Academic literature on the topic 'Heparinoid'
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Journal articles on the topic "Heparinoid"
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Успенская, М. С., М. Г. Ляпина, and Е. С. Майстренко. "A heparinoid from peony roots (Paeonia anomala): effects on polymerization and dissolution of fibrin in thrombosis." ZHurnal «Patologicheskaia fiziologiia i eksperimental`naia terapiia», no. 2() (June 8, 2020): 80–84. http://dx.doi.org/10.25557/0031-2991.2020.02.80-84.
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Исследование гепаринов и гепариноидов в качестве антитромботических агентов актуально для физиологии и медицины. Многие растения включают гепариноподобные компоненты (гепариноиды), которые препятствуют тромбообразованию. Цель - установление влияния экстракта из корней пиона «Марьин корень» (Paeonia anomala), содержащего гепариноид, на полимеризацию фибрина при процессах тромбообразования ex vivo и определение возможных механизмов его антитромботического действия. Методика. Исследовано влияние гепариноида из пиона (Paeonia anomala) на процессы растворения фибрина в условиях тромбообразования ex vivo. Разработана модель тромбоза (МТ) ex vivo. К плазме крови крыс (объем 0,2 мл) добавляли 2 NIH ед. тромбина (0,05 мл), фибриновый сгусток образовывался в течение 2-3 мин. Экстракт гепариноида из пиона (0,1 мл 0.5%-й) добавляли к предобразованному сгустку через 12 мин после моделирования тромбоза (опыт А), или одновременно с добавлением тромбина к плазме крови (опыт Б). Использовали венозную (из v. jugularis) кровь крыс-самцов Wistar. Полимеризацию фибрина выявляли по тесту фибриндеполимеризационной активности (ФДПА) плазмы крови на нестабилизированном фибрине. В продуктах растворения фибрина под влиянием гепариноида оценивали активность тромбина (по тесту тромбинового времени), cвертывающего фактора XIIIa (по определению активности фактора XIIIa) и ФДПА. Результаты. В опыте А спустя 10 мин после добавления гепариноида к предобразованному сгустку отмечалось появление в нем жидкой фазы, что свидетельствовало о способности исследуемого гепариноида растворять фибрин. В опыте Б сгусток или не образовывался, или же был рыхлым. Полученные данные свидетельствовали об ингибировании процесса полимеризации фибрина под влиянием гепариноида. Выявлены антитромбиновые и антифибринстабилизирующие эффекты гепариноида из пиона при добавлении к фибриновому сгустку. Рассматриваются возможные механизмы действия гепариноида на блокаду полимеризации фибрина. Заключение. Растительный гепариноид препятствовал процессам полимеризации фибрина или растворял образующиеся фибриновые сгустки, что связано с его антитромбиновым и антифибринстабилизирующим действием. Studying heparins and heparinoids as antithrombotic agents is relevant for physiology and medicine. Many plants contain heparin-like components (heparinoids) that prevent thrombosis. The aim of the study was to identify effects of a heparinoid obtained from peony (Maryin root, P. anomala) roots on polymerization of fibrin and fibrinolytic activity of blood plasma and to suggest possible mechanisms of these effects in experimentally induced ex vivo thrombosis in rats. Methods. The effect of peony (Paeonia anomala) root heparinoid on fibrin dissolution was studied in the ex vivo conditions of thrombosis. For ex vivo modeling of thrombosis (MT), 2 NIH units of thrombin (0.05 ml) were added to 0.2 ml of rat plasma. A fibrin clot formed within 2-3 minutes. The peony heparinoid extract (0.5%, 0.1 ml) was added either to the pre-formed clot at 12 min after MT induction (experiment A) or simultaneously with the addition of thrombin to plasma (experiment B). Jugular vein blood from Wistar male rats was used. Fibrin polymerization was detected using a plasma fibrin-depolymerization activity (FDPA) test on non-stabilized fibrin. Thrombin activity (thrombin time test), coagulation factor XIIIa activity, and FDPA were evaluated in products of fibrin dissolution induced by the heparinoid. Results. In experiment A, at 10 min after the addition of heparinoid to the pre-formed clot, a liquid phase emerged, which indicated an ability of the pion heparinoid to dissolve fibrin. In experiment B, the clot either did not form or was liquid. These results indicated inhibition of fibrin polymerization under the action of the heparinoid. Therefore, the peony heparinoid added to the fibrin clot antagonized thrombin and fibrin stabilization. The article addresses possible mechanisms of the heparinoid inhibition of fibrin polymerization. Conclusion. The studied plant heparinoid prevented processes of fibrin polymerization or dissolved formed fibrin clots due to depression of thrombin activity and fibrin stabilization.
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Alban, S., and A. Greinacher. "Heparinoide als eine Alternative für die parenterale Antikoagulation bei Patienten mit Heparin-induzierter Thrombozytopenie." Hämostaseologie 16, no. 01 (January 1996): 41–49. http://dx.doi.org/10.1055/s-0038-1656637.
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ZusammenfassungDie Heparin-induzierte Thrombozytopenie (HIT Typ II) ist eine lebensbedrohliche Komplikation der Heparintherapie. Da betroffene Patienten durch diese immunologische, unerwünschte Wirkung der Heparingabe gefährdet sind, neue throm-boembolische Gefäßverschlüsse zu entwickeln, ist bei hinreichendem klinischen Verdacht die sofortige Umstellung auf ein kompatibles Antikoagulans notwendig. Hierfür kommen, neben rekombinantem Hirudin, verschiedene Heparinoide in Betracht. Die Pathophysiologie der HIT Typ II sowie die Struktur und die anti-koagulatorischen Eigenschaften verschiedener Heparinoide werden dargestellt. Der letzte Teil des Artikels faßt den gegenwärtigen Stand der Dosierungsempfehlungen für das Heparinoid Danaparoid (Orgaran®, NV Organon, Niederlande) bei HIT-Typ-Il-Patienten zusammen.
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Greinacher, A., I. Michels, V. Kiefel, and C. Mueller-Eckhardt. "A Rapid and Sensitive Test for Diagnosing Heparin-Associated Thrombocytopenia." Thrombosis and Haemostasis 66, no. 06 (1991): 734–36. http://dx.doi.org/10.1055/s-0038-1646493.
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SummaryHeparin-associated thrombocytopenia (HAT) is a severe complication of heparin therapy. Its diagnosis is difficult. Conventional assays employ platelet aggregometry (PAA) and/or 14C-serotonin release (SRA) which are either insensitive (PAA) or require radioactive tracers (SRA). We here describe a newly developed sensitive and rapid assay based on visual evaluation of heparin-induced platelet activation (HIPA) in microtiter wells. Using sera of 34 patients with clinically suspected HAT we found the HIPA assay to be as sensitive as the SRA and superior to PAA. The HIPA assay allows investigation of crossreactivity with different types of heparins, low molecular weight (LMW) heparins and heparinoids. Three patients who required further parenteral anticoagulation and in whom the HIPA assay was negative before treatment with the LMW heparinoid Org 10172, were treated with this new heparinoid without adverse reactions. We conclude that the HIPA assay may be a useful tool for differential diagnosis and therapy in patients with HAT.
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Ishihara, Masayuki, Shingo Nakamura, Yoko Sato, Tomohiro Takayama, Koichi Fukuda, Masanori Fujita, Kaoru Murakami, and Hidetaka Yokoe. "Heparinoid Complex-Based Heparin-Binding Cytokines and Cell Delivery Carriers." Molecules 24, no. 24 (December 17, 2019): 4630. http://dx.doi.org/10.3390/molecules24244630.
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Heparinoid is the generic term that is used for heparin, heparan sulfate (HS), and heparin-like molecules of animal or plant origin and synthetic derivