0.05). Despite significantly higher labour induction rates (50% vs 29.2% p<0.01), there was no difference in CS rates compared to the general hospital population (15.4% vs 18.9%, NS). If carefully managed, these high-risk women can achieve similar vaginal delivery rates as the general obstetric population.

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

    Science.gov (United States)

    Linkins, Lori-Ann; Warkentin, Theodore E

    2011-09-01

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

  16. Hypoxia and the anticoagulants dalteparin and acetylsalicylic acid affect human placental amino acid transport.

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    Marc-Jens Kleppa

    Full Text Available BACKGROUND: Anticoagulants, e.g. low-molecular weight heparins (LMWHs and acetylsalicylic acid (ASA are prescribed to women at risk for pregnancy complications that are associated with impaired placentation and placental hypoxia. Beyond their role as anticoagulants these compounds exhibit direct effects on trophoblast but their impact on placental function is unknown. The amino acid transport systems A and L, which preferably transfer essential amino acids, are well-described models to study placental nutrient transport. We aimed to examine the effect of hypoxia, LMWHs and ASA on the activity of the placental amino acid transport systems A and L and associated signalling mechanisms. METHODS: The uptake of C14-MeAIB (system A or H3-leucin (system L was investigated after incubation of primary villous fragments isolated from term placentas. Villous tissue was incubated at 2% O2 (hypoxia, 8% O2 and standard culture conditions (21% O2 or at 2% O2 and 21% O2 with dalteparin or ASA. Activation of the JAK/STAT or mTOR signalling pathways was determined by Western analysis of total and phosphorylated STAT3 or Raptor. RESULTS: Hypoxia decreased system A mediated MeAIB uptake and increased system L mediated leucine uptake compared to standard culture conditions (21% O2. This was accompanied by an impairment of STAT3 and a stimulation of Raptor signalling. System L activity increased at 8% O2. Dalteparin treatment reduced system A and system L activity under normoxic conditions and ASA (1 mM decreased system A and L transporter activity under normoxic and hypoxic conditions. CONCLUSIONS: Our data underline the dependency of placental function on oxygen supply. LMWHs and ASA are not able to reverse the effects of hypoxia on placental amino acid transport. These findings and the uncovering of the signalling mechanisms in more detail will help to understand the impact of LMWHs and ASA on placental function and fetal growth.

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

    NARCIS (Netherlands)

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

    1999-01-01

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

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

    Science.gov (United States)

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

    1998-09-10

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

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

    NARCIS (Netherlands)

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

    2002-01-01

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

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

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    Henning Hagmann

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

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    Giuseppe Camporese

    2009-09-01

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

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

    Science.gov (United States)

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

    2013-11-01

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

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

    Science.gov (United States)

    O'Connell, Casey L; Liebman, Howard A

    2008-12-01

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

  5. Determination of the Molecular Weight of Low-Molecular-Weight Heparins by Using High-Pressure Size Exclusion Chromatography on Line with a Triple Detector Array and Conventional Methods

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    Antonella Bisio

    2015-03-01

    Full Text Available The evaluation of weight average molecular weight (Mw and molecular weight distribution represents one of the most controversial aspects concerning the characterization of low molecular weight heparins (LMWHs. As the most commonly used method for the measurement of such parameters is high performance size exclusion chromatography (HP-SEC, the soundness of results mainly depends on the appropriate calibration of the chromatographic columns used. With the aim of meeting the requirement of proper Mw standards for LMWHs, in the present work the determination of molecular weight parameters (Mw and Mn by HP-SEC combined with a triple detector array (TDA was performed. The HP-SEC/TDA technique permits the evaluation of polymeric samples by exploiting the combined and simultaneous action of three on-line detectors: light scattering detectors (LALLS/RALLS; refractometer and viscometer. Three commercial LMWH samples, enoxaparin, tinzaparin and dalteparin, a γ-ray depolymerized heparin (γ-Hep and its chromatographic fractions, and a synthetic pentasaccharide were analysed by HP-SEC/TDA. The same samples were analysed also with a conventional HP-SEC method employing refractive index (RI and UV detectors and two different chromatographic column set, silica gel and polymeric gel columns. In both chromatographic systems, two different calibration curves were built up by using (i γ-Hep chromatographic fractions and the corresponding Mw parameters obtained via HP-SEC/TDA; (ii the whole γ-Hep preparation with broad Mw dispersion and the corresponding cumulative distribution function calculated via HP-SEC/TDA. In addition, also a chromatographic column calibration according to European Pharmacopoeia indication was built up. By comparing all the obtained results, some important differences among Mw and size distribution values of the three LMWHs were found with the five different calibration methods and with HP-SEC/TDA method. In particular, the detection of

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

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    Sabrina Bertini

    2017-07-01

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

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

    Science.gov (United States)

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

    2017-07-19

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

  8. Low-molecular-weight heparin in the treatment of patients with venous thromboembolism

    NARCIS (Netherlands)

    tenCate, JW; Buller, HR; Gent, M; Hirsh, J; Prins, MH; Baildon, R; Lensing, AWA; Anderson, DR; vanBeek, EJR; Fiesinger, JN; Tijssen, JGP; vanBarneveld, A; Eimers, LT; Graafsma, YP; Hettiarachchi, R; Hutten, B; Redekop, K; Haley, S; LIberale, L; Finch, T; Whittaker, S; Wilkinson, L; Prandoni, P; Villalta, S; Girolami, B; Bagatella, P; Rossi, L; Girolami, A; Piovella, F; Barone, M; Beltrametti, C; Serafini, S; Siragusa, S; Ascari, E; Kovacs, MJ; Morrow, B; Kovacs, J; Kuijer, PMM; Koopman, MMW; Jagt, H; Weitz, J; Kearon, C; Biagioni, L; Haas, S; Lossner, F; Spengel, FA; Berger, M; Demers, C; Poulin, J; vanderMeer, J; Que, GTH; Smid, WM; Robinson, KS; Boyle, E; Leclerc, [No Value; StJacques, B; Finkenbine, S; Gallus, AS; Cohlan, D; Rich, C; Brandjes, DPM; Hoefnagel, CA; deRijk, M; Turkstra, F; Desjardins, L; CoteDesjardins, J; Couture, L; Ruel, M; Villenueve, J; Geerts, WH; Jay, RM; Code, EKI; Turpie, AGG; Johnson, J; Nguyen, P; Cusson, [No Value; Roy, S; Wells, PS; Bormanis, J; Goudie, D; Cruickshank, M; vonLewinski, M; Monreal, M; Sahuquillo, JC; Lafoz, E; Simonneau, G; Parent, F; Jagot, J; Douketis, JD; Kinnon, K; Ginsberg, JS; BrillEdwards, P; Donovan, D; Ockelford, PA; Kassis, J; Bornais, S; Planchon, B; ElKouri, D; Pistorius, MA; Escribano, M; Garrido, G; Chesterman, CN; Chong, BH; Pritchard, S; Cade, JF; Bynon, T; Stanford, J; Brien, WM; Palmer, B; Faivre, R; Petiteau, B; Manucci, PM; Moia, M; Bucciarelli, P

    1997-01-01

    Background Low-molecular-weight heparin is known to be safe and effective for the initial Treatment of patients with proximal deep-vein thrombosis. However, its application to patients with pulmonary embolism or previous episodes of thromboembolism has not been studied. Methods We randomly assigned

  9. Venous thromboembolism in pregnancy: prophylaxis and treatment with low molecular weight heparin

    DEFF Research Database (Denmark)

    Andersen, Anita Sylvest; Berthelsen, Jørgen G; Bergholt, Thomas

    2010-01-01

    OBJECTIVE: To evaluate the safety of individually dosed low molecular weight heparin (LMWH) for prophylaxis and treatment of thromboembolic complications in pregnancy. DESIGN: Cohort study with a chronologic register-based control group. SETTING: Department of Obstetrics and Gynecology, Hillerød ...

  10. Venous thromboembolism in pregnancy: prophylaxis and treatment with low molecular weight heparin

    DEFF Research Database (Denmark)

    Andersen, Anita Sylvest; Berthelsen, Jørgen G.; Bergholt, Thomas

    2010-01-01

    OBJECTIVE: To evaluate the safety of individually dosed low molecular weight heparin (LMWH) for prophylaxis and treatment of thromboembolic complications in pregnancy. DESIGN: Cohort study with a chronologic register-based control group. SETTING: Department of Obstetrics and Gynecology, Hillerød...

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

    NARCIS (Netherlands)

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

    2000-01-01

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

  12. Bilateral rectal sheath hematomas after low-molecular weight heparin treatment in uremia.

    Science.gov (United States)

    Xu, Lu; Liu, Lei; Li, Xinjian

    2017-11-01

    Rectus sheath hematomas (RSHs) are uncommon. They are usually unilateral and rarely bilateral. In this paper, we report the first case of spontaneous bilateral RSHs in a uremic patient after the administration of the first dose of low-molecular weight heparin during hemodialysis. The most interesting aspect of this case is that the main symptom of RSH in our patient was urinary bladder irritation. We highlight the importance of the prompt diagnosis and management of this medical emergency.

  13. LOW-MOLECULAR-WEIGHT HEPARIN TREATMENT FAILURE IN PREVENTION OF PROSTHETIC MITRAL VALVE THROMBOSIS

    OpenAIRE

    David Šuran; Vojko Kanič; Tatjana Golob Gulič; Husam Franjo Naji; Robert Lipovec

    2009-01-01

    Background Prosthetic heart valve thrombosis (PHVT) represents a dangerous postoperative complication following prosthetic heart valve replacement. Incidence varies according to different data from 0.5–4 % per year following mitral or aortic valve replacement in spite of adequate oral anticoagulation with coumarins. Case report We are presenting a case of prosthetic mitral valve thrombosis as a result of 6-month lowmolecular-weight heparin (LMWH) (nadroparine) treatment failure. Our pat...

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

    Science.gov (United States)

    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

  15. Low molecular weight heparins in the prevention of deep-vein thrombosis in general surgery.

    Science.gov (United States)

    Breddin, H K

    1999-01-01

    Unfractionated heparin (UFH) was the established treatment in the early 1980s for the prophylaxis of venous thromboembolic disease (VTED) in patients undergoing general surgery. This was one of the earliest indications in which low molecular weight heparins (LMWHs) were tested, and about 40 trials have revealed that these agents are at least as effective and safe as UFH with a tendency of superiority when higher dosages are used. In most trials, the fibrinogen uptake test has been used to assess the frequency of deep vein thrombosis. LMWHs exhibit a number of improved features over UFH, including ease of administration and convenient once daily dosing, facilitating outpatient management. A still open question is the ideal time and dose of the first one or two injections of a LMWH. To determine the clinical relevance of product differentiation further, clinical trials, directly comparing different LMWHs, are required.

  16. Mapping of low molecular weight heparins using reversed phase ion pair liquid chromatography-mass spectrometry.

    Science.gov (United States)

    Li, Daoyuan; Chi, Lequan; Jin, Lan; Xu, Xiaohui; Du, Xuzhao; Ji, Shengli; Chi, Lianli

    2014-01-01

    Low molecular weight heparins (LMWHs) are structurally complex, highly sulfated and negatively charged, linear carbohydrate polymers prepared by chemical or enzymatic depolymerization of heparin. They are widely used as anticoagulant drugs possessing better bioavailability, longer half-life, and lower side effects than heparin. Comprehensive structure characterization of LMWHs is important for drug quality assurance, generic drug application, and new drug research and development. However, fully characterization of all oligosaccharide chains in LMWHs is not feasible for current available analytical technologies due to their structure complexity and heterogeneity. Fingerprinting profiling is an efficient way for LMWHs' characterization and comparison. In this work, we present a simple, sensitive, and powerful analytical approach for structural characterization of LMWHs. Two different LMWHs, enoxaparin and nadroparin, were analyzed using reversed phase ion pair electrospray ionization mass spectrometry (RPIP-ESI-MS). More than 200 components were identified, including major structures, minor structures, and process related impurities. This approach is robust for high resolution and complementary fingerprinting analysis of LMWHs. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2017-11-03

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

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

    Science.gov (United States)

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

    2016-06-01

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

  19. Use of low molecular weight Heparin for Hemodialysis: A short term study

    International Nuclear Information System (INIS)

    Al-Arrayed, S.; Seshadri, R.

    2002-01-01

    Although unfractionated heparin (UFH) is the anticoagulant commonly usedfor Hemodialysis (HD), low molecular weight heparin (LMWH) has been found tobe equally efficacious. The aim of this study was to explore the safety andefficacy of a single bolus dose of the LMWH, enoxaparin. Thirty-eightpatients on maintenance HD were randomly divided into two equal groups. Themean age and body-weight of the two were comparable. While one group received1 mg/kg body-weight (the manufacturer's recommended dose) of enoxaparin forthree dialysis sessions of three-hour duration each, the either groupreceived a fixed dose of 40 mg for the same number of dialysis. For the nextthree dialysis sessions, these doses were exchanged between the groups. Inall, total of 228 HD sessions were monitored for clotting of bloodlines/dialyzers and bleeding from vascular access and other sites. The rateof complications was compared with the historical data while UFH was beingused for the same patients. In general, enoxapirin was associated with fewerepisodes of bleeding and clotting. Our study confirms that LMWH is ofcomparable efficacy to UFH and probably a lesser than recommended dose isadequate for three-hour HD session. (author)

  20. Analysis of sulfates on low molecular weight heparin using mass spectrometry: structural characterization of enoxaparin.

    Science.gov (United States)

    Gupta, Rohitesh; Ponnusamy, Moorthy P

    2018-05-21

    Structural characterization of Low Molecular Weight Heparin (LMWH) is critical to meet biosimilarity standards. In this context, the review focuses on structural analysis of labile sulfates attached to the side-groups of LMWH using mass spectrometry. A comprehensive review of this topic will help readers to identify key strategies for tackling the problem related to sulfate loss. At the same time, various mass spectrometry techniques are presented to facilitate compositional analysis of LMWH, mainly Enoxaparin. Areas covered: This review summarizes findings on mass spectrometry application for LMWH, including modulation of sulfates, using enzymology and sample preparation approaches. Furthermore, popular open-source software packages for automated spectral data interpretation are also discussed. Successful use of LC/MS can decipher structural composition for LMWH and help evaluate their sameness or biosimilarity with the innovator molecule. Overall, the literature has been searched using PubMed by typing various search queries such as "enoxaparin", "mass spectrometry", "low molecular weight heparin", "structural characterization", etc. Expert commentary: This section highlights clinically relevant areas that need improvement to achieve satisfactory commercialization of LMWHs. It also primarily emphasizes the advancements in instrumentation related to mass spectrometry, and discusses building automated software for data interpretation and analysis.

  1. Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery

    DEFF Research Database (Denmark)

    Rasmussen, Morten Schnack; Jørgensen, Lars Nannestad; Wille-Jørgensen, Peer

    2009-01-01

    BACKGROUND: Major abdominal and pelvic surgery carries a high risk of venous thromboembolism (VTE). The efficacy of thromboprophylaxis with low-molecular weight heparin (LMWH) administered during the in-hospital period is well documented, but the optimal duration of thromboprophylaxis after surgery...... evaluating prolonged thromboprophylaxis with LMWH as compared to control or placebo. 133 studies were found in the searches, of which only 4 were found eligible for inclusion, and 129 were excluded. The incidence of overall VTE after major abdominal or pelvic surgery was 14.3% (95% confidence interval 11...... significant reduction of even the incidence of symptomatic VTE from 1.7% (95% CI 0.8% - 3.4%) in the control group to 0.2 % (95% CI 0.0% - 1.2%) in patients receiving prolonged thromboprophylaxis, Peto Odds ratio 0.22 (95% CI 0.06 -0.80), P = 0.02. The respective incidence of bleeding in the control and LMWH...

  2. Spontaneous Hemocholecyst in an End-Stage Renal Failure Patient on Low Molecular Weight Heparin Hemodialysis

    Directory of Open Access Journals (Sweden)

    Konstantinos Blouhos

    2012-01-01

    Full Text Available The present paper describes a case of spontaneous hemocholecyst in a patient with end-stage renal failure on low molecular weight heparin hemodialysis. The patient presented with acute right upper quadrant pain. An initial ultrasound scan demonstrated a distended gallbladder containing echogenic bile without stones. During hospitalization the patient became febrile, and jaundiced, developed leukocytosis, and had an elevation in serum bilirubin, transaminases, and alkaline phosphatase. A new ultrasound demonstrated a thick-walled gallbladder containing echogenic bile and pericholecystic fluid. MRI depicted a distended gallbladder containing material of mixed signal intensity and a normal biliary tract. Open cholecystectomy revealed a gallbladder filled with blood and clots, and transcystic common bile duct exploration flushed blood clots out of the bile duct. To our knowledge this is the second case of spontaneous hemocholecyst reported in the literature as a consequence of uremic bleeding and LMWH hemodialysis in the absence of other pathology.

  3. Low molecular weight heparin for prevention of venous thromboembolism in patients with lower-leg immobilization.

    Science.gov (United States)

    Testroote, Mark; Stigter, Willem A H; Janssen, Loes; Janzing, Heinrich M J

    2014-04-25

    Immobilization of the lower leg is associated with venous thromboembolism (VTE). Low molecular weight heparin (LMWH) is an anticoagulant treatment which might be used in adult patients with lower-leg immobilization to prevent deep venous thrombosis (DVT) and its complications. This is an update of the review first published in 2008. To assess the effectiveness of low molecular weight heparin for the prevention of venous thromboembolism in patients with lower-leg immobilization in an ambulant setting. For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched June 2013) and CENTRAL (2013, Issue 5). Randomized controlled trials (RCTs) and controlled clinical trials (CCTs) that described thromboprophylaxis by means of LMWH compared with no prophylaxis or placebo in adult patients with lower-leg immobilization. Immobilization was by means of a plaster cast or brace. Two authors independently assessed trial quality and extracted data. The review authors contacted the trial authors for additional information if required. Statistical analysis was carried out using Review Manager (RevMan 5). We included six RCTs fulfilling the above criteria with a total of 1490 patients. We found an incidence of VTE ranging from 4.3% to 40% in patients who had a leg injury that had been immobilized in a plaster cast or a brace for at least one week and who received no prophylaxis, or placebo. This number was significantly lower in patients who received daily subcutaneous injections of LMWH during immobilization (event rates ranging from 0% to 37%; odds ratio (OR) 0.49; fixed 95% confidence interval (CI) 0.34 to 0.72; with minimal evidence of heterogeneity with an I(2) of 20%, P = 0. 29). Comparable results were seen in the following subcategories: operated patients, conservatively treated patients, patients with fractures, patients with soft-tissue injuries, patients with proximal thrombosis, patients with

  4. Comparison of the effect of dabigatran and dalteparin on thrombus stability in a murine model of venous thromboembolism.

    Science.gov (United States)

    Shaya, S A; Saldanha, L J; Vaezzadeh, N; Zhou, J; Ni, R; Gross, P L

    2016-01-01

    ESSENTIALS: Does thrombus stability alter the presentation of venous thromboembolism and do anticoagulants alter this? In a murine model, we imaged a femoral vein thrombus and quantified emboli in the pulmonary arteries. Dabigatran decreases thrombus stability via factor XIII increasing embolization and pulmonary emboli. This cautions against the unapproved use of dabigatran for acute initial treatment of deep vein thrombosis. Venous thromboembolism (VTE) is a collective term for deep vein thrombosis (DVT) and pulmonary embolism (PE). Thrombus instability possibly contributes to progression of DVT to PE, and direct thrombin inhibitors (DTIs) may alter this. To develop a model to assess thrombus stability and its link to PE burden, and identify whether DTIs, in contrast to low-molecular-weight heparin (LMWH), alter this correlation. Twelve minutes after ferric chloride-induced thrombus formation in the femoral vein of female mice, saline, dalteparin (LMWH) or dabigatran (DTI) was administered. Thrombus size and embolic events breaking off from the thrombus were quantified before treatment and at 10-min intervals after treatment for 2 h using intravital videomicroscopy. Lungs were stained for the presence of PE. Thrombus size was similar over time and between treatment groups. Total and large embolic events and pulmonary emboli were highest after treatment with dabigatran. Variations in amounts of pulmonary embolic events were not attributed to variations in thrombus size. Large embolic events correlated with the number of emboli per lung slice independent of treatment. Embolization in factor XIII deficient (FXIII(-/-) ) saline-treated mice was greater than that in wild-type (WT) saline-treated mice, but was similar to WT dabigatran-treated mice. We have developed a mouse model of VTE that can quantify emboli and correlate this with PE burden. Consistent with clinical data, dabigatran, a DTI, acutely decreases thrombus stability and increases PE burden compared with

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

    Science.gov (United States)

    Kast, Constantia E; Guggi, Davide; Langoth, Nina; Bernkop-Schnürch, Andreas

    2003-06-01

    It was the purpose of this study to develop a new oral drug delivery system for low molecular weight heparin (LMWH) providing an improved bioavailability and a prolonged therapeutic effect. The permeation enhancing polycarbophil-cysteine conjugate (PCP-Cys) used in this study displayed 111.4 +/- 6.4 microM thiol groups per gram polymer. Permeation studies on freshly excised intestinal mucosa were performed in Ussing chambers demonstrating a 2-fold improved uptake of heparin as a result of the addition of 0.5% (w/v) PCP-Cys and the permeation mediator glutathione (GSH). Tablets containing PCP-Cys, GSH, and 279 IU of LMWH showed a sustained drug release over 4 h. To guarantee the swelling of the polymeric carrier matrix in the small intestine tablets were enteric coated. They were orally given to rats. For tablets being based on the thiomer/GSH system an absolute bioavailability of 19.9 +/- 9.3% (means +/- SD; n = 5) vs. intravenous injection could be achieved. whereas tablets comprising unmodified PCP did not lead to a significant (p < 0.01) heparin concentration in plasma. The permeation enhancing effect and subsequently a therapeutic heparin level was maintained for 24 h after a single dose. Because of the strong and prolonged lasting permeation enhancing effect of the thiomer/GSH system, the oral bioavailability of LMWH could be significantly improved. This new delivery system represents therefore a promising tool for the oral administration of heparin.

  6. Efficacy and safety of once daily low molecular weight heparin (tinzaparin sodium) in high risk pregnancy.

    LENUS (Irish Health Repository)

    Ní Ainle, Fionnuala

    2008-10-01

    Low molecular weight heparin (LMWH) is widely regarded as the anticoagulant treatment of choice for the prevention and treatment of venous thromboembolism during pregnancy. However, previous studies have demonstrated that the pharmacokinetic profiles of LMWH vary significantly with increasing gestation. Consequently, it remains unclear whether LMWH regimens recommended for use in nonpregnant individuals can be safely extrapolated to pregnant women. The aims of this study were to assess the safety and the efficacy of tinzaparin sodium (Innohep) administered only once daily during pregnancy. A systematic retrospective review identified a cohort of 37 high-risk pregnancies which had been managed using tinzaparin 175 IU\\/kg once daily. In 26 cases, the index pregnancy had been complicated by development of an acute venous thromboembolism (17 deep vein thrombosis and nine pulmonary embolism). For each individual, case notes were examined and data extracted using a predetermined questionnaire. No episodes of recurrent venous thromboembolism were identified amongst this cohort of pregnancies managed using once daily LMWH administration. However, two unusual thrombotic complications were observed, including a parietal infarct in one patient, and a postpartum cerebral venous thrombosis in another. Once daily tinzaparin was well tolerated, with no cases of heparin-induced thrombocytopaenia, symptomatic osteoporosis, or foetal malformations. Tinzaparin dose modification based upon peak anti-Xa levels occurred in 45% of the cases examined. The present study is the largest study to have examined the clinical efficacy of once daily LMWH for use in pregnant women at high risk of venous thromboembolism. Our data support the safety and efficacy of antenatal tinzaparin at a dose of 175 IU\\/kg. In order to determine whether this once daily regimen provides equivalent (or indeed greater) thromboprophylaxis to twice daily LMWH regimens during pregnancy will require highly powered

  7. [Impact of low-molecular-weight heparin practice guidelines in a geriatric hospital].

    Science.gov (United States)

    d'Arailh, Lydie; Gaubert-Dahan, Marie-Line; Muller, Florence; Lechowski, Laurent; Teillet, Laurent

    2011-06-01

    The purpose of this study was to assess the impact of good use of anticoagulants guidelines implementation on low molecular weight heparin (LMWH) prescription in a french geriatric hospital. This interventional "before and after" study was conduced by the same geriatrician on a d-day in 2006 and 2009. Guidelines for anticoagulant's prescription based on selected references in the literature was established by an expert's consensus and implemented in 2008. Data were collected in all departments at the Sainte-Perine geriatric hospital for each patient with an LMWH prescription. Assessment was based on quality judgment criteria (indication, dosage, treatment duration, biological monitoring of LMWH). Data were collected for 72 prescriptions prior to the guidelines implementation and for 54 after. Sex-ratio, mean age and percentage of LMWH prescription did not differ significantly between the two periods. There was a better conformity for LMWH dosage prescription (p = 0.002) and biological monitoring prescription (p = 0.036) after the guidelines implementation. Conformity of LMWH indication and treatment duration were improved but the difference remained not significant (respectively p = 0.49 and p = 0.80). Implementing guidelines for LMWH use in geriatrics can improve quality of prescription. The impact was effective but limited. These guidelines are now in general use in the Sainte-Perine hospital.

  8. Effect of low molecular weight heparin in combined with Shuxuetong in preventing the post-traumatic deep venous thrombosis

    Directory of Open Access Journals (Sweden)

    Li-Mian Xu

    2016-05-01

    Full Text Available Objective: To observe the effect of low molecular weight heparin in combined with Shuxuetong in preventing the post-traumatic deep venous thrombosis (DVT. Methods: A total of 120 patients with post-traumatic DVT who were admitted in our hospital from February, 2014 to February, 2015 were included in the study and divided into the treatment group and the control group with 60 cases in each group according to different treatment protocols. The patients in the treatment group were given subcutaneous injection of low molecular weight heparin calcium and intravenous drip of Shuxuetong, while the patients in the control group were only given subcutaneous injection of low molecular weight heparin calcium. The changes of swelling degrees and coagulation indicators of the affected limb before and after treatment, and the clinical efficacy in the two groups were compared. Results: The total effective rate in the treatment group was significantly higher than that in the control group. The mean range of the perimeter 15cm above and below the bilateral knee joints after treatment in the treatment group was significantly lower than that in the control group. The shrinking rate of the mean range of the perimeter of the bilateral limbs in the treatment group was significantly higher than that in the control group. The comparison of PT, APTT, FIB, and INR before treatment between the two groups was not statistically significant. PT, APTT, and INR after treatment in the treatment group were significantly higher than those in the control group, while FIB was significantly lower than that in the control group. Conclusions: The low molecular weight heparin in combined with Shuxuetong can effectively prevent the post-traumatic DVT, with no requirement of monitoring of the bleeding tendency and safety.

  9. Low molecular weight heparin for prevention of venous thromboembolism in patients with lower-limb immobilization.

    Science.gov (United States)

    Zee, Aniek Ag; van Lieshout, Kelly; van der Heide, Maaike; Janssen, Loes; Janzing, Heinrich Mj

    2017-08-06

    Immobilization of the lower limb is a risk factor for venous thromboembolism (VTE). Low molecular weight heparins (LMWHs) are anticoagulants, which might be used in adult patients with lower-limb immobilization to prevent deep venous thrombosis (DVT) and its complications. This is an update of the review first published in 2008. To assess the effectiveness of low molecular weight heparin for the prevention of venous thromboembolism in patients with lower-limb immobilization in an ambulatory setting. For this update, the Cochrane Vascular Information Specialist searched the Specialised Register, CENTRAL, and three trials registers (April 2017). Randomized controlled trials (RCTs) and controlled clinical trials (CCTs) that described thromboprophylaxis by means of LMWH compared with no prophylaxis or placebo in adult patients with lower-limb immobilization. Immobilization was by means of a plaster cast or brace. Two review authors independently selected trials, assessed risk of bias and extracted data. The review authors contacted the trial authors for additional information if required. Statistical analysis was carried out using Review Manager 5. We included eight RCTs that fulfilled our criteria, with a total of 3680 participants. The quality of evidence, according GRADE, varied by outcome and ranged from low to moderate. We found an incidence of DVT ranging from 4.3% to 40% in patients who had a leg injury that had been immobilized in a plaster cast or a brace for at least one week, and who received no prophylaxis, or placebo. This number was significantly lower in patients who received daily subcutaneous injections of LMWH during immobilization, with event rates ranging from 0% to 37% (odds ratio (OR) 0.45, 95% confidence interval (CI) 0.33 to 0.61; with minimal evidence of heterogeneity: I² = 26%, P = 0.23; seven studies; 1676 participants, moderate-quality evidence). Comparable results were seen in the following groups of participants: patients with below

  10. Effect of low molecular weight heparin (enoxaparin) on congenital cataract surgery.

    Science.gov (United States)

    Caça, Ihsan; Sahin, Alparslan; Cingü, Abdullah Kürsat; Ari, Seyhmus; Alakuş, Fuat; Cinar, Yasin

    2012-01-01

    To assess the efficacy of intracameral enoxaparin (a low-molecular-weight heparin) infusion, in variable doses on postoperative inflammatory response in congenital cataract surgery. It is a prospective, randomized controlled trial. Eighty eyes of 53 children with congenital cataract were enrolled in this study. Every eye had primary posterior capsulorrhexis and intraocular lens (IOL) implantation after lens aspiration. The eyes were divided into 4 equal groups. In group 1 balanced salt solution (BSS) without enoxaparin was used as an irrigation solution. Whereas in group 2, 3 and 4, 40mg, 20mg and 10mg enoxaparin in 500mL BSS was used respectively. The inflammatory response in the anterior chamber was compared among the groups with slit-lamp biomicroscopy. The mean follow-up period was (17.75±3.95) months in group 1, (18.00±5.15) months in group 2, (19.20±5.47) months in group 3 and (18.65±5.16) months in group 4. Mean number of inflammatory cells in the anterior chamber in group 1 was significantly higher than that of group 2, 3, 4 (P0.05). There were IOL precipitates in 4 eyes of group 1 and 2 eyes of group 4. IOL precipitate formation was significantly higher in group 1 than that of group 2 and 3 in which there was no IOL precipitate (P=0.048). There was IOL subluxation in only one eye of group 1, 3 and 4 while no subluxation was observed in group 2 (P>0.05). There was no statistically significant difference detected about IOL subluxation occurance in all 4 groups (P>0.05). Complications of cataract surgery in congenital cataract patients associated with postoperative inflammatory response found to be decreased with the use of enoxaparin in intraocular infusion solutions. Furthermore according to our results the anti-inflammatory effect of enoxaparin was dose dependant.

  11. Low Molecular Weight Heparin Improves Endothelial Function in Pregnant Women at High Risk of Preeclampsia.

    Science.gov (United States)

    McLaughlin, Kelsey; Baczyk, Dora; Potts, Audrey; Hladunewich, Michelle; Parker, John D; Kingdom, John C P

    2017-01-01

    Low molecular weight heparin (LMWH) has been investigated for the prevention of severe preeclampsia, although the mechanisms of action are unknown. The objective of this study was to investigate the cardiovascular effects of LMWH in pregnant women at high risk of preeclampsia. Pregnant women at high risk of preeclampsia (n=25) and low-risk pregnant controls (n=20) at 22 to 26 weeks' gestation underwent baseline cardiovascular assessments. High-risk women were then randomized to LMWH or saline placebo (30 mg IV bolus and 1 mg/kg subcutaneous dose). Cardiovascular function was assessed 1 and 3 hours post randomization. The in vitro endothelial effects of patient serum and exogenous LMWH on human umbilical venous endothelial cells were determined. High-risk women demonstrated a reduced cardiac output, high resistance hemodynamic profile with impaired radial artery flow-mediated dilation compared with controls. LMWH increased flow-mediated dilation in high-risk women 3 hours after randomization compared with baseline and increased plasma levels of placental growth factor, soluble fms-like tyrosine kinase-1, and myeloperoxidase. Serum from high-risk women impaired endothelial cell angiogenesis and increased PlGF-1 and PlGF-2 transcription compared with serum from low-risk controls. Coexposure of high-risk serum with LMWH improved the in vitro angiogenic response such that it was equivalent to that of low-risk serum and promoted placental growth factor secretion. LMWH improves maternal endothelial function in pregnant women at high risk of developing preeclampsia, possibly mediated through increased placental growth factor bioavailability. © 2016 American Heart Association, Inc.

  12. Aspirin and low-molecular weight heparin combination therapy effectively prevents recurrent miscarriage in hyperhomocysteinemic women.

    Directory of Open Access Journals (Sweden)

    Pratip Chakraborty

    Full Text Available The management of recurrent pregnancy loss (RPL still remains a great challenge, and women with polycystic ovarian syndrome (PCOS are at a greater risk for spontaneous abortion. Treatment with low-molecular-weight heparin (LMWH has become an accepted treatment option for women with RPL; however, the subgroup of women, who are likely to respond to LMWH, has not been precisely identified. The present study evaluated the efficacy of LMWH with reference to PCOS and associated metabolic phenotypes including hyperhomocysteinemia (HHcy, insulin resistance (IR and obesity. This prospective observational study was conducted at Institute of Reproductive Medicine, Kolkata, India. A total of 967 women with history of 2 or more consecutive first trimester abortions were screened and 336 were selected for the study. The selected patients were initially divided on the basis of presence or absence of PCOS, while subsequent stratification was based on HHcy, IR and/or obesity. The subjects had treatment with aspirin during one conception cycle and aspirin-LMWH combined anticoagulant therapy for the immediate next conception cycle, if the first treated cycle was unsuccessful. Pregnancy salvage was the sole outcome measure. The overall rate of pregnancy salvage following aspirin therapy was 43.15%, which was mostly represented by normohomocysteinemic women, while the salvage rate was lower in the HHcy populations irrespective of the presence or absence of PCOS, IR, or obesity. By contrast, aspirin-LMWH combined therapy could rescue 66.84% pregnancies in the aspirin-failed cases. Logistic regression analyses showed that HHcy remained a significant factor in predicting salvage rates in the PCOS, IR, and obese subpopulations controlled for other confounding factors. With regard to pregnancy salvage, combined anticoagulant therapy with aspirin and LMWH conferred added benefit to those with HHcy phenotype.

  13. The safety of low molecular-weight heparin after blunt liver and spleen injuries.

    Science.gov (United States)

    Rostas, Jack W; Manley, Justin; Gonzalez, Richard P; Brevard, Sidney B; Ahmed, Naveed; Frotan, Mohammad Amin; Mitchell, Ellen; Simmons, Jon D

    2015-07-01

    Anticoagulation is routinely administered to all trauma patients owing to the high incidence of venous thromboembolism (VTE). However, the timing of administration of anticoagulation is not clearly defined when patients have blunt spleen or liver injuries because of the perceived risk of hemorrhage with early administration. A retrospective chart review was performed of all blunt trauma patients who sustained blunt liver and/or spleen injuries during the 5-year period from 2007 to 2011. Data were collected for all patients managed with nonoperative therapy for these injuries while also receiving routine prophylactic anticoagulation with low molecular-weight heparin. Patients were categorized based on the initiation of enoxaparin therapy after injury: early (72 hours). Primary and secondary outcomes were designated as need for operative or radiologic intervention secondary to spleen or liver hemorrhage, number of transfusions, and incidence of VTE. Three hundred and twenty-eight patients were included. There were no enoxaparin-related hemorrhagic complications or hemorrhage necessitating operative intervention. Patients in the early, intermediate, and late groups received an average of .9, .93, and 1.55 units of blood, respectively. There was 1 pulmonary embolism in the early group, and there were 6 VTE complications in the late group (3 deep venous thromboses and 3 pulmonary embolisms). There are currently no standards for the initiation of prophylactic anticoagulation in trauma patients with blunt liver and spleen injuries. Early administration may be safe and reduce the incidence of thrombotic complications in patients with blunt spleen and liver injuries. Prospective studies in this area are warranted. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Effect of adjuvant low-molecular-weight heparin therapy on placental hypoxia and cell apoptosis in puerperae with severe preeclampsia

    Directory of Open Access Journals (Sweden)

    Miao Zhou1

    2017-04-01

    Full Text Available Objective: To study the effect of adjuvant low-molecular-weight heparin therapy on placental hypoxia and cell apoptosis in puerperae with severe preeclampsia. Methods: A total of 94 puerperae with severe preeclampsia who received treatment and safely gave birth in our hospital between May 2014 and May 2016 were selected as the research subjects and randomly divided into the LMWH group who received low-molecular-weight heparin combined with conventional symptomatic treatment and the control group who received conventional symptomatic treatment. Before and after treatment, serum was collected respectively to determine the levels of placental hypoxia-related cytokines, and after delivery, the placentas were collected to detect oxidative stress indexes and cell apoptosis indexes. Results: After treatment, serum PLGF and PAPP-A levels of both groups were significantly higher than those before treatment while sFlt-1 and sEng levels were significantly lower than those before treatment, and after treatment, serum PLGF and PAPP-A levels of LMWH group were significantly higher than those of control group while sFlt-1 and sEng levels were significantly lower than those of control group; ROS and RNS levels as well as Fas, FasL, caspase-3 and caspase-8 protein expression in placenta tissue of LMWH group were significantly lower than those of control group while GPx-1, SOD-1 and Trx levels as well as Survivin, XIAP and Bcl-2 protein expression were significantly higher than those of control group. Conclusion: Adjuvant low-molecular-weight heparin therapy can relieve the placental hypoxia, improve oxidative stress reaction and inhibit cell apoptosis in puerperae with severe preeclampsia.

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

    Directory of Open Access Journals (Sweden)

    Tracy Stokol

    2018-05-01

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

  16. Fragment profiling of low molecular weight heparins using reversed phase ion pair liquid chromatography-electrospray mass spectrometry.

    Science.gov (United States)

    Xu, Xiaohui; Li, Daoyuan; Chi, Lequan; Du, Xuzhao; Bai, Xue; Chi, Lianli

    2015-04-30

    Low molecular weight heparins (LMWHs) are linear and highly charged carbohydrate polymers prepared by chemical or enzymatic depolymerization of heparin. Compared to unfractionated heparin (UFH), LMWHs are prevalently used as clinical anticoagulant drugs due to their lower side effects and better bioavailability. The work presented herein provides a rapid and powerful fragment mapping method for structural characterization of LMWHs. The chain fragments of two types of LMWHs, enoxaparin and nadroparin, were generated by controlled enzymatic digestion with each of heparinase I (Hep I, Enzyme Commission (EC) # 4.2.2.7), heparinase II (Hep II, no EC # assigned) and heparinase III (Hep III, EC # 4.2.2.8). Reversed phase ion pair high performance liquid chromatography (RPIP-HPLC) coupled with electrospray ion trap time-of-flight mass spectrometry (ESI-IT-TOF-MS) was used to profile the oligosaccharide chains ranging from disaccharides to decasaccharides. A database containing all theoretical structural compositions was established to assist the mass spectra interpretation. The six digests derived by three enzymes from two types of LMWHs exhibited distinguishable fingerprinting patterns. And a total of 94 enoxaparin fragments and 109 nadroparin fragments were detected and identified. Besides the common LMWH oligosaccharides, many components containing characteristic LMWH structures such as saturated L-idopyranosuronic acid, 2,5-anhydro-D-mannitol, 1,6-anhydro-D-aminopyranose, as well as odd number oligosaccharides were also revealed. Quantitative comparison of major components derived from innovator and generic nadroparin products was presented. This approach to profile LMWHs' fragments offers a highly reproducible, high resolution and information-rich tool for evaluating the quality of this category of anticoagulant drugs or comparing structural similarities among samples from various sources. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Incidence of postpartum haemorrhage in women receiving therapeutic doses of low-molecular-weight heparin: results of a retrospective cohort study

    NARCIS (Netherlands)

    Roshani, Sara; Cohn, Danny M.; Stehouwer, Alexander C.; Wolf, Hans; van der Post, Joris A. M.; Büller, Harry R.; Kamphuisen, Pieter W.; Middeldorp, Saskia

    2011-01-01

    Background Low-molecular-weight heparin (LMWH) is the drug of choice to prevent venous thrombosis in pregnancy, but the optimal dose for prevention while avoiding bleeding is unclear. This study investigated whether therapeutic doses of LMWH increase the incidence of postpartum haemorrhage (PPH) in

  18. Incidence of postpartum haemorrhage in women receiving therapeutic doses of low-molecular-weight heparin : results of a retrospective cohort study

    NARCIS (Netherlands)

    Roshani, Sara; Cohn, Danny M; Stehouwer, Alexander C; Wolf, Hans; van der Post, Joris A M; Büller, Harry R; Kamphuisen, Pieter W; Middeldorp, Saskia

    2011-01-01

    Background Low-molecular-weight heparin (LMWH) is the drug of choice to prevent venous thrombosis in pregnancy, but the optimal dose for prevention while avoiding bleeding is unclear. This study investigated whether therapeutic doses of LMWH increase the incidence of postpartum haemorrhage (PPH) in

  19. Low-molecular-weight heparin and aspirin in the prevention of recurrent early-onset pre-eclampsia in women with antiphospholipid antibodies : the FRUIT-RCT

    NARCIS (Netherlands)

    van Hoorn, Marion E.; Hague, William M.; Pampus , van Mariëlle G.; Bezemer, Dick; de Vries, Johanna I. P.

    Objective: To examine whether combined treatment with low-molecular-weight heparin (LMWH) and aspirin reduces recurrent hypertensive disorders of pregnancy (HD: pre-eclampsia, eclampsia or HELLP syndrome) in women with antiphospholipid antibodies (aPLA) and a previous delivery for HD and/or

  20. Heparin kinetics

    International Nuclear Information System (INIS)

    Swart, C.A.M. de.

    1983-01-01

    The author has studied the kinetics of heparin and heparin fractions after intravenous administration in humans and in this thesis the results of this study are reported. Basic knowledge about the physico-chemical properties of heparin and its interactions with proteins resulting in anticoagulant and lipolytic effects are discussed in a review (chapter II), which also comprises some clinical aspects of heparin therapy. In chapter III the kinetics of the anticoagulant effect are described after intravenous administration of five commercial heparin preparations. A mathematical model is presented that fits best to these kinetics. The kinetics of the anticoagulant and lipolytic effects after intravenous injection of various 35 S-radiolabelled heparin fractions and their relationship with the disappearance of the radiolabel are described in chapter IV. Chapter V gives a description of the kinetics of two radiolabels after injection of in vitro formed complexes consisting of purified, 125 I-radiolabelled antithrombin III and various 35 S-radiolabelled heparin fractions. (Auth.)

  1. Effects of Sildenafil Citrate and Heparin Treatments on Placental Cell Morphology in a Murine Model of Pregnancy Loss.

    Science.gov (United States)

    Luna, Rayana Leal; Vasconcelos, Anne Gabrielle; Nunes, Ana Karolina Santana; de Oliveira, Wilma Helena; Barbosa, Karla Patricia de Sousa; Peixoto, Christina Alves

    2016-01-01

    Lipopolysaccharide (LPS) injections during pregnancy are well established as models for pregnancy complications, including fetal growth restriction (FGR), thrombophilia, preterm labor and abortion. Indeed, inflammation, as induced by LPS injection has been described as a pivotal factor in cases of miscarriage related to placental tissue damage. The phosphodiesterase-5 inhibitor sildenafil (Viagra®) is currently used to treat FGR cases in women, while low-molecular weight heparin (Fragmin®) is a standard treatment for recurrent miscarriage (RM). However, the pathways and cellular dynamics involved in RM are not completely understood. The aim of this study was to evaluate the protective effect of sildenafil and dalteparin in a mouse model of LPS-induced abortion. Histopathology, ultrastructural analysis and immunofluorescence for P-selectin were studied in two different placental cell types: trophoblast cells and labyrinth endothelial cells. Treatment with sildenafil either alone or in combination with heparin showed the best response against LPS-induced injury during pregnancy. In conclusion, our results support the use of these drugs as future therapeutic agents that may protect the placenta against inflammatory injury in RM events. Analyses of the ultrastructure and placental immunophysiology are important to understand the mechanism underlying RM. These findings may spark future studies and aid in the development of new therapies in cases of RM. © 2016 S. Karger AG, Basel.

  2. Interactions between nattokinase and heparin/GAGs.

    Science.gov (United States)

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

    2015-12-01

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

  3. A Prevention of Pre-eclampsia with the Use of Acetylsalicylic Acid and Low-molecular Weight Heparin - Molecular Mechanisms.

    Science.gov (United States)

    Darmochwal-Kolarz, Dorota; Kolarz, Bogdan; Korzeniewski, Michal; Kimber-Trojnar, Zaneta; Patro-Malysza, Jolanta; Mierzynski, Radzisław; Przegalinska-Kałamucka, Monika; Oleszczuk, Jan

    Pre-eclampsia appears to be the main cause for the maternal and fetal morbidity and mortality. Pregnant women with pre-eclampsia are more likely to be threatened with conditions which potentially may be lethal, such as: disseminated intravascular coagulation, cerebral hemorrhage, liver and renal failure. Pregnancy complicated with pre-eclampsia is also associated with a greater risk for iatrogenic prematurity, intrauterine growth retardation, premature abruption of placenta, and even intrauterine fetal death. In the majority of cases the reasons for arterial hypertension among pregnant women remain obscure. For the past decades, there were many abortive attempts in the use of some microelements, vitamins or specific diets, such as polyunsaturated fatty acids, for the prophylaxis of pre-eclampsia. Recently, it has been shown that a prevention of pre-eclampsia with the use of a lowmolecular- weight heparins (LMWHs) and acetylsalicylic acid (ASA) could considerably reduce the frequency of preeclampsia. In this review, we present the studies concerning the applications of LMWHs and aspirin in the prophylaxis of pre-eclampsia and some important data about the mechanisms of anti-inflammatory actions of LMWHs and ASA.

  4. Effects of low molecular weight heparin on the polarization and cytokine profile of macrophages and T helper cells in vitro.

    Science.gov (United States)

    Bruno, Valentina; Svensson-Arvelund, Judit; Rubér, Marie; Berg, Göran; Piccione, Emilio; Jenmalm, Maria C; Ernerudh, Jan

    2018-03-08

    Low molecular weight heparin (LMWH) is widely used in recurrent miscarriage treatment. The anti-coagulant effects are established, while immunological effects are not fully known. Our aim was to assess LMWH effects on activation and polarization of central regulatory immune cells from healthy women, and on placenta tissues from women undergoing elective abortions. Isolated blood monocytes and T helper (Th) cells under different activation and polarizing conditions were cultured with or without LMWH. Flow cytometry showed that LMWH exposure induced increased expression of HLA-DR and CD206 in macrophages. This phenotype was associated with increased secretion of Th17-associated CCL20, and decreased secretion of CCL2 (M2-associated) and CCL22 (Th2), as measured by multiplex bead array. In accordance, LMWH exposure to Th cells reduced the proportion of CD25highFoxp3+ regulatory T-cells, intensified IFN-γ secretion and showed a tendency to increase the lymphoblast proportions. Collectively, a mainly pro-inflammatory effect was noted on two essential tolerance-promoting cells. Although the biological significancies of these in vitro findings are uncertain and need to be confirmed in vivo, they suggest the possibility that immunological effects of LMWH may be beneficial mainly at an earlier gestational age to provide an appropriate implantation process in women with recurrent miscarriage.

  5. Patient compliance with extended low molecular weight heparin injections following hip and knee arthroplasty.

    Science.gov (United States)

    Deakin, Dan E; Mishreki, Andrew; Aslam, Nadim; Docker, Charles

    2010-01-01

    The use of extended duration thromboprophylaxis following hip and knee arthroplasty is becoming widespread. The aim of our study was to determine patient compliance with extended duration thromboprophylaxis using low molecular weight (LMWH) injections following hip and knee arthroplasty. 42 consecutive patients undergoing hip and knee arthroplasty were prospectively contacted during their fifth post operative week. A fully anonymised questionnaire was completed by each patient. All patients responded. One was excluded having been prescribed warfarin for pre existing atrial fibrillation. Twenty nine (71%) patients were discharged with the intention of self administering LMWH injections. Eight (20%) and four (9%) patients were discharged with the intention of administration by a relative or district nurse respectively. No patient required the person administering the injections to be changed after discharge from hospital. 90% (n=37) of patients reported not missing any doses. 10% (n=2) of patients missed one dose and 10% (n=2) missed two doses. Patient compliance with extended duration thromboprophylaxis using LMWH injections is extremely high. Oral thromboprophylaxis may be useful in the minority of patients requiring daily visits by a nurse to administer injections.

  6. Efficacy and safety of rivaroxaban versus low-molecular-weight heparin therapy in patients with lower limb fractures.

    Science.gov (United States)

    Long, Anhua; Zhang, Lihai; Zhang, Yingze; Jiang, Baoguo; Mao, Zhi; Li, Hongda; Zhang, Shanbao; Xie, Zongyan; Tang, Peifu

    2014-10-01

    Thromboprophylaxis with rivaroxaban has proved effective and safe in patients undergoing hip and knee replacement surgery. As it is unclear whether it is also effective and safe in fracture patients, the aim of the present study was to evaluate the efficacy and safety of rivaroxaban in patients with lower limb fractures. We performed a retrospective cohort study of 2,050 consecutive patients treated for lower limb fractures at our trauma center, comparing rates of venous thromboembolism (VTE), bleeding and surgical complications, and the length of hospital stay for 608 patients who received rivaroxaban and 717 who received a low-molecular-weight heparin (LMWH). Rates of symptomatic VTE were 4.9 and 8.6% in the rivaroxaban and LMWH groups, respectively (p = 0.008), and distal VTE rates were 1.8 and 5.7%, respectively (p = 0.036). The incidence of major bleeding events in the rivaroxaban group was also lower than in the LMWH group (0.2 vs 0.6%), but the difference between the groups was not statistically significant. The mean length of hospital stay was significantly shorter in the rivaroxaban group (12.2 vs 13.1 days, respectively; p = 0.016). This retrospective cohort study is the first report documenting the efficacy and safety of rivaroxaban in patients with lower extremity fractures. In comparison with LMWH, rivaroxaban reduced the incidence of VTE by 45% without increasing the risk of bleeding. However, prospective, randomized controlled trials comparing rivaroxaban and LMWH are needed to confirm our findings.

  7. Angiogenic Factor Profiles in Pregnant Women With a History of Early-Onset Severe Preeclampsia Receiving Low-Molecular-Weight Heparin Prophylaxis.

    Science.gov (United States)

    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.

  8. A single center retrospective cohort study comparing low-molecular-weight heparins to direct oral anticoagulants for the treatment of venous thromboembolism in patients with cancer - A real world experience.

    Science.gov (United States)

    Phelps, Megan K; Wiczer, Tracy E; Erdeljac, H Paige; Van Deusen, Kelsey R; Porter, Kyle; Philips, Gary; Wang, Tzu-Fei

    2018-01-01

    Introduction Low-molecular-weight heparins are the standard treatment for cancer-associated thrombosis. Recently, direct oral anticoagulants are a new option for thrombosis treatment; however, data supporting the use of direct oral anticoagulants for cancer-associated thrombosis are limited. Objectives The primary objective of this study was to determine the rate of recurrent cancer-associated thrombosis and major bleeding within 6 months of starting either low-molecular-weight heparin or direct oral anticoagulant for treatment of cancer-associated thrombosis. Secondary objectives were to determine the rates of clinically relevant-non-major bleeding and all-cause mortality. Patients/methods This is a retrospective cohort study including adults with cancer-associated thrombosis treated with low-molecular-weight heparin or direct oral anticoagulant between 2010 and 2016 at the Ohio State University. Medical records were reviewed for 6 months after initiation of anticoagulation or until the occurrence of recurrent cancer-associated thrombosis, major bleeding, cessation of anticoagulation of interest, or death, whichever occurred first. Results Four hundred and eighty patients were included (290 low-molecular-weight heparin and 190 direct oral anticoagulant). Patients treated with direct oral anticoagulant were found to carry "lower risk" features including cancer with lower VTE risk and lower rate of metastatic disease. After adjustment for baseline differences, there was no significant difference in the rate of recurrent cancer-associated thrombosis (7.2% low-molecular-weight heparin vs 6.3% direct oral anticoagulant, p = 0.71) or major bleeding (7.6% low-molecular-weight heparin vs 2.6% direct oral anticoagulant, p = 0.08). Conclusions Our study demonstrates that in a select population of cancer patients with VTE, direct oral anticoagulant use can be as effective and safe compared to the standard therapy with low-molecular-weight heparin.

  9. Low molecular weight heparin may benefit nephrotic remission in steroid‑sensitive nephrotic syndrome via inhibiting elastase.

    Science.gov (United States)

    Zhai, Songhui; Hu, Lijuan; Zhong, Lin; Tao, Yuhong; Wang, Zheng

    2017-12-01

    Low molecular weight heparin (LMWH) has a structure similar to heparan sulfate, which exerts anti‑inflammatory effects via inhibiting elastase (Ela) activity. Release of Ela along the glomerular capillary wall may induce glomerular injury and proteinuria. The present study aimed to investigate the influence of LMWH on steroid‑sensitive nephrotic syndrome (SSNS) and the potential underlying mechanism. A total of 40 SSNS patients and 20 healthy controls were recruited. SSNS patients were treated with LMWH and prednisone simultaneously (LMWH+pred group) or with prednisone alone (pred group). Proteinuria, urinary glycosaminoglycans (GAGs), serum Ela and urinary creatinine levels were measured. The nephrotic period of SSNS was 15.93±5.78 days. The nephrotic period of SSNS in LMWH+pred group was significantly reduced compared with the pred group (14.13±4.56 vs. 18.63±6.49 days; PEla levels (77.64±10.99 ng/l) were significantly greater in the nephrotic period of SSNS compared with the remission period (0.107±0.026 g/24 h, 1.53±0.27 mg/mmol Cr and 41.92±7.81 ng/l, respectively) and the healthy control group (0.098±0.027 g/24 h, 1.40±0.26 mg/mmol creatinine and 38.43±9.83 ng/l, respectively; PEla levels in the LMWH+pred group were significantly reduced compared with the pred group (P0.05). Positive correlations were revealed between urinary GAG excretion and proteinuria (r=0.877; PEla levels (r=0.844; PEla levels and urinary GAG excretion (r=0.881; PEla levels may induce proteinuria by degrading GAGs in the glomerular basement membrane in children with SSNS. LMWH may benefit nephrotic remission of SSNS via inhibiting Ela.

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

  11. An open-label randomized controlled trial of low molecular weight heparin compared to heparin and coumadin for the treatment of venous thromboembolic events in children: the REVIVE trial.

    Science.gov (United States)

    Massicotte, Patricia; Julian, Jim A; Gent, Michael; Shields, Karen; Marzinotto, Velma; Szechtman, Barbara; Andrew, Maureen

    2003-01-25

    Venous thromboembolic events (VTE) are serious complications in children and for which the standard of care, unfractionated heparin followed by oral anticoagulation (UFH/OA), is problematic. The objective of REVIVE was to compare the efficacy and safety of a low molecular weight heparin (reviparin-sodium) to UFH/OA for the treatment of VTE in children. This multicenter, open-label study, with blinded central outcome adjudication, randomized patients with objectively confirmed VTE to receive either reviparin-sodium or UFH/OA. Dose adjustments were made using nomograms. The efficacy outcome was based on recurrent VTE and death due to VTE during the 3-month treatment period. The safety outcomes were major bleeding, minor bleeding and death. Due to slow patient accrual, REVIVE was closed prematurely. At 3 months, with reviparin-sodium, 2/36 patients (5.6%) had recurrent VTE or death compared to 4/40 patients (10.0%) receiving UFH/OA (odds ratio=0.53; 95% CI=(0.05, 4.00); Fisher's exact test: 2P=0.677). There were 7 major bleeds, 2/36 (5.6%) in the reviparin-sodium group and 5/40 (12.5%) in UFH/OA group (odds ratio=0.41; 95% confidence interval 0.04, 2.76); Fisher's exact test: P=0.435). There were 5 deaths during the study period, 1 (2.8%) in the reviparin-sodium group and 4 (10.0%) in the UFH/OA group. All five deaths were unrelated to VTE but one was due to an intracranial hemorrhage in the UFH/OA group. Although limited by small sample size, REVIVE provides valuable information on the incidence of recurrent VTE, major bleeding and problematic issues associated with therapy of VTE in children.

  12. Heparin for assisted reproduction.

    Science.gov (United States)

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

    2013-08-17

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

  13. [Effects of low molecular weight heparin on the inflammatory response and vascular injury in rat after electric burn].

    Science.gov (United States)

    Jiang, Nanhong; Xie, Weiguo; Wang, Hui; Jin, Dongmei; Tan, Hong; Zhao, Chaoli

    2014-04-01

    To observe the effects of low molecular weight heparin (LMWH) on the inflammatory response and vascular injury in rat after electric burn. A homemade regulator and transformer apparatus was used to reproduce the model of electric burn (0.5 cm×0.5 cm in size) with depth from full-thickness to full-thickness skin plus muscle and bone on the middle of the inside of right hind limb in 60 Wistar rats. The open wounds were covered with 20 g/L sulfadiazine silver paste immediately after injury. The wound condition was observed every day. The injured rats were divided into group LMWH and control group (C) according to the random number table, with 30 rats in each group. Rats in group LMWH were given subcutaneous injection of LMWH (1 U/g) in abdominal wall, 2 times a day. No other treatment was given in rats in group C. On post burn day (PBD) 3, 5, and 10, 10 rats respectively of two groups were sacrificed. The damaged tissue of wound and that around the wound (1.0 cm×0.5 cm in size) were excised, and heart blood was obtained. The pathological changes and thrombosis in damaged tissue were observed with HE, Masson, and aldehyde fuchsin staining, and the thrombosis rate was calculated. Serum contents of TNF-α and endothelin-1 were determined with ELISA. The mRNA expression of TNF-α in damaged tissue was detected with RT-PCR. Data were processed with Levene homogeneity test, analysis of variance of factorial design, LSD- t test, SNK- q test, and Friedman M nonparametric test. (1) The injured limb of rats was obviously swollen after electric burn, which reached deeply to the muscle and bone. Compared with those of group C, the swelling of rats subsided slightly faster and the inflammatory response was lighter in group LMWH at each time point. (2) The necrosis of damaged tissue and profuse infiltration of inflammatory cells were observed. Dilatation of blood vessels, congestion and thrombosis, and swelling, necrosis, and desquamation of vascular endothelial cells were

  14. Top-down approach for the direct characterization of low molecular weight heparins using LC-FT-MS.

    Science.gov (United States)

    Li, Lingyun; Zhang, Fuming; Zaia, Joseph; Linhardt, Robert J

    2012-10-16

    Low molecular heparins (LMWHs) are structurally complex, heterogeneous, polydisperse, and highly negatively charged mixtures of polysaccharides. The direct characterization of LMWH is a major challenge for currently available analytical technologies. Electrospray ionization (ESI) liquid chromatography-mass spectrometry (LC-MS) is a powerful tool for the characterization complex biological samples in the fields of proteomics, metabolomics, and glycomics. LC-MS has been applied to the analysis of heparin oligosaccharides, separated by size exclusion, reversed phase ion-pairing chromatography, and chip-based amide hydrophilic interaction chromatography (HILIC). However, there have been limited applications of ESI-LC-MS for the direct characterization of intact LMWHs (top-down analysis) due to their structural complexity, low ionization efficiency, and sulfate loss. Here we present a simple and reliable HILIC-Fourier transform (FT)-ESI-MS platform to characterize and compare two currently marketed LMWH products using the top-down approach requiring no special sample preparation steps. This HILIC system relies on cross-linked diol rather than amide chemistry, affording highly resolved chromatographic separations using a relatively high percentage of acetonitrile in the mobile phase, resulting in stable and high efficiency ionization. Bioinformatics software (GlycReSoft 1.0) was used to automatically assign structures within 5-ppm mass accuracy.

  15. Profiling analysis of low molecular weight heparins by multiple heart-cutting two dimensional chromatography with quadruple time-of-flight mass spectrometry.

    Science.gov (United States)

    Ouyang, Yilan; Zeng, Yangyang; Rong, Yinxiu; Song, Yue; Shi, Lv; Chen, Bo; Yang, Xinlei; Xu, Naiyu; Linhardt, Robert J; Zhang, Zhenqing

    2015-09-01

    Low molecular weight heparins (LMWHs) are polydisperse and microheterogenous mixtures of polysaccharides used as anticoagulant drugs. Profiling analysis is important for obtaining deeper insights into the structure of LMWHs. Previous oligosaccharide mapping methods are relatively low resolution and are unable to show an entire picture of the structural complexity of LMWHs. In the current study a profiling method was developed relying on multiple heart-cutting, two-dimensional, ultrahigh performance liquid chromatography with quadruple time-of-flight mass spectrometry. This represents an efficient, automated, and robust approach for profiling LMWHs. Using size-exclusion chromatography and ion-pairing reversed-phase chromatography in a two-dimensional separation, LMW components of different sizes and LMW components of the same size but with different charges and polarities can be resolved, providing a more complete picture of a LMWH. Structural information on each component was then obtained with quadrupole time-of-flight mass spectrometry. More than 80 and 120 oligosaccharides were observed and unambiguously assigned from the LMWHs, nadroparin and enoxaparin, respectively. This method might be useful for quality control of LMWHs and as a powerful tool for heparin-related glycomics.

  16. Parent heparin and daughter LMW heparin correlation analysis using LC-MS and NMR

    International Nuclear Information System (INIS)

    Liu, Xinyue; St Ange, Kalib; Wang, Xiaohua; Lin, Lei; Zhang, Fuming

    2017-01-01

    Heparin is a structurally complex, polysaccharide anticoagulant derived from livestock, primarily porcine intestinal tissues. Low molecular weight (LMW) heparins are derived through the controlled partial depolymerization of heparin. Increased manufacturing and regulatory concerns have provided the motivation for the development of more sophisticated analytical methods for determining both their structure and pedigree. A strategy, for the comprehensive comparison of parent heparins and their LMW heparin daughters, is described that relies on the analysis of monosaccharide composition, disaccharide composition, and oligosaccharide composition. Liquid chromatography-mass spectrometry is rapid, robust, and amenable to automated processing and interpretation of both top-down and bottom-up analyses. Nuclear magnetic resonance spectroscopy provides complementary top-down information on the chirality of the uronic acid residues and glucosamine substitution. Principal component analysis (PCA) was applied to the normalized abundance of oligosaccharides, calculated in the bottom-up analysis, to show parent and daughter correlation in oligosaccharide composition. Using these approaches, six pairs of parent heparins and their daughter generic enoxaparins from two different manufacturers were comprehensively analyzed. Enoxaparin is the most widely used LMW heparin and is prepared through controlled chemical β-eliminative cleavage of porcine intestinal heparin. Lovenox"®, the innovator version of enoxaparin marketed in the US, was analyzed as a reference for the daughter LMW heparins. The results, show similarities between LMW heparins from two different manufacturers with Lovenox"®, excellent lot-to-lot consistency of products from each manufacturer, and detects a correlation between each parent heparin and daughter LMW heparin. - Highlights: • Low molecular weight heparins prepared from different heparin parents were analyzed. • An integrated analytical approach relied

  17. Parent heparin and daughter LMW heparin correlation analysis using LC-MS and NMR

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xinyue, E-mail: liux22@rpi.edu [National Glycoengineering Research Center, Shandong Provincial Key Laboratory of Carbohydrate Chemistry and Glycobiology, State Key Laboratory of Microbial Technology, Shandong University, Jinan, Shandong, 250100 (China); Department of Chemistry and Chemical Biology, Department of Chemical and Biological Engineering, Department of Biology, Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 12180 (United States); St Ange, Kalib, E-mail: stangk2@rpi.edu [Department of Chemistry and Chemical Biology, Department of Chemical and Biological Engineering, Department of Biology, Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 12180 (United States); Wang, Xiaohua, E-mail: wangx35@rpi.edu [Department of Chemistry and Chemical Biology, Department of Chemical and Biological Engineering, Department of Biology, Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 12180 (United States); School of Computer and Information, Hefei University of Technology, Hefei (China); Lin, Lei, E-mail: Linl5@rpi.edu [Department of Chemistry and Chemical Biology, Department of Chemical and Biological Engineering, Department of Biology, Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 12180 (United States); Zhang, Fuming, E-mail: zhangf2@rpi.edu [Department of Chemistry and Chemical Biology, Department of Chemical and Biological Engineering, Department of Biology, Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 12180 (United States); and others

    2017-04-08

    Heparin is a structurally complex, polysaccharide anticoagulant derived from livestock, primarily porcine intestinal tissues. Low molecular weight (LMW) heparins are derived through the controlled partial depolymerization of heparin. Increased manufacturing and regulatory concerns have provided the motivation for the development of more sophisticated analytical methods for determining both their structure and pedigree. A strategy, for the comprehensive comparison of parent heparins and their LMW heparin daughters, is described that relies on the analysis of monosaccharide composition, disaccharide composition, and oligosaccharide composition. Liquid chromatography-mass spectrometry is rapid, robust, and amenable to automated processing and interpretation of both top-down and bottom-up analyses. Nuclear magnetic resonance spectroscopy provides complementary top-down information on the chirality of the uronic acid residues and glucosamine substitution. Principal component analysis (PCA) was applied to the normalized abundance of oligosaccharides, calculated in the bottom-up analysis, to show parent and daughter correlation in oligosaccharide composition. Using these approaches, six pairs of parent heparins and their daughter generic enoxaparins from two different manufacturers were comprehensively analyzed. Enoxaparin is the most widely used LMW heparin and is prepared through controlled chemical β-eliminative cleavage of porcine intestinal heparin. Lovenox{sup ®}, the innovator version of enoxaparin marketed in the US, was analyzed as a reference for the daughter LMW heparins. The results, show similarities between LMW heparins from two different manufacturers with Lovenox{sup ®}, excellent lot-to-lot consistency of products from each manufacturer, and detects a correlation between each parent heparin and daughter LMW heparin. - Highlights: • Low molecular weight heparins prepared from different heparin parents were analyzed. • An integrated analytical

  18. Successful Treatment of Dental Infection-Induced Chronic Cavernous Sinus Thrombophlebitis With Antibiotics and Low-Molecular-Weight Heparin: Two Case Reports.

    Science.gov (United States)

    Li, Yuan; Zheng, Bo; Chen, Kangning; Gui, Li

    2015-08-01

    Two patients developed cavernous sinus thrombophlebitis from a tooth infection. A 36-year-old man experienced a severe headache with bilateral third and sixth cranial nerve palsies after extraction of his left upper third molar. Another 53-year-old diabetic man developed fever, headache, and bilateral complete ophthalmoplegia after a tooth infection. The brain magnetic resonance imaging scans of both patients showed bilateral cavernous sinus partial thrombosis. Broad-spectrum antibiotics plus low-molecular-weight heparin successfully resolved all symptoms. Both patients recovered fully without any recurrence at the 3-month follow-up visit. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  19. Safety and Efficacy of Bridging With Low-Molecular-Weight Heparin During Temporary Interruptions of Warfarin: A Register-Based Cohort Study.

    Science.gov (United States)

    Sjögren, Vilhelm; Grzymala-Lubanski, Bartosz; Renlund, Henrik; Svensson, Peter J; Själander, Anders

    2017-11-01

    Low-molecular-weight heparin (LMWH) is often recommended as a bridging therapy during temporary interruptions in warfarin treatment, despite lack of evidence. The aim of this study was to see whether we could find benefit from LMWH bridging. We studied all planned interruptions of warfarin within the Swedish anticoagulation register Auricula during 2006 to 2011. Low-molecular-weight heparin bridging was compared to nonbridging (control) after propensity score matching. Complications were identified in national clinical registers for 30 days following warfarin cessation, and defined as all-cause mortality, bleeding (intracranial, gastrointestinal, or other), or thrombosis (ischemic stroke or systemic embolism, venous thromboembolism, or myocardial infarction) that was fatal or required hospital care. Of the 14 556 identified warfarin interruptions, 12 659 with a known medical background had a mean age of 69 years, 61% were males, mean CHADS 2 (1 point for each of congestive heart failure, hypertension, age ≥75 years, diabetes, and 2 points for stroke or transient ischemic attack) score was 1.7, and CHA 2 DS 2 -VASc score was 3.4. The total number of LMWH bridgings was 7021. Major indications for anticoagulation were mechanical heart valve prostheses 4331, atrial fibrillation 1097, and venous thromboembolism 1331. Bridging patients had a higher rate of thrombotic events overall. Total risk of any complication did not differ significantly between bridging (1.5%) and nonbridging (1.2%). Regardless of indication for warfarin treatment, we found no benefit from bridging. The type of procedure prompting bridging was not known, and the likely reason for the observed higher risk of thrombosis with LMWH bridging is that low-risk procedures more often meant no bridging. Results from randomized trials are needed, especially for patients with mechanical heart valves.

  20. Biomedical Application of Low Molecular Weight Heparin/Protamine Nano/Micro Particles as Cell- and Growth Factor-Carriers and Coating Matrix

    Directory of Open Access Journals (Sweden)

    Masayuki Ishihara

    2015-05-01

    Full Text Available Low molecular weight heparin (LMWH/protamine (P nano/micro particles (N/MPs (LMWH/P N/MPs were applied as carriers for heparin-binding growth factors (GFs and for adhesive cells including adipose-derived stromal cells (ADSCs and bone marrow-derived mesenchymal stem cells (BMSCs. A mixture of LMWH and P yields a dispersion of N/MPs (100 nm–3 μm in diameter. LMWH/P N/MPs can be immobilized onto cell surfaces or extracellular matrix, control the release, activate GFs and protect various GFs. Furthermore, LMWH/P N/MPs can also bind to adhesive cell surfaces, inducing cells and LMWH/P N/MPs-aggregate formation. Those aggregates substantially promoted cellular viability, and induced vascularization and fibrous tissue formation in vivo. The LMWH/P N/MPs, in combination with ADSCs or BMSCs, are effective cell-carriers and are potential promising novel therapeutic agents for inducing vascularization and fibrous tissue formation in ischemic disease by transplantation of the ADSCs and LMWH/P N/MPs-aggregates. LMWH/P N/MPs can also bind to tissue culture plates and adsorb exogenous GFs or GFs from those cells. The LMWH/P N/MPs-coated matrix in the presence of GFs may provide novel biomaterials that can control cellular activity such as growth and differentiation. Furthermore, three-dimensional (3D cultures of cells including ADSCs and BMSCs using plasma-medium gel with LMWH/P N/MPs exhibited efficient cell proliferation. Thus, LMWH/P N/MPs are an adequate carrier both for GFs and for stromal cells such as ADSCs and BMSCs, and are a functional coating matrix for their cultures.

  1. [Effect of Low Molecular Weight Heparin Calcium Combined Compound Danshen Injection on Perinatal Outcomes of Nephrotic Syndrome Patients with Early Onset Severe Pre-eclampsia].

    Science.gov (United States)

    Tong, Chong-xin; Xing, Xiao-fen; Qiao, Shu-hua; Liu, Lin; Shan, Ling

    2015-08-01

    To observe the effect of low molecular weight heparin calcium (LMWHC) combined Compound Danshen Injection (DI) on nephrotic syndrome patients with early onset severe preeclampsia. Totally 80 nephrotic syndrome patients with early onset severe pre-eclampsia were randomly assigned to four groups voluntarily, i.e., Group A (22 cases, treated by magnesium sulfate), B (19 cases, treated by magnesium sulfate plus LMWHC), C (21 cases, magnesium sulfate plus DI), D (18 cases, magnesium sulfate plus LMWHC and DI). Umbilical arterial S/D ratios, amniotic fluid index (AFI), prolonged gestational age, placenta weight, neonatal weight, and Apgar score were compared among the four groups. Compared with before treatment in the same group, umbilical arterial S/D ratios decreased in the four groups (P <0. 05). AFI decreased in Group A, while it increased in Group B, C, and D (P<0. 05). Compared with Group A at the same time point, umbilical arterial S/D ratios decreased, and AFI increased in Group B, C, and D (P <0. 01 , P <0. 05). Prolonged gestational age and neonatal weight were increased in Group B, C, and D (P <0. 01, P <0. 05). Placenta weight were increased in Group B and D (P <0. 05). Apgar scores at 1 and 5 min were improved in Group D (P <0. 05). Compared with Group B and C at the same time point, umbilical arterial S/D ratios decreased, and AFI increased in Group D (P<0. 05). Compared with Group B, prolonged gestational age and placenta weight were decreased in Group C, but prolonged gestational age and placenta weight were increased in Group D (P <0.05). Compared with Group C, prolonged gestational age, placenta weight, and neonatal weight were increased in Group D (P <0. 05). Treatment of nephrotic syndrome patients with early onset severe pre-eclampsia by LMWHC combined DI could prolong gestational ages, obviously improve prenatal outcomes, with better effect obtained than using any of them alone.

  2. Major bleeding risks of different low-molecular-weight heparin agents: a cohort study in 12 934 patients treated for acute venous thrombosis.

    Science.gov (United States)

    van Rein, N; Biedermann, J S; van der Meer, F J M; Cannegieter, S C; Wiersma, N; Vermaas, H W; Reitsma, P H; Kruip, M J H A; Lijfering, W M

    2017-07-01

    Essentials Low-molecular-weight-heparins (LMWH) kinetics differ which may result in different bleeding risks. A cohort of 12 934 venous thrombosis patients on LMWH was followed until major bleeding. The absolute major bleeding risk was low among patients registered at the anticoagulation clinic. Once-daily dosing was associated with a lower bleeding risk as compared with twice-daily. Background Low-molecular-weight heparins (LMWHs) are considered members of a class of drugs with similar anticoagulant properties. However, pharmacodynamics and pharmacokinetics between LMWHs differ, which may result in different bleeding risks. As these agents are used by many patients, small differences may lead to a large effect on numbers of major bleeding events. Objectives To determine major bleeding risks for different LMWH agents and dosing schedules. Methods A cohort of acute venous thrombosis patients from four anticoagulation clinics who used an LMWH and a vitamin K antagonist were followed until they ceased LMWH treatment or until major bleeding. Exposures were classified according to different types of LMWHs and for b.i.d. and o.d. use. Cumulative incidences for major bleeding per 1000 patients and risk ratios were calculated and adjusted for study center. Results The study comprised 12 934 patients with a mean age of 59 years; 6218 (48%) were men. The cumulative incidence of major bleeding was 2.5 per 1000 patients (95% confidence interval [CI], 1.7-3.5). Enoxaparin b.i.d. or o.d. was associated with a relative bleeding risk of 1.7 (95% CI, 0.2-17.5) compared with nadroparin o.d. In addition, a nadroparin b.i.d. dosing schedule was associated with a 2.0-fold increased major bleeding risk (95% CI, 0.8-5.1) as compared with a nadroparin o.d. dosing schedule. Conclusions Absolute major bleeding rates were low for all LMWH agents and dosing schedules in a large unselected cohort. Nevertheless, twice-daily dosing with nadroparin appeared to be associated with an increased

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

    Science.gov (United States)

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

    2013-05-01

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

  4. [Long-term treatment with a low-molecular-weight heparin administered subcutaneously compared with a vitamin K antagonist: subanalysis of patients with cancer].

    Science.gov (United States)

    Romera-Villegas, Antonio; Martí Mestre, Xavier; Vila Coll, Ramón; Colomé Nafría, Esteve

    2015-01-01

    We performed a subanalysis of cancer patients enrolled in a clinical trial that compared long-term (6 months) treatment with a low-molecular-weight heparin (LMWH) administered subcutaneously or with acenocoumarol. The subanalysis assessed whether the characteristics of the tumor had an influence on the clinical response. A randomized open trial included 69 patients with cancer and symptomatic proximal deep vein thrombosis of the lower limbs. The tumor characteristics and treatment type were recorded. The main assessment criterion was the 12-month incidence of recurrent symptomatic venous thromboembolism (VTE). Sixty-one patients (88.4%) were analyzed. At the time of inclusion, the cancer characteristics and treatment were comparable between the 2 groups. Over the course of 12 months, the recurrent VTE was significantly greater in the elderly patients (71.5 ± 6.4 vs. 62.0 ± 15.1; p=.006). The logistic regression analysis showed no association between VTE recurrence and the location or extent of the tumor. However, the use of thrombogenic chemotherapy (p=.045) was independently associated with VTE recurrence, and longterm treatment with tinzaparin was almost a protective factor (p=.15). In this small sample, we observed an association between thrombogenic chemotherapy and recurrent VTE. The tendency towards a reduction in VTE recurrence at 12 months in patients with cancer in the LMWH group could be attributed to the effect of the full LMWH dosage. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  5. 低分子肝素治疗不稳定型心绞痛疗效观察%Low Molecular Weight Heparin in the Treatment of Unstable Angina Efficacy Observation

    Institute of Scientific and Technical Information of China (English)

    仁青措

    2013-01-01

    Objective: unstable angina pectoris (UAP) is a syndrome of coronary heart disease after transmural myocardial infarction, clinical treatment and prognosis is poor. Ef ect of low molecular weight heparin in treatment of UAP significantly, which has important clinical significance for improving the prognosis of. Methods: on the basis of conventional therapy plus low molecular weight heparin subcutaneous injection and oral administration of low-dose aspirin. Results:low molecular weight heparin plus aspirin in the treatment of UAP, frequency of angina pectoris at ack reduced, prolong the interval of electrocardiogram and dynamic electrocardiogram, myocardial ischemia significantly improved.%稳定型心绞痛(UAP)是冠心病中仅次于透壁性心肌梗死的综合征,临床治疗及预后较差。低分子肝素治疗UAP疗效显著,对改善预后有重要临床意义。常规治疗基础上+低分子肝素皮下注射+口服小剂量阿司匹林。低分子肝素+阿司匹林治疗UAP后,心绞痛发作频率减少,间隔时间延长,心电图及动态心电图心肌缺血明显改善。

  6. Characterization of heparin aerosols generated in jet and ultrasonic nebulizers

    DEFF Research Database (Denmark)

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

    1999-01-01

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

  7. pH-responsive thiolated chitosan nanoparticles for oral low-molecular weight heparin delivery: in vitro and in vivo evaluation.

    Science.gov (United States)

    Fan, Bo; Xing, Yang; Zheng, Ying; Sun, Chuan; Liang, Guixian

    2016-01-01

    The aim of present study was to investigate a pH-responsive and mucoadhesive nanoparticle system for oral bioavailability enhancement of low-molecular weight heparin (LMWH). The thioglycolic acid (TGA) was first covalently attached to chitosan (CS) with 396.97 ± 54.54 μmol thiol groups per gram of polymer and then the nanoparticles were prepared with thiolated chitosan (TCS) and pH-sensitive polymer hydroxypropyl methylcellulose phthalate (HPMCP) by ionic cross-linking method. The obtained nanoparticles were characterized for the shape, particle size, zeta potential, drug entrapment efficiency and loading capacity. In vitro results revealed the acid stability of pH-responsive nanoparticles, which had a significant control over LMWH release and could effectively protect entrapped drugs in simulated gastric conditions. By the attachment of the thiol ligand, an improvement of permeation-enhancing effect on freshly excised carp intestine (1.86-fold improvement) could be found. The mucoadhesive properties were evaluated using fluorescently labeled TCS or CS nanoparticles. As compared with the controls, a significant improvement of mucoadhesion on rat intestinal mucosa was observed in TCS/HPMCP nanoparticles via confocal laser scanning microscopy. The activated partial thromboplastin time (APTT) was significantly prolonged and an increase in the oral bioavailability of LMWH was turned out to be pronounced after oral delivered LMWH-loaded TCS/HPMCP nanoparticles in rats, which suggested enhanced anticoagulant effects and improved absorption of LMWH. In conclusion, pH-responsive TCS/HPMCP nanoparticles hold promise for oral delivery of LMWH.

  8. Mr 25,000 heparin-binding protein from guinea pig brain is a high molecular weight form of basic fibroblast growth factor.

    OpenAIRE

    Moscatelli, D; Joseph-Silverstein, J; Manejias, R; Rifkin, D B

    1987-01-01

    A Mr 25,000 form of basic fibroblast growth factor (bFGF) has been isolated from guinea pig brain along with the typical Mr 18,000 form. Both forms were purified to homogeneity by a combination of heparin-affinity chromatography and ion-exchange chromatography on an FPLC Mono S column. The Mr 25,000 form, like the Mr 18,000 form, was not eluted from the heparin-affinity column with 0.95 M NaCl, but was eluted with 2 M NaCl. The Mr 25,000 guinea pig protein stimulated plasminogen activator pro...

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

    International Nuclear Information System (INIS)

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

    1985-01-01

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

  10. Dalteparin or vitamin K antagonists to prevent recurrent venous thromboembolism in cancer patients: a patient-level economic analysis for France and Austria.

    Science.gov (United States)

    Dranitsaris, George; Shane, Lesley G; Galanaud, Jean-Philippe; Stemer, Gunar; Debourdeau, Philippe; Woodruff, Seth

    2017-07-01

    International guidelines recommend extended duration secondary prophylaxis in cancer patients who develop primary venous thromboembolism (VTE). Agent selection is guided in part by one large randomized trial (i.e., CLOT; Lee et al., N Engl J Med 349:146-53, 2003) which demonstrated that dalteparin reduced the relative risk of recurrence by 52% compared with oral vitamin K antagonists (VKA; HR = 0.48, 95% CI, 0.30 to 0.77). In a subgroup analysis from that same trial, patients with renal impairment also derived benefit with dalteparin (VTE rates = 3% vs. 17%; p = 0.011). To measure the economic value of secondary VTE prophylaxis with dalteparin, a patient-level pharmacoeconomic analysis was conducted from the Austrian and French healthcare system perspectives. Chapter 1 Healthcare resource use collected during the CLOT trial was extracted and converted into direct cost estimates. Incremental cost differences between the dalteparin and VKA groups were then combined with health state utilities to measure the cost per quality-adjusted life year (QALY) gained. The dalteparin group had significantly higher costs than the VKA group in both countries (Austria: dalteparin = €2687 vs. VKA = €2012; France: dalteparin = €2053 vs. VKA = €1352: p Austria and France, respectively. The analyses in patients with renal impairment suggested an even better economic profile, with the cost per QALY gained being less than €4000 in both countries. Secondary prophylaxis with dalteparin is a cost-effective alternative to VKA for the prevention of recurrent VTE in patients with cancer.

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

    Science.gov (United States)

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

    2011-05-01

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

  12. Extended thromboprophylaxis with low-molecular-weight heparins after hospital discharge in high-risk surgical and medical patients: a review.

    Science.gov (United States)

    Huo, Michael H; Muntz, James

    2009-06-01

    Prophylaxis against venous thromboembolism (VTE) is routinely administered during the hospital stay in at-risk surgical and medical patients. However, in high-risk groups, the risk of deep-vein thrombosis or pulmonary embolism may persist for several weeks after discharge. The standard duration of thromboprophylaxis (6-14 days) may not provide adequate protection against such events. This article reviews published data on the efficacy and safety profile of extended-duration thromboprophylaxis in patients at high risk for VTE, the potential cost-effectiveness of such treatment, and practical aspects of ensuring an effective transition from the inpatient to the outpatient setting. MEDLINE and the Cochrane Database of Systematic Reviews were searched through January 2009 for relevant English-language reports of clinical trials, abstracts, and case reports. The search terms included, but were not limited to, venous thromboembolism, pulmonary embolism, anticoagulation, thromboprophylaxis, prolonged duration, and extended duration. The reference lists of the identified articles were reviewed for additional relevant publications. Congress Web sites were also consulted. The principal criteria for inclusion of a study were that it have a prospective, randomized design and include a control group. Case series and retrospective analyses were excluded. Studies have found that extended-duration thromboprophylaxis (28-45 days) with low-molecular-weight heparins (LMWHs) can reduce the risk of VTE in high-risk patients. In separate meta-analyses, extended-duration thromboprophylaxis with LMWH was associated with significant reductions in the likelihood of symptomatic VTE compared with standard-duration thromboprophylaxis in patients undergoing major orthopedic surgery (odds ratio [OR] = 0.38; 95% CI, 0.24-0.61) or major abdominal or pelvic surgery (Peto OR = 0.22; 95% CI, 0.06-0.80). There was large heterogeneity in the reported rates of major and minor bleeding. The occurrence of

  13. Monitoring low molecular weight heparins at therapeutic levels: dose-responses of, and correlations and differences between aPTT, anti-factor Xa and thrombin generation assays.

    Directory of Open Access Journals (Sweden)

    Owain Thomas

    Full Text Available Low molecular weight heparins (LMWH's are used to prevent and treat thrombosis. Tests for monitoring LMWH's include anti-factor Xa (anti-FXa, activated partial thromboplastin time (aPTT and thrombin generation. Anti-FXa is the current gold standard despite LMWH's varying affinities for FXa and thrombin.To examine the effects of two different LMWH's on the results of 4 different aPTT-tests, anti-FXa activity and thrombin generation and to assess the tests' concordance.Enoxaparin and tinzaparin were added ex-vivo in concentrations of 0.0, 0.5, 1.0 and 1.5 anti-FXa international units (IU/mL, to blood from 10 volunteers. aPTT was measured using two whole blood methods (Free oscillation rheometry (FOR and Hemochron Jr (HCJ and an optical plasma method using two different reagents (ActinFSL and PTT-Automat. Anti-FXa activity was quantified using a chromogenic assay. Thrombin generation (Endogenous Thrombin Potential, ETP was measured on a Ceveron Alpha instrument using the TGA RB and more tissue-factor rich TGA RC reagents.Methods' mean aPTT at 1.0 IU/mL LMWH varied between 54s (SD 11 and 69s (SD 14 for enoxaparin and between 101s (SD 21 and 140s (SD 28 for tinzaparin. ActinFSL gave significantly shorter aPTT results. aPTT and anti-FXa generally correlated well. ETP as measured with the TGA RC reagent but not the TGA RB reagent showed an inverse exponential relationship to the concentration of LMWH. The HCJ-aPTT results had the weakest correlation to anti-FXa and thrombin generation (Rs0.62-0.87, whereas the other aPTT methods had similar correlation coefficients (Rs0.80-0.92.aPTT displays a linear dose-response to LMWH. There is variation between aPTT assays. Tinzaparin increases aPTT and decreases thrombin generation more than enoxaparin at any given level of anti-FXa activity, casting doubt on anti-FXa's present gold standard status. Thrombin generation with tissue factor-rich activator is a promising method for monitoring LMWH's.

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

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

    Science.gov (United States)

    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. A sensitive competitive binding assay for exogenous and endogenous heparins

    International Nuclear Information System (INIS)

    Dawes, J.; Pepper, D.S.

    1982-01-01

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

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

    Science.gov (United States)

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

    2012-06-01

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

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

    Science.gov (United States)

    Schönig, Jette C; Mischke, Reinhard H

    2016-07-01

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

  19. Heparin and heparin-induced thrombocytopenia

    African Journals Online (AJOL)

    2007-06-15

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

  20. Heparin pharmacovigilance in Brazil.

    Science.gov (United States)

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Atheer Ahmed

    2012-01-01

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

  2. Heparin-Induced Thrombocytopenia

    Science.gov (United States)

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

  3. Severe heparin osteoporosis in pregnancy.

    OpenAIRE

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

    1984-01-01

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

  4. M/sub r/ 25,000 heparin-binding protein from guinea pig brain is a high molecular weight form of basic fibroblast growth factor

    International Nuclear Information System (INIS)

    Moscatelli, D.; Joseph-Silverstein, J.; Manejias, R.; Rifkin, D.B.

    1987-01-01

    A M/sub r/ 25,000 form of basic fibroblast growth factor (bFGF) has been isolated from guinea pig grain along with the typical M/sub r/ 18,000 form. Both forms were purified to homogeneity by a combination of heparin-affinity chromatography and ion-exchange chromatography on an FPLC Mono S column. The M/sub r/ 25,000 form, like the M/sub r/ 18,000 form was not eluted from the heparin-affinity column with 0.95 M NaCl, but was eluted with 2 M NaCl. The M/sub r/ 25,000 guinea pig protein stimulated plasminogen activator production by cultured bovine capillary endothelial cells in a dose-dependent manner at concentration of 0.1-10 ngml, the same range that was effective for guinea pig and human M/sub r/ 18,000 bFGFs. The binding of human 125 I-labeled bFGF to baby hamster kidney cells is inhibited equally by the M/sub r/ 25,000 guinea pig protein and the M/sub r/ 18,000 guinea pig and human bFGFs. Polyclonal antibodies raised against human bFGF recognize both the M/sub r/ 25,000 and 18,000 guinea pig proteins in an immunoblot analysis. In a radioimmunoassay, both the M/sub r/ 25,000 and M/sub r/ 18,000 guinea pig proteins compete equally well with iodinated human bFGF for binding to the anti-human bFGF antibodies. When treated with low concentrations of trypsin, the M/sub r/ 25,000 guinea pig bFGF was converted to a M/sub r/ 18,000 protein. These results show that the two molecules are closely related and suggest that the M/sub r/ 25,000 protein shares substantial homology with the M/sub r/ 18,000 bFGF

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

    Science.gov (United States)

    Lynch, D M; Howe, S E

    1985-11-01

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

  6. Influence of heparin on radioimmunological assay of ACTH

    International Nuclear Information System (INIS)

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

    1986-01-01

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

  7. Heparin: Past, Present, and Future.

    Science.gov (United States)

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

    2016-07-04

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

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

    International Nuclear Information System (INIS)

    Durran, Alexandra C.; Watts, Christopher

    2012-01-01

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

  9. Sterilization of heparinized cuprophan hemodialysis membranes

    OpenAIRE

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

    1996-01-01

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

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

    NARCIS (Netherlands)

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

    1983-01-01

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

  11. Collection of heparinized plasma by plasmapheresis

    NARCIS (Netherlands)

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

    1999-01-01

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

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

    Science.gov (United States)

    Saba, T M; Antikatzides, T G

    1979-04-01

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

  13. How to give a heparin shot

    Science.gov (United States)

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

  14. Interference of heparin in carcinoembryonic antigen radioimmunoassays

    International Nuclear Information System (INIS)

    Wu, J.T.

    1983-01-01

    A false Roche carcinoembryonic antigen (CEA) activity could be detected in all commercial and noncommercial heparin preparations examined. The possibility of 'due to contamination' has been ruled out. Using the Roche procedure, heparin solutions, in the absence of CEA, gave positive CEA activity; on the other hand, no CEA activity was detected in solutions containing only heparin when the Abbott Kit was used. When heparin was present in specimens containing CEA, the Abbott Kit underestimated the CEA activity, whereas the Roche Kit gave false elevated values. However, the negative effect of heparin could be reduced by heat treatment in the presence of plasma proteins. (Auth.)

  15. Analysis and characterization of heparin impurities.

    Science.gov (United States)

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

    2011-01-01

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

  16. Improved assay for measuring heparin binding to bull sperm

    International Nuclear Information System (INIS)

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

    1988-01-01

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

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

    Science.gov (United States)

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

    2018-03-27

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

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

    Directory of Open Access Journals (Sweden)

    Antonijević Nebojša

    2004-01-01

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

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

    Science.gov (United States)

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

    2004-01-01

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

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

    Science.gov (United States)

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

    2011-02-02

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

  1. Sterilization of heparinized cuprophan hemodialysis membranes

    NARCIS (Netherlands)

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

    1996-01-01

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

  2. 21 CFR 864.7525 - Heparin assay.

    Science.gov (United States)

    2010-04-01

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

  3. Allergic anaphylaxis due to subcutaneously injected heparin

    Directory of Open Access Journals (Sweden)

    Anders Diana

    2013-01-01

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

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

    Science.gov (United States)

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

    2016-08-16

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

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

    Science.gov (United States)

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

    2013-09-01

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

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

    Science.gov (United States)

    Mikus, Peter; Valásková, Iva; Havránek, Emil

    2004-11-15

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

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

    DEFF Research Database (Denmark)

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

    2000-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Giuliana Zisa

    2013-03-01

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

  9. Preparation and characterization of microspheres of albumin-heparin conjugates

    NARCIS (Netherlands)

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

    1991-01-01

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

  10. Click-coated, heparinized, decellularized vascular grafts.

    Science.gov (United States)

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

    2015-02-01

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

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

    International Nuclear Information System (INIS)

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

    1986-01-01

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

  12. 77 FR 7584 - Draft Guidance for Industry on Heparin for Drug and Medical Device Use; Monitoring Crude Heparin...

    Science.gov (United States)

    2012-02-13

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

  13. 78 FR 38058 - Guidance for Industry on Heparin for Drug and Medical Device Use: Monitoring Crude Heparin for...

    Science.gov (United States)

    2013-06-25

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

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

    Directory of Open Access Journals (Sweden)

    Alireza Jahangirifard

    2016-08-01

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

  15. Cationization of heparin for film applications

    Czech Academy of Sciences Publication Activity Database

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Milne Ruairidh

    2001-10-01

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

  17. Pharmacokinetics of heparin and related polysaccharides

    International Nuclear Information System (INIS)

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

    1989-01-01

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

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

    International Nuclear Information System (INIS)

    Sawakami, Kimihiko; Ishikawa, Seiichi; Ito, Takui

    2011-01-01

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

  19. DEGRADATION AND INTRAHEPATIC COMPATIBILITY OF ALBUMIN-HEPARIN CONJUGATE MICROSPHERES

    NARCIS (Netherlands)

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

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

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

    Science.gov (United States)

    1975-07-12

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

  1. Endogenous heparin levels in the controlled asthmatic patient ...

    African Journals Online (AJOL)

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

  2. Heparin increases food intake through AgRP neurons

    Science.gov (United States)

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

  3. Multifunctional silk-heparin biomaterials for vascular tissue engineering applications

    Science.gov (United States)

    Seib, F. Philipp; Herklotz, Manuela; Burke, Kelly A.; Maitz, Manfred F.; Werner, Carsten; Kaplan, David L.

    2013-01-01

    Over the past 30 years, silk has been proposed for numerous biomedical applications that go beyond its traditional use as a suture material. Silk sutures are well tolerated in humans, but the use of silk for vascular engineering applications still requires extensive biocompatibility testing. Some studies have indicated a need to modify silk to yield a hemocompatible surface. This study examined the potential of low molecular weight heparin as a material for refining silk properties by acting as a carrier for vascular endothelial growth factor (VEGF) and improving silk hemocompatibility. Heparinized silk showed a controlled VEGF release over 6 days; the released VEGF was bioactive and supported the growth of human endothelial cells. Silk samples were then assessed using a humanized hemocompatibility system that employs whole blood and endothelial cells. The overall thrombogenic response for silk was very low and similar to the clinical reference material polytetrafluoroethylene. Despite an initial inflammatory response to silk, apparent as complement and leukocyte activation, the endothelium was maintained in a resting, anticoagulant state. The low thrombogenic response and the ability to control VEGF release support the further development of silk for vascular applications. PMID:24099708

  4. Antiproliferative heparin (glycosaminoglycans) isolated from giant ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-05-18

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

  5. Biological distribution of 51Cr-heparin

    International Nuclear Information System (INIS)

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

    1979-01-01

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

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

    Science.gov (United States)

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

    2017-08-30

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

  7. Preventive role of low-molecular-weight heparin in unexplained ...

    African Journals Online (AJOL)

    Hospital, Islamabad, during April 2013 to January 2014, who had a history of ... 2 Department of Obstetrics and Gynecology, Alnafees Medical College, ISRA University, Islamabad, Pakistan ..... Terminology for pregnancy loss prior to viability:.

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

    African Journals Online (AJOL)

    Results: No significant difference in general characteristics or the incidence of tube occlusion was detected ... position adjustment, the reverse connection of .... and the incidence of fibrin shells was highest in the control group (11.40 %; Table 3). Table 1: Occurrence of tube occlusion (N = 70). Variable. Tube occlusion.

  9. Low-molecular-weight heparins allow selected outpatient treatment ...

    African Journals Online (AJOL)

    tor a I. 3. LMWHs may also cause fewer haemorrhagic complications as a result of their less pronounced effect on platelet and vascular endothelial function. These characteristics result in a longer half-life, better bio- availability, and more predictable anticoagulant activity.3.' The LMWHs can therefore be administered ...

  10. Estudo experimental dos efeitos da heparina de baixo peso molecular (Enoxaparina na formação de calo ósseo em fêmures de ratos The effects of low-molecular-weight heparin (Enoxaparin on bony callus formation in rats' femurs - an experimental study

    Directory of Open Access Journals (Sweden)

    Salim Mussi Filho

    2006-01-01

    Full Text Available O tromboembolismo venoso é uma complicação grave que pode ocorrer após fraturas. O tratamento anticoagulante mais utilizado é com a heparina de baixo peso molecular (HBPM. Existem estudos que mostram que essa droga pode interferir no metabolismo ósseo. Com o objetivo de avaliar a influência da HBPM no processo de formação de calo ósseo, realizamos um estudo experimental em ratos. A amostra constituiu-se de 22 ratos de linhagem Wistar, machos, que foram submetidos à fratura diafisária de seus fêmures direitos. Foram divididos em dois grupos de 11. No grupo controle, os animais recebiam soro fisiológico e no grupo de estudo, recebiam HBPM, enoxaparina, diariamente, por 28 dias. Após este período os ratos foram submetidos à eutanásia e os fêmures foram avaliados. No estudo macroscópico foi constatada consolidação em 11 animais (100% que não receberam enoxaparina, e, em dez animais (90,9% que receberam a droga em estudo. No estudo histológico foi constatada a formação de calo ósseo em todos os fêmures. Concluiu-se neste experimento que a enoxaparina não altera o processo de consolidação óssea em fêmures de ratos Wistar.Venous thromboembolism is a serious complication that may follow fractures. The most commonly used anticoagulant treatment is low-molecular-weight heparin (LMWH. There are some studies showing that this drug may interfere on bone metabolism. With the objective of evaluating the LMWH influence on the process of bony callus formation, we conducted an experimental study on rats. Sample was constituted of 22 Wistar male rats, which were submitted to diaphyseal fracture on their right femurs. They were divided into two groups of 11 subjects each. In the control group, the animals received saline solution and in the study group, they received LMWH - enoxaparin - in a daily basis, during 28 days. After that period, the rats were submitted to euthanasia for femur assessment purposes. At the macroscopic study

  11. The effect of prophylactic dose of a low molecular weight heparin on skin wound healing of rats Efeito da dose profilática de heparina de baixo peso molecular na cicatrização de feridas na pele de ratos

    Directory of Open Access Journals (Sweden)

    Ozdamar Fuad Oken

    2009-12-01

    Full Text Available PURPOSE: To investigate the effect of prophylactic dose of a low molecular weight heparin, enoxaparin, on skin wound healing of rats. METHODS: Forty rats were used for the study. Rats were randomly assigned to two equal groups. Experimental group received prophylactic dose of enoxaparin. Physiologic saline was administered to the control group. Parameters of wound healing of experimental and control groups were compared. For comparison of the groups in terms of fibrosis, vascularization, inflammation, epithelization, and tensile strength test (Newton. Mann-Whitney-U test was used because variables were categorical data (fibrosis, vascularization, inflammation and epithelization. Differences between groups were analyzed with independent samples t-test (tensile strength. Significance was set at pOBJETIVO: Investigar o efeito de dose profilática da heparina de baixo peso molecular, enoxaparina, na cicatrização de feridas na pele de ratos. MÉTODOS: Quarenta ratos foram utilizados para o estudo. Ratos foram distribuídos aleatoriamente a dois grupos iguais. O grupo experimental recebeu profilática de enoxaparina. Solução salina fisiologica foi administrada ao grupo controle. Foram comparados parâmetros de cicatrização dos grupos experimental e controle.Os grupos foram comparados em termos de fibrose, vascularização, inflamação, epitelização e força tensil (teste de Newton. Foi realizado o teste de Mann-Whitney-U para variáveis com dados categóricos (fibrose, cicatrização, inflamação e epitelização. Diferenças entre os grupos foram analisadas como amostras independentes pelo t-teste (força tensil. Significância foi fixada para p < 0,05. RESULTADOS: A ferida do grupo experimental apresentou força tensil diminuída significativamente (p < 0,001, o exame histopatológico revelou um significativo (p < 0,001 retardo na epitelização e diminuição na fibrose, cicatrização, inflamação (p < 0,001 no grupo experimental

  12. A spectroscopic study of interaction of cationic dyes with heparin

    Directory of Open Access Journals (Sweden)

    R. Nandini

    2010-01-01

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

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

    Science.gov (United States)

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

    2015-04-01

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

  14. Does ′heparin-induced thrombocytopenia′ hit our minds?

    Directory of Open Access Journals (Sweden)

    Arun R Thangavel

    2016-01-01

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

  15. Immunomodulating effects of heparin on human B cell proliferation

    International Nuclear Information System (INIS)

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

    1993-01-01

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

  16. [Obstetrical APS: Is there a place for additional treatment to aspirin-heparin combination?

    Science.gov (United States)

    Mekinian, A; Kayem, G; Cohen, J; Carbillon, L; Abisror, N; Josselin-Mahr, L; Bornes, M; Fain, O

    2017-01-01

    Obstetrical APS is defined by thrombosis and/or obstetrical morbidity associated with persistent antiphospholipid antibodies. The aspirin and low molecular weighted heparin combination dramatically improved obstetrical outcome in APS patients. Several factors could be associated with obstetrical prognosis, as previous history of thrombosis, associated SLE, the presence of lupus anticoagulant and triple positivity of antiphospholipid antibodies. Obstetrical APS with isolated recurrent miscarriages is mostly associated with isolated anticardiolipids antibodies and have better obstetrical outcome. The pregnancy loss despite aspirin and heparin combination define the refractory obstetrical APS, and the prevalence could be estimated to 20-39%. Several other treatments have been used in small and open labeled studies, as steroids, intravenous immunoglobulins, plasma exchanges and hydroxychloroquine to improve the obstetrical outcome. Some other drugs as eculizumab and statins could also have physiopathological rational, but studies are necessary to define the place of these various drugs. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  17. SPECIFIC ASPECTS OF INTERACTION OF PLATELETS WITH THE HEPARINIZED MATERIALS

    Directory of Open Access Journals (Sweden)

    E.A. Nemets

    2012-01-01

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

  18. 99m Tc-labeled heparin test in orthopaedic surgery

    International Nuclear Information System (INIS)

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

    1983-01-01

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

  19. Citrate Anticoagulation for CRRT in Children: Comparison with Heparin

    Directory of Open Access Journals (Sweden)

    Sara Nicole Fernández

    2014-01-01

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

  20. Heparin release from thermosensitive polymer coatings: in vivo studies

    NARCIS (Netherlands)

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

    1995-01-01

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

  1. Use of heparin in the investigation of obscure gastrointestinal bleeding

    International Nuclear Information System (INIS)

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

    2001-01-01

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

  2. Printed microfluidic filter for heparinized blood.

    Science.gov (United States)

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

    2017-05-01

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

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2010-01-01

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

  5. Effects of heparin on insulin binding and biological activity

    International Nuclear Information System (INIS)

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

    1987-01-01

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

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

    Science.gov (United States)

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

    2013-11-01

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

  7. Increased accuracy in heparin and protamine administration decreases bleeding

    DEFF Research Database (Denmark)

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

    2009-01-01

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

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

    Science.gov (United States)

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

    2018-05-20

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

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

    NARCIS (Netherlands)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2015-05-01

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

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

    International Nuclear Information System (INIS)

    Mor, Visesato; Chatterjee, Tapati

    2007-01-01

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

  12. Heparin: The Silver Bullet of Aneurysmal Subarachnoid Hemorrhage?

    Directory of Open Access Journals (Sweden)

    Nicolas K. Khattar

    2018-03-01

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

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

    Science.gov (United States)

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

    2014-11-01

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

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

    Science.gov (United States)

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

    2015-02-09

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

  15. The efficacy and safety of enoxaparin versus unfractionated heparin for prevention of deep vein thrombosis in elective cancer surgery. A double blind randomized multicentre trail with venographic assesment

    DEFF Research Database (Denmark)

    Bergkvist, A; Eldor, A; Thorlacius-Ussing, O.

    1997-01-01

    BACKGROUND: Surgery for malignant disease carries a high risk of deep vein thrombosis. The aim of this study was to evaluate the prophylactic effect of a low molecular weight heparin, enoxaparin, 40 mg once daily, beginning 2 h before surgery, compared with that of unfractionated low-dose heparin...... three times daily. METHODS: Patients included were over 40 years of age and undergoing planned elective curative abdominal or pelvic surgery for cancer. The study was designed as a prospective double-blind randomized multicentre trial with participating departments from ten countries. Primary outcome...... severe thrombocytopenia. There were no differences in mortality at either 30 days or 3 months. CONCLUSION: Enoxaparin, 40 mg once daily, is as safe and effective as unfractionated heparin three times daily in preventing venous thromboembolism in patients undergoing major elective surgery for abdominal...

  16. Profiling Heparin-Chemokine Interactions Using Synthetic Tools

    Science.gov (United States)

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

    2009-01-01

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

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

    NARCIS (Netherlands)

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

    1989-01-01

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

  18. Successful Deep Inferior Epigastric Perforator Flap Harvest despite Preoperative Therapeutic Subcutaneous Heparin Administration into the Abdominal Pannus.

    Science.gov (United States)

    Duncumb, Joseph W; Miyagi, Kana; Forouhi, Parto; Malata, Charles M

    2016-01-01

    Abdominal free flaps for microsurgical breast reconstruction are most commonly harvested based on the deep inferior epigastric vessels that supply skin and fat via perforators through the rectus muscle and sheath. Intact perforator anatomy and connections are vital for subsequent optimal flap perfusion and avoidance of necrosis, be it partial or total. The intraflap vessels are delicate and easily damaged and it is generally advised that patients should avoid heparin injection into the abdominal pannus preoperatively as this may compromise the vascular perforators through direct needle laceration, pressure from bruising, haematoma formation, or perforator thrombosis secondary to external compression. We report three cases of successful deep inferior epigastric perforator (DIEP) flap harvest despite patients injecting therapeutic doses of low molecular weight heparin into their abdomens for thrombosed central venous lines (portacaths™) used for administering primary chemotherapy in breast cancer.

  19. Successful Deep Inferior Epigastric Perforator Flap Harvest despite Preoperative Therapeutic Subcutaneous Heparin Administration into the Abdominal Pannus

    Directory of Open Access Journals (Sweden)

    Joseph W. Duncumb

    2016-01-01

    Full Text Available Abdominal free flaps for microsurgical breast reconstruction are most commonly harvested based on the deep inferior epigastric vessels that supply skin and fat via perforators through the rectus muscle and sheath. Intact perforator anatomy and connections are vital for subsequent optimal flap perfusion and avoidance of necrosis, be it partial or total. The intraflap vessels are delicate and easily damaged and it is generally advised that patients should avoid heparin injection into the abdominal pannus preoperatively as this may compromise the vascular perforators through direct needle laceration, pressure from bruising, haematoma formation, or perforator thrombosis secondary to external compression. We report three cases of successful deep inferior epigastric perforator (DIEP flap harvest despite patients injecting therapeutic doses of low molecular weight heparin into their abdomens for thrombosed central venous lines (portacaths™ used for administering primary chemotherapy in breast cancer.

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

    International Nuclear Information System (INIS)

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

    1989-01-01

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

  1. Quantitation of heparosan with heparin lyase III and spectrophotometry.

    Science.gov (United States)

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

    2014-02-15

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

  2. Heparin-Based Nanoparticles: An Overview of Their Applications

    Directory of Open Access Journals (Sweden)

    Maria del Pilar Rodriguez-Torres

    2018-01-01

    Full Text Available This review deals with nanoparticles synthesized using heparin. Such nanoparticles have been widely studied since a long time ago, obtaining satisfactory outcomes. An outstanding aspect of these nanoparticles is that they possess good biocompatible characteristics, and since heparin is produced in the human body within the mast cells, this makes these nanoparticles useful for future applications like imaging, disease and cancer treatment, and antibacterial activity. They can also be used for applications that are not oriented directly to the medical and biological areas such as in the case of analyte detection in aqueous solution, although such studies are very few. These nanoparticles synthesis is mainly through wet chemistry methods, using heparin that could have been modified or not.

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

    Science.gov (United States)

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

    2017-09-01

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

  4. Prevention of deep vein thrombosis after hip replacement: randomised comparison between unfractionated heparin and low molecular weight heparin

    NARCIS (Netherlands)

    Leyvraz, P. F.; Bachmann, F.; Hoek, J.; Büller, H. R.; Postel, M.; Samama, M.; Vandenbroek, M. D.

    1991-01-01

    To evaluate the efficacy and safety of two subcutaneous prophylactic regimens for postoperative deep vein thrombosis after total hip replacement. Prospective open randomised multicentre trial. 28 European departments of orthopaedic surgery. All patients had bilateral phlebography 10 days after

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

    Science.gov (United States)

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

    2016-02-01

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

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

    African Journals Online (AJOL)

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

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

    Directory of Open Access Journals (Sweden)

    Samuel Adediran

    2017-01-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    Science.gov (United States)

    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.

  10. 12500 E heparin and 12500 E of a semisynthetic heparin analogue (SSHA) in preventing thrombosis during radiotherapy of gynaecological carcinomas

    International Nuclear Information System (INIS)

    Hilscher, T.M.

    1983-01-01

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

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

    Science.gov (United States)

    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.

  12. Cyclic Voltammetry of Biopolymer Heparin at PVC Plasticized Liquid Membrane

    Czech Academy of Sciences Publication Activity Database

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

    2003-01-01

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

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

    Indian Academy of Sciences (India)

    Prakash

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

  14. 21 CFR 864.5680 - Automated heparin analyzer.

    Science.gov (United States)

    2010-04-01

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

  15. Alternative method for determination of contaminated heparin using chiral recognition.

    Science.gov (United States)

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

    2014-05-15

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

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

    Science.gov (United States)

    Piepkorn, Michael W.

    1981-01-01

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

  17. Highly sensitive ratiometric detection of heparin and its oversulfated chondroitin sulfate contaminant by fluorescent peptidyl probe.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    Shahbazi, Mohammad-Ali; Hamidi, Mehrdad

    2013-11-01

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

  19. Bleeding risk during treatment of acute thrombotic events with subcutaneous LMWH compared to intravenous unfractionated heparin; a systematic review.

    Directory of Open Access Journals (Sweden)

    Giorgio Costantino

    Full Text Available BACKGROUND: Low Molecular Weight Heparins (LMWH are at least as effective antithrombotic drugs as Unfractionated Heparin (UFH. However, it is still unclear whether the safety profiles of LMWH and UFH differ. We performed a systematic review to compare the bleeding risk of fixed dose subcutaneous LMWH and adjusted dose UFH for treatment of venous thromboembolism (VTE or acute coronary syndromes (ACS. Major bleeding was the primary end point. METHODS: Electronic databases (MEDLINE, EMBASE, and the Cochrane Library were searched up to May 2010 with no language restrictions. Randomized controlled trials in which subcutaneous LMWH were compared to intravenous UFH for the treatment of acute thrombotic events were selected. Two reviewers independently screened studies and extracted data on study design, study quality, incidence of major bleeding, patients' characteristics, type, dose and number of daily administrations of LMWH, co-treatments, study end points and efficacy outcome. Pooled odds ratios (OR and 95% confidence intervals (CI were calculated using the random effects model. RESULTS: Twenty-seven studies were included. A total of 14,002 patients received UFH and 14,635 patients LMWH. Overall, no difference in major bleeding was observed between LMWH patients and UFH (OR = 0.79, 95% CI 0.60-1.04. In patients with VTE LMWH appeared safer than UFH, (OR = 0.68, 95% CI 0.47-1.00. CONCLUSION: The results of our systematic review suggest that the use of LMWH in the treatment of VTE might be associated with a reduction in major bleeding compared with UFH. The choice of which heparin to use to minimize bleeding risk must be based on the single patient, taking into account the bleeding profile of different heparins in different settings.

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

    Directory of Open Access Journals (Sweden)

    Erik G. Hayman

    2017-05-01

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

  1. Postpartum Osteoporosis and Thoracic Vertebral Fracture in a Patient Treated with Heparin During Pregnancy

    Directory of Open Access Journals (Sweden)

    Ayse Aydemir Ekim

    2016-05-01

    Full Text Available Postpartum osteoporosis (PPO is a rare form of osteoporosis related to pregnancy. We report the case of a 35-year-old woman who consulted for severe low-back pain one week after her delivery. This woman had a personal history of protein C deficiency and was treated with low-molecular-weight heparin (LMWH 40 mg/day during her pregnancy. Her body mass index was 19.8 and she had only gained 8 kg during pregnancy. Magnetic resonance imaging (MRI revealed a fracture of thoracic 11. Dual-energy X-ray absorptiometry (DEXA measured T score = - 4,9 and Z score = -4,8 in Lumbar 1-4 vertebrae. These findings suggest that PPO may be one of the causes of severe back pain in postpartum patients. We think that PPO risk is higher in those patients with low BMI who were treated with LMWH during pregnancy.

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

    Science.gov (United States)

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

    2017-06-01

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

  3. Voltammetric determination of heparin based on its interaction with ...

    African Journals Online (AJOL)

    ... with the linear regression equation as ∆ip″ (nA) = 360.19 C (mg/L) + 178.88 (n = 15, γ = 0.998) and the detection limit as 0.28 mg/L (3σ). The effects of coexisting substances such as metal ions, amino acids on the determination of heparin were investigated and the results showed that this method had good selectivity.

  4. Protein interactions with quaternized chitosan/heparin multilayers

    Czech Academy of Sciences Publication Activity Database

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

    2016-01-01

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

  5. Heparin defends against the toxicity of circulating histones in sepsis.

    Science.gov (United States)

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

    2015-06-01

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

  6. The Use of Heparin during Endovascular Peripheral Arterial Interventions: A Synopsis

    Directory of Open Access Journals (Sweden)

    Arno M. Wiersema

    2016-01-01

    Full Text Available A large variety exists for many aspects of the use of heparin as periprocedural prophylactic antithrombotics (PPAT during peripheral arterial interventions (PAI. This variation is present, not only within countries, but also between them. Due to a lack of (robust data, no systematic review on the use of heparin during PAI could be justified. A synopsis of all available literature on heparin during PAI describes that heparin is used on technical equipment to reduce the thrombogenicity and in the flushing solution with saline. Heparin could have a cumulative anticoagulant effect when used in combination with ionic contrast medium. No level-1 evidence exists on the use of heparin. A measurement of actual anticoagulation status by means of an activated clotting time should be mandatory.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1986-02-01

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

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

    OpenAIRE

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2017-06-21

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

    McKinney, Mark C; Riley, Jeffrey B

    2007-12-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

  13. A need for evidence-based clinical practice guidelines for the use of heparins in the elderly

    Directory of Open Access Journals (Sweden)

    Isabelle Gouin-Thibault

    2010-04-01

    Full Text Available Isabelle Gouin-Thibault1,2, Virginie Siguret1,2, Eric Pautas2,31Assistance Publique Hôpitaux de Paris, Laboratoire d’Hématologie, Hôpital Charles Foix, Paris, France; 2Université Paris Descartes, INSERM U, Paris, France; 3Assistance Publique Hôpitaux de Paris, Unité de Gériatrie Aiguë, Hôpital Charles Foix, Paris, FranceAbstract: Low-molecular-weight heparins (LMWHs have been widely studied in pivotal clinical trials or in several meta-analyses. However, the safety and optimal use of LMWHs in high-risk patients such as the very elderly remains uncertain since these patients are usually excluded from clinical trials. In terms of LMWHs in the elderly, the main concerns are renal failure and the risk of accumulation. A clinical approach consisting of a LMWH dose reduction in the elderly should be considered with great caution in terms of efficacy, since it has been tested neither in the treatment of VTE nor in VTE prophylaxis. If monitoring is considered in patients receiving therapeutic dose LMWHs, appropriate target ranges for peak anti-Xa activity levels should be used and so far, no anti-Xa activity-based guidelines have been issued. Moreover, no data support any laboratory monitoring in elderly patients treated with prophylactic dose LMWHs.Keywords: elderly patients, low-molecular-weight heparin, renal insufficiency, evidence-based medicine

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

    Science.gov (United States)

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

    2016-03-01

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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Meital Cohen-Mazor

    2015-01-01

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

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

    Science.gov (United States)

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

    2016-12-12

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

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

    NARCIS (Netherlands)

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

    1991-01-01

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

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

    NARCIS (Netherlands)

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

    1997-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Sara C. Meyer

    2017-01-01

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

  1. Heparinization of alimentation solutions administered through peripheral veins in premature infants: a controlled study.

    Science.gov (United States)

    Alpan, G; Eyal, F; Springer, C; Glick, B; Goder, K; Armon, J

    1984-09-01

    A randomized controlled study was done to determine whether the addition of heparin (1 U/mL) to peripheral intravenous alimentation solutions would affect the incidence of phlebitis and duration of patency of intravenous catheters in premature infants. Twenty-two-gauge Teflon catheters were uniformly used. One hundred five catheters infused with heparin were placed in 13 infants, and 122 catheters were placed in the control group of 13 infants. The time, nature, and incidence of complications were noted for each infusion site. Infusion of heparin was found to double the duration of patency of intravenous catheters and to reduce significantly the incidence of phlebitis. No complications related to the administration of heparin were noted. Heparinization of intravenous alimentation solutions should therefore be considered in premature infants as a means of reducing the work load and incidence of complications associated with peripheral lines.

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

    Directory of Open Access Journals (Sweden)

    Ho-Ming Su

    2005-03-01

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

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

    Science.gov (United States)

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

    2016-06-09

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

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

    International Nuclear Information System (INIS)

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

    1985-01-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

  6. Oral heparin delivery: design and in vivo evaluation of a stomach-targeted mucoadhesive delivery system.

    Science.gov (United States)

    Schmitz, Thierry; Leitner, Verena M; Bernkop-Schnürch, Andreas

    2005-05-01

    Low molecular weight heparin (LMWH) is an agent of choice in the anti-coagulant therapy and prophylaxis of thrombosis and coronary syndromes. However, the therapeutic use is partially limited due to a poor oral bioavailability. It was therefore the aim of this study to design and evaluate a highly efficient stomach-targeted oral delivery system for LMWH. In order to appraise the influence of the molecular weight on the oral bioavailability, mini-tablets comprising 3 kDa (279 IU) and 6 kDa (300 IU) LMWH, respectively, were generated and tested in vivo in rats. The potential of the test formulations based on thiolated polycarbophil, was evaluated in comparison to hydroxyethylcellulose (HEC) as control carrier matrix. The plasma levels of LMWH after oral versus subcutaneous administration were determined in order to calculate the relative bioavailability. With the delivery system containing 3 kDa LMWH (279 IU) a relative bioavailability of 19.1% was achieved, offering a significantly (p thiolated polymers are a promising tool for the non-invasive stomach-targeted systemic delivery of LMWH as model for a hydrophilic macromolecular polysaccharide. Copyright 2005 Wiley-Liss, Inc

  7. [Effect of early intervention with heparin on function of coagulopathy, liver and kidney in rats with exertional heatstroke under the ambient air of high temperature and low humidity].

    Science.gov (United States)

    Yu, Yang; Wei, Yuying; Zhang, Xiangrong; Li, Xinyu

    2018-03-01

    To explore the effects of early intervention with heparin on function of coagulopathy, liver and kidney as well as the prognosis in rats with exertional heatstroke (EHS) under the ambient air of high temperature and low humidity. 108 healthy SPF male Sprague-Dawley (SD) rats were randomly divided into normal temperature control group, EHS + normal saline (NS) group and EHS + heparin group. Of which 54 rats were collected for survival analysis (18 rats in each group), the weight change and 8-hour survival rate were observed, and Kaplan-Meier survival curves were drawn. Other 54 rats were collected for intervention experiment, the rats in each group were subdivided into 0, 1, 2 hours subgroups according to the time points of intervention with heparin after model reproduction, with 6 rats in each subgroup. The rats were placed in an artificial experiment cabin with northwest special environment, and the temperature and the relative humidity were (25.0±1.0) centigrade and (35±5)%, respectively, in normal temperature control group, and the rats were not treated in the cabin. The rats in EHS + NS group and EHS + heparin group kept running in the cabin which temperature and relative humidity were set at (43.0±0.5) centigrade and (35±5)% until the anus temperature of rats reached 43.0 centigrade, and then the rats were placed in room temperature. The rats were injected with 1 mL/kg NS or 250 U/kg heparin sodium injection through their caudal veins at 0, 1, and 2 hours, respectively, and then the blood was collected after 1.5 hours to determine the biochemical parameters including coagulation, liver and kidney as well as platelet count (PLT). (1) The weight loss of EHS + NS group and EHS + heparin group was more significant than that of normal temperature control group (g: 8.28±1.41, 8.39±1.38 vs. 2.06±1.06, both P < 0.05), but there was no significant difference between EHS + NS group and EHS + heparin group. (2) As the time went on after modeling, serum creatinine

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

    LENUS (Irish Health Repository)

    Shuhaibar, M N

    2012-02-03

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

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

    Directory of Open Access Journals (Sweden)

    Nipaporn Ngernyuang

    2018-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Gerd Bendas

    2012-01-01

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

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

    International Nuclear Information System (INIS)

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

    2006-01-01

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

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

    Science.gov (United States)

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

    2001-01-01

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

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

    International Nuclear Information System (INIS)

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

    1986-01-01

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

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

    Science.gov (United States)

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

    2017-09-01

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

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2007-11-01

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

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

    Science.gov (United States)

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

    2015-06-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-09-15

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

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

    Science.gov (United States)

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

    2015-10-28

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

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

    Science.gov (United States)

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

    2011-01-01

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

  1. Community nurse resource implications for a change in heparin prophylaxis policy

    Directory of Open Access Journals (Sweden)

    Parker Martyn J.

    2015-01-01

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

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

    Science.gov (United States)

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

    2006-04-01

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

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

  4. Hyaluronan- and heparin-reduced silver nanoparticles with antimicrobial properties

    Science.gov (United States)

    Kemp, Melissa M; Kumar, Ashavani; Clement, Dylan; Ajayan, Pulickel; Mousa, Shaker

    2009-01-01

    Aims Silver nanoparticles exhibit unique antibacterial properties that make these ideal candidates for biological and medical applications. We utilized a clean method involving a single synthetic step to prepare silver nanoparticles that exhibit antimicrobial activity. Materials & methods These nanoparticles were prepared by reducing silver nitrate with diaminopyridinylated heparin (DAPHP) and hyaluronan (HA) polysaccharides and tested for their efficacy in inhibiting microbial growth. Results & discussion The resulting silver nanoparticles exhibit potent antimicrobial activity against Staphylococcus aureus and modest activity against Escherichia coli. Silver–HA showed greater antimicrobial activity than silver–DAPHP, while silver–glucose nanoparticles exhibited very weak antimicrobial activity. Neither HA nor DAPHP showed activity against S. aureus or E. coli. Conclusion These results suggest that DAPHP and HA silver nanoparticles have potential in antimicrobial therapeutic applications. PMID:19505245

  5. Low Molecular Weight Heparin in Portal Vein Thrombosis of Cirrhotic Patients: Only Therapeutic Purposes?

    Directory of Open Access Journals (Sweden)

    Raffaele Licinio

    2014-01-01

    Full Text Available Cirrhosis has always been regarded as hemorrhagic coagulopathy caused by the reduction in the hepatic synthesis of procoagulant proteins. However, with the progression of liver disease, the cirrhotic patient undergoes a high rate of thrombotic phenomena in the portal venous system. Although the progression of liver failure produces a reduction in the synthesis of anticoagulant molecules, a test able to detect the patients with hemostatic balance shifting towards hypercoagulability has not yet been elaborated. The need of treatment and/or prophylaxis of cirrhotic patients is demonstrated by the increased mortality, the risk of bleeding from esophageal varices, and the mortality of liver transplantation, when portal vein thrombosis (PVT occurs even if current guidelines do not give indications about PVT treatment in cirrhosis. In view of the general feeling that the majority of cirrhotic patients at an advanced stage may be in a procoagulant condition (suggested by the sharp increase in the prevalence of PVT, it is presumable that a prophylaxis of this population could be of benefit. The safety and the efficacy of prophylaxis and treatment with enoxaparin in patients with cirrhosis demonstrated by a single paper suggest this option only in controlled trials and, currently, there are no sufficient evidences for a recommendation in the clinical practice.

  6. Does low-molecular-weight heparin influence the antimyeloma effects of thalidomide?

    DEFF Research Database (Denmark)

    Beksac, Meral; Waage, Anders; Bringhen, Sara

    2015-01-01

    of thalidomide treatment, response rate was higher among those receiving LMWH vs. none vs. other anticoagulants (58.1 vs. 44.9 vs. 50.4%, p = 0.01). PFS was significantly longer (median 32 vs. 21 and 17 vs. 17 months, p = 0.004) only among international scoring system (ISS) I patients receiving MPT ± LMWH vs. MP...... ± LMWH. The group of MPT patients who also received LMWH had a better OS compared to those who did not [45 months, 95% confidence interval (CI) 27.7-62.3, vs. 32 months, 95% CI 26.1-37.9; p = 0.034]. When multivariate analysis was repeated in subgroups, thalidomide was no longer a significant factor...

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

    International Nuclear Information System (INIS)

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

    2012-12-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1976-06-01

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

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

    Science.gov (United States)

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

    2014-10-14

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

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

    Directory of Open Access Journals (Sweden)

    Ha Na Kim

    2017-05-01

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

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

    International Nuclear Information System (INIS)

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

    1982-01-01

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

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

    Science.gov (United States)

    Fu, Xiuli; Chen, Lingxin; Li, Jinhua

    2012-08-21

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-07-01

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

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

    Science.gov (United States)

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

    2012-03-01

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

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

    Science.gov (United States)

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

    2014-07-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2017-04-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-06-01

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

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

    Science.gov (United States)

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

    2001-01-01

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

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

    Science.gov (United States)

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

    2014-12-01

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

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

    Science.gov (United States)

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

    2016-10-12

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

  2. Endostatin competes with bFGF for binding to heparin-like glycosaminoglycans

    International Nuclear Information System (INIS)

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

    2005-01-01

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

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

    International Nuclear Information System (INIS)

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

    1990-01-01

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

  4. Heparin octasaccharide decoy liposomes inhibit replication of multiple viruses

    Science.gov (United States)

    Hendricks, Gabriel L.; Velazquez, Lourdes; Pham, Serena; Qaisar, Natasha; Delaney, James C.; Viswanathan, Karthik; Albers, Leila; Comolli, James C.; Shriver, Zachary; Knipe, David M.; Kurt-Jones, Evelyn A.; Fygenson, Deborah K.; Trevejo, Jose M.

    2016-01-01

    Heparan sulfate (HS) is a ubiquitous glycosaminoglycan that serves as a cellular attachment site for a number of significant human pathogens, including respiratory syncytial virus (RSV), human parainfluenza virus 3 (hPIV3), and herpes simplex virus (HSV). Decoy receptors can target pathogens by binding to the receptor pocket on viral attachment proteins, acting as ‘molecular sinks’ and preventing the pathogen from binding to susceptible host cells. Decoy receptors functionalized with HS could bind to pathogens and prevent infection, so we generated decoy liposomes displaying HS-octasaccharide (HS-octa). These decoy liposomes significantly inhibited RSV, hPIV3, and HSV infectivity in vitro to a greater degree than the original HS-octa building block. The degree of inhibition correlated with the density of HS-octa displayed on the liposome surface. Decoy liposomes with HS-octa inhibited infection of viruses to a greater extent than either full-length heparin or HS-octa alone. Decoy liposomes were effective when added prior to infection or following the initial infection of cells in vitro. By targeting the well-conserved receptor-binding sites of HS-binding viruses, decoy liposomes functionalized with HS-octa are a promising therapeutic antiviral agent and illustrate the utility of the liposome delivery platform. PMID:25637710

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

    Science.gov (United States)

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

    2014-01-01

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

  6. Convective Leakage Makes Heparin Locking of Central Venous Catheters Ineffective Within Seconds: Experimental Measurements in a Model Superior Vena Cava.

    Science.gov (United States)

    Barbour, Michael C; McGah, Patrick M; Ng, Chin H; Clark, Alicia M; Gow, Kenneth W; Aliseda, Alberto

    2015-01-01

    Central venous catheters (CVCs), placed in the superior vena cava (SVC) for hemodialysis or chemotherapy, are routinely filled while not in use with heparin, an anticoagulant, to maintain patency and prevent thrombus formation at the catheter tip. The heparin-locking procedure, however, places the patient at risk for systemic bleeding, as heparin is known to leak from the catheter into the blood stream. We provide evidence from detailed in vitro experiments that shows the driving mechanism behind heparin leakage to be convective-diffusive transport due to the pulsatile flow surrounding the catheter. This novel mechanism is supported by experimental planar laser-induced fluorescence (PLIF) and particle image velocimetry (PIV) measurements of flow velocity and heparin transport from a CVC placed inside a model SVC inside a pulsatile flow loop. The results predict an initial, fast (<10 s), convection-dominated phase that rapidly depletes the concentration of heparin in the near-tip region, the region of the catheter with side holes. This is followed by a slow, diffusion-limited phase inside the catheter lumen, where the concentration is still high, that is insufficient at replenishing the lost heparin concentration in the near-tip region. The results presented here, which are consistent with previous in vivo estimates of 24 hour leakage rates, predict that the concentration of heparin in the near-tip region is essentially zero for the majority of the interdialytic phase, rendering the heparin locking procedure ineffective.

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

    International Nuclear Information System (INIS)

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

    1981-01-01

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

  8. Voltammetric determination of heparin based on its interaction with malachite green

    Directory of Open Access Journals (Sweden)

    Xueliang Niu

    2008-08-01

    Full Text Available In this paper malachite green (MG was used as a bioprobe to determine heparin concentration by linear sweep voltammetry on the dropping mercury working electrode (DME. In Britton-Robinson (B-R buffer solution of pH 1.5, MG had a well-defined second order derivative linear sweep voltammetric reductive peak at –0.618 V (vs. SCE. After the addition of heparin into the MG solution, the reductive peak current decreased apparently without the movement of peak potential. Based on the difference of the peak current, a new voltammetric method for the determination of heparin was established. The conditions for the binding reaction and the electrochemical detection were optimized. Under the selected experimental conditions the difference of peak current was directly proportional to the concentration of heparin in the range from 0.3 to 10.0 mg/L with the linear regression equation as ∆ip″ (nA = 360.19 C (mg/L + 178.88 (n = 15, γ = 0.998 and the detection limit as 0.28 mg/L (3σ. The effects of coexisting substances such as metal ions, amino acids on the determination of heparin were investigated and the results showed that this method had good selectivity. This method was further applied to determine the heparin content in heparin sodium injection samples with satisfactory results and good recovery. The stoichiometry of the biocomplex was calculated by the electrochemical method and the binding mechanism was further discussed.

  9. Short-Term Heparin Kinetics during Catheter Ablation of Atrial Fibrillation.

    Science.gov (United States)

    Gabus, Vincent; Rollin, Anne; Maury, Philippe; Forclaz, Andrei; Pascale, Patrizio; Dhutia, Harshil; Bisch, Laurence; Pruvot, Etienne

    2015-10-01

    Percutaneous catheter ablation of atrial fibrillation (CA-AF) is a treatment option for symptomatic drug-refractory atrial fibrillation (AF). CA-AF carries a risk for thromboembolic complications that has been minimized by the use of intraprocedural intravenous unfractionated heparin (UFH). The optimal administration of UFH as well as its kinetics are not well established and need to be precisely determined. A total 102 of consecutive patients suffering from symptomatic drug-refractory AF underwent CA-AF. The mean age was 61 ± 10 years old. After transseptal puncture of the fossa ovalis, weight-adjusted UFH bolus (100 U/kg) was infused. A significant increase in activated clotting time (ACT) was observed from an average value of 100 ± 27 seconds at baseline, to 355 ± 94 seconds at 10 min (T10), to 375 ± 90 seconds at 20 min (T20). Twenty-four patients failed to reach the targeted ACT value of ≥300 seconds at T10 and more than half of these remained with subtherapeutic ACT values at T20. This subset of patients showed similar clinical characteristics and amount of UFH but were more frequently prescribed preprocedural vitamin K1 than the rest of the study population. In a typical intervention setting, UFH displays unexpected slow anticoagulation kinetics in a significant proportion of procedures up to 20 minutes after infusion. These findings support the infusion of UFH before transseptal puncture or any left-sided catheterization with early ACT measurements to identify patients with delayed kinetics. They are in line with recent guidelines to perform CA-AF under therapeutic anticoagulation. © 2015 Wiley Periodicals, Inc.

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

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

    Science.gov (United States)

    Favaloro, Emmanuel J

    2018-02-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2018-01-15

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

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

    International Nuclear Information System (INIS)

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

    1987-01-01

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

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

    Science.gov (United States)

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

    2017-11-01

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

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Edva Noel

    2015-01-01

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

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

    International Nuclear Information System (INIS)

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

    1985-01-01

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

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

    Science.gov (United States)

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

    1984-01-01

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

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

    Science.gov (United States)

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

    2018-01-31

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

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

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

    Science.gov (United States)

    Li, Xu; Ma, Xiaochun

    2017-11-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

  4. Low molecular weight heparin versus unfractionated heparin in the management of cerebral venous thrombosis: A systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Anjum Qureshi

    2017-05-01

    Conclusion: Trends towards improved mortality and improved functional outcomes were seen in patients treated with LMWH. No result reached statistical significance due to low numbers of studies available for inclusion. There is a need for further large scale randomized trials to definitively investigate the potential benefits of LMWH in the treatment of CVT.

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

    Directory of Open Access Journals (Sweden)

    Bernd Saugel

    2011-01-01

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

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

    DEFF Research Database (Denmark)

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

    2002-01-01

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

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

    Science.gov (United States)

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

    2017-10-05

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2011-11-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2017-08-01

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

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

    Science.gov (United States)

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

    2013-08-06

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

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

    Directory of Open Access Journals (Sweden)

    Marcelo A Lima

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

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

    International Nuclear Information System (INIS)

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

    1984-01-01

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

  15. The physiologic and therapeutic role of heparin in implantation and placentation

    Directory of Open Access Journals (Sweden)

    Michela Quaranta

    2015-01-01

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

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

    International Nuclear Information System (INIS)

    Chaudhuri, T.K.; Brantly, M.

    1984-01-01

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

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

    Science.gov (United States)

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

    1979-02-01

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

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

    Science.gov (United States)

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

    2010-06-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  20. Weight Management

    Science.gov (United States)

    ... Health Information Weight Management English English Español Weight Management Obesity is a chronic condition that affects more ... Liver (NASH) Heart Disease & Stroke Sleep Apnea Weight Management Topics About Food Portions Bariatric Surgery for Severe ...

  1. Blood interaction with a Bioline heparin coated HIA-VAD : A study on calves

    NARCIS (Netherlands)

    vanderKamp, KWHJ; Magielse, CPE; Elstrodt, JM; vanderMeer, J; vanOeveren, W; Rakhorst, G

    The blood compatibility of ventricular assist devices developed by the Helmholtz institute Aachen (HA-VAD's) was tested on calves. Seven calves received a non-coated HIA-VAD (control) and three a Bioline heparin coated device. The circulatory support of these HIA-VAD's lasted one week. Mechanical

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

    Science.gov (United States)

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

    2015-03-01

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

  3. Improved distribution and reduced toxicity of adriamycin bound to albumin-heparin microspheres

    NARCIS (Netherlands)

    Cremers, Harry; Cremers, H.F.M.; Bayon, L.G.; Verrijk, R.; Wesseling, M.M.; Wondergem, J.; Heuff, G.; Kwon, G.S.; Bae, Y.H.; Feijen, Jan; Kim, S.W.

    1995-01-01

    Adriamycin (ADR) was formulated in albumin-heparin conjugate microspheres (AHCMS) to improve site-specific delivery and to reduce the toxicity of the drug. The effect of formulating ADR in AHCMS was investigated upon intrahepatic administration to male Wag/Rij rats. After intraveno-portal (i.v.p.)

  4. Transfer of heparin polyion across a polarized water/ionic liquid membrane interface

    Czech Academy of Sciences Publication Activity Database

    Langmaier, Jan; Samec, Zdeněk; Samcová, E.; Tůma, P.

    2012-01-01

    Roč. 24, OCT 2012 (2012), s. 25-27 ISSN 1388-2481 R&D Projects: GA ČR GAP206/11/0707 Institutional support: RVO:61388955 Keywords : heparin polyion * ionic liquid membrane * amperometric detection Subject RIV: CG - Electrochemistry Impact factor: 4.425, year: 2012

  5. Immobilization of heparin to EDC/NHS-crosslinked collagen. Characterization and in vitro evaluation

    NARCIS (Netherlands)

    Wissink, M.J.B.; Beernink, R.; Pieper, J.S.; Poot, Andreas A.; Engbers, G.H.M.; Beugeling, T.; Beugeling, T.; van Aken, W.G.; Feijen, Jan

    2001-01-01

    In the present study, heparin immobilization to a non-cytotoxic crosslinked collagen substrate for endothelial cell seeding was investigated. Crosslinking of collagen using N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (EDC) and N-hydroxysuccinimide (NHS) resulted in a material containing 14 free

  6. Effect of low-dose heparin on urinary albumin excretion in insulin-dependent diabetes mellitus

    DEFF Research Database (Denmark)

    Myrup, B; Hansen, P M; Jensen, T

    1995-01-01

    We investigated the effect of heparin on urinary albumin excretion in patients with insulin-dependent diabetes mellitus. 39 patients with persistent urinary albumin excretion of 30-300 mg/24 h were randomly treated for 3 months with subcutaneous injections twice daily of isotonic saline, 5000 IU...

  7. Amperometric Sensor for Heparin: Sensing Mechanism and Application in Human Blood Plasma Analysis

    Czech Academy of Sciences Publication Activity Database

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

    2006-01-01

    Roč. 18, 13-14 (2006), s. 1329-1338 ISSN 1040-0397 R&D Projects: GA ČR GA203/04/0424 Institutional research plan: CEZ:AV0Z40400503 Keywords : heparin * amperometry * PVC membrane electrode * sensing mechanism * human blood plasma Subject RIV: CG - Electrochemistry Impact factor: 2.444, year: 2006

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

    Directory of Open Access Journals (Sweden)

    Stefan Asbach

    2011-01-01

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

  9. Extrapulmonary colony formation after intravenous injection of tumour cells into heparin treated animals

    NARCIS (Netherlands)

    Maat, B.

    1978-01-01

    Recent data on extrapulmonary colony formation after heparin administration are inconclusive. A systemic study of this topic was undertaken with 4 experimental tumour systems and 2 distinct periods of reduced clotting capacity in rats and mice. I.v. injection of various numbers of tumour cells into

  10. Influence of heparin on the assay of amitriptyline, clomipramine, and their metabolites

    NARCIS (Netherlands)

    Levering, S.C.M.; Oostelbos, M.C.J.M.; Toll, P.J.M.M.; Loonen, A.J.M.

    1996-01-01

    In this study the effect of the use of lithium heparin containers on the plasma levels of amitriptyline, clomipramine, and their metabolites was investigated. Twenty-five patients (10 men and 15 women, mean age 51.8 ± 14.9 years) taking either amitriptyline or clomipramine in a daily dosage varying

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

    International Nuclear Information System (INIS)

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

    1985-01-01

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

  12. Synthesis and characterization of polystyrene-poly(ethylene oxide)-heparin block copolymers

    NARCIS (Netherlands)

    Vulić, I.; Okano, T.; Kim, S.W.; Feijen, Jan

    1988-01-01

    A procedure for the preparation of new block copolymers composed of a hydrophobic block of polystyrene, a hydrophilic spacer-block of poly(ethylene oxide) and a bioactive block of heparin was investigated. Polystyrene with one amino group per chain was synthesized by free radical oligomerization of

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

    NARCIS (Netherlands)

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

    1990-01-01

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

  14. Heparin interferes with the radioenzymatic and homogeneous enzyme immunoassays for aminoglycosides

    International Nuclear Information System (INIS)

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

    1981-01-01

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

  15. In vitro Heparin Precipitation in the Plasma of Euthyroid women with ...

    African Journals Online (AJOL)

    OBJECTIVE: Women with elevated Lp(a), who are susceptible to atherosclerosis, get to reduce, their cardiovascular disease by in-vivo administration of low dose heparin. And history of recurrent miscarriage associated with auto antibodies have had a high rate of life births in subsequent pregnancies when they were ...

  16. Ergotism of the lower limb complicating DHE-heparin thrombosis prophylaxis. Observation by serial angiography

    Energy Technology Data Exchange (ETDEWEB)

    Warmuth-Metz, M.

    1988-10-01

    Today ergotism is becoming more and more important as a complication in the treatment of migraine headache or thrombosis prophylaxis with DHE heparin. Although complete recovery is seldom reported in the current literature, in our case it was possible to resolve a spasm of the left lower limb completely by early diagnosis and adaequate pharmacological treatment. The case was well documented by serial angiography.

  17. Endothelial glycocalyx degradation induces endogenous heparinization in patients with severe injury and early traumatic coagulopathy

    DEFF Research Database (Denmark)

    Ostrowski, Sisse R; Johansson, Pär I

    2012-01-01

    There is emerging evidence that early trauma-induced coagulopathy (TIC) is mechanistically linked to disruption of the vascular endothelium and its glycocalyx, assessed by thrombomodulin and syndecan 1, respectively. This study evaluated if degradation of the endothelial glycocalyx and ensuing...... release of its heparin-like substances induce autoheparinization and thereby contributes to TIC....

  18. Low dose intravesical heparin as prophylaxis against recurrent noninvasive (stage Ta) bladder cancer

    DEFF Research Database (Denmark)

    Bitsch, M; Hermann, G G; Andersen, J P

    1990-01-01

    A controlled randomized clinical trial was conducted to examine the efficacy of topical low dose heparin (0.125 gm./l., 25,000 units per l.) as prophylaxis against recurrent noninvasive (stage Ta) transitional cell bladder cancer. Transurethral tumor resection was done with irrigation fluid conta...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-05-01

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

  20. Optical sensing of sulfate by polymethinium salt receptors: colorimetric sensor for heparin

    Czech Academy of Sciences Publication Activity Database

    Bříza, T.; Kejík, Z.; Císařová, I.; Králová, Jarmila; Martásek, P.; Král, V.

    2008-01-01

    Roč. 16, - (2008), s. 1901-1903 ISSN 1359-7345 R&D Projects: GA AV ČR KAN200200651; GA ČR(CZ) GA203/06/1038 Institutional research plan: CEZ:AV0Z50520514 Keywords : colorimetric sensor * heparin * polymethinium salt Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.340, year: 2008

  1. The impact of heparin-coated circuits on hemodynamics during and after cardiopulmonary bypass

    NARCIS (Netherlands)

    de Vroege, R; Huybregts, R; van Oeveren, W; van Klarenbosch, J; Linley, G; Mutlu, J; Jansen, E; Hack, E; Eijsman, L; Wildevuur, C

    This study was performed to investigate if heparin-coated extracorporeal circuits can reduce the systemic inflammatory reaction with the subsequent release of vasoactive substances during and after cardiopulmonary bypass. Fifty-one patients scheduled for coronary artery bypass grafting were perfused

  2. ADRIAMYCIN-LOADED ALBUMIN-HEPARIN CONJUGATE MICROSPHERES FOR INTRAPERITONEAL CHEMOTHERAPY

    NARCIS (Netherlands)

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

    1994-01-01

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

  3. Release of proteins via ion exchange from albumin-heparin microspheres

    NARCIS (Netherlands)

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

    1992-01-01

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

  4. Role of the A+ helix in heparin binding to protein C inhibitor

    NARCIS (Netherlands)

    Elisen, M. G.; Maseland, M. H.; Church, F. C.; Bouma, B. N.; Meijers, J. C.

    1996-01-01

    Interactions between proteins and heparin(-like) structures involve electrostatic forces and structural features. Based on charge distributions in the linear sequence of protein C inhibitor (PCI), two positively charged regions of PCI were proposed as possible candidates for this interaction. The

  5. Effect of low-dose heparin on urinary albumin excretion in insulin-dependent diabetes mellitus

    NARCIS (Netherlands)

    Myrup, B.; Hansen, P.M.; Jensen, T.; Kofoed-Enevoldsen, A.; Feldt-Rasmussen, B.; Gram, J.; Kluft, C.; Jespersen, J.; Deckert, T.

    1995-01-01

    We investigated the effect of heparin on urinary albumin excretion in patients with insulin-dependent diabetes mellitus. 39 patients with persistent urinary albumin excretion of 30-300 mg/24 h were randomly treated for 3 months with subcutaneous injections twice daily of isotonic saline, 5000 IU

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

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

    Science.gov (United States)

    Chow, Lesleyann W.

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

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

    Directory of Open Access Journals (Sweden)

    Gbureck Uwe

    2007-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Qiong-Ying Hu

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

  10. 111In-labeled platelets: effects of heparin on uptake by venous thrombi and relationship to the activated partial thromboplastin time

    International Nuclear Information System (INIS)

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

    1982-01-01

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

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

    Science.gov (United States)

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

    2012-10-01

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

  12. Factors Influencing ACT After Intravenous Bolus Administration of 100 IU/kg of Unfractionated Heparin During Cardiac Catheterization in Children.

    Science.gov (United States)

    Muster, Ileana; Haas, Thorsten; Quandt, Daniel; Kretschmar, Oliver; Knirsch, Walter

    2017-10-01

    Anticoagulation using intravenous bolus administration of unfractionated heparin (UFH) aims to prevent thromboembolic complications in children undergoing cardiac catheterization (CC). Optimal UFH dosage is needed to reduce bleeding complications. We analyzed the effect of bolus UFH on activated clotting time (ACT) in children undergoing CC focusing on age-dependent, anesthesia-related, or disease-related influencing factors. This retrospective single-center study of 183 pediatric patients receiving UFH during CC analyzed ACT measured at the end of CC. After bolus administration of 100 IU UFH/kg body weight, ACT values between 105 and 488 seconds were reached. Seventy-two percent were within target level of 160 to 240 seconds. Age-dependent differences were not obtained ( P = .407). The ACT values were lower due to hemodilution (total fluid and crystalloid administration during CC, both P ACT values but occurred more frequently in children between 1 month and 1 year of age (91%). In conclusion, with a bolus of 100 IU UFH/kg, an ACT target level of 160 to 240 seconds can be achieved during CC in children in 72%, which is influenced by hemodilution and anticoagulant and antiplatelet premedication but not by age.

  13. Weighted Clustering

    DEFF Research Database (Denmark)

    Ackerman, Margareta; Ben-David, Shai; Branzei, Simina

    2012-01-01

    We investigate a natural generalization of the classical clustering problem, considering clustering tasks in which different instances may have different weights.We conduct the first extensive theoretical analysis on the influence of weighted data on standard clustering algorithms in both...... the partitional and hierarchical settings, characterizing the conditions under which algorithms react to weights. Extending a recent framework for clustering algorithm selection, we propose intuitive properties that would allow users to choose between clustering algorithms in the weighted setting and classify...

  14. Blend membrane of succinic acid-crosslinked chitosan grafted with heparin/PVA-PEG (polyvinyl alcohol-polyethylene glycol) and its characterization

    Science.gov (United States)

    Sangkota, V. D. A.; Lusiana, R. A.; Astuti, Y.

    2018-04-01

    Crosslinking and grafting reactions are required to modify the functional groups on chitosan to increase the number of its active groups. In this study, crosslinking reaction of succinic acid and grafting reaction of heparin on chitosan were conducted to produce a membrane as a candidate of a hemodialysis membrane. The mole ratio between chitosan and succinate acids was varied to obtain the best composition of modified materials. By blending all the material composition with PVA-PEG, the blend was transformed into a membrane. The resulted membrane was then characterized by various test methods such as tests of thickness, weight, water uptake, pH resistance, tensile strength and membrane hydrophilicity. The results showed that the best composition of the membrane reached in the addition of 0.011 gram of succinic acid proved by its highest mechanical strength compared to the other membranes.

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

    Science.gov (United States)

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

    2005-04-15

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

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

    Science.gov (United States)

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

    2015-08-01

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

  17. Taurolidine lock is superior to heparin lock in the prevention of catheter related bloodstream infections and occlusions.

    Directory of Open Access Journals (Sweden)

    Evelyn D Olthof

    Full Text Available Patients on home parenteral nutrition (HPN are at risk for catheter-related complications; mainly infections and occlusions. We have previously shown in HPN patients presenting with catheter sepsis that catheter locking with taurolidine dramatically reduced re-infections when compared with heparin. Our HPN population therefore switched from heparin to taurolidine in 2008. The aim of the present study was to compare long-term effects of this catheter lock strategy on the occurrence of catheter-related bloodstream infections and occlusions in HPN patients.Data of catheter-related complications were retrospectively collected from 212 patients who received HPN between January 2000 and November 2011, comprising 545 and 200 catheters during catheter lock therapy with heparin and taurolidine, respectively. We evaluated catheter-related bloodstream infection and occlusion incidence rates using Poisson-normal regression analysis. Incidence rate ratios were calculated by dividing incidence rates of heparin by those of taurolidine, adjusting for underlying disease, use of anticoagulants or immune suppressives, frequency of HPN/fluid administration, composition of infusion fluids, and duration of HPN/fluid use before catheter creation.Bloodstream infection incidence rates were 1.1/year for heparin and 0.2/year for taurolidine locked catheters. Occlusion incidence rates were 0.2/year for heparin and 0.1/year for taurolidine locked catheters. Adjusted incidence ratios of heparin compared to taurolidine were 5.9 (95% confidence interval, 3.9-8.7 for bloodstream infections and 1.9 (95% confidence interval, 1.1-3.1 for occlusions.Given that no other procedural changes than the catheter lock strategy were implemented during the observation period, these data strongly suggest that taurolidine decreases catheter-related bloodstream infections and occlusions in HPN patients compared with heparin.

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

    Science.gov (United States)

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

    2018-03-01

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

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

    International Nuclear Information System (INIS)

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

    1989-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Wagner A S Judice

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

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

    Science.gov (United States)

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

    2014-09-25

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

  2. Comparison of Efficacy Compressive Stockings with Heparin in Prevention of Deep Vein Thrombosis in Stroke Patients

    Directory of Open Access Journals (Sweden)

    Nastaran Majdi-Nasab

    2013-04-01

    Full Text Available Background: The present study is carried out to make a comparison between two pharmacological (heparin and physical (compression stockings in the prevention of deep vein thrombosis in lower limb of the patients suffered from acute stroke. Materials and Methods: In this investigation as a clinical trial, the effectiveness of the above methods on 100 patients with the stroke was compared in two groups of 50 persons. Results: Three patients in physical group and two patients in pharmacological group got deep vein thrombosis that showed no significant difference between two groups.Conclusion: In spite of no significant relationship and due to less incurrence of thrombosis in heparin group, it is more reasonable to use pharmacological methods.

  3. Heparin binding sites on Ross River virus revealed by electron cryo-microscopy

    International Nuclear Information System (INIS)

    Zhang Wei; Heil, Marintha; Kuhn, Richard J.; Baker, Timothy S.

    2005-01-01

    Cell surface glycosaminoglycans play important roles in cell adhesion and viral entry. Laboratory strains of two alphaviruses, Sindbis and Semliki Forest virus, have been shown to utilize heparan sulfate as an attachment receptor, whereas Ross River virus (RRV) does not significantly interact with it. However, a single amino acid substitution at residue 218 in the RRV E2 glycoprotein adapts the virus to heparan sulfate binding and expands the host range of the virus into chicken embryo fibroblasts. Structures of the RRV mutant, E2 N218R, and its complex with heparin were determined through the use of electron cryo-microscopy and image reconstruction methods. Heparin was found to bind at the distal end of the RRV spikes, in a region of the E2 glycoprotein that has been previously implicated in cell-receptor recognition and antibody binding

  4. Disparate effects of heparin on free thyroxine measured by two different radioimmunoassays

    International Nuclear Information System (INIS)

    McDougall, I.R.; Bayer, M.F.; Nierenberg, D.; Lewis, S.J.

    1983-01-01

    Heparin causes a rise in free thyroxine (FT4) measured by equilibrium dialysis (E.D.). With the introduction of at least 4 commercial radioimmunoassays (RIA) for FT4, FT4 measurements have become accepted as one of the best routine thyroid function tests. Investigators have indicated that FT4 levels determined by RIA may be of particular value in patients hospitalized for various severe nonthyroidal illnesses in whom conventional thyroid function tests tend to be abnormal. However, very little information is as yet available on possible effects of various drugs on FT4 levels measured by these new methods. A study was undertaken to evaluate the effect of heparin on FT4 measured by 2 different RIA procedures: RIA-I, GammaCoat FT4 by clinical Assays and RIA-II, Amerlex FT4 by Amersham

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

    Science.gov (United States)

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

    2014-01-01

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

  6. Increased synthesis of heparin affin regulatory peptide in the perforant path lesioned mouse hippocampal formation

    DEFF Research Database (Denmark)

    Poulsen, F R; Lagord, C; Courty, J

    2000-01-01

    Heparin affin regulatory peptide (HARP), also known as pleiotrophin or heparin-binding growth-associated molecule, is a developmentally regulated extracellular matrix protein that induces cell proliferation and promotes neurite outgrowth in vitro as well as pre- and postsynaptic developmental...... differentiation in vivo. Here we have investigated the expression of HARP mRNA and protein in the perforant path lesioned C57B1/6 mouse hippocampal formation from 1 to 35 days after surgery. This type of lesion induces a dense anterograde and terminal axonal degeneration, activation of glial cells, and reactive...... axonal sprouting within the perforant path zones of the fascia dentata and hippocampus as well as axotomy-induced retrograde neuronal degeneration in the entorhinal cortex. Analysis of sham- and unoperated control mice showed that HARP mRNA is expressed in neurons and white and gray matter glial cells...

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

    International Nuclear Information System (INIS)

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

    1983-01-01

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

  8. Isolation of non-heprin-binding and heparin-binding proteins of boar prostate

    Czech Academy of Sciences Publication Activity Database

    Maňásková, Pavla; Liberda, J.; Tichá, M.; Jonáková, Věra

    2002-01-01

    Roč. 770, - (2002), s. 137-143 ISSN 1570-0232. [International Symposium /2./ - Separation in the BioSciences. Praha, 17.09.2001-20.09.2001] R&D Projects: GA ČR GA303/99/0357; GA ČR GV524/96/K162 Institutional research plan: CEZ:AV0Z5052915 Keywords : isolation * prostatic proteins * heparin Subject RIV: CE - Biochemistry Impact factor: 1.913, year: 2002

  9. Aggregated forms of bull seminal plasma proteins and their heparin-binding activity

    Czech Academy of Sciences Publication Activity Database

    Jelínková, Petra; Ryšlavá, H.; Liberda, J.; Jonáková, Věra; Tichá, M.

    2004-01-01

    Roč. 69, - (2004), s. 616-630 ISSN 0010-0765 R&D Projects: GA ČR GA303/02/0433; GA ČR GP303/02/P069; GA MZd NJ7463 Institutional research plan: CEZ:AV0Z5052915; CEZ:MSM 113100001 Keywords : bull seminal plasma proteins * heparin-binding proteins * aggregated forms of proteins Subject RIV: CE - Biochemistry Impact factor: 1.062, year: 2004

  10. Low-thrombogenic fibrin-heparin coating promotes in vitro endothelialization

    Czech Academy of Sciences Publication Activity Database

    Kaplan, Ondřej; Hierlemann, T.; Krajewski, S.; Kurz, J.; Nevoralová, Martina; Houska, Milan; Riedel, Tomáš; Riedelová, Zuzana; Zárubová, Jana; Wendel, H. P.; Brynda, Eduard

    2017-01-01

    Roč. 105, č. 11 (2017), s. 2995-3005 ISSN 1549-3296 R&D Projects: GA MZd(CZ) NV15-29153A Institutional support: RVO:61389013 ; RVO:67985823 Keywords : fibrin-heparin coating * hemocompatibility * endothelialization Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery; FA - Cardiovascular Diseases incl. Cardiotharic Surgery (FGU-C) OBOR OECD: Cardiac and Cardiovascular systems; Cardiac and Cardiovascular systems (FGU-C) Impact factor: 3.076, year: 2016

  11. Relationship between heparin anticoagulation and clinical outcomes in coronary stent intervention: observations from the ESPRIT trial.

    Science.gov (United States)

    Tolleson, Thaddeus R; O'Shea, J Conor; Bittl, John A; Hillegass, William B; Williams, Kathryn A; Levine, Glenn; Harrington, Robert A; Tcheng, James E

    2003-02-05

    We evaluated the relationship between the degree of heparin anticoagulation and clinical efficacy and bleeding in patients undergoing contemporary percutaneous coronary intervention (PCI) with stent implantation. Despite universal acceptance of heparin anticoagulation as a standard of care in PCI, considerable controversy still exists regarding the appropriate dosing of heparin. The study population (n = 2,064) comprised all patients enrolled in the Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial. The index activated clotting time (ACT) was defined as the ACT measured after the last heparin dose and before first device activation and was correlated with outcome and bleeding events. No association was observed between decreasing ACT levels and the rate of ischemic events in the treatment or placebo arms. The incidence of the primary composite end point (death, myocardial infarction, urgent target vessel revascularization, and thrombotic bailout glycoprotein IIb/IIIa inhibitor therapy at 48 h) was actually lowest in the lowest ACT tertile for both the placebo (10.0%) and treatment groups (6.1%). When analyzed by tertile, major bleeding rates did not increase in the lowest ACT tertile in patients given placebo (0.6%) versus those receiving eptifibatide (0.7%). Major bleeding rates increased as the ACT increased in the eptifibatide-treated patients. Ischemic end points in patients undergoing contemporary PCI with stent placement do not increase by decreasing ACT levels, at least to a level of 200 s. Bleeding events do increase with increasing ACT levels and are enhanced with eptifibatide treatment. An ACT of 200 to 250 s is reasonable in terms of efficacy and safety with the use of contemporary technology and pharmacotherapy.

  12. Polyguluronate sulfate and its oligosaccharides but not heparin promotes FGF19/FGFR1c signaling

    Science.gov (United States)

    Lan, Ying; Zeng, Xuan; Guo, Zhihua; Zeng, Pengjiao; Hao, Cui; Zhao, Xia; Yu, Guangli; Zhang, Lijuan

    2017-06-01

    Fibroblast growth factor 19(FGF19) functions as a hormone by affecting glucose metabolism. FGF19 improves glucose tolerance when overexpressed in mice with impaired glucose tolerance or diabetes. A functional cellular FGF19 receptor consists of FGF receptor (FGFR) and glycosaminoglycan complexed with either α Klotho or β Klotho. Interestingly, in mice with diet-induced diabetes, a single injection of FGF1 is enough to restore blood sugar levels to a healthy range. FGF1 binds heparin with high affinity whereas FGF19 does not, indicating that polysaccharides other than heparin might enhance FGF19/FGFR signaling. Using a FGFs/FGFR1c signaling-dependent BaF3 cell proliferation assay, we discovered that polyguluronate sulfate (PGS) and its oligosaccharides, PGS12 and PGS25, but not polyguluronate (PG), a natural marine polysaccharide, enhanced FGF19/FGFR1c signaling better than that of heparin based on 3H-thymidine incorporation. Interestingly, PGS6, PGS8, PGS10, PGS12, PGS25, and PGS, but not PG, had comparable FGF1/FGFR1c signal-stimulating activity compared to that of heparin. These results indicated that PGS and its oligosaccharides were excellent FGF1/FGFR1c and FGF19/FGFR1c signaling enhancers at cellular level. Since the inexpensive PGS and PGS oligosaccharides can be absorbed through oral route, these seaweed-derived compounds merit further investigation as novel agents for the treatment of type 2 diabetes through enhancing FGF1/FGFR1c and FGF19/FGFR1c signaling in future.

  13. Human Endothelial Cells: Use of Heparin in Cloning and Long-Term Serial Cultivation

    Science.gov (United States)

    Thornton, Susan C.; Mueller, Stephen N.; Levine, Elliot M.

    1983-11-01

    Endothelial cells from human blood vessels were cultured in vitro, with doubling times of 17 to 21 hours for 42 to 79 population doublings. Cloned human endothelial cell strains were established for the first time and had similar proliferative capacities. This vigorous cell growth was achieved by addition of heparin to culture medium containing reduced concentrations of endothelial cell growth factor. The routine cloning and long-term culture of human endothelial cells will facilitate studying the human endothelium in vitro.

  14. Cefotaxime-heparin lock prophylaxis against hemodialysis catheter-related sepsis among Staphylococcus aureus nasal carriers

    Directory of Open Access Journals (Sweden)

    Anil K Saxena

    2012-01-01

    Full Text Available Staphylococcus aureus nasal carriers undergoing hemodialysis (HD through tunneled cuffed catheters (TCCs form a high-risk group for the development of catheter-related bloodstream infections (CRBSI and ensuing morbidity. The efficacy of antibiotic-locks on the outcomes of TCCs among S. aureus nasal carriers has not been studied earlier. Persistent nasal carriage was defined by two or more positive cultures for methicillin-susceptible (MSSA or methicillin-resistant (MRSA S. aureus of five standardized nasal swabs taken from all the participants dialyzed at a large out-patient HD center affiliated to a tertiary care hospital. Of 218 participants, 82 S. aureus nasal carriers dialyzed through TCCs (n = 88 were identified through April 2005 to March 2006 and randomized to two groups. Group I comprised of 39 nasal carriers who had TCCs (n = 41 "locked" with cefotaxime/heparin while group II included 43 patients with TCCs (n = 47 filled with standard heparin. The CRBSI incidence and TCC survival at 365 days were statistically compared between the two groups. A significantly lower CRBSI incidence (1.47 vs. 3.44/1000 catheter-days, P <0.001 and higher infection-free TCC survival rates at 365 days (80.5 vs. 40.4%, P <0.0001 were observed in the cefotaxime group compared with the stan-dard heparin group. However, no significant difference in MRSA-associated CRBSI incidence was observed between the two groups. Cefotaxime-heparin "locks" effectively reduced CRBSI-incidence associated with gram-positive cocci, including MSSA, among S. aureus nasal carriers. There remains a compelling requirement for antibiotic-locks effective against MRSA.

  15. Subcutis calcinosis caused by injection of calcium-containing heparin in a chronic kidney injury patient

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    Lilia Ben Fatma

    2014-01-01

    Full Text Available Subcutis calcinosis, characterized by abnormal calcium deposits in the skin, is a rare complication of using calcium-containing heparin occurring in patients with advanced renal failure. We report the case of an 83-year-old female, a known case of chronic kidney disease (CKD for four years with recent worsening of renal failure requiring hospitalization and hemodialysis. She developed subcutis calcinosis following injection of calcium-containing heparin. Biochemical tests showed serum parathormone level at 400 pg/dL, hypercalcemia, elevated calcium-phosphate product and monoclonal gammopathy related to multiple myeloma. She developed firm subcu-taneous nodules in the abdomen and the thighs, the injection sites of Calciparin ® (calcium nadroparin that was given as a preventive measure against deep vein thrombosis. The diagnosis of subcutis calcinosis was confirmed by the histological examination showing calcium deposit in the dermis and hypodermis. These lesions completely disappeared after discontinuing calcium nadro-parin injections. Subcutis calcinosis caused by injections of calcium-containing heparin is rare, and, to the best our knowledge, not more than 12 cases have been reported in the literature. Pathogenesis is not well established but is attributed to the calcium disorders usually seen in advanced renal failure. Diagnosis is confirmed by histological tests. Outcome is mostly favorable. The main differential diagnosis is calciphylaxis, which has a poor prognosis. Even though rarely reported, we should be aware that CKD patients with elevated calcium-phosphorus product can develop subcutis calcinosis induced by calcium-containing heparin. When it occurs, fortunately and unlike calci-phylaxis, outcome is favorable.

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

    Science.gov (United States)

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

    1999-08-15

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

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

    International Nuclear Information System (INIS)

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

    1987-01-01

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

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

    Science.gov (United States)

    Vidya, Raj; Saji, Alex

    2018-05-01

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

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

    Science.gov (United States)

    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.

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

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    Thanyaphoo Suphannee

    2016-09-01

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

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

    Science.gov (United States)

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

    2017-05-01

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

  2. Thrombolytic treatment for acute ischemic cerebral stroke: intraarterial urokinase infusion vs. intravenous heparin and urokinase infusion

    International Nuclear Information System (INIS)

    Ko, Gi Young; Suh, Dae Chul; Lee, Jae Hong; Kim, Jun Hyoung; Choi, Choong Gon; Lee, Ho Kyu; Lee, Myoung Chong

    1996-01-01

    To evaluate the efficacy and limitation of intra-arterial urokinase (IAUK) infusion for treatment of acute cerebral stroke. Twenty-seven acute cerebral stroke patients treated with IAUK infusion within six hours of stroke onset were reviewed. All patients showed normal initial brain findings on CT. In 21 patients, urokinase(5-15 x 10 5 IU) was administered through a microcatheter placed into or proximal to occluded segment. Mechanical disruption of thrombus by guidewire was performed in 17 patients. Angiographic and clinical responses and complications after IAUK infusion, were evaluated and the results were compared with those of intravenous heparin(N=19) and urokinase infusion(N=19). Complete or partial angiographic recanalization of occluded segment was found in 18 patients (67%), and neurologic improvement was followed in 14 patients(52%). The degree of improvement on the stroke scale score after IAUK infusion was statistically more significant(p<0.05) than that shown after intravenous heparin and urokinase infusion. Complications after IAUK infusion were large(15%) and small amount intracerebral hemorrhage(15%), contrast leakage into brain parenchyma(11%), and gastrointestinal bleeding(4%). Between the IAVK and the intravenous urokinase infusion group, differences in extent and types of complications were statistically insignificant, but were significantly higher in those two groups than in the intravenous heparin infusion group. IAUK infusion may be effective for the treatment of acute cerebral stroke

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

    Science.gov (United States)

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

    2017-08-01

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

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

    Science.gov (United States)

    Rosania, Larry

    2010-01-01

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

  5. Capillary electrophoresis of heparin and other glycosaminoglycans using a polyamine running electrolyte

    International Nuclear Information System (INIS)

    Loegel, Thomas N.; Trombley, John D.; Taylor, Richard T.; Danielson, Neil D.

    2012-01-01

    Highlights: ► Ethylenediamine is likely acting as an ion-pairing agent. ► Oversulfated chondroitin sulfate is last peak instead of first peak. ► There is about a factor of five improved detectability with a 12.5 min analysis time. ► Use of a 50 μm ID capillary is possible. - Abstract: This study involves the use of polyamines as potential resolving agents for the capillary electrophoresis (CE) of glycosaminoglycans (GAGs), specifically heparin, dermatan sulfate, chondroitin sulfate, over-sulfated chondroitin sulfate (OSCS), and hyaluronan. All of the compounds can be separated from each other with the exception of chondroitin sulfate and hyaluronan. Using optimization software, the final run conditions are found to be 200 mM ethylenediamine and 45.5 mM phosphate as the electrolyte with −14 V applied across a 50 μm ID × 24.5 cm fused silica capillary at 15 °C. The ion migration order, with OSCS as the last instead of the first peak, is in contrast to previous reports using either a high molarity TRIS or lithium phosphate run buffer with narrower bore capillaries. Total analysis time is 12. 5 min and the relative standard deviation of the heparin migration time is about 2.5% (n = 5). The interaction mechanism between selected polyamines and heparin is explored using conductivity measurements in addition to CE experiments to show that an ion-pairing mechanism is likely.

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

    Science.gov (United States)

    Michels, Rike; Michels, Stephan; Kaminski, Stephan

    2012-01-01

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

  7. Prediction of the oversulphated chondroitin sulphate contamination of unfractionated heparin by ATR-IR spectrophotometry.

    Science.gov (United States)

    Norwig, J; Beyer, T; Brinz, D; Holzgrabe, U; Diller, M; Manns, D

    2009-03-01

    The detection of a contamination of heparin with oversulphated chondroitin sulphate (OSCS) was first analysed in an unfractionated heparin batch supplied to the US API-market in April 2006. OSCS is a semi-synthetic derivative of the natural occuring glycosaminoglycan chondroitin sulphate. Moreover some spectroscopic characteristics of the substance overlap with those of heparin, so that the infrared (IR) spectra are visually difficult to distinguish whereas (1)H-NMR (Nuclear Magnetic Resonance) spectroscopy or capillary electrophoresis (CE) provides identification by a simple visual inspection of either the spectrum or the electropherogram respectively. However, applying special tools of Multivariate Data Analysis (MVA) to the IR spectra an identification of the contaminated samples is possible. In detail a rapid Attenuation Total Reflectance-Infrared (ATR-IR) measurement was selected, which does not require any sample preparation. The result (contaminated or not contaminated) is predicted within a few minutes. A method transfer to mobile ATR-IR spectrometers seems to be possible. The analysis is based on the fact that the fingerprint of the OSCS IR spectrum (1st derivative) complies with a theoretically calculated principal component in the MVA.

  8. Farmacovigilância da heparina no Brasil Heparin pharmacovigilance in Brazil

    Directory of Open Access Journals (Sweden)

    Daniela Rezende Garcia Junqueira

    2011-06-01

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

  9. Determination of Oversulphated Chondroitin Sulphate and Dermatan Sulphate in unfractionated heparin by (1)H-NMR - Collaborative study for quantification and analytical determination of LoD.

    Science.gov (United States)

    McEwen, I; Mulloy, B; Hellwig, E; Kozerski, L; Beyer, T; Holzgrabe, U; Wanko, R; Spieser, J-M; Rodomonte, A

    2008-12-01

    Oversulphated Chondroitin Sulphate (OSCS) and Dermatan Sulphate (DS) in unfractionated heparins can be identified by nuclear magnetic resonance spectrometry (NMR). The limit of detection (LoD) of OSCS is 0.1% relative to the heparin content. This LoD is obtained at a signal-to-noise ratio (S/N) of 2000:1 of the heparin methyl signal. Quantification is best obtained by comparing peak heights of the OSCS and heparin methyl signals. Reproducibility of less than 10% relative standard deviation (RSD) has been obtained. The accuracy of quantification was good.

  10. Economic impact of enoxaparin versus unfractionated heparin for venous thromboembolism prophylaxis in patients with acute ischemic stroke: a hospital perspective of the PREVAIL trial.

    Science.gov (United States)

    Pineo, Graham; Lin, Jay; Stern, Lee; Subrahmanian, Tarun; Annemans, Lieven

    2012-03-01

    The PREVAIL (Prevention of VTE [venous thromboembolism] after acute ischemic stroke with LMWH [low-molecular-weight heparin] and UFH [unfractionated heparin]) study demonstrated a 43% VTE risk reduction with enoxaparin versus UFH in patients with acute ischemic stroke (AIS). A 1% rate of symptomatic intracranial and major extracranial hemorrhage was observed in both groups. To determine the economic impact, from a hospital perspective, of enoxaparin versus UFH for VTE prophylaxis after AIS. A decision-analytic model was constructed and hospital-based costs analyzed using clinical information from PREVAIL. Total hospital costs were calculated based on mean costs in the Premier™ database and from wholesalers acquisition data. Costs were also compared in patients with severe stroke (National Institutes of Health Stroke Scale [NIHSS] score ≥14) and less severe stroke (NIHSS score <14). The average cost per patient due to VTE or bleeding events was lower with enoxaparin versus UFH ($422 vs $662, respectively; net savings $240). The average anticoagulant cost, including drug-administration cost per patient, was lower with UFH versus enoxaparin ($259 vs $360, respectively; net savings $101). However, when both clinical events and drug-acquisition costs were considered, the total hospital cost was lower with enoxaparin versus UFH ($782 vs $922, respectively; savings $140). Hospital cost-savings were greatest ($287) in patients with NIHSS scores ≥14. The higher drug cost of enoxaparin was offset by the reduction in clinical events as compared to the use of UFH for VTE prophylaxis after an AIS, particularly in patients with severe stroke. Copyright © 2011 Society of Hospital Medicine.

  11. Weight Loss

    Science.gov (United States)

    ... Rights Employment Discrimination Health Care Professionals Law Enforcement Driver's License For Lawyers Food & Fitness Home Food MyFoodAdvisor ... Fit Types of Activity Weight Loss Assess Your Lifestyle Getting Started Food Choices In My Community Home ...

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2018-05-01

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

  14. Comparison on Anticoagulation and Antiplatelet Aggregation Effects of Puerarin with Heparin Sodium and Tirofiban Hydrochloride: An In Vitro Study.

    Science.gov (United States)

    Li, Si-Wei; Feng, Xue; Xu, Hao; Chen, Ke-Ji

    2018-02-01

    To detect the anticoagulation and antiplatelet effects of different concentrations of puerarin, heparin sodium and tirofiban hydrochloride on the blood samples of healthy volunteers by Sonoclot coagulation and platelet function analyzer. Peripheral blood samples were extracted from 20 healthy volunteers, followed by adding different concentrations of puerarin, heparin sodium and tirofiban hydrochloride. Samples were detected for activated clotting time (ACT), clot rate (CR) and platelet function (PF) by Sonoclot coagulation and platelet function analyzer instrument. For puerarin and heparin sodium, the values of ACT gradually increased, and the values of CR and PF gradually decreased with increasing in drug concentration. There was a linear (or log linear) relationship between ACT, CR, PF value and drug concentration (Phydrochloride, the values of ACT and CR had no significant changes, while PF values gradually decreased with concentration increasing. There was also a linear relationship between PF values and concentrations of tirofiban hydrochloride (Psodium. For high concentrations of puerarin (e.g. 3.8 mg/600 μL) and tirofiban hydrochloride (e.g. 0.8 μg/600 μL), PF values had no significant difference. However, PF values for high puerarin concentration had a larger variance. Puerarin has similar anticoagulant and antiplatelet effects with the heparin sodium, and may have a lower hemorrhage risk than heparin sodium when obtained the same anticoagulation effect in the concentration range of this experiment. In addition, for high concentration, puerarin had the same antiplatelet function as tirofiban hydrochloride but with a larger individual variability.

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

    Science.gov (United States)

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

    2015-07-01

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

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

    International Nuclear Information System (INIS)

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

    1985-01-01

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

  17. Reoperation for haematoma after breast reduction with preoperative administration of low-molecular-weight heparin: Experience in 720 patients

    NARCIS (Netherlands)

    Lapid, Oren; Pietersen, Lars; van der Horst, Chantal M.

    2012-01-01

    Background: Venous thrombo-embolism (VTE) prophylaxis is of paramount importance in the management of surgical patients. Mechanical as well as pharmacologic modalities may be used. With the use of anticoagulative agents, there is a potential for increased operative and postoperative bleeding. Aim:

  18. POSSIBILITIES OF USING LOW-MOLECULAR-WEIGHT HEPARIN IN THE COMPLEX TREATMENT OF WOMEN WITH TUMORS OF THE REPRODUCTIVE SYSTEM

    Directory of Open Access Journals (Sweden)

    A. G. Kedrova

    2017-01-01

    Full Text Available Benign and malignant tumors of the organs of the female reproductive system are the most common diseases requiring medical and surgical treatment. They are rarely the cause of acute complications. However, the thromboembolic disease is a serious illness, sometimes causing death due to acute the pulmonary embolism. Venous thromboembolism secondary to Benign and malignant tumors of the organs of the female reproductive system should be considered in a female presenting with abdominal mass and pelvic pressure. Thromboembolic disease secondary to large tumors should be treated with anticoagulation then hysterectomy. The article presents an analysis of modern literature on optimal prevention of the pulmonary thromboembolism in patients with tumors of the female reproductive system. There are analysis data of 17 (0.7 % cases of the pulmonary thromboembolism that occurred of 2358 gynecological and oncogynecologic patients.

  19. Enhancement of antibacterial properties of polyurethanes by chitosan and heparin immobilization

    International Nuclear Information System (INIS)

    Kara, Filiz; Aksoy, E. Ayse; Yuksekdag, Zehranur; Aksoy, Serpil; Hasirci, Nesrin

    2015-01-01

    Graphical abstract: - Highlights: • Polyurethane elastomer was synthesized in medical purity. • Chitosan (CH) and heparin (Hep) were immobilized on polyurethane films. • Modification with CH and Hep increased hydrophilicity and surface free energy. • Immobilized films had high antibacterial activity against four bacteria. • Bacterial adhesion significantly decreased on the modified surfaces. - Abstract: Being antibacterial is a required property for the materials used in medical devices and instruments. Polyurethanes (PUs) are one class of polymers widely used in the production of devices that especially come in contact with blood (e.g. heart valves, blood vessels, vascular grafts and catheters). In this study, hexamethylene diisocyanate based polyurethanes (PUh) were synthesized and antibacterial and anti-adhesive properties were added by immobilizing chitosan (CH) and heparin (Hep) on the samples of PUh via a stepwise process. Chemistry and topography of the modified film samples (PUh-CH and PUh-CH-Hep) were examined by Fourier Transform Infrared Spectrophotometry-Attenuated Total Reflectance (FTIR-ATR), Electron Spectroscopy for Chemical Analysis (ESCA) and Atomic Force Microscopy (AFM), and surface free energy (SFE) values after each step were determined by goniometer. PUh-CH and PUh-CH-Hep samples were found to be antibacterial against Staphylococcus aureus (S. aureus) and Staphylococcus epidermidis (S. epidermidis) (both Gram positive) and Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa) (both Gram negative) bacteria, and bacterial adhesion results showed a significant decrease in the number of viable bacteria on both modified samples where PUh-CH-Hep was the most effective. The findings of this study show that polymeric surfaces can be effectively modified and converted to be antibacterial by chitosan and heparin immobilization, and presence of both chemicals enhance efficacy against bacteria.

  20. Centrifugation protocols: tests to determine optimal lithium heparin and citrate plasma sample quality.

    Science.gov (United States)

    Dimeski, Goce; Solano, Connie; Petroff, Mark K; Hynd, Matthew

    2011-05-01

    Currently, no clear guidelines exist for the most appropriate tests to determine sample quality from centrifugation protocols for plasma sample types with both lithium heparin in gel barrier tubes for biochemistry testing and citrate tubes for coagulation testing. Blood was collected from 14 participants in four lithium heparin and one serum tube with gel barrier. The plasma tubes were centrifuged at four different centrifuge settings and analysed for potassium (K(+)), lactate dehydrogenase (LD), glucose and phosphorus (Pi) at zero time, poststorage at six hours at 21 °C and six days at 2-8°C. At the same time, three citrate tubes were collected and centrifuged at three different centrifuge settings and analysed immediately for prothrombin time/international normalized ratio, activated partial thromboplastin time, derived fibrinogen and surface-activated clotting time (SACT). The biochemistry analytes indicate plasma is less stable than serum. Plasma sample quality is higher with longer centrifugation time, and much higher g force. Blood cells present in the plasma lyse with time or are damaged when transferred in the reaction vessels, causing an increase in the K(+), LD and Pi above outlined limits. The cells remain active and consume glucose even in cold storage. The SACT is the only coagulation parameter that was affected by platelets >10 × 10(9)/L in the citrate plasma. In addition to the platelet count, a limited but sensitive number of assays (K(+), LD, glucose and Pi for biochemistry, and SACT for coagulation) can be used to determine appropriate centrifuge settings to consistently obtain the highest quality lithium heparin and citrate plasma samples. The findings will aid laboratories to balance the need to provide the most accurate results in the best turnaround time.

  1. Endothelial cell capture of heparin-binding growth factors under flow.

    Directory of Open Access Journals (Sweden)

    Bing Zhao

    2010-10-01

    Full Text Available Circulation is an important delivery method for both natural and synthetic molecules, but microenvironment interactions, regulated by endothelial cells and critical to the molecule's fate, are difficult to interpret using traditional approaches. In this work, we analyzed and predicted growth factor capture under flow using computer modeling and a three-dimensional experimental approach that includes pertinent circulation characteristics such as pulsatile flow, competing binding interactions, and limited bioavailability. An understanding of the controlling features of this process was desired. The experimental module consisted of a bioreactor with synthetic endothelial-lined hollow fibers under flow. The physical design of the system was incorporated into the model parameters. The heparin-binding growth factor fibroblast growth factor-2 (FGF-2 was used for both the experiments and simulations. Our computational model was composed of three parts: (1 media flow equations, (2 mass transport equations and (3 cell surface reaction equations. The model is based on the flow and reactions within a single hollow fiber and was scaled linearly by the total number of fibers for comparison with experimental results. Our model predicted, and experiments confirmed, that removal of heparan sulfate (HS from the system would result in a dramatic loss of binding by heparin-binding proteins, but not by proteins that do not bind heparin. The model further predicted a significant loss of bound protein at flow rates only slightly higher than average capillary flow rates, corroborated experimentally, suggesting that the probability of capture in a single pass at high flow rates is extremely low. Several other key parameters were investigated with the coupling between receptors and proteoglycans shown to have a critical impact on successful capture. The combined system offers opportunities to examine circulation capture in a straightforward quantitative manner that

  2. THE IMPACT OF HEPARIN IMPLEMENTER (GAG IN THE RABBIT INSEMINATION DOSE

    Directory of Open Access Journals (Sweden)

    Martin Fik

    2013-10-01

    Full Text Available The aim of this work was to evaluate the impact of implementer heparin in insemination dose in rabbits selected on reproductive parameters.The experiment was monitored reproductive parameters (conceptual relationship, the number of live-born pups per litter, the number of dead-born pups per litter, the number of live-born pups per inseminated does 156 does in the experimental group and 165 does in the control group. We used the ejaculate of synthetic broiler rabbit population with concentration of sperm 25-50 mil. / 0.5 ml / 1 ID. Heparin was added at a dose - 0.06 ml = 10 mg per 0.5 ml semen / 1 ID. Assessing selected reproductive parameters in does inseminated with insemination dose with the addition of heparin, we observed a higher conceptual proportion of 14.12 % in the experimental group compared to the control group. These differences did not show a statistically significant difference (χ 2 3.56-. The number of live-born pups per litter was 8.69 ± 4.10 pc in the experimental group and 8.41 ± 3.62 pc in the control group (P> 0.05. The number of dead-born pups was recorded 0.74 pc in the experimental group and 0.76 pc in the control group (P> 0.05. The number of live-born pups per litter per inseminated does we have seen improvement in favor of experimental group by 1.39 pc. This parameter was within each of experiments ranged from 0.91 to 1.66 pc live-born pups to inseminated does.

  3. Enhancement of antibacterial properties of polyurethanes by chitosan and heparin immobilization

    Energy Technology Data Exchange (ETDEWEB)

    Kara, Filiz [Department of Chemistry, Faculty of Science, Gazi University, 06500 Ankara (Turkey); Aksoy, E. Ayse [Department of Basic Pharmaceutical Sciences, Faculty of Pharmacy, Hacettepe University, 06100 Ankara (Turkey); Yuksekdag, Zehranur [Biotechnology Laboratory, Department of Biology, Faculty of Science, Gazi University, 06500 Ankara (Turkey); Aksoy, Serpil [Department of Chemistry, Faculty of Science, Gazi University, 06500 Ankara (Turkey); Hasirci, Nesrin, E-mail: nhasirci@metu.edu.tr [BIOMATEN, Center of Excellence in Biomaterials and Tissue Engineering, Middle East Technical University, 06800 Ankara (Turkey); Department of Chemistry, Faculty of Arts and Sciences, Middle East Technical University, 06800 Ankara (Turkey)

    2015-12-01

    Graphical abstract: - Highlights: • Polyurethane elastomer was synthesized in medical purity. • Chitosan (CH) and heparin (Hep) were immobilized on polyurethane films. • Modification with CH and Hep increased hydrophilicity and surface free energy. • Immobilized films had high antibacterial activity against four bacteria. • Bacterial adhesion significantly decreased on the modified surfaces. - Abstract: Being antibacterial is a required property for the materials used in medical devices and instruments. Polyurethanes (PUs) are one class of polymers widely used in the production of devices that especially come in contact with blood (e.g. heart valves, blood vessels, vascular grafts and catheters). In this study, hexamethylene diisocyanate based polyurethanes (PUh) were synthesized and antibacterial and anti-adhesive properties were added by immobilizing chitosan (CH) and heparin (Hep) on the samples of PUh via a stepwise process. Chemistry and topography of the modified film samples (PUh-CH and PUh-CH-Hep) were examined by Fourier Transform Infrared Spectrophotometry-Attenuated Total Reflectance (FTIR-ATR), Electron Spectroscopy for Chemical Analysis (ESCA) and Atomic Force Microscopy (AFM), and surface free energy (SFE) values after each step were determined by goniometer. PUh-CH and PUh-CH-Hep samples were found to be antibacterial against Staphylococcus aureus (S. aureus) and Staphylococcus epidermidis (S. epidermidis) (both Gram positive) and Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa) (both Gram negative) bacteria, and bacterial adhesion results showed a significant decrease in the number of viable bacteria on both modified samples where PUh-CH-Hep was the most effective. The findings of this study show that polymeric surfaces can be effectively modified and converted to be antibacterial by chitosan and heparin immobilization, and presence of both chemicals enhance efficacy against bacteria.

  4. Capillary electrophoresis of heparin and other glycosaminoglycans using a polyamine running electrolyte

    Energy Technology Data Exchange (ETDEWEB)

    Loegel, Thomas N.; Trombley, John D.; Taylor, Richard T. [Department of Chemistry and Biochemistry, Miami University, Oxford, OH 45056 (United States); Danielson, Neil D., E-mail: danielnd@muohio.edu [Department of Chemistry and Biochemistry, Miami University, Oxford, OH 45056 (United States)

    2012-11-13

    Highlights: Black-Right-Pointing-Pointer Ethylenediamine is likely acting as an ion-pairing agent. Black-Right-Pointing-Pointer Oversulfated chondroitin sulfate is last peak instead of first peak. Black-Right-Pointing-Pointer There is about a factor of five improved detectability with a 12.5 min analysis time. Black-Right-Pointing-Pointer Use of a 50 {mu}m ID capillary is possible. - Abstract: This study involves the use of polyamines as potential resolving agents for the capillary electrophoresis (CE) of glycosaminoglycans (GAGs), specifically heparin, dermatan sulfate, chondroitin sulfate, over-sulfated chondroitin sulfate (OSCS), and hyaluronan. All of the compounds can be separated from each other with the exception of chondroitin sulfate and hyaluronan. Using optimization software, the final run conditions are found to be 200 mM ethylenediamine and 45.5 mM phosphate as the electrolyte with -14 V applied across a 50 {mu}m ID Multiplication-Sign 24.5 cm fused silica capillary at 15 Degree-Sign C. The ion migration order, with OSCS as the last instead of the first peak, is in contrast to previous reports using either a high molarity TRIS or lithium phosphate run buffer with narrower bore capillaries. Total analysis time is 12. 5 min and the relative standard deviation of the heparin migration time is about 2.5% (n = 5). The interaction mechanism between selected polyamines and heparin is explored using conductivity measurements in addition to CE experiments to show that an ion-pairing mechanism is likely.

  5. Cellular responses modulated by FGF-2 adsorbed on albumin/heparin layer-by-layer assemblies

    Czech Academy of Sciences Publication Activity Database

    Kumorek, Marta M.; Kubies, Dana; Filová, Elena; Houska, Milan; Kasoju, Naresh; Mázl Chánová, Eliška; Matějka, Roman; Krýslová, Markéta; Bačáková, Lucie; Rypáček, František

    2015-01-01

    Roč. 10, č. 5 (2015), e0125484_1-e0125484_23 E-ISSN 1932-6203 R&D Projects: GA MŠk(CZ) EE2.3.30.0029; GA ČR(CZ) GAP108/11/1857; GA ČR GPP108/12/P624; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:61389013 ; RVO:67985823 Keywords : self-assembly * layer-by-layer * heparin Subject RIV: CD - Macromolecular Chemistry; EI - Biotechnology ; Bionics (FGU-C) Impact factor: 3.057, year: 2015

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

    Science.gov (United States)

    Garland, Cassandra; Somogyi, David

    2014-01-01

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

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

    Science.gov (United States)

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

    2018-02-19

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

  8. Post-heparin plasma lipoprotein lipase, but not hepatic lipase activity, is related to plasma adiponectin in type 2 diabetic patients and healthy subjects

    NARCIS (Netherlands)

    De Vries, R; Wolffenbuttel, BHR; Sluiter, WJ; Van Tol, A; Dullaart, RPF

    2005-01-01

    The aim of this study was to determine the relationships of plasma adiponectin with post-heparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities, and to evaluate whether plasma adiponectin contributes to diabetes-associated dyslipidaemia. Plasma adiponectin, post-heparin plasma

  9. FRAGMATIC: A randomised phase III clinical trial investigating the effect of fragmin® added to standard therapy in patients with lung cancer

    Directory of Open Access Journals (Sweden)

    Macbeth Fergus R

    2009-10-01

    Full Text Available Abstract Background Venous thromboembolism (VTE occurs when blood clots in the leg, pelvic or other deep vein (deep vein thrombosis with or without transport of the thrombus into the pulmonary arterial circulation (pulmonary embolus. VTE is common in patients with cancer and is increased by surgery, chemotherapy, radiotherapy and disease progression. Low molecular weight heparin (LMWH is routinely used to treat VTE and some evidence suggests that LMWH may also have an anticancer effect, by reduction in the incidence of metastases. The FRAGMATIC trial will assess the effect of adding dalteparin (FRAGMIN, a type of LMWH, to standard treatment for patients with lung cancer. Methods/Design The study design is a randomised multicentre phase III trial comparing standard treatment and standard treatment plus daily LMWH for 24 weeks in patients with lung cancer. Patients eligible for this study must have histopathological or cytological diagnosis of primary bronchial carcinoma (small cell or non-small cell within 6 weeks of randomisation, be 18 or older, and must be willing and able to self-administer 5000 IU dalteparin by daily subcutaneous injection or have it administered to themselves or by a carer for 24 weeks. A total of 2200 patients will be recruited from all over the UK over a 3 year period and followed up for a minimum of 1 year after randomisation. Patients will be randomised to one of the two treatment groups in a 1:1 ratio, standard treatment or standard treatment plus dalteparin. The primary outcome measure of the trial is overall survival. The secondary outcome measures include venous thrombotic event (VTE free survival, serious adverse events (SAEs, metastasis-free survival, toxicity, quality of life (QoL, levels of breathlessness, anxiety and depression, cost effectiveness and cost utility. Trial registration Current Controlled Trials ISRCTN80812769

  10. FRAGMATIC: A randomised phase III clinical trial investigating the effect of fragmin® added to standard therapy in patients with lung cancer

    International Nuclear Information System (INIS)

    Griffiths, Gareth O; Burns, Sarah; Noble, Simon I; Macbeth, Fergus R; Cohen, David; Maughan, Timothy S

    2009-01-01

    Venous thromboembolism (VTE) occurs when blood clots in the leg, pelvic or other deep vein (deep vein thrombosis) with or without transport of the thrombus into the pulmonary arterial circulation (pulmonary embolus). VTE is common in patients with cancer and is increased by surgery, chemotherapy, radiotherapy and disease progression. Low molecular weight heparin (LMWH) is routinely used to treat VTE and some evidence suggests that LMWH may also have an anticancer effect, by reduction in the incidence of metastases. The FRAGMATIC trial will assess the effect of adding dalteparin (FRAGMIN), a type of LMWH, to standard treatment for patients with lung cancer. The study design is a randomised multicentre phase III trial comparing standard treatment and standard treatment plus daily LMWH for 24 weeks in patients with lung cancer. Patients eligible for this study must have histopathological or cytological diagnosis of primary bronchial carcinoma (small cell or non-small cell) within 6 weeks of randomisation, be 18 or older, and must be willing and able to self-administer 5000 IU dalteparin by daily subcutaneous injection or have it administered to themselves or by a carer for 24 weeks. A total of 2200 patients will be recruited from all over the UK over a 3 year period and followed up for a minimum of 1 year after randomisation. Patients will be randomised to one of the two treatment groups in a 1:1 ratio, standard treatment or standard treatment plus dalteparin. The primary outcome measure of the trial is overall survival. The secondary outcome measures include venous thrombotic event (VTE) free survival, serious adverse events (SAEs), metastasis-free survival, toxicity, quality of life (QoL), levels of breathlessness, anxiety and depression, cost effectiveness and cost utility. Current Controlled Trials ISRCTN80812769

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

    Science.gov (United States)

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

    2015-08-15

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

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

    Science.gov (United States)

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

    2000-01-01

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

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

    Science.gov (United States)

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

    2018-04-26

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

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

    Science.gov (United States)

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

    2018-03-20

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

  15. Graft patency after off-pump coronary artery bypass surgery is inferior even with identical heparinization protocols

    DEFF Research Database (Denmark)

    Houlind, Kim; Fenger-Grøn, Morten; Holme, Susanne J

    2014-01-01

    OBJECTIVE: To determine whether graft patency after on-pump and off-pump coronary artery bypass surgery is similar when performed using the same heparinization protocol. METHODS: In a randomized, controlled, multicenter trial, 900 patients more than 70 years of age received either on-pump or off......-pump coronary artery bypass surgery. Heparin was given to achieve an activated clotting time of 400 seconds before arteriotomy in both groups. After the procedure, protamine sulfate was given to revert the activated clotting time to less than 120 seconds. Coronary angiography was performed 6 months after...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-08-15

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

  17. Healthy Weight

    Science.gov (United States)

    ... such diets limit your nutritional intake, can be unhealthy, and tend to fail in the long run. The key to achieving and maintaining a healthy weight isn't about short-term dietary changes. It's about a lifestyle that includes healthy eating, regular physical activity, and ...

  18. Weighted approximation with varying weight

    CERN Document Server

    Totik, Vilmos

    1994-01-01

    A new construction is given for approximating a logarithmic potential by a discrete one. This yields a new approach to approximation with weighted polynomials of the form w"n"(" "= uppercase)P"n"(" "= uppercase). The new technique settles several open problems, and it leads to a simple proof for the strong asymptotics on some L p(uppercase) extremal problems on the real line with exponential weights, which, for the case p=2, are equivalent to power- type asymptotics for the leading coefficients of the corresponding orthogonal polynomials. The method is also modified toyield (in a sense) uniformly good approximation on the whole support. This allows one to deduce strong asymptotics in some L p(uppercase) extremal problems with varying weights. Applications are given, relating to fast decreasing polynomials, asymptotic behavior of orthogonal polynomials and multipoint Pade approximation. The approach is potential-theoretic, but the text is self-contained.

  19. A heparin-functionalized carbon nanotube-based affinity biosensor for dengue virus.

    Science.gov (United States)

    Wasik, Daniel; Mulchandani, Ashok; Yates, Marylynn V

    2017-05-15

    Dengue virus is an arthropod-borne virus transmitted primarily by Aedes mosquitos and is major cause of disease in tropical and subtropical regions. Colloquially known as Dengue Fever, infection can cause hemorrhagic disorders and death in humans and non-human primates. We report a novel electronic biosensor based on a single-walled carbon nanotube network chemiresistive transducer that is functionalized with heparin for low-cost, label-free, ultra-sensitive, and rapid detection of whole dengue virus (DENV). Heparin, an analog of the heparan sulfate proteoglycans that are receptors for dengue virus during infection of Vero cells and hepatocytes, was used for the first time in a biosensor as a biorecognition element instead of traditional antibody. Detection of DENV in viral culture supernatant has similar sensitivity as the corresponding viral titer in phosphate buffer despite the presence of growth media and Vero cell lysate. The biosensor demonstrated sensitivity within the clinically relevant range for humans and infected Aedes aegypti. It has potential application in clinical diagnosis and can improve point-of-care diagnostics of dengue infection. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Heparin surface stent-graft for the treatment of a carotid pseudoaneurysm.

    Science.gov (United States)

    Tsolaki, Elpiniki; Elpiniki, Tsolaki; Salviato, Elisabetta; Rocca, Tiberio; Braccini, Lucia; Galeotti, Roberto; Mascoli, Francesco

    2010-10-01

    Carotid pseudoaneurysms are a rare consequence of carotid surgery, trauma, and infection. Historically, carotid aneurysms and pseudoaneurysms were treated surgically. However, endovascular techniques have recently become a valid alternative for the treatment of carotid pseudoaneurysms. The case of a 57-year-old male patient with a pseudoaneurysm of the right internal carotid artery is described. The patient came to our unit with a painless and pulsatile mass in the neck, which was growing slowly. Five years earlier, he had undergone surgery on a saccular aneurysm located on the distal extracranial segment of the right internal carotid artery. The pseudoaneurysm was successfully treated with a heparin surface Viabahn stent-graft system (Gore AL, Flagstaff, AZ). Heparin surface stent-grafts can be used for the treatment of carotid lesions and may offer protection against intimal hyperplasia and thrombosis. Further studies are needed to evaluate the long-term results. Copyright © 2010 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Metod Kolar

    2015-03-01

    Full Text Available 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.

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

    Science.gov (United States)

    Krawczyk, Z; Wu, C

    1987-08-15

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

  3. In Vitro and In Vivo Biocompatibility Evaluation of Polyallylamine and Macromolecular Heparin Conjugates Modified Alginate Microbeads.

    Science.gov (United States)

    Vaithilingam, Vijayaganapathy; Steinkjer, Bjørg; Ryan, Liv; Larsson, Rolf; Tuch, Bernard Edward; Oberholzer, Jose; Rokstad, Anne Mari

    2017-09-15

    Host reactivity to biocompatible immunoisolation devices is a major challenge for cellular therapies, and a human screening model would be of great value. We designed new types of surface modified barium alginate microspheres, and evaluated their inflammatory properties using human whole blood, and the intraperitoneal response after three weeks in Wistar rats. Microspheres were modified using proprietary polyallylamine (PAV) and coupled with macromolecular heparin conjugates (Corline Heparin Conjugate, CHC). The PAV-CHC strategy resulted in uniform and stable coatings with increased anti-clot activity and low cytotoxicity. In human whole blood, PAV coating at high dose (100 µg/ml) induced elevated complement, leukocyte CD11b and inflammatory mediators, and in Wistar rats increased fibrotic overgrowth. Coating of high dose PAV with CHC significantly reduced these responses. Low dose PAV (10 µg/ml) ± CHC and unmodified alginate microbeads showed low responses. That the human whole blood inflammatory reactions paralleled the host response shows a link between inflammatory potential and initial fibrotic response. CHC possessed anti-inflammatory activity, but failed to improve overall biocompatibility. We conclude that the human whole blood assay is an efficient first-phase screening model for inflammation, and a guiding tool in development of new generation microspheres for cell encapsulation therapy.

  4. Structural and functional characterization of the interaction between cyclophilin B and a heparin-derived oligosaccharide.

    Science.gov (United States)

    Hanoulle, Xavier; Melchior, Aurélie; Sibille, Nathalie; Parent, Benjamin; Denys, Agnès; Wieruszeski, Jean-Michel; Horvath, Dragos; Allain, Fabrice; Lippens, Guy; Landrieu, Isabelle

    2007-11-23

    The chemotaxis and integrin-mediated adhesion of T lymphocytes triggered by secreted cyclophilin B (CypB) depend on interactions with both cell surface heparan sulfate proteoglycans (HSPG) and the extracellular domain of the CD147 membrane receptor. Here, we use NMR spectroscopy to characterize the interaction of CypB with heparin-derived oligosaccharides. Chemical shift perturbation experiments allowed the precise definition of the heparan sulfate (HS) binding site of CypB. The N-terminal extremity of CypB, which contains a consensus sequence for heparin-binding proteins was modeled on the basis of our experimental NMR data. Because the HS binding site extends toward the CypB catalytic pocket, we measured its peptidyl-prolyl cis-trans isomerase (PPIase) activity in the absence or presence of a HS oligosaccharide toward a CD147-derived peptide. We report the first direct evidence that CypB is enzymatically active on CD147, as it is able to accelerate the cis/trans isomerization of the Asp(179)-Pro(180) bond in a CD147-derived peptide. However, HS binding has no significant influence on this PPIase activity. We thus conclude that the glycanic moiety of HSPG serves as anchor for CypB at the cell surface, and that the signal could be transduced by CypB via its PPIase activity toward CD147.

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

    Directory of Open Access Journals (Sweden)

    Delong Zhao

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

  6. Heparin Injection

    Science.gov (United States)

    ... prevent blood clots from forming in catheters (small plastic tubes through which medication can be administered or ... discoloration in the arms or legs itching and burning, especially on the bottoms of the feet chills ...

  7. Changes in perfusion scintigraphy in the first days of heparin therapy in patients with acute pulmonary embolism

    NARCIS (Netherlands)

    de Groot, M. R.; Oostdijk, A. H.; Engelage, A. H.; van Marwijk Kooy, M.; Büller, H. R.

    2000-01-01

    Patients with suspected pulmonary embolism often receive heparin therapy for hours to days before ventilation/perfusion scintigraphy is completed. We assessed to what extent the lung scan classification and pulmonary vascular perfusion changed over a period of 2-4 days of full anticoagulant therapy.

  8. Tissue factor pathway inhibitor (TFPI) release after heparin stimulation is increased in Type 1 diabetic patients with albuminuria

    NARCIS (Netherlands)

    Leurs, PB; van Oerle, R; Hamulyak, K; Wolffenbuttel, BHR

    Aims To study heparin-stimulated TFPI release in relation to complications in Type 1 diabetic patients. Subjects and methods Nineteen uncomplicated Type 1 diabetic patients (group I) were compared with 18 patients with retinopathy (group II), and nine patients with retinopathy and albuminuria (group

  9. Standardization of heparins by means of high performance liquid chromatography equipped with a low angle laser light scattering detector

    NARCIS (Netherlands)

    Hennink, W.E.; van den Berg, J.W.A.; Feijen, Jan

    1987-01-01

    This study shows that HPLC-LALLS (high performance liquid chromatography with a light-scattering detector) is a convenient and reliable method for the characterization of standard heparin samples, provided that polyelectrolyte artefacts are suppressed by a suitable dialysis procedure. The method has

  10. Effects of chronic intraventricular infusion of heparin glycosaminoglycan on learning and brain acetylcholine parameters in aged rats

    Czech Academy of Sciences Publication Activity Database

    Ježek, Karel; Schulz, D.; De Souza Silva, M. A.; Müller, H. W.; Huston, J. P.; Hasenöhrl, R. U.

    2003-01-01

    Roč. 147, 1-2 (2003), s. 115-123 ISSN 0166-4328 Grant - others:Deutsche Forschungsgemeinschaft(DE) HU 306/11-3 Institutional research plan: CEZ:AV0Z5011922 Keywords : heparin * memory * ageing Subject RIV: FH - Neurology Impact factor: 2.817, year: 2003

  11. Surface biomimetic modification with laminin-loaded heparin/poly-L-lysine nanoparticles for improving the biocompatibility

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Tao, E-mail: 11140021@hyit.edu.cn [Jiangsu Provincial Key Laboratory for Interventional Medical Devices, Huaiyin Institute of Technology, Huai' an (China); Hu, Youdong [Department of Geriatrics, The Affiliated Huai' an Hospital of Xuzhou Medical College, Huai' an (China); Tan, Jianying [Key Lab. of Advanced Technology for Materials of Chinese Education Ministry, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu (China); Liu, Shihui [Jiangsu Provincial Key Laboratory for Interventional Medical Devices, Huaiyin Institute of Technology, Huai' an (China); Chen, Junying [Key Lab. of Advanced Technology for Materials of Chinese Education Ministry, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu (China); Guo, Xin; Pan, Changjiang [Jiangsu Provincial Key Laboratory for Interventional Medical Devices, Huaiyin Institute of Technology, Huai' an (China); Li, Xia, E-mail: xial_li@qq.com [Department of Geriatrics, The Affiliated Huai' an Hospital of Xuzhou Medical College, Huai' an (China)

    2017-02-01

    Late thrombus and restenosis caused by delayed endothelialization and insufficient biocompatibility of polymer coating continue to be the greatest limitations of drug-eluting stents. In this study, based on the specific structure of vascular basement membrane, a novel biomimetic nano-coating was constructed by incorporating laminin into electrostatic-assembled heparin/poly-L-lysine nanoparticles. Alteration of heparin and poly-L-lysine concentration ratio in a certain range has no significantly influence nanoparticle size, uniformity and stability, but may affect the chemical property and subsequently the binding efficiency to dopamine-coated titanium surface. By use of this feature, four different nanoparticles were synthesized and immobilized on titanium surface for creating gradient nanoparticle binding density. According to in vitro biocompatibility evaluation, the nanoparticle modified surfaces were found to effectively block coagulation pathway and reduce thrombosis formation. Moreover, NP10L and NP15L modified surface with relatively low heparin exposing density (4.9 to 7.1 μg/cm2) showed beneficial effect in selective promoting EPCs and ECs proliferation, as well as stimulating cell migration and NO synthesis. - Highlights: • A novel laminin-loaded anticoagulant nanoparticle was prepared and used for titanium surface modification. • The nanoparticle binding density was adjustable by alteration the concentration ratio of heparin and poly-L-lysine. • In a certain range of NPs density, the surface was found to selectively direct platelet and vascular cells behavior.

  12. Diagnostic value of post-heparin lipase testing in detecting common genetic variants in the LPL and LIPC genes

    NARCIS (Netherlands)

    van Hoek, Mandy; Dallinga-Thie, Geesje M.; Steyerberg, Ewout W.; Sijbrands, Eric J. G.

    2009-01-01

    Post-heparin lipoprotein lipase and hepatic lipase activities are used to identify primary disorders of triglyceride and HDL-cholesterol metabolism. Their ability to identify common variants in the lipoprotein lipase (LPL) and hepatic lipase (LIPC) genes is unclear. To investigate the ability of

  13. Cellular adhesion responses to the heparin-binding (HepII) domain of fibronectin require heparan sulfate with specific properties

    DEFF Research Database (Denmark)

    Mahalingam, Yashithra; Gallagher, John T; Couchman, John R

    2006-01-01

    of fibronectin (HepII domain) through its HS chains. The fine structure of HS is critical to growth factor responses, and whether this extends to matrix ligands is unknown but is suggested from in vitro experiments. Cell attachment to HepII showed that heparin oligosaccharides of >or=14 sugar residues were...

  14. Timing of heparin prophylaxis and bleeding complications in hysterectomy a nationwide prospective cohort study of 9,949 Danish women

    DEFF Research Database (Denmark)

    Hansen, Charlotte T; Kehlet, Henrik; Møller, Charlotte

    2008-01-01

    's experience, route and type of hysterectomy and additional surgery, and stratification on assistant's experience, peri-operative pain prophylaxis with NSAID and daily use of Acetyl Salicylic Acid (ASA)/NSAID. RESULTS: 9,051 women (92%) received thromboprophylaxis with heparin, initiated pre-operatively in 48...

  15. Construction of mussel-inspired coating via the direct reaction of catechol and polyethyleneimine for efficient heparin immobilization

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yujie [School of Material Science and Engineering, Southwest Jiaotong University, Chengdu 610031 (China); The Institute of Biomaterials and Surface Engineering, Southwest Jiaotong University, Chengdu 610031 (China); Luo, Rifang, E-mail: lrifang@126.com [School of Material Science and Engineering, Southwest Jiaotong University, Chengdu 610031 (China); The Institute of Biomaterials and Surface Engineering, Southwest Jiaotong University, Chengdu 610031 (China); Shen, Fangyu; Tang, Linlin [School of Material Science and Engineering, Southwest Jiaotong University, Chengdu 610031 (China); The Institute of Biomaterials and Surface Engineering, Southwest Jiaotong University, Chengdu 610031 (China); Wang, Jin, E-mail: jinxxwang@263.net [School of Material Science and Engineering, Southwest Jiaotong University, Chengdu 610031 (China); The Institute of Biomaterials and Surface Engineering, Southwest Jiaotong University, Chengdu 610031 (China); Huang, Nan [School of Material Science and Engineering, Southwest Jiaotong University, Chengdu 610031 (China); The Institute of Biomaterials and Surface Engineering, Southwest Jiaotong University, Chengdu 610031 (China)

    2015-02-15

    Highlights: • Catechol (CA) and PEI copolymerization was a mimetic and dopamine-like coating method. • CA/PEI film provided amine groups and was effective in heparin immobilization. • CA/PEI coating could inhibit smooth muscle cell proliferation. • CA/PEI coating did not show any significant cytotoxicity to endothelial cell. - Abstract: Dopamine could self-polymerize to form the coating on various substrates and the co-existence of catechols and amines was crucial in performing such polymerization process. In this work, a mimetic approach of coating formation was carried out based on the co-polymerization of catechol (CA) and polyethyleneimine (PEI). Mussel-inspired CA/PEI coating was deposited on 316L stainless steel (SS). Fourier transform infrared spectra (FTIR) and X-ray photoelectron spectroscopy (XPS) demonstrated the successful coating formation. QCM measurement showed good affinity of heparin immobilization on CA/PEI coating surface ascribed to the amine groups. Herein, vascular cell-material interactions like endothelial cells (ECs) and smooth muscle cells (SMCs) were also investigated. Interestingly, CA/PEI and heparin modified coatings presented no cytotoxicity to ECs, however to a certain extent, decreased SMCs proliferation. Moreover, heparin-binding surface presented significant anti-platelet adhesion and activation properties. These results effectively suggested that the mussel-inspired CA/PEI coating might be promising when served as a platform for biomolecule immobilization.

  16. Surface biomimetic modification with laminin-loaded heparin/poly-L-lysine nanoparticles for improving the biocompatibility

    International Nuclear Information System (INIS)

    Liu, Tao; Hu, Youdong; Tan, Jianying; Liu, Shihui; Chen, Junying; Guo, Xin; Pan, Changjiang; Li, Xia

    2017-01-01

    Late thrombus and restenosis caused by delayed endothelialization and insufficient biocompatibility of polymer coating continue to be the greatest limitations of drug-eluting stents. In this study, based on the specific structure of vascular basement membrane, a novel biomimetic nano-coating was constructed by incorporating laminin into electrostatic-assembled heparin/poly-L-lysine nanoparticles. Alteration of heparin and poly-L-lysine concentration ratio in a certain range has no significantly influence nanoparticle size, uniformity and stability, but may affect the chemical property and subsequently the binding efficiency to dopamine-coated titanium surface. By use of this feature, four different nanoparticles were synthesized and immobilized on titanium surface for creating gradient nanoparticle binding density. According to in vitro biocompatibility evaluation, the nanoparticle modified surfaces were found to effectively block coagulation pathway and reduce thrombosis formation. Moreover, NP10L and NP15L modified surface with relatively low heparin exposing density (4.9 to 7.1 μg/cm2) showed beneficial effect in selective promoting EPCs and ECs proliferation, as well as stimulating cell migration and NO synthesis. - Highlights: • A novel laminin-loaded anticoagulant nanoparticle was prepared and used for titanium surface modification. • The nanoparticle binding density was adjustable by alteration the concentration ratio of heparin and poly-L-lysine. • In a certain range of NPs density, the surface was found to selectively direct platelet and vascular cells behavior.

  17. Activation of M1 macrophages in sepsis-induced acute kidney injury in response to heparin-binding protein.

    Directory of Open Access Journals (Sweden)

    Li Xing

    Full Text Available In the early stage of sepsis, M1 macrophages result in the production of inflammatory mediators and AKI. Heparin-binding protein (HBP have been shown to play important roles in sepsis-induced AKI. In this study, we investigate the association of HBP with M1 macrophages in sepsis-induced AKI.Male C57BL6 mice were subjected to cecal ligation and puncture (CLP or sham surgery. Biochemical and histological renal damage was assessed. Macrophage infiltration was assessed by immunohistochemistry. RT-PCR was used to investigate the expression of heparin-binding protein (HBP, the inducible nitric oxide synthase (iNOS and arginase 1 (Arg-1 mRNAs. Western blots were performed to assay the tissue levels of HBP, tumor necrosis factor alpha (TNF-α and interleukin-6 (IL-6.High levels of HBP were obviously detected 24 h after sepsis-induced AKI. Heparin inhibited HBP expression during sepsis-induced AKI. The suppression of HBP expression by heparin injection after the establishment of sepsis-induced AKI resulted in a reduction in renal injury severity accompanied with a significant repression of M1 macrophage activation and expression of TNF-α and IL-6.HBP plays an important role in the initial inflammatory reaction associated with sepsis-induced AKI, presumably by activating M1 macrophages and suppressing TNF-α and IL-6 secretion.

  18. Identification of chondroitin sulfate E proteoglycans and heparin proteoglycans in the secretory granules of human lung mast cells

    International Nuclear Information System (INIS)

    Stevens, R.L.; Austen, K.F.; Fox, C.C.; Lichtenstein, L.M.

    1988-01-01

    The predominant subclasses of mast cells in both the rat and the mouse can be distinguished from one another by their preferential synthesis of 35 S-labeled proteoglycans that contain either heparin or oversulfated chondroitin sulfate glycosaminoglycans. Although [ 35 S]heparin proteoglycans have been isolated from human lung mast cells of 40-70% purity and from a skin biopsy specimen of a patient with urticaria pigmentosa, no highly sulfated chondroitin sulfate proteoglycan has been isolated from any enriched or highly purified population of human mast cells. The authors demonstrate that human lung mast cells of 96% purity incorporate [ 35 S]sulfate into separate heparin and chondroitin sulfate proteoglycans in an ∼2:1 ratio. As assessed by HPLC of the chondroitinase ABC digests, the chondroitin [ 35 S]sulfate proteoglycans isolated from these human lung mast cells contain the same unusual chondroitin sulfate E disaccharide that is present in proteoglycans produced by interleukin 3-dependent mucosal-like mouse mast cells. Both the chondroitin [ 35 S]sulfate E proteoglycans and the [ 35 S]heparin proteoglycans were exocytosed from the [ 35 S]sulfate-labeled cells via perturbation of the IgE receptor, indicating that both types of 35 S-labeled proteoglycans reside in the secretory granules of these human lung mast cells

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

    Science.gov (United States)

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

    1976-10-01

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

  20. Clinical effectiveness of a Bayesian algorithm for the diagnosis and management of heparin-induced thrombocytopenia.

    Science.gov (United States)

    Raschke, R A; Gallo, T; Curry, S C; Whiting, T; Padilla-Jones, A; Warkentin, T E; Puri, A

    2017-08-01

    Essentials We previously published a diagnostic algorithm for heparin-induced thrombocytopenia (HIT). In this study, we validated the algorithm in an independent large healthcare system. The accuracy was 98%, sensitivity 82% and specificity 99%. The algorithm has potential to improve accuracy and efficiency in the diagnosis of HIT. Background Heparin-induced thrombocytopenia (HIT) is a life-threatening drug reaction caused by antiplatelet factor 4/heparin (anti-PF4/H) antibodies. Commercial tests to detect these antibodies have suboptimal operating characteristics. We previously developed a diagnostic algorithm for HIT that incorporated 'four Ts' (4Ts) scoring and a stratified interpretation of an anti-PF4/H enzyme-linked immunosorbent assay (ELISA) and yielded a discriminant accuracy of 0.97 (95% confidence interval [CI], 0.93-1.00). Objectives The purpose of this study was to validate the algorithm in an independent patient population and quantitate effects that algorithm adherence could have on clinical care. Methods A retrospective cohort comprised patients who had undergone anti-PF4/H ELISA and serotonin release assay (SRA) testing in our healthcare system from 2010 to 2014. We determined the algorithm recommendation for each patient, compared recommendations with the clinical care received, and enumerated consequences of discrepancies. Operating characteristics were calculated for algorithm recommendations using SRA as the reference standard. Results Analysis was performed on 181 patients, 10 of whom were ruled in for HIT. The algorithm accurately stratified 98% of patients (95% CI, 95-99%), ruling out HIT in 158, ruling in HIT in 10 and recommending an SRA in 13 patients. Algorithm adherence would have obviated 165 SRAs and prevented 30 courses of unnecessary antithrombotic therapy for HIT. Diagnostic sensitivity was 0.82 (95% CI, 0.48-0.98), specificity 0.99 (95% CI, 0.97-1.00), PPV 0.90 (95% CI, 0.56-0.99) and NPV 0.99 (95% CI, 0.96-1.00). Conclusions An

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

    Science.gov (United States)

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

    2008-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Zhong-Qing Li

    2013-08-01

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

  3. Coagulation profile in patients undergoing video-assisted thoracoscopic lobectomy

    DEFF Research Database (Denmark)

    Christensen, Thomas Decker; Vad, Henrik; Pedersen, Søren

    2017-01-01

    -, and the first two days postoperatively by standard coagulation blood test, thromboelastometry (ROTEM®) and thrombin generation. Results: Patients undergoing potential curative surgery for lung cancer were not hypercoagulable preoperatively. There was no statistically significant difference in the majority......Background: Knowledge about the impact of Low-Molecular-Weight Heparin (LMWH) on the coagulation system in patients undergoing minimal invasive lung cancer surgery is sparse. The aim of this study was to assess the effect of LMWH on the coagulation system in patients undergoing Video......-Assisted Thoracoscopic Surgery (VATS) lobectomy for primary lung cancer. Methods: Sixty-three patients diagnosed with primary lung cancer undergoing VATS lobectomy were randomized to either subcutaneous injection with dalteparin (Fragmin®) 5000 IE once daily or no intervention. Coagulation was assessed pre-, peri...

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

    Science.gov (United States)

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

    2014-12-10

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

  5. Effects of inhaled nitric oxide on hemostasis in healthy adults treated with heparin: a randomized, controlled, blinded crossover study

    Directory of Open Access Journals (Sweden)

    Goldstein Brahm

    2012-01-01

    Full Text Available Abstract Background Effects of nitric oxide (NO on hemostasis have been studied in various investigational settings, but data regarding inhaled NO on bleeding and platelet function are conflicting. It is not known if inhaled NO has an effect when administered with drugs that influence hemostasis. This trial evaluated effects of inhaled NO on hemostasis in the presence of heparin using aspirin as a positive control. Patients/Methods Twelve healthy adult males were enrolled in a single-center, randomized, single-blind, four-way crossover trial. Subjects received 80 ppm NO or medical air (placebo inhalation for 30 min with simultaneous injection of placebo or heparin. Aspirin capsules were used as a positive control. Parameters of hemostasis were measured before treatment and at post-treatment intervals. Results Activated clotting time (ACT, prothrombin time (PT and activated partial thromboplastin time (aPTT increased only in groups that received heparin. Areas under the curve for ACT in heparin groups receiving inhaled NO were judged to be equivalent to those receiving medical air for both 0- to 4-h (ratio: 1.00; 90% CI, 0.90-1.11 and 0- to 24-h time intervals (ratio: 1.01; 90% CI, 0.92-1.12. Changes in bleeding time and platelet aggregation were observed only in aspirin groups. No clinically significant changes in hemoglobin, red blood cell counts or haematocrit were observed in any group. Conclusions Inhaled NO, when administered with heparin, exhibited no significant additive effects on ACT, PT, aPTT, bleeding time or platelet aggregation.

  6. Comparison of heparinized saline and 0.9% sodium chloride for maintaining peripheral intravenous catheter patency in dogs.

    Science.gov (United States)

    Ueda, Yu; Odunayo, Adesola; Mann, F A

    2013-01-01

    To determine whether heparinized saline would be more effective in maintaining the patency of peripheral IV catheters in dogs compared to 0.9% sodium chloride. Prospective blinded randomized study. University Veterinary Teaching Hospital. Thirty healthy purpose bred dogs, intended for use in the junior surgery laboratory, were utilized. The dogs were randomized into 1 of 3 groups, 2 treatment groups and a control group. An 18-Ga cephalic catheter was placed in the cephalic vein of each dog. Each dog in the treatment group had their catheter flushed with either 10 IU/mL heparinized saline or 0.9% sodium chloride every 6 hours for 42 hours. The dogs in the control group did not have their catheters flushed until the end of the study period. Immediately prior to flushing catheters, each catheter was evaluated for patency by aspiration of blood and the catheter site was evaluated for phlebitis. All dogs in the heparinized saline and 0.9% sodium chloride group had catheters that flushed easily at each evaluation point. More dogs in the saline group had catheters from which blood could not be aspirated, but there was no significant difference between these groups. All dogs in the control group had catheters that flushed easily at the end of the assigned 6 hour interval except in 1 dog. Phlebitis was not detected in any dog. Flushes of 0.9% sodium chloride were found to be as effective as 10 IU/mL heparinized saline flushes in maintaining patency of 18-Ga peripheral venous catheters in dogs for up to 42 hours. For peripheral catheters placed with the intention of performing serial blood draws, heparinized flushes may be warranted. © Veterinary Emergency and Critical Care Society 2013.

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

    Science.gov (United States)

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

    2015-07-01

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

  8. Proteolytic activation transforms heparin cofactor II into a host defense molecule.

    Science.gov (United States)

    Kalle, Martina; Papareddy, Praveen; Kasetty, Gopinath; Tollefsen, Douglas M; Malmsten, Martin; Mörgelin, Matthias; Schmidtchen, Artur

    2013-06-15

    The abundant serine proteinase inhibitor heparin cofactor II (HCII) has been proposed to inhibit extravascular thrombin. However, the exact physiological role of this plasma protein remains enigmatic. In this study, we demonstrate a previously unknown role for HCII in host defense. Proteolytic cleavage of the molecule induced a conformational change, thereby inducing endotoxin-binding and antimicrobial properties. Analyses employing representative peptide epitopes mapped these effects to helices A and D. Mice deficient in HCII showed increased susceptibility to invasive infection by Pseudomonas aeruginosa, along with a significantly increased cytokine response. Correspondingly, decreased levels of HCII were observed in wild-type animals challenged with bacteria or endotoxin. In humans, proteolytically cleaved HCII forms were detected during wounding and in association with bacteria. Thus, the protease-induced uncovering of cryptic epitopes in HCII, which transforms the molecule into a host defense factor, represents a previously unknown regulatory mechanism in HCII biology and innate immunity.

  9. Gold and silver nanoparticles conjugated with heparin derivative possess anti-angiogenesis properties

    International Nuclear Information System (INIS)

    Kemp, Melissa M; Linhardt, Robert J; Kumar, Ashavani; Ajayan, Pulickel; Mousa, Shaymaa; Dyskin, Evgeny; Yalcin, Murat; Mousa, Shaker A

    2009-01-01

    Silver and gold nanoparticles display unique physical and biological properties that have been extensively studied for biological and medical applications. Typically, gold and silver nanoparticles are prepared by chemical reductants that utilize excess toxic reactants, which need to be removed for biological purposes. We utilized a clean method involving a single synthetic step to prepare metal nanoparticles for evaluating potential effects on angiogenesis modulation. These nanoparticles were prepared by reducing silver nitrate and gold chloride with diaminopyridinyl (DAP)-derivatized heparin (HP) polysaccharides. Both gold and silver nanoparticles reduced with DAPHP exhibited effective inhibition of basic fibroblast growth factor (FGF-2)-induced angiogenesis, with an enhanced anti-angiogenesis efficacy with the conjugation to DAPHP (P<0.01) as compared to glucose conjugation. These results suggest that DAPHP-reduced silver nanoparticles and gold nanoparticles have potential in pathological angiogenesis accelerated disorders such as cancer and inflammatory diseases.

  10. Gold and silver nanoparticles conjugated with heparin derivative possess anti-angiogenesis properties

    Science.gov (United States)

    Kemp, Melissa M.; Kumar, Ashavani; Mousa, Shaymaa; Dyskin, Evgeny; Yalcin, Murat; Ajayan, Pulickel; Linhardt, Robert J.; Mousa, Shaker A.

    2009-11-01

    Silver and gold nanoparticles display unique physical and biological properties that have been extensively studied for biological and medical applications. Typically, gold and silver nanoparticles are prepared by chemical reductants that utilize excess toxic reactants, which need to be removed for biological purposes. We utilized a clean method involving a single synthetic step to prepare metal nanoparticles for evaluating potential effects on angiogenesis modulation. These nanoparticles were prepared by reducing silver nitrate and gold chloride with diaminopyridinyl (DAP)-derivatized heparin (HP) polysaccharides. Both gold and silver nanoparticles reduced with DAPHP exhibited effective inhibition of basic fibroblast growth factor (FGF-2)-induced angiogenesis, with an enhanced anti-angiogenesis efficacy with the conjugation to DAPHP (Pcancer and inflammatory diseases.

  11. Gold and silver nanoparticles conjugated with heparin derivative possess anti-angiogenesis properties

    Energy Technology Data Exchange (ETDEWEB)

    Kemp, Melissa M; Linhardt, Robert J [Department of Biology, Rensselaer Polytechnic Institute, Troy, NY 12180 (United States); Kumar, Ashavani; Ajayan, Pulickel [Department of Mechanical Engineering and Materials Science, Rice University, Houston, TX 77005 (United States); Mousa, Shaymaa; Dyskin, Evgeny; Yalcin, Murat; Mousa, Shaker A, E-mail: Shaker.mousa@acphs.ed [Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, NY 12208 (United States)

    2009-11-11

    Silver and gold nanoparticles display unique physical and biological properties that have been extensively studied for biological and medical applications. Typically, gold and silver nanoparticles are prepared by chemical reductants that utilize excess toxic reactants, which need to be removed for biological purposes. We utilized a clean method involving a single synthetic step to prepare metal nanoparticles for evaluating potential effects on angiogenesis modulation. These nanoparticles were prepared by reducing silver nitrate and gold chloride with diaminopyridinyl (DAP)-derivatized heparin (HP) polysaccharides. Both gold and silver nanoparticles reduced with DAPHP exhibited effective inhibition of basic fibroblast growth factor (FGF-2)-induced angiogenesis, with an enhanced anti-angiogenesis efficacy with the conjugation to DAPHP (P<0.01) as compared to glucose conjugation. These results suggest that DAPHP-reduced silver nanoparticles and gold nanoparticles have potential in pathological angiogenesis accelerated disorders such as cancer and inflammatory diseases.

  12. Thermodynamic parameters associated with the binding of adrenalin and norephedrine to heparin

    International Nuclear Information System (INIS)

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

    1983-01-01

    Pulse radiolysis has been used to determine the thermodynamic parameters (ΔG', ΔH' and ΔS') governing the binding of adrenalin and norephedrine to heparin. These complexes were completely dissociated by increasing concentrations of inorganic salts. Lower concentrations of divalent cations (e.g. Ca 2+ ) than of monovalent cations (e.g. Na + ) were necessary to effect dissociation of the complex. For each interaction an increase in drug binding occurred as the temperature was increased from ambient. However, a transition temperature was observed (48 0 C) above which the drug was progressively released as the temperature was increased. These observations are discussed in terms of conformational changes induced in the polymer below and above its melting temperature. (author)

  13. HIT or miss? A comprehensive contemporary investigation of laboratory tests for heparin induced thrombocytopenia.

    Science.gov (United States)

    Favaloro, Emmanuel J; McCaughan, Georgia; Mohammed, Soma; Lau, Kun Kan Edwin; Gemmell, Rosalie; Cavanaugh, Lauren; Donikian, Dea; Kondo, Mayuko; Brighton, Timothy; Pasalic, Leonardo

    2018-04-17

    Heparin induced thrombocytopenia (HIT) is a rare but potentially fatal complication of heparin therapy, which in a proportion of patients causes platelet activation and thrombosis. Initial clinical assessment of the likelihood of HIT is facilitated by laboratory testing to confirm or exclude HIT. This prospective investigation was performed over an 18-month period, and has involved testing of over 300 test samples from over 100 consecutive patients. Clinical assessment by 4T score was supplemented by laboratory tests that comprised both immunological [lateral flow ('STiC'), chemiluminescence (AcuStar; HIT-IgG (PF4-H) ), ELISA (Asserachrom HPIA IgG)] and functional assays [SRA, platelet aggregation using whole blood ('Multiplate') and platelet rich plasma ('LTA')]. We observed both false positive and false negative test findings with most assays. Overall, the whole blood aggregation method provided a reasonable alternative to SRA for identifying functional HIT. STiC, AcuStar and ELISA procedures were fairly comparable in terms of screening for HIT, although STiC and AcuStar both yielded false negatives, albeit also resulting in fewer false positives than ELISA. The 4T score had less utility in our patient cohort than we were expecting, although there was an association with the likelihood of HIT. Nevertheless, we accept that our observations are based on limited test numbers. In conclusion, no single approach (clinical or laboratory) was associated with optimal sensitivity or specificity of HIT exclusion or identification, and thus, a combination of clinical evaluation and laboratory testing will best ensure the accuracy of diagnosis. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

  14. Cellular Responses Modulated by FGF-2 Adsorbed on Albumin/Heparin Layer-by-Layer Assemblies.

    Science.gov (United States)

    Kumorek, Marta; Kubies, Dana; Filová, Elena; Houska, Milan; Kasoju, Naresh; Mázl Chánová, Eliška; Matějka, Roman; Krýslová, Markéta; Bačáková, Lucie; Rypáček, František

    2015-01-01

    In a typical cell culture system, growth factors immobilized on the cell culture surfaces can serve as a reservoir of bio-signaling molecules, without the need to supplement them additionally into the culture medium. In this paper, we report on the fabrication of albumin/heparin (Alb/Hep) assemblies for controlled binding of basic fibroblast growth factor (FGF-2). The surfaces were constructed by layer-by-layer adsorption of polyelectrolytes albumin and heparin and were subsequently stabilized by covalent crosslinking with glutaraldehyde. An analysis of the surface morphology by atomic force microscopy showed that two Alb/Hep bilayers are required to cover the surface of substrate. The formation of the Alb/Hep assemblies was monitored by the surface plasmon resonance (SPR), the infrared multiinternal reflection spectroscopy (FTIR MIRS) and UV/VIS spectroscopy. The adsorption of FGF-2 on the cross-linked Alb/Hep was followed by SPR. The results revealed that FGF-2 binds to the Alb/Hep assembly in a dose and time-dependent manner up to the surface concentration of 120 ng/cm(2). The bioactivity of the adsorbed FGF-2 was assessed in experiments in vitro, using calf pulmonary arterial endothelial cells (CPAE). CPAE cells could attach and proliferate on Alb/Hep surfaces. The adsorbed FGF-2 was bioactive and stimulated both the proliferation and the differentiation of CPAE cells. The improvement was more pronounced at a lower FGF-2 surface concentration (30 ng/cm(2)) than on surfaces with a higher concentration of FGF-2 (120 ng/cm(2)).

  15. Prevention of adverse events of interferon γ gene therapy by gene delivery of interferon γ-heparin-binding domain fusion protein in mice

    Directory of Open Access Journals (Sweden)

    Mitsuru Ando

    2014-01-01

    Full Text Available Sustained gene delivery of interferon (IFN γ can be an effective treatment, but our previous study showed high levels of IFNγ-induced adverse events, including the loss of body weight. These unwanted events could be reduced by target-specific delivery of IFNγ after in vivo gene transfer. To achieve this, we selected the heparin-binding domain (HBD of extracellular superoxide dismutase as a molecule to anchor IFNγ to the cell surface. We designed three IFNγ derivatives, IFNγ-HBD1, IFNγ-HBD2, and IFNγ-HBD3, each of which had 1, 2, or 3 HBDs, respectively. Each plasmid-encoding fusion proteins was delivered to the liver, a model target in this study, by hydrodynamic tail vein injection. The serum concentration of IFNγ-HBD2 and IFNγ-HBD3 after gene delivery was lower than that of IFNγ or IFNγ-HBD1. Gene delivery of IFNγ-HBD2, but not of IFNγ-HBD3, effectively increased the mRNA expression of IFNγ-inducible genes in the liver, suggesting liver-specific distribution of IFNγ-HBD2. Gene delivery of IFNγ-HBD2-suppressed tumor growth in the liver as efficiently as that of IFNγ with much less symptoms of adverse effects. These results indicate that the adverse events of IFNγ gene transfer can be prevented by gene delivery of IFNγ-HBD2, a fusion protein with high cell surface affinity.

  16. Heparin free dialysis in critically sick children using sustained low efficiency dialysis (SLEDD-f: A new hybrid therapy for dialysis in developing world.

    Directory of Open Access Journals (Sweden)

    Sidharth Kumar Sethi

    Full Text Available In critically sick adults, sustained low efficiency dialysis [SLED] appears to be better tolerated hemodynamically and outcomes seem to be comparable to CRRT. However, there is paucity of data in critically sick children. In children, two recent studies from Taiwan (n = 11 and India (n = 68 showed benefits of SLED in critically sick children.The objective of the study was to look at the feasibility and tolerability of sustained low efficiency daily dialysis-filtration [SLEDD-f] in critically sick pediatric patients.Design: Retrospective study Inclusion criteria: All pediatric patients who had undergone heparin free SLEDD-f from January 2012 to October 2017. Measurements: Data collected included demographic details, vital signs, PRISM III at admission, ventilator parameters (where applicable, number of inotropes, blood gas and electrolytes before, during, and on conclusion of SLED therapy. Technical information was gathered regarding SLEDD-f prescription and complications.Between 2012-2017, a total of 242 sessions of SLEDD-f were performed on 70 patients, out of which 40 children survived. The median age of patients in years was 12 (range 0.8-17 years, and the median weight was 39 kg (range 8.5-66 kg. The mean PRISM score at admission was 8.77±7.22. SLEDD-f sessions were well tolerated, with marked improvement in fluid status and acidosis. Premature terminations had to be done in 23 (9.5% of the sessions. There were 21 sessions (8.6% terminated due to hypotension and 2 sessions (0.8% terminated due to circuit clotting. Post- SLEDD-f hypocalcemia occurred in 15 sessions (6.2%, post- SLEDD-f hypophosphatemia occurred in 1 session (0.4%, and post- SLEDD-f hypokalemia occurred in 17 sessions (7.0%.This study is the largest compiled data on pediatric SLEDD-f use in critically ill patients. Our study confirms the feasibility of heparin free SLEDD-f in a larger pediatric population, and even in children weighing <20 kg on inotropic support.

  17. Impact of anticoagulation strategy with bivalirudin or heparin on nonaccess site bleeding in percutaneous coronary interventions: A meta-analysis of randomized trials

    NARCIS (Netherlands)

    Verdoia, M.; Barbieri, L.; Parodi, G.; Bellandi, B.; Schaffer, A.; Suryapranata, H.; Luca, G. De

    2017-01-01

    BACKGROUND: Transradial approach has significantly decreased the rate of access site bleeding in patients undergoing percutaneous coronary interventions (PCI), therefore potentially mitigating the benefits offered by bivalirudin in lowering major bleeding complications as compared to heparin.

  18. Heparin-bonded, expanded polytetrafluoroethylene-lined stent graft in the treatment of femoropopliteal artery disease: 1-year results of the VIPER (Viabahn Endoprosthesis with Heparin Bioactive Surface in the Treatment of Superficial Femoral Artery Obstructive Disease) trial.

    Science.gov (United States)

    Saxon, Richard R; Chervu, Arun; Jones, Paul A; Bajwa, Tanvir K; Gable, Dennis R; Soukas, Peter A; Begg, Richard J; Adams, John G; Ansel, Gary M; Schneider, Darren B; Eichler, Charles M; Rush, Michael J

    2013-02-01

    To evaluate the performance of a heparin-bonded, expanded polytetrafluoroethylene (ePTFE)-lined nitinol endoprosthesis in the treatment of long-segment occlusive disease of the femoropopliteal artery (FPA) and to identify factors associated with loss of patency. In a single-arm, prospective, 11-center study (VIPER [Gore Viabahn Endoprosthesis with Heparin Bioactive Surface in the Treatment of Superficial Femoral Artery Obstructive Disease] trial), 119 limbs (113 patients; 69 men; mean age, 67 y), including 88 with Rutherford category 3-5 disease and 72 with Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II) C or D lesions of the FPA, underwent stent graft implantation. The mean lesion length was 19 cm; 56% of lesions were occlusions. Follow-up evaluations included color duplex ultrasonography in all patients, with patency defined as a peak systolic velocity ratio20% was 70% (P = .047). Primary patency was not significantly affected by device diameter (5 vs 6 vs 7 mm) or lesion length (≤20 cm vs>20 cm). The 30-day major adverse event rate was 0.8%. The heparin-bonded, ePTFE/nitinol stent graft provided clinical improvement and a primary patency rate of 73% at 1 year in the treatment of long-segment FPA disease. Careful sizing of the device relative to vessel landing zones is essential for achieving optimal outcomes. Copyright © 2013 SIR. Published by Elsevier Inc. All rights reserved.

  19. Heparin sodium compliance to the new proposed USP monograph: elucidation of a minor structural modification responsible for a process dependent 2.10 ppm NMR signal.

    Science.gov (United States)

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

    2011-01-25

    Heparin is a highly sulfated hetero polysaccharide mixture found and extracted from mammalian tissues. It has been widely used as an anticoagulant drug during the past decades. In the new proposed USP heparin monograph, the ¹H NMR acceptance criteria to prevent contamination by over sulfated chondroitin sulfate (OSCS), or other persulfated glycosaminoglycans, specifies that no unidentified signals greater than 4% of the mean of signal height of 1 and 2 should be present in the following ranges: 0.10-2.00, 2.10-3.20, and 5.70-8.00 ppm. However, those criteria do not take into account the impact of potential structural modifications generated by the heparin manufacturing processes. In fact, starting from pig mucosa, heparin purification involves oxidizing reagents such as sodium peroxide, potassium permanganate and peracetic acid. In the present work, we demonstrate that potassium permanganate treated heparins show a small but characteristic extra signal at 2.10 ppm. Controlled heparinase I depolymerisation is used to target and excise the oligosaccharide responsible for this extra signal from the polysaccharide backbone. By using orthogonal chromatographic techniques, the fingerprint oligosaccharide was isolated and its structure elucidated. Without the identification of this structural moiety, such purified heparins may have been considered as non-compliant drug substance and not suitable for pharmaceutical use. Copyright © 2010 Elsevier B.V. All rights reserved.

  20. A triad of lys12, lys41, arg78 spatial domain, a novel identified heparin binding site on tat protein, facilitates tat-driven cell adhesion.

    Directory of Open Access Journals (Sweden)

    Jing Ai

    Full Text Available Tat protein, released by HIV-infected cells, has a battery of important biological effects leading to distinct AIDS-associated pathologies. Cell surface heparan sulfate protoglycans (HSPGs have been accepted as endogenous Tat receptors, and the Tat basic domain has been identified as the heparin binding site. However, findings that deletion or substitution of the basic domain inhibits but does not completely eliminate Tat-heparin interactions suggest that the basic domain is not the sole Tat heparin binding site. In the current study, an approach integrating computational modeling, mutagenesis, biophysical and cell-based assays was used to elucidate a novel, high affinity heparin-binding site: a Lys12, Lys41, Arg78 (KKR spatial domain. This domain was also found to facilitate Tat-driven β1 integrin activation, producing subsequent SLK cell adhesion in an HSPG-dependent manner, but was not involved in Tat internalization. The identification of this new heparin binding site may foster further insight into the nature of Tat-heparin interactions and subsequent biological functions, facilitating the rational design of new therapeutics against Tat-mediated pathological events.

  1. Improved patency and reduced intimal hyperplasia in PTFE grafts with luminal immobilized heparin compared with standard PTFE grafts at six months in a sheep model.

    Science.gov (United States)

    Pedersen, G; Laxdal, E; Ellensen, V; Jonung, T; Mattsson, E

    2010-06-01

    The aim of this study was to compare the performance of polytetrafluoroethylene (PTFE) grafts with luminal coating of immobilized heparin to that of standard PTFE grafts at six months. Twenty-eight common carotid arteries in fourteen sheep were bypassed with heparin-coated PTFE grafts (6 mm diameter, 6 cm length) on one side and standard PTFE grafts on the other. The grafts were explanted after six months. The thickness of intimal hyperplasia (IH) in open grafts was measured with histomorphometrical methods. Two of 14 heparinized PTFE grafts and nine of 14 grafts in the control PTFE-group were occluded at explantation (P=0.006). Six-month patency rates for heparinized PTFE grafts and for standard PTFE grafts were 86% and 36%, respectively. Mean graft anastomotic IH thickness in open grafts were 0.074 mm for heparinized PTFE grafts and 0.259 mm for PTFE-grafts (P=0.006). PTFE grafts with luminal coating containing immobilized heparin had significantly better patency and recruited less intimal hyperplasia than standard PTFE grafts at six months.

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

    Science.gov (United States)

    Tabassum, Rana; Gupta, Banshi D

    2016-12-15

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

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

    Science.gov (United States)

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

    2013-09-10

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

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

  5. Overweight, Obesity, and Weight Loss

    Science.gov (United States)

    ... Back to section menu Healthy Weight Weight and obesity Underweight Weight, fertility, and pregnancy Weight loss and ... section Home Healthy Weight Healthy Weight Weight and obesity Underweight Weight, fertility, and pregnancy Weight loss and ...

  6. Effect of crosslinking chemistry of albumin/heparin multilayers on FGF-2 adsorption and endothelial cell behavior

    Czech Academy of Sciences Publication Activity Database

    Kumorek, Marta M.; Janoušková, Olga; Höcherl, Anita; Houska, Milan; Mázl Chánová, Eliška; Kasoju, Naresh; Cuchalová, Lucie; Matějka, R.; Kubies, Dana

    2017-01-01

    Roč. 411, 31 July (2017), s. 240-250 ISSN 0169-4332 R&D Projects: GA MŠk(CZ) LQ1604; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:61389013 Keywords : basic fibroblast growth factor * heparin * cross-linking Subject RIV: CD - Macromolecular Chemistry OBOR OECD: Polymer science Impact factor: 3.387, year: 2016

  7. Impact of INR monitoring, reversal agent use, heparin bridging, and anticoagulant interruption on rebleeding and thromboembolism in acute gastrointestinal bleeding.

    Directory of Open Access Journals (Sweden)

    Naoyoshi Nagata

    Full Text Available Anticoagulant management of acute gastrointestinal bleeding (GIB during the pre-endoscopic period has not been fully addressed in American, European, or Asian guidelines. This study sought to evaluate the risks of rebleeding and thromboembolism in anticoagulated patients with acute GIB.Baseline, endoscopy, and outcome data were reviewed for 314 patients with acute GIB: 157 anticoagulant users and 157 age-, sex-, and important risk-matched non-users. Data were also compared between direct oral anticoagulants (DOACs and warfarin users.Between anticoagulant users and non-users, of whom 70% underwent early endoscopy, no endoscopy-related adverse events or significant differences were found in the rate of endoscopic therapy need, transfusion need, rebleeding, or thromboembolism. Rebleeding was associated with shock, comorbidities, low platelet count and albumin level, and low-dose aspirin use but not HAS-BLED score, any endoscopic results, heparin bridge, or international normalized ratio (INR ≥ 2.5. Risks for thromboembolism were INR ≥ 2.5, difference in onset and pre-endoscopic INR, reversal agent use, and anticoagulant interruption but not CHA2DS2-VASc score, any endoscopic results, or heparin bridge. In patients without reversal agent use, heparin bridge, or anticoagulant interruption, there was only one rebleeding event and no thromboembolic events. Warfarin users had a significantly higher transfusion need than DOACs users.Endoscopy appears to be safe for anticoagulant users with acute GIB compared with non-users. Patient background factors were associated with rebleeding, whereas anticoagulant management factors (e.g. INR correction, reversal agent use, and drug interruption were associated with thromboembolism. Early intervention without reversal agent use, heparin bridge, or anticoagulant interruption may be warranted for acute GIB.

  8. Comparative study of heparin-binding proteins profile of Murrah buffalo (Bubalus bubalis semen

    Directory of Open Access Journals (Sweden)

    S. S. Ramteke

    2014-09-01

    Full Text Available Aim: The experiment was conducted to study the total seminal plasma protein (TSPP and heparin-binding proteins (HBPs in relation to initial semen quality of buffalo bull. Materials and Methods: Semen from two Murrah buffalo bulls (bull no. 605 and 790 with mass motility of ≥3+ were used for the study and categorized into three groups (Group I- Mass motility 3+, Group II- Mass motility 4+ and Group III- Mass motility 5+. Seminal plasma from semen was separated by centrifugation. HBPs was isolated and purified from heparin-agarose affinity column by modified elution buffer. TSPP and isolated HBPs concentration was estimated by Lowry’s method. The purified HBPs were resolved on Sodium dodecyl sulfate polyacrylamide gel electrophoresis to check the protein profile of two bulls. Results: The mean values of TSPP concentrations in bull no. 605 and 790 in Group I, II and III were 30.64±0.12, 31.66±0.09, 32.53±0.19 and 28.51±0.09, 29.49±0.15, 30.45±0.17 mg/mL, respectively. The mean values of HBPs concentrations in bull no. 605 and 790 in Group I, II and III were 3.11±0.07, 3.32±0.06, 3.46±0.08 and 2.51±0.08, 2.91±0.05, 3.10±0.03 mg/mL, respectively. Both the values of TSPP and HBPs were significantly higher (p<0.01 in bull no. 605 when compared to 790 in all the three groups. 31 kDa HBP was more intensely present in bull no. 605, thus may indicate its superiority over bull no. 790 in relation to fertility potential. Conclusion: TSPP and HBPs shows variation in concentration with respect to initial semen quality. Furthermore, presence of fertility related 31 kDa HBPs in one of the bull may be an indication of high fertility of a bull. In future, in-vivo and in-vitro correlative study on larger basis is needed for the establishment of fertility-related HBPs in semen which might establish criteria for selection of buffalo bull with high fertility potential.

  9. Heparin-binding peptide as a novel affinity tag for purification of recombinant proteins.

    Science.gov (United States)

    Morris, Jacqueline; Jayanthi, Srinivas; Langston, Rebekah; Daily, Anna; Kight, Alicia; McNabb, David S; Henry, Ralph; Kumar, Thallapuranam Krishnaswamy Suresh

    2016-10-01

    Purification of recombinant proteins constitutes a significant part of the downstream processing in biopharmaceutical industries. Major costs involved in the production of bio-therapeutics mainly depend on the number of purification steps used during the downstream process. Affinity chromatography is a widely used method for the purification of recombinant proteins expressed in different expression host platforms. Recombinant protein purification is achieved by fusing appropriate affinity tags to either N- or C- terminus of the target recombinant proteins. Currently available protein/peptide affinity tags have proved quite useful in the purification of recombinant proteins. However, these affinity tags suffer from specific limitations in their use under different conditions of purification. In this study, we have designed a novel 34-amino acid heparin-binding affinity tag (HB-tag) for the purification of recombinant proteins expressed in Escherichia coli (E. coli) cells. HB-tag fused recombinant proteins were overexpressed in E. coli in high yields. A one-step heparin-Sepharose-based affinity chromatography protocol was developed to purify HB-fused recombinant proteins to homogeneity using a simple sodium chloride step gradient elution. The HB-tag has also been shown to facilitate the purification of target recombinant proteins from their 8 M urea denatured state(s). The HB-tag has been demonstrated to be successfully released from the fusion protein by an appropriate protease treatment to obtain the recombinant target protein(s) in high yields. Results of the two-dimensional NMR spectroscopy experiments indicate that the purified recombinant target protein(s) exist in the native conformation. Polyclonal antibodies raised against the HB-peptide sequence, exhibited high binding specificity and sensitivity to the HB-fused recombinant proteins (∼10 ng) in different crude cell extracts obtained from diverse expression hosts. In our opinion, the HB-tag provides a

  10. Use of transsplenic injection of agitated saline and heparinized blood for the ultrasonographic diagnosis of macroscopic portosystemic shunts in dogs.

    Science.gov (United States)

    Gómez-Ochoa, Pablo; Llabrés-Díaz, Francisco; Ruiz, Sergio; Corda, Andrea; Prieto, Saul; Sosa, Ivan; Gregori, Tommaso; Gascón, Manuel; Couto, Guillermo C

    2011-01-01

    We describe the use of ultrasonography-guided percutaneous splenic injection of agitated saline and heparinized blood for the diagnosis of portosystemic shunts (PSS) in 34 dogs. Agitated saline mixed with 1 ml of heparinized autologous blood was injected into the spleen of 34 sedated dogs under sonographic guidance. The transducer was then sequentially repositioned to visualize the portal vein, the caudal vena cava, and the right atrium through different acoustic windows. It was possible to differentiate between intrahepatic and extrahepatic shunts depending on the entry point of the microbubbles into the caudal vena cava. Portoazygos shunts and portocaval shunts could be differentiated based on the presence of microbubbles in the caudal vena cava and/or the right atrium. In one dog, collateral circulation due to portal hypertension was identified. In dogs with a single extrahepatic shunt, the microbubbles helped identify the shunting vessel. The technique was also used postoperatively to assess the efficacy of shunt closure. All abnormal vessels were confirmed by exploratory laparotomy or with ultrasonographic identification of the shunting vessel. Ultrasound-guided transsplenic injection of agitated saline with heparinized blood should be considered as a valuable technique for the diagnosis of PSS; it is easy to perform, safe, and the results are easily reproducible.

  11. Self-Assembled Lipid Nanoparticles for Oral Delivery of Heparin-Coated Iron Oxide Nanoparticles for Theranostic Purposes.

    Science.gov (United States)

    Truzzi, Eleonora; Bongio, Chiara; Sacchetti, Francesca; Maretti, Eleonora; Montanari, Monica; Iannuccelli, Valentina; Vismara, Elena; Leo, Eliana

    2017-06-09

    Recently, solid lipid nanoparticles (SLNs) have attracted increasing attention owing to their potential as an oral delivery system, promoting intestinal absorption in the lymphatic circulation which plays a role in disseminating metastatic cancer cells and infectious agents throughout the body. SLN features can be exploited for the oral delivery of theranostics. Therefore, the aim of this work was to design and characterise self-assembled lipid nanoparticles (SALNs) to encapsulate and stabilise iron oxide nanoparticles non-covalently coated with heparin (Fe@hepa) as a model of a theranostic tool. SALNs were characterised for physico-chemical properties (particle size, surface charge, encapsulation efficiency, in vitro stability, and heparin leakage), as well as in vitro cytotoxicity by methyl thiazole tetrazolium (MTT) assay and cell internalisation in CaCo-2, a cell line model used as an indirect indication of intestinal lymphatic absorption. SALNs of about 180 nm, which are stable in suspension and have a high encapsulation efficiency (>90%) were obtained. SALNs were able to stabilise the heparin coating of Fe@hepa, which are typically unstable in physiological environments. Moreover, SALNs-Fe@hepa showed no cytotoxicity, although their ability to be internalised into CaCo-2 cells was highlighted by confocal microscopy analysis. Therefore, the results indicated that SALNs can be considered as a promising tool to orally deliver theranostic Fe@hepa into the lymphatic circulation, although further in vivo studies are needed to comprehend further potential applications.

  12. THROMBOPHILIA IN PREGNANCY – CURRENT ISSUE OF MODERN PERINATOLOGY

    Directory of Open Access Journals (Sweden)

    Dragana Radović-Janošević

    2015-09-01

    Full Text Available Pregnancy is a condition of increased affinity to blood clotting. The most important changes of coagulation system in pregnancy involve the increase of the following coagulation factors: fibrinogen production, level of numerous blood coagulation factors- FII, FVII, FVIII, FX, FXII, acquired activated protein C resistance, and the decrease of: fibrinolysis due to the increase of a large number of fibrinolytic activator inhibitors PAI-1 and PAI-2, thrombin activatable fibrinolysis inhibitor TAFI, and levels of proteins S and C. This disease is not a disease on its own, but a group of inherited and acquired coagulation disorders that increase the predisposition to thrombosis. The treatment of choice in pregnancy are low-molecular-weight heparins (LMWHs which are derived from standard heparin by controlled hydrolysis, thus obtaining heparins of a lower molecular mass. The most commonly used LMWHs are: dalteparin sodium, enoxaparin, nadroparin-calcium, reviparin. LMWH is given in prophylactic doses – low and medium doses in therapeutic doses. Thromboprophylaxis in pregnancy is implemented as: intrapartal, intra- and postpartum according to the official recommendations of the American Association of Obstetricians and Gynecologists (ACOG. Specific recommendations of ACOG refer to the treatment of hereditary thrombophilia in pregnancy.

  13. Weight Loss Surgery

    Science.gov (United States)

    Weight loss surgery helps people with extreme obesity to lose weight. It may be an option if you cannot lose weight ... obesity. There are different types of weight loss surgery. They often limit the amount of food you ...

  14. Heparin/heparan sulfate analysis by covalently modified reverse polarity capillary zone electrophoresis-mass spectrometry.

    Science.gov (United States)

    Sanderson, Patience; Stickney, Morgan; Leach, Franklin E; Xia, Qiangwei; Yu, Yanlei; Zhang, Fuming; Linhardt, Robert J; Amster, I Jonathan

    2018-04-13

    Reverse polarity capillary zone electrophoresis coupled to negative ion mode mass spectrometry (CZE-MS) is shown to be an effective and sensitive tool for the analysis of glycosaminoglycan mixtures. Covalent modification of the inner wall of the separation capillary with neutral or cationic reagents produces a stable and durable surface that provides reproducible separations. By combining CZE-MS with a cation-coated capillary and a sheath flow interface, a rapid and reliable method has been developed for the analysis of sulfated oligosaccharides from dp4 to dp12. Several different mixtures have been separated and detected by mass spectrometry. The mixtures were selected to test the capability of this approach to resolve subtle differences in structure, such as sulfation position and epimeric variation of the uronic acid. The system was applied to a complex mixture of heparin/heparan sulfate oligosaccharides varying in chain length from dp3 to dp12 and more than 80 molecular compositions were identified by accurate mass measurement. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Is There an Association Between Heparin-Induced Thrombocytopenia (HIT) and Autoimmune Disease?

    Science.gov (United States)

    Klinkhammer, Brent; Gruchalla, Michael

    2018-03-01

    Heparin-induced thrombocytopenia (HIT) is a drug-induced, immunoglobulin G medicated autoimmune disorder associated with several negative clinical outcomes including increased morbidity, mortality, and increased medical costs. Previous studies have shown associations between comorbid autoimmune diseases, but there is little known about associations between HIT and autoimmunity. To provide clinical data to suggest an association between HIT and autoimmunity. Retrospective chart review of 59 cases with a diagnosis of HIT and 251 matched controls without a HIT diagnosis, comparing the prevalence of autoimmunity in each group. A single, large upper Midwest health care system. Patients with a diagnosis of HIT were significantly more likely to have a comorbid autoimmune disease than those without a HIT diagnosis (55.9% vs 10.8%, P HIT were significantly more likely to have a diagnosis of antiphospholipid syndrome (15.3% vs 0.0%, P HIT were significantly older than controls ( P HIT and autoimmune disease and suggests a need for more research into the relationship between HIT and autoimmunity. These results could alter the anticoagulation management of venous thromboembolism and acute coronary syndrome in patients with a previously identified autoimmune disease. Copyright© Wisconsin Medical Society.

  16. Elevated urine levels of heparin-binding protein in children with urinary tract infection.

    Science.gov (United States)

    Kjölvmark, Charlott; Akesson, Per; Linder, Adam

    2012-08-01

    Urinary tract infection (UTI) is a common infection diagnosis in children, and efficient diagnosis and treatment are important to avoid serious complications. In this study we investigated whether urinary levels of neutrophil-derived heparin-binding protein (HBP) can be used as a marker of UTI in children. These results were compared to those of dipstick analysis, interleukin-6 (IL-6) analysis in urine, and bacterial culturing. Seventy-eight children aged 0-18 years with fever and/or symptoms indicating UTI were enrolled in a prospective consecutive study. Urine samples were cultured and analyzed with dipstick, and concentrations of HBP and IL-6 were measured. Fifteen patients were classified as having UTI, 30 patients had fever but were diagnosed with a non-urinary tract infection, and 33 patients had neither UTI nor fever. Using a urine HBP (U-HBP) cut-off level of 32 ng/mL, the sensitivity and specificity for detecting UTI were 93.3 and 90.3 %, respectively. Receiver operating characteristic curves demonstrated that U-HBP levels were a higher specificity indicator of UTI than urine white blood cell counts or urine IL-6 levels; they also showed a higher sensitivity than the results of the urine nitrite test. All patients with significant growth of clinically relevant bacteria had elevated U-HBP levels. The results indicate that rapid analysis of U-HBP can provide helpful guidance in the management of children with suspected UTI.

  17. A peptide of heparin cofactor II inhibits endotoxin-mediated shock and invasive Pseudomonas aeruginosa infection.

    Directory of Open Access Journals (Sweden)

    Martina Kalle

    Full Text Available Sepsis and septic shock remain important medical problems with high mortality rates. Today's treatment is based mainly on using antibiotics to target the bacteria, without addressing the systemic inflammatory response, which is a major contributor to mortality in sepsis. Therefore, novel treatment options are urgently needed to counteract these complex sepsis pathologies. Heparin cofactor II (HCII has recently been shown to be protective against Gram-negative infections. The antimicrobial effects were mapped to helices A and D of the molecule. Here we show that KYE28, a 28 amino acid long peptide representing helix D of HCII, is antimicrobial against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive Bacillus subtilis and Staphylococcus aureus, as well as the fungus Candida albicans. Moreover, KYE28 binds to LPS and thereby reduces LPS-induced pro-inflammatory responses by decreasing NF-κB/AP-1 activation in vitro. In mouse models of LPS-induced shock, KYE28 significantly enhanced survival by dampening the pro-inflammatory cytokine response. Finally, in an invasive Pseudomonas infection model, the peptide inhibited bacterial growth and reduced the pro-inflammatory response, which lead to a significant reduction of mortality. In summary, the peptide KYE28, by simultaneously targeting bacteria and LPS-induced pro-inflammatory responses represents a novel therapeutic candidate for invasive infections.

  18. An antimicrobial helix A-derived peptide of heparin cofactor II blocks endotoxin responses in vivo.

    Science.gov (United States)

    Papareddy, Praveen; Kalle, Martina; Singh, Shalini; Mörgelin, Matthias; Schmidtchen, Artur; Malmsten, Martin

    2014-05-01

    Host defense peptides are key components of the innate immune system, providing multi-facetted responses to invading pathogens. Here, we describe that the peptide GKS26 (GKSRIQRLNILNAKFAFNLYRVLKDQ), corresponding to the A domain of heparin cofactor II (HCII), ameliorates experimental septic shock. The peptide displays antimicrobial effects through direct membrane disruption, also at physiological salt concentration and in the presence of plasma and serum. Biophysical investigations of model lipid membranes showed the antimicrobial action of GKS26 to be mirrored by peptide incorporation into, and disordering of, bacterial lipid membranes. GKS26 furthermore binds extensively to bacterial lipopolysaccharide (LPS), as well as its endotoxic lipid A moiety, and displays potent anti-inflammatory effects, both in vitro and in vivo. Thus, for mice challenged with ip injection of LPS, GKS26 suppresses pro-inflammatory cytokines, reduces vascular leakage and infiltration in lung tissue, and normalizes coagulation. Together, these findings suggest that GKS26 may be of interest for further investigations as therapeutic against severe infections and septic shock. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. A peptide of heparin cofactor II inhibits endotoxin-mediated shock and invasive Pseudomonas aeruginosa infection.

    Science.gov (United States)

    Kalle, Martina; Papareddy, Praveen; Kasetty, Gopinath; van der Plas, Mariena J A; Mörgelin, Matthias; Malmsten, Martin; Schmidtchen, Artur

    2014-01-01

    Sepsis and septic shock remain important medical problems with high mortality rates. Today's treatment is based mainly on using antibiotics to target the bacteria, without addressing the systemic inflammatory response, which is a major contributor to mortality in sepsis. Therefore, novel treatment options are urgently needed to counteract these complex sepsis pathologies. Heparin cofactor II (HCII) has recently been shown to be protective against Gram-negative infections. The antimicrobial effects were mapped to helices A and D of the molecule. Here we show that KYE28, a 28 amino acid long peptide representing helix D of HCII, is antimicrobial against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive Bacillus subtilis and Staphylococcus aureus, as well as the fungus Candida albicans. Moreover, KYE28 binds to LPS and thereby reduces LPS-induced pro-inflammatory responses by decreasing NF-κB/AP-1 activation in vitro. In mouse models of LPS-induced shock, KYE28 significantly enhanced survival by dampening the pro-inflammatory cytokine response. Finally, in an invasive Pseudomonas infection model, the peptide inhibited bacterial growth and reduced the pro-inflammatory response, which lead to a significant reduction of mortality. In summary, the peptide KYE28, by simultaneously targeting bacteria and LPS-induced pro-inflammatory responses represents a novel therapeutic candidate for invasive infections.

  20. Flow cytometric quantitation of phagocytosis in heparinized complete blood with latex particles and Candida albicans

    Directory of Open Access Journals (Sweden)

    Jesús M. Egido

    1997-12-01

    Full Text Available We report a rapid method for the flow cytometric quantitation of phagocytosis in heparinized complete peripherial blood (HCPB, using commercially available phycoerythrin-conjugated latex particles of 1µm diameter. The method is faster and shows greater reproducibility than Bjerknes' (1984 standard technique using propidium iodide-stained Candida albicans, conventionally applied to the leukocytic layer of peripherial blood but here modified for HCPB. We also report a modification of Bjerknes' Intracellular Killing Test to allow its application to HCPB.Se da cuenta de un método rápido para la cuantización del flujo citométrico de la fagocitosis en sangre periférica completamente heparinizada (HCPB, mediante la utilización de partículas de látex phycoerythrin-conjugadas de 1µm de diámetro disponibles comercialmente. El método es más rápido y presenta mayor reproducibilidad que la técnica estandar de Bjerknes' (1984 utilizando propidium iodide-teñida Candida albicans, aplicada convencionalmente a la capa leucocitica de sangre periférica pero modificada por HCPB. Tambien damos cuenta de una modificación de Bjerknes' Intracellular Killing Test para permitir su aplicación a HCPB.

  1. Diagnostic leg scanning for deep venous thrombosis in the recently heparinized patient

    International Nuclear Information System (INIS)

    Mant, M.J.; O'Brien, B.D.; Russell, D.B.

    1981-01-01

    Leg scanning with fibrinogen 125I, either alone on in combination with other procedures, has been proposed as an alternative to venography for diagnosis of deep venous thrombi. Clinical circumstances may necessitate anticoagulation before scanning can be performed, which could alter its reliability. We have compared the results of scanning with venographic findings in heparinized patients with venous thromboembolism. Different criteria for an abnormal leg scan gave different sensitivities and specificities. During the first four days of scanning with a requirement for a persistently abnormal result, five of eight criteria had high specificity (greater than 92%). However, sensitivities did not exceed 55%. With the use of transiently abnormal results and six days of scanning, higher sensitivities were obtained but specificities were reduced. No criterion gave results considered acceptable for a diagnostic test for deep venous thrombosis. Leg scanning should therefore not be used for this purpose in patients who have received anticoagulants. Our results also suggest that duration of symptoms has little effect on the sensitivity of leg scanning and that the test is more reliable for establishing the presence of thrombus than at defining its location

  2. Improving pancreatic islet in vitro functionality and transplantation efficiency by using heparin mimetic peptide nanofiber gels.

    Science.gov (United States)

    Uzunalli, Gozde; Tumtas, Yasin; Delibasi, Tuncay; Yasa, Oncay; Mercan, Sercan; Guler, Mustafa O; Tekinay, Ayse B

    2015-08-01

    Pancreatic islet transplantation is a promising treatment for type 1 diabetes. However, viability and functionality of the islets after transplantation are limited due to loss of integrity and destruction of blood vessel networks. Thus, it is important to provide a proper mechanically and biologically supportive environment for enhancing both in vitro islet culture and transplantation efficiency. Here, we demonstrate that heparin mimetic peptide amphiphile (HM-PA) nanofibrous network is a promising platform for these purposes. The islets cultured with peptide nanofiber gel containing growth factors exhibited a similar glucose stimulation index as that of the freshly isolated islets even after 7 days. After transplantation of islets to STZ-induced diabetic rats, 28 day-long monitoring displayed that islets that were transplanted in HM-PA nanofiber gels maintained better blood glucose levels at normal levels compared to the only islet transplantation group. In addition, intraperitoneal glucose tolerance test revealed that animals that were transplanted with islets within peptide gels showed a similar pattern with the healthy control group. Histological assessment showed that islets transplanted within peptide nanofiber gels demonstrated better islet integrity due to increased blood vessel density. This work demonstrates that using the HM-PA nanofiber gel platform enhances the islets function and islet transplantation efficiency both in vitro and in vivo. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  3. Agarose-gel electrophoresis for the quality assurance and purity of heparin formulations.

    Science.gov (United States)

    Volpi, Nicola; Buzzega, Dania

    2012-01-01

    The adulteration of raw heparin (Hep) with a synthetic oversulfated chondroitin sulfate (OSCS) not found in nature produced in 2007-2008 a global crisis giving rise to the development of additional, new and specific methods for its quality assurance and purity. In this study, a simple and sensitive agarose-gel electrophoresis method has been developed for the visualization of OSCS in Hep samples along with other natural glycosaminoglycans possibly present as "process-related impurities", in particular dermatan sulfate (DS) and chondroitin sulfate (CS). Agarose-gel electrophoresis under non-conventional conditions is able to separate OSCS from Hep with its two components, the slow-moving and fast-moving species, DS and CS by performing separation for 15 h (overnight) and under high voltage (100 mA, ∼200 V). Densitometric scanning enabled us to calculate a limit of detection of ∼0.5 μg OSCS with a linear behaviour from 0.1 to 5 μg, comparable to CS/DS. Contaminated samples from Hep manufacturers were analyzed and quantitative data were found comparable to previous studies. Due to its capacity to process many samples in a single run and to the equipment commonly available in laboratories, this analytical method would be suitable for the identification and quantification of contamination by other polysaccharides, in particular OSCS and DS, within Hep preparations and formulations. Copyright © 2012 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    Campi-Azevedo, Ana Carolina; Peruhype-Magalhães, Vanessa; Coelho-Dos-Reis, Jordana Grazziela; Costa-Pereira, Christiane; Yamamura, Anna Yoshida; Lima, Sheila Maria Barbosa de; Simões, Marisol; Campos, Fernanda Magalhães Freire; de Castro Zacche Tonini, Aline; Lemos, Elenice Moreira; Brum, Ricardo Cristiano; de Noronha, Tatiana Guimarães; Freire, Marcos Silva; Maia, Maria de Lourdes Sousa; Camacho, Luiz Antônio Bastos; Rios, Maria; Chancey, Caren; Romano, Alessandro; Domingues, Carla Magda; Teixeira-Carvalho, Andréa; Martins-Filho, Olindo Assis

    2017-09-01

    Technological innovations in vaccinology have recently contributed to bring about novel insights for the vaccine-induced immune response. While the current protocols that use peripheral blood samples may provide abundant data, a range of distinct components of whole blood samples are required and the different anticoagulant systems employed may impair some properties of the biological sample and interfere with functional assays. Although the interference of heparin in functional assays for viral neutralizing antibodies such as the functional plaque-reduction neutralization test (PRNT), considered the gold-standard method to assess and monitor the protective immunity induced by the Yellow fever virus (YFV) vaccine, has been well characterized, the development of pre-analytical treatments is still required for the establishment of optimized protocols. The present study intended to optimize and evaluate the performance of pre-analytical treatment of heparin-collected blood samples with ecteola-cellulose (ECT) to provide accurate measurement of anti-YFV neutralizing antibodies, by PRNT. The study was designed in three steps, including: I. Problem statement; II. Pre-analytical steps; III. Analytical steps. Data confirmed the interference of heparin on PRNT reactivity in a dose-responsive fashion. Distinct sets of conditions for ECT pre-treatment were tested to optimize the heparin removal. The optimized protocol was pre-validated to determine the effectiveness of heparin plasma:ECT treatment to restore the PRNT titers as compared to serum samples. The validation and comparative performance was carried out by using a large range of serum vs heparin plasma:ECT 1:2 paired samples obtained from unvaccinated and 17DD-YFV primary vaccinated subjects. Altogether, the findings support the use of heparin plasma:ECT samples for accurate measurement of anti-YFV neutralizing antibodies. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Comparison of a priori versus provisional heparin therapy on radial artery occlusion after transradial coronary angiography and patent hemostasis (from the PHARAOH Study).

    Science.gov (United States)

    Pancholy, Samir B; Bertrand, Olivier F; Patel, Tejas

    2012-07-15

    Systemic anticoagulation decreases the risk of radial artery occlusion (RAO) after transradial catheterization and standard occlusive hemostasis. We compared the efficacy and safety of provisional heparin use only when the technique of patent hemostasis was not achievable to standard a priori heparin administration after radial sheath introduction. Patients referred for coronary angiography were randomized in 2 groups. In the a priori group, 200 patients received intravenous heparin (50 IU/kg) immediately after sheath insertion. In the provisional group, 200 patients did not receive heparin during the procedure. After sheath removal, hemostasis was obtained using a TR band (Terumo corporation, Tokyo, Japan) with a plethysmography-guided patent hemostasis technique. In the provisional group, no heparin was given if radial artery patency could be obtained and maintained. If radial patency was not achieved, a bolus of heparin (50 IU/kg) was given. Radial artery patency was evaluated at 24 hours (early RAO) and 30 days after the procedure (late RAO) by plethysmography. Patent hemostasis was obtained in 67% in the a priori group and 74% in the provisional group (p = 0.10). Incidence of RAO remained similar in the 2 groups at the early (7.5% vs 7.0%, p = 0.84) and late (4.5% vs 5.0%, p = 0.83) evaluations. Women, patients with diabetes, patients having not received heparin, and patients without radial artery patency during hemostasis had more RAO. By multivariate analysis, patent radial artery during hemostasis (odds ratio [OR] 0.03, 95% confidence interval [CI] 0.004 to 0.28, p = 0.002) and diabetes (OR 11, 95% CI 3 to 38,p patent hemostasis is maintained. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. The differences in heparin binding for the C-terminal basic-sequence-rich peptides of HPV-16 and HPV-18 capsid protein L1

    International Nuclear Information System (INIS)

    Sun Jian; Yu Jisheng; Yu Zhiwu; Zha Xiao; Wu Yuqing

    2012-01-01

    Graphial abstract: The differences in heparin binding for the C-terminal basic-sequence-rich peptides of HPV-16 and HPV-18 capsid protein L1. Highlights: ► Several driving forces contribute to the interaction between heparin and peptides. ► C-terminal of HPV L1 is a potential candidate for the attachment to host cells. ► The C-terminal peptides of HPV-16 and -18 L1 have different heparin-binding. ► The different heparin-binding provides an explanation for the distinct prevalences. - Abstract: The high-risk types of human papillomaviruses (HPV) HPV-16 and -18 are the predominant types associated with cervical cancer. HPV-16 and -18 account for about 50% and 20%, respectively, of cervical cancers worldwide. While the reason and molecular mechanism of the distinct prevalence and distributions between them remain poorly understood, the binding affinity of cell surface receptor with capsid proteins, especially L1, may be involved. We examined heparin binding with two synthetic peptides corresponding to the 14 amino acid C-terminal peptides of HPV-16 and -18 L1 with the goal of comparing the equivalent residues in different HPV types. Using isothermal titration calorimetry (ITC) and static right-angle light scattering (SLS), we determined the binding constant K, reaction enthalpy ΔH, and other thermodynamic parameters in the interaction. Especially, we assessed the role of specific residues in binding with heparin by comparing the NMR spectra of free and heparin-bound peptides.

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

    Science.gov (United States)

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

    2017-11-01

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

  8. Mindfulness Approaches and Weight Loss, Weight Maintenance, and Weight Regain.

    Science.gov (United States)

    Dunn, Carolyn; Haubenreiser, Megan; Johnson, Madison; Nordby, Kelly; Aggarwal, Surabhi; Myer, Sarah; Thomas, Cathy

    2018-03-01

    There is an urgent need for effective weight management techniques, as more than one third of US adults are overweight or obese. Recommendations for weight loss include a combination of reducing caloric intake, increasing physical activity, and behavior modification. Behavior modification includes mindful eating or eating with awareness. The purpose of this review was to summarize the literature and examine the impact of mindful eating on weight management. The practice of mindful eating has been applied to the reduction of food cravings, portion control, body mass index, and body weight. Past reviews evaluating the relationship between mindfulness and weight management did not focus on change in mindful eating as the primary outcome or mindful eating as a measured variable. This review demonstrates strong support for inclusion of mindful eating as a component of weight management programs and may provide substantial benefit to the treatment of overweight and obesity.

  9. Cost-effectiveness analysis of apixaban compared to low-molecularweight heparins and vitamin k antagonists for treatment and secondary prevention of venous thromboembolism

    Directory of Open Access Journals (Sweden)

    Isabel Elías

    2016-05-01

    Full Text Available Objective: Cost-effectiveness analysis of a 6-month treatment of apixaban (10 mg/12h, first 7 days; 5 mg/12h afterwards for the treatment of the first event of venous thromboembolism (VTE and prevention of recurrences, versus low-molecular-weight heparins/vitamin K antagonists treatment (LMWH/VKA. Material and methods: A lifetime Markov model with 13 health states was used for describing the course of the disease. Efficacy and safety data were obtained from AMPLIFY and AMPLIFY-EXT clinical trials; health outcomes were measured as life years gained (LYG and quality-adjusted life years (QALY. The chosen perspective of this analysis has been the Spanish National Health System (NHS. Drugs, management of VTE and complications costs were obtained from several Spanish data sources (€, 2014. A 3% discount rate was applied to health outcomes and costs. Univariate and probabilistic sensitivity analyses (SA were performed in order to assess the robustness of the results. Results: Apixaban was the most effective therapy with 7.182 LYG and 5.865 QALY, versus 7.160 LYG and 5.838 QALYs with LMWH/VKA. Furthermore, apixaban had a lower total cost (€13,374.70 vs €13,738.30. Probabilistic SA confirmed dominance of apixaban (led to better health outcomes with less associated costs in 89% of the simulations. Conclusions: Apixaban 5 mg/12h versus LMWH/VKA was an efficient therapeutic strategy for the treatment and prevention of recurrences of VTE from the NHS perspective.

  10. Nuclear androgen receptors in human prostatic tissue. Extraction with heparin and estimation of the number of binding sites with different methods

    International Nuclear Information System (INIS)

    Foekens, J.A.; Bolt-de Vries, J.; Mulder, E.; Blankenstein, M.A.; Schroeder, F.H.; Molen, H.J. van der

    1981-01-01

    A procedure for the estimation of nuclear androgen receptors in benign prostatic hyperplastic tissue is described, which employs extraction of receptors from nuclei with buffers containing heparin. Extraction of a nuclear pellet with a heparin-containing (1 g/l) buffer appeared to have definite advantages over 0.4 mol/l KCl extraction. Heparin appeared to be twice as efficient in extracting androgen receptors. In addition aggregated receptor proteins, formed after storage at -80 0 C, were partly deaggregated by heparin. Specific isolation of the androgen receptor was performed using either agar gel electrophoresis, protamine sulphate precipitation or LH-20 gel filtration. A comparison was made between the amounts of estimated receptors with these different techniques. Protamine sulphate precipitation resulted in the highest estimates of receptor-bound 5α-[ 3 H]dihydrotestosterone ( 3 H-DHT). Treatment of the labelled nuclear extracts with a charcoal suspension prior to the receptor assay resulted in lower amounts of estimated androgen receptors. A method for routine evaluation of nuclear androgen receptors in prostatic tissue has been evaluated, which involves extraction of nuclear pellets with a heparin-containing (1 g/l) buffer, exchange labelling of the nuclear extracts for 20 h at 10 0 C and quantification of the receptors with protamine sulphate precipitation. (Auth.)

  11. Successful Use of Alternative Anticoagulants in the Management of Heparin-induced Thrombocytopenia with Thrombotic Complications: Report of 5 cases and review of literature.

    LENUS (Irish Health Repository)

    Alkindi, Salam

    2011-08-01

    Heparin is one of the most frequently used anticoagulants. It is easy to use, but can be associated with life-threatening side effects. One of these is heparin-induced thrombocytopenia syndrome (HITS), which develops in about 3-5% of patients exposed to heparin and is associated with thrombosis in 1% of cases. We report here the successful treatment of five patients with HITS who were treated with alternative anticoagulants namely danaparoid or hirudin. The median time between their exposure to heparin and onset of symptoms and or signs was 10.2 days (range 7-14 days). Platelet counts decreased to a mean of 38.4 x 10(9) \\/l (12-82 x 10(9)\\/l). All five patients had evidence of thrombosis; four patients had clinical and radiological evidence of pulmonary emboli, one patient had confirmed deep vein thrombosis (DVT) and one patient had extensive skin necrosis of the thighs and abdomen. Platelet aggregation test were positive in two patients, inconclusive in one patient and negative in two patients. Two patients were anticoagulated with danaparoid and three with hirudin until their platelet counts returned to normal between 4 and 14 days (average 6 days) following the recognition of the syndrome. Our patients had significant morbidity, but no mortality. Immediate withdrawal of heparin is of paramount importance and introduction of alternative anticoagulant is necessary in the presence of thrombosis.

  12. Sustained Thromboresistant Bioactivity with Reduced Intimal Hyperplasia of Heparin-Bonded Polytetrafluoroethylene Propaten Graft in a Chronic Canine Femoral Artery Bypass Model.

    Science.gov (United States)

    Freeman, John; Chen, Aaron; Weinberg, Roy J; Okada, Tamuru; Chen, Changyi; Lin, Peter H

    2018-05-01

    Bypass graft thrombosis remains a significant mode of failure in prosthetic graft revascularization. The purpose of this investigation was to evaluate the long-term thromboresistant effect of heparin-bonded expanded polytetrafluoroethylene (ePTFE) graft using Carmeda BioActive Surface technology in a canine model. Bilateral femorofemoral artery bypass grafts with ePTFE grafts were performed in 25 adult grayhound dogs. In each animal, a heparin-bonded ePTFE graft (Propaten, WL Gore) was placed on one side, whereas a control nonheparin graft was placed on the contralateral side. The graft patency was assessed at 1, 6, 12, 18, and 24 months (n = 5 per group) following the bypass. Heparin bioactivity of the graft material was analyzed. The effect of intimal hyperplasia was also assessed. All bypass grafts were patent at 1 month. Significantly greater patency rates were noted in the Propaten group compared to the control group at 12, 18, and 24 months, which were 84%, 80%, and 80% vs. 55%, 35%, and 20%, respectively (P  0.05). Heparin-bonded ePTFE graft provides a thromboresistant surface and reduced anastomotic intimal hyperplasia at 2 years. The stable heparin bioactivity of the Propaten graft confers an advantage in long-term graft patency. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  13. Renal unit practitioners’ knowledge, attitudes and practice regarding the safety of unfractionated heparin for chronic haemodialysis

    Directory of Open Access Journals (Sweden)

    Debra Ockhuis

    2015-09-01

    Full Text Available Background: Chronic haemodialysis for adult patients with end-stage kidney failure requires a patent extracorporeal circuit, maintained by anticoagulants such as unfractionated heparin (UFH. Incorrect administration of UFH has safety implications for patients. Objectives: Firstly, to describe renal practitioners’ self-reported knowledge, attitudes and practice (KAP regarding the safe use of UFH and its effects; secondly, to determine an association between KAP and selected independent variables. Method: A cross-sectional descriptive survey by self-administered questionnaire and non-probability convenience sampling was conducted in two tertiary hospital dialysis units and five private dialysis units in 2013. Results: The mean age of 74/77 respondents (96.1%, was 41.1 years. Most (41/77, 53.2% had 0–5 years of renal experience. The odds of enrolled nurses having poorer knowledge of UFH than registered nurses were 18.7 times higher at a 95% Confidence Interval (CI (1.9–187.4 and statistically significant (P = 0.013. The odds of delivering poor practice having ≤ five years of experience and no in-service education were 4.6 times higher at a 95% CI (1.4–15.6, than for respondents who had ≥ six years of experience (P = 0.014 and 4.3 times higher (95% CI 1.1–16.5 than for respondents who received in-service education (P = 0.032, the difference reaching statistical significance in both cases. Conclusion: Results suggest that the category of the professional influences knowledge and, thus, safe use of UFH, and that there is a direct relationship between years of experience and quality of haemodialysis practice and between having in-service education and quality of practice.

  14. Importance of lipopolysaccharide aggregate disruption for the anti-endotoxic effects of heparin cofactor II peptides.

    Science.gov (United States)

    Singh, Shalini; Papareddy, Praveen; Kalle, Martina; Schmidtchen, Artur; Malmsten, Martin

    2013-11-01

    Lipid membrane and lipopolysaccharide (LPS) interactions were investigated for a series of amphiphilic and cationic peptides derived from human heparin cofactor II (HCII), using dual polarization interferometry, ellipsometry, circular dichroism (CD), cryoTEM, and z-potential measurements. Antimicrobial effects of these peptides were compared to their ability to disorder bacterial lipid membranes, while their capacity to block endotoxic effects of LPS was correlated to the binding of these peptides to LPS and its lipid A moiety, and to charge, secondary structure, and morphology of peptide/LPS complexes. While the peptide KYE28 (KYEITTIHNLFRKLTHRLFRRNFGYTLR) displayed potent antimicrobial and anti-endotoxic effects, its truncated variants KYE21 (KYEITTIHNLFRKLTHRLFRR) and NLF20 (NLFRKLTHRLFRRNFGYTLR) provide some clues on structure-activity relations, since KYE21 retains both the antimicrobial and anti-endotoxic effects of KYE28 (although both attenuated), while NLF20 retains the antimicrobial but only a fraction of the anti-endotoxic effect, hence locating the anti-endotoxic effects of KYE28 to its N-terminus. The antimicrobial effect, on the other hand, is primarily located at the C-terminus of KYE28. While displaying quite different endotoxic effects, these peptides bind to a similar extent to both LPS and lipid A, and also induce comparable LPS scavenging on model eukaryotic membranes. In contrast, fragmentation and densification of LPS aggregates, in turn dependent on the secondary structure in the peptide/LPS aggregates, correlate to the anti-endotoxic effect of these peptides, thus identifying peptide-induced packing transitions in LPS aggregates as key for anti-endotoxic functionality. This aspect therefore needs to be taken into account in the development of novel anti-endotoxic peptide therapeutics. Copyright © 2013. Published by Elsevier B.V.

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

    Science.gov (United States)

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

    2012-12-24

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

  16. New synthetic peptide with efficacy for heparin reversal and low toxicity and immunogenicity in comparison to protamine sulfate

    Energy Technology Data Exchange (ETDEWEB)

    Li, Tong; Meng, Zhiyun; Zhu, Xiaoxia; Gan, Hui; Gu, Ruolan; Wu, Zhuona; Li, Jian; Zheng, Ying; Liu, Taoyun; Han, Peng; Han, Su; Dou, Guifang, E-mail: douguifang@vip.sina.com

    2015-11-20

    Protamine sulfate (PS), the only clinically approved antidote to unfractionated heparin (UFH), is widely used for cardiopulmonary surgery or other extracorporeal circulation situations. However, the applications of PS have accompanied various severe side-effects. In this study, we presented a novel synthesized peptide compound (RRRRR-RRRRR-RRRRR-sulfate, R15S) served as a safer UFH antidote. Comparison studies were conducted between PS and R15S on efficacy and safety, aided by heparin neutralization studies, drug toxicity studies and anaphylactic analysis. Our research demonstrated that R15S contained comparable UFH neutralization activity in vitro and in rats in vivo as to active partial thromboplastin time (APTT) and anti-FXa assays. There was no cytotoxicity for R15S at 60 μg mg{sup −1} or below and the median lethal dose (LD{sub 50}) of R15S in mice was 35.4 mg kg{sup −1}, both of which were similar to that of PS. Furthermore, R15S exhibited no immunogenicity while it was obvious in guinea pigs immunized with PS. The level of cross-reactivity to anti-PS antibodies of R15S was about 30%. Both of which indicated much safer properties of R15S than PS. In conclusion, we presented a promising candidate R15S for UFH reversal, which is effective in neutralizing UFH and potentially safer in use. - Highlights: • R15 sulfate has a comparable unfractionated heparin neutralization activity to PS. • R15 sulfate avoided severe anaphylactic responses which happened to PS in clinical use. • R15 sulfate could provide a stricter quality control compared to PS which may vary with different batches.

  17. Weight Gain during Pregnancy

    Science.gov (United States)

    ... Global Map Premature Birth Report Cards Careers Archives Pregnancy Before or between pregnancies Nutrition, weight & fitness Prenatal ... fitness > Weight gain during pregnancy Weight gain during pregnancy E-mail to a friend Please fill in ...

  18. Should I Gain Weight?

    Science.gov (United States)

    ... Videos for Educators Search English Español Should I Gain Weight? KidsHealth / For Teens / Should I Gain Weight? ... something about it. Why Do People Want to Gain Weight? Some of the reasons people give for ...

  19. Effects of enoxaparin and unfractionated heparin in prophylactic and therapeutic doses on the fertility of female Wistar rats.

    Science.gov (United States)

    Figueiró-Filho, Ernesto Antonio; Aydos, Ricardo Dutra; Senefonte, Flávio Renato de Almeida; Ferreira, Cristiane Munaretto; Pereira, Erica Freire de Vasconcelos; Oliveira, Vanessa Marcon de; Menezes, Giovanna Pádoa de; Bósio, Marco Antonio Costa

    2014-07-01

    To evaluate the effects of exposure of enoxaparin and unfractionated heparin (UFH) in prophylactic and therapeutic doses on the fertility rates of pregnant healthy Wistar rats. Enoxaparin and UFH were administered in prophylactic doses 1 mg/Kg/day 72 UI/Kg/day, and in therapeutic doses at 2 mg/kg/day 400UI/Kg/day. The rats were divided into five groups. The number of live and dead foetuses was quantified. The uterine horns were dissected and the presence of early and late reabsorptions (abortions) was determined. A peffect on fertility with the use of anticoagulant drugs in pregnant healthy Wistar rats.

  20. Octasaccharide is the minimal length unit required for efficient binding of cyclophilin B to heparin and cell surface heparan sulphate.

    Science.gov (United States)

    Vanpouille, Christophe; Denys, Agnès; Carpentier, Mathieu; Pakula, Rachel; Mazurier, Joël; Allain, Fabrice

    2004-09-01

    Cyclophilin B (CyPB) is a heparin-binding protein first identified as a receptor for cyclosporin A. In previous studies, we reported that CyPB triggers chemotaxis and integrin-mediated adhesion of T-lymphocytes by way of interaction with two types of binding sites. The first site corresponds to a signalling receptor; the second site has been identified as heparan sulphate (HS) and appears crucial to induce cell adhesion. Characterization of the HS-binding unit is critical to understand the requirement of HS in pro-adhesive activity of CyPB. By using a strategy based on gel mobility shift assays with fluorophore-labelled oligosaccharides, we demonstrated that the minimal heparin unit required for efficient binding of CyPB is an octasaccharide. The mutants CyPB(KKK-) [where KKK- refers to the substitutions K3A(Lys3-->Ala)/K4A/K5A] and CyPB(DeltaYFD) (where Tyr14-Phe-Asp16 has been deleted) failed to interact with octasaccharides, confirming that the Y14FD16 and K3KK5 clusters are required for CyPB binding. Molecular modelling revealed that both clusters are spatially arranged so that they may act synergistically to form a binding site for the octasaccharide. We then demonstrated that heparin-derived octasaccharides and higher degree of polymerization oligosaccharides inhibited the interaction between CyPB and fluorophore-labelled HS chains purified from T-lymphocytes, and strongly reduced the HS-dependent pro-adhesive activity of CyPB. However, oligosaccharides or heparin were unable to restore adhesion of heparinase-treated T-lymphocytes, indicating that HS has to be present on the cell membrane to support the pro-adhesive activity of CyPB. Altogether, these results demonstrate that the octasaccharide is likely to be the minimal length unit required for efficient binding of CyPB to cell surface HS and consequent HS-dependent cell responses.

  1. Cerebral venous thrombosis due to cryptogenic organising pneumopathy with antiphospholipid syndrome worsened by heparin-induced thrombocytopenia.

    Science.gov (United States)

    Hsieh, J; Kuzmanovic, I; Vargas, M I; Momjian-Mayor, I

    2013-07-09

    Cerebral venous thrombosis (CVT) has usually been ascribed to prothrombotic conditions, oral contraceptives, pregnancy, malignancy, infection, head injury or mechanical precipitants. The case reported here illustrates two rare causes of CVT observed in the same patient: the presence of antiphospholipid antibodies associated with an asymptomatic cryptogenic organising pneumopathy (COP) which were considered the origin of the venous cerebral thrombosis and heparin-induced thrombocytopenia (HIT) which was responsible for the worsening of the thrombosis observed a few days after the introduction of treatment. Moreover, we provide here additional positive experience in the treatment of both, CVT and HIT, by fondaparinux with bridging to warfarin given their successful evolution under this anticoagulant option.

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

    Science.gov (United States)

    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.

  3. Dosagem da heparina em cirurgia cardíaca com circulação extracorpórea Measurement of heparin in cardiac surgery wilh extracorporea circulation

    Directory of Open Access Journals (Sweden)

    Fernando Moraes

    1996-09-01

    Full Text Available Com o objetivo de quantificar o nível sérico de heparina, sua atenuação em função do tempo e o valor residual após a neutralização com sulfato de protamina, foram coletadas amostras de sangue em tempos pré-estabelecidos em 27 pacientes submetidos a revascularização do miocárdio com circulação extracorpórea. Após a heparinização (400 Ul/kg as amostras de sangue foram coletadas nos tempos de 5, 10,30 e 60 minutos e subseqüentemente a cada 30 minutos, dependendo do tempo da circulação extracorpórea. A cada hora, após a heparinização, administrava-se nova dose de heparina (200 Ul/kg. As amostras eram armazenadas à temperatura de 4ºC antes do processo de extração da heparina que foi realizado por métodos físico-químicos. As dosagens mostraram que 5 minutos após a heparinização os pacientes apresentaram concentração sangüínea máxima de heparina e, ao tempo de 60 minutos, a sua concentração é de aproximadamente 68% da encontrada aos 5 minutos. Ao tempo de 90 minutos, ou seja, após a reheparinização a concentração de heparina é 96% da evidenciada aos cinco minutos e, após a neutralização com sulfato de protamina (1,5:1, ainda se encontra um valor residual de heparina que corresponde a 4% do observado inicialmente. Observou-se que os pacientes mais idosos têm uma tendência a manter um nível sérico mais prolongado e através da equação (Cone. de heparina = 104,7 + (- 12,85 x minutos (In + 0,25 x idade podemos estimar a concentração de heparina em determinado tempo.In order to quantify seric levels of heparin, its attenuation as a time function and its residual value after neutralization with protamine sulfate, blood samples were collected, at pre-set intervals, from 27 patients undergoing myocardial revascularization surgery under extracorporeal circulation. After heparinization (400 Ul/Kg, blood samples were collected at 5, 10, 30 and 60 minutes and subsequently every 30 minutes depending upon

  4. Potentiation of C1-esterase inhibitor by heparin and interactions with C1s protease as assessed by surface plasmon resonance.

    Science.gov (United States)

    Rajabi, Mohsen; Struble, Evi; Zhou, Zhaohua; Karnaukhova, Elena

    2012-01-01

    Human C1-esterase inhibitor (C1-INH) is a multifunctional plasma protein with a wide range of inhibitory and non-inhibitory properties, mainly recognized as a key down-regulator of the complement and contact cascades. The potentiation of C1-INH by heparin and other glycosaminoglycans (GAGs) regulates a broad spectrum of C1-INH activities in vivo both in normal and disease states. SCOPE OF RESEARCH: We have studied the potentiation of human C1-INH by heparin using Surface Plasmon Resonance (SPR), circular dichroism (CD) and a functional assay. To advance a SPR for multiple-unit interaction studies of C1-INH we have developed a novel (consecutive double capture) approach exploring different immobilization and layout. Our SPR experiments conducted in three different design versions showed marked acceleration in C1-INH interactions with complement protease C1s as a result of potentiation of C1-INH by heparin (from 5- to 11-fold increase of the association rate). Far-UV CD studies suggested that heparin binding did not alter C1-INH secondary structure. Functional assay using chromogenic substrate confirmed that heparin does not affect the amidolytic activity of C1s, but does accelerate its consumption due to C1-INH potentiation. This is the first report that directly demonstrates a significant acceleration of the C1-INH interactions with C1s due to heparin by using a consecutive double capture SPR approach. The results of this study may be useful for further C-INH therapeutic development, ultimately for the enhancement of current C1-INH replacement therapies. Published by Elsevier B.V.

  5. Degranulating mast cells in fibrotic regions of human tumors and evidence that mast cell heparin interferes with the growth of tumor cells through a mechanism involving fibroblasts

    International Nuclear Information System (INIS)

    Samoszuk, Michael; Kanakubo, Emi; Chan, John K

    2005-01-01

    The purpose of this study was to test the hypothesis that mast cells that are present in fibrotic regions of cancer can suppress the growth of tumor cells through an indirect mechanism involving peri-tumoral fibroblasts. We first immunostained a wide variety of human cancers for the presence of degranulated mast cells. In a subsequent series of controlled in vitro experiments, we then co-cultured UACC-812 human breast cancer cells with normal fibroblasts in the presence or absence of different combinations and doses of mast cell tryptase, mast cell heparin, a lysate of the human mast cell line HMC-1, and fibroblast growth factor-7 (FGF-7), a powerful, heparin-binding growth factor for breast epithelial cells. Degranulating mast cells were localized predominantly in the fibrous tissue of every case of breast cancer, head and neck cancer, lung cancer, ovarian cancer, non-Hodgkin's lymphoma, and Hodgkin's disease that we examined. Mast cell tryptase and HMC-1 lysate had no significant effect on the clonogenic growth of cancer cells co-cultured with fibroblasts. By contrast, mast cell heparin at multiple doses significantly reduced the size and number of colonies of tumor cells co-cultured with fibroblasts, especially in the presence of FGF-7. Neither heparin nor FGF-7, individually or in combination, produced any significant effect on the clonogenic growth of breast cancer cells cultured without fibroblasts. Degranulating mast cells are restricted to peri-tumoral fibrous tissue, and mast cell heparin is a powerful inhibitor of clonogenic growth of tumor cells co-cultured with fibroblasts. These results may help to explain the well-known ability of heparin to inhibit the growth of primary and metastatic tumors

  6. Degranulating mast cells in fibrotic regions of human tumors and evidence that mast cell heparin interferes with the growth of tumor cells through a mechanism involving fibroblasts

    Directory of Open Access Journals (Sweden)

    Kanakubo Emi

    2005-09-01

    Full Text Available Abstract Background The purpose of this study was to test the hypothesis that mast cells that are present in fibrotic regions of cancer can suppress the growth of tumor cells through an indirect mechanism involving peri-tumoral fibroblasts. Methods We first immunostained a wide variety of human cancers for the presence of degranulated mast cells. In a subsequent series of controlled in vitro experiments, we then co-cultured UACC-812 human breast cancer cells with normal fibroblasts in the presence or absence of different combinations and doses of mast cell tryptase, mast cell heparin, a lysate of the human mast cell line HMC-1, and fibroblast growth factor-7 (FGF-7, a powerful, heparin-binding growth factor for breast epithelial cells. Results Degranulating mast cells were localized predominantly in the fibrous tissue of every case of breast cancer, head and neck cancer, lung cancer, ovarian cancer, non-Hodgkin's lymphoma, and Hodgkin's disease that we examined. Mast cell tryptase and HMC-1 lysate had no significant effect on the clonogenic growth of cancer cells co-cultured with fibroblasts. By contrast, mast cell heparin at multiple doses significantly reduced the size and number of colonies of tumor cells co-cultured with fibroblasts, especially in the presence of FGF-7. Neither heparin nor FGF-7, individually or in combination, produced any significant effect on the clonogenic growth of breast cancer cells cultured without fibroblasts. Conclusion Degranulating mast cells are restricted to peri-tumoral fibrous tissue, and mast cell heparin is a powerful inhibitor of clonogenic growth of tumor cells co-cultured with fibroblasts. These results may help to explain the well-known ability of heparin to inhibit the growth of primary and metastatic tumors.

  7. Cell adhesion to fibrillin-1: identification of an Arg-Gly-Asp-dependent synergy region and a heparin-binding site that regulates focal adhesion formation

    DEFF Research Database (Denmark)

    Bax, Daniel V; Mahalingam, Yashithra; Cain, Stuart

    2007-01-01

    We have defined the molecular basis of cell adhesion to fibrillin-1, the major structural component of extracellular microfibrils that are associated with elastic fibres. Using human dermal fibroblasts, and recombinant domain swap fragments containing the Arg-Gly-Asp motif, we have demonstrated...... a requirement for upstream domains for integrin-alpha(5)beta(1)-mediated cell adhesion and migration. An adjacent heparin-binding site, which supports focal adhesion formation, was mapped to the fibrillin-1 TB5 motif. Site-directed mutagenesis revealed two arginine residues that are crucial for heparin binding...

  8. Comparison of two doses of heparin on outcome in off-pump coronary artery bypass surgery patients: A prospective randomized control study

    Directory of Open Access Journals (Sweden)

    Murali Chakravarthy

    2017-01-01

    Full Text Available Introduction: While off pump coronary artery bypass surgery is practiced with an intention to reduce the morbidity associated with cardiopulmonary bypass, the resultant ′hypercoagulability′ needs to be addressed. Complications such as cavitary thrombus possibly due to the hyper coagulability after off pump coronary artery bypass surgery have been described. Many clinicians use higher doses of heparin - up to 5 mg/kg in order to thwart this fear. Overall, there appears to be no consensus on the dose of heparin in off pump coronary artery bypass surgeries. Aim of the Study: The aim of the study was understand the differences in outcome of such as transfusion requirement, myocardial ischemia, and morbidity when two different doses were used for systemic heparinization. Methods: Elective patients scheduled for off pump coronary artery bypass surgery were included. Ongoing anti platelet medication was not an exclusion criteria, however, anti platelet medications were ceased about a week prior to surgery when possible. Thoracic epidural anesthesia was administered as an adjunct in patients who qualified for it. By computer generated randomization chart, patients were chosen to receive either 2 or 3 mg/kg of intravenous unfractioned heparin to achieve systemic heparinization with activated clotting time targeted at >240 secs. Intraoperative blood loss, postoperative blood loss, myocardial ischemic episodes, requirement of intraaortic balloon counter pulsation and transfusion requirement were analyzed. Results: Sixty two patients participated in the study. There was one conversion to cardiopulmonary bypass. The groups had comparable ACT at baseline (138.8 vs. 146.64 seconds, P = 0.12; 3 mg/kg group had significantly higher values after heparin, as expected. But after reversal with protamine, ACT and need for additional protamine was similar among the groups. Intraoperative (685.56 ± 241.42 ml vs. 675.15 ± 251.86 ml, P = 0.82 and postoperative

  9. Mechanisms of Weight Regain following Weight Loss.

    Science.gov (United States)

    Blomain, Erik Scott; Dirhan, Dara Anne; Valentino, Michael Anthony; Kim, Gilbert Won; Waldman, Scott Arthur

    2013-01-01

    Obesity is a world-wide pandemic and its incidence is on the rise along with associated comorbidities. Currently, there are few effective therapies to combat obesity. The use of lifestyle modification therapy, namely, improvements in diet and exercise, is preferable over bariatric surgery or pharmacotherapy due to surgical risks and issues with drug efficacy and safety. Although they are initially successful in producing weight loss, such lifestyle intervention strategies are generally unsuccessful in achieving long-term weight maintenance, with the vast majority of obese patients regaining their lost weight during followup. Recently, various compensatory mechanisms have been elucidated by which the body may oppose new weight loss, and this compensation may result in weight regain back to the obese baseline. The present review summarizes the available evidence on these compensatory mechanisms, with a focus on weight loss-induced changes in energy expenditure, neuroendocrine pathways, nutrient metabolism, and gut physiology. These findings have added a major focus to the field of antiobesity research. In addition to investigating pathways that induce weight loss, the present work also focuses on pathways that may instead prevent weight regain. Such strategies will be necessary for improving long-term weight loss maintenance and outcomes for patients who struggle with obesity.

  10. Heparin modified graphene oxide for pH-sensitive sustained release of doxorubicin hydrochloride

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Baomei; Yang, Xiaoye; Wang, Yang; Zhai, Guangxi, E-mail: professorgxzhai@126.com

    2017-06-01

    A novel nanocarrier of heparin (Hep) modified graphene oxide (GO) was fabricated via a linker (adipic dihydrazide) and used as a pH-sensitive drug delivery system for controlling the release of anticancer drug doxorubicin (DOX) for anti-tumor therapy. The finally obtained nanocarrier was GO-ADH-Hep with better stability, blood compatibility and biocompatibility confirmed by the hemolytic test and in vitro cytotoxicity study. Its safety issue was greatly improved via Hep modification. The amount of DOX loaded onto GO-ADH-Hep was significantly high and dependent on pH value. The release rate of DOX from GO- ADH-Hep/DOX was pH-sensitive and much-slower than that of free DOX solution suggesting the sustained drug-release capacity of this prepared nanocomplexes. In addition, the results of cytotoxicity study illustrated that this fabricated nanocomplexes displayed effective cytotoxicity to MCF-7 and HepG2 cells. What's more, the results of the in vivo pharmacokinetic study was also indicated that the GO-ADH-Hep/DOX nanocomplexes could significantly prolong the retention time of DOX in vivo and this was consistent with the in vitro drug release performance. And finally, according to the biodistribution study, DOX delivered by GO-ADH-Hep could reduce cardiotoxicity deriving from DOX solution and also decrease the pulmonary toxicity deriving from unmodified GO. Based on the in vitro and in vivo investigations, the fabricated GO-ADH-Hep could be a promising candidate as an ideal nano-carrier for drug delivery and anti-cancer therapy. - Highlights: • Firstly, a novel nanocarrier-GO-ADH-Hep was fabricated with improved stability, little cytotoxicity and little hemolysis ratio. • Secondly, GO-ADH-Hep was used to load the anticancer drug (DOX) with high drug loading and pH-sensitive sustained drug release. • Thirdly, the anti-cancer efficacy of GO-ADH-Hep/DOX was dose- and time-dependent in vitro. • Finally, according to the in vivo studies, this synthesized nano

  11. Dual Affinity Heparin-Based Hydrogels Achieve Pro-Regenerative Immunomodulation and Microvascular Remodeling.

    Science.gov (United States)

    Ogle, Molly E; Krieger, Jack R; Tellier, Liane E; McFaline-Figueroa, Jennifer; Temenoff, Johnna S; Botchwey, Edward A

    2018-04-09

    The immune response to biomaterial implants critically regulates functional outcomes such as vascularization, transplant integration/survival, and fibrosis. To create "immunologically smart" materials, the host-material response may be engineered to optimize the recruitment of pro-regenerative leukocyte subsets which mature into corresponding wound-healing macrophages. We have recently identified a unique feature of pro-regenerative Ly6C low monocytes that is a higher expression of both the bioactive lipid receptor sphingosine-1-phosphate receptor 3 (S1PR3) and the stromal derived factor-1α (SDF-1α) receptor CXCR4. Therefore, we designed a bifunctional hydrogel to harnesses a mechanistic synergy between these signaling axes to enhance the recruitment of endogenous pro-regenerative monocytes. To overcome the challenge of codelivering two physiochemically distinct molecules-a large hydrophilic protein and hydrophobic small molecule-we engineered a dual affinity hydrogel that exploits the growth factor affinity of a heparin derivative (Hep -N ) and lipid chaperone activity of albumin. The sphingosine analog FTY720 and SDF-1α are successfully loaded and coreleased from the Hep -N -functionalized PEG-DA hydrogels while maintaining bioactivity. Placement of these hydrogels into a murine partial thickness skin wound demonstrates that corelease of FTY720 and SDF-1α yields superior recruitment of myeloid cells to the implant interface compared to either factor alone. Although in vivo delivery of FTY720 or SDF-1α individually promotes the enhanced recruitment of Ly-6C low anti-inflammatory monocytes, codelivery enhances the early accumulation and persistence of the differentiated wound healing CD206 + macrophages in the tissue surrounding the gel. Co-delivery similarly promoted the synergistic expansion of vasculature adjacent to the implant, a key step in tissue healing. Taken together, these findings suggest that the combination of chemotactic molecules may provide

  12. Efficacy of a protocol including heparin ointment for treatment of multikinase inhibitor-induced hand-foot skin reactions.

    Science.gov (United States)

    Li, Jian-ri; Yang, Chi-rei; Cheng, Chen-li; Ho, Hao-chung; Chiu, Kun-yuan; Su, Chung-Kuang; Chen, Wen-Ming; Wang, Shian-Shiang; Chen, Chuan-Shu; Yang, Cheng-Kuang; Ou, Yen-chuan

    2013-03-01

    The purpose of this study is to evaluate the efficacy of a protocol including topical heparin therapy for hand-foot skin reactions (HFSR) during multikinase (MKI) treatment. We prospectively collected 26 patients who had HFSRs during treatment with the MKIs, sunitinib, sorafenib, or axitinib. The age distribution ranged from 46 to 87 years, with a mean of 66 years. The distribution of HFSR severity was 12 patients with grade 1, 12 with grade 2, and 2 with grade 3. A heparin-containing topical ointment treatment, combined with hand-foot shock absorbers and skin moisturizers, was used at the lesion sites. Changes in the grade of HFSR, MKI dosage, and interruptions of MKI therapy were recorded. The results showed that 66.7% of grade 1 patients were cured of disease, 83.3% of grade 2 patients had improved symptoms, and both grade 3 patients (100%) had improved symptoms and were downgraded to grade 2. Four (15.4%) patients required reduction of MKI dosage, but there were no treatment interruptions or dropouts. Our protocol is beneficial in promoting resolution of HFSRs induced by MKIs. Further validation in large control studies should be investigated.

  13. Extracellular matrix inspired surface functionalization with heparin, fibronectin and VEGF provides an anticoagulant and endothelialization supporting microenvironment

    International Nuclear Information System (INIS)

    Wang, Xue; Liu, Tao; Chen, Yuan; Zhang, Kun; Maitz, Manfred F.; Pan, Changjiang; Chen, Junying; Huang, Nan

    2014-01-01

    Highlights: • Surface modification with fibronectin, heparin and VEGF could selectively anticoagulant and promote endothelialization. • The bioactivity of biomolecules was more efficiently maintained via specific intermolecular interaction. • Poly-l-lysine interlayer was more feasible and the degradation product had no harm to human body. - Abstract: The biocompatibility of currently used coronary artery stent is still far from perfect, which closely related to insufficient endothelialization and thrombus formation. In this study, heparin, fibronectin and VEGF were immobilized on Ti surface to construct a multifunctional microenvironment with favorable properties to inhibit thrombosis formation and promote endothelialization simultaneously. The microenvironment on Ti surface was characterized in detail and demonstrated that the Hep/Fn/VEGF biofunctional coating was constructed successfully on Ti surface. The influence of surface properties such as chemical composition, roughness, hydrophilicity, and binding density of biomolecules on the performances of hemocompatibility and cytocompatibility was evaluated and discussed. Modified surface significantly enhanced the AT III binding density and prolonged the clotting time. In vitro platelet adhesion and activation assays further proved that the modified surface presented favorable anti-coagulant property. In addition, the proliferation of endothelial progenitor cells (EPCs) and endothelial cells (ECs) on the Hep/Fn/VEGF biofunctional coating was significantly promoted. In conclusion, the Hep/Fn/VEGF biofunctional coating was successfully constructed with desirable anticoagulant and endothelialization supporting properties. This work may provide a promising approach for biofunctional surface modification of coronary artery stent to acquire a desired multifunctional microenvironment

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

    Science.gov (United States)

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

    2008-07-01

    The goal of this work is to explore the effects of solution ionic strength and pH on polyelectrolyte multilayer (PEM) assembly, using biologically derived polysaccharides as the polyelectrolytes. We used the layer-by-layer (LBL) technique to assemble PEM of the polysaccharides heparin (a strong polyanion) and chitosan (a weak polycation) and characterized the sensitivity of the PEM composition and layer thickness to changes in processing parameters. Fourier-transform surface plasmon resonance (FT-SPR) and spectroscopic ellipsometry provided in situ and ex situ measurements of the PEM thickness, respectively. Vibrational spectroscopy and X-ray photoelectron spectroscopy (XPS) provided details of the chemistry (i.e., composition, electrostatic interactions) of the PEM. We found that when PEM were assembled from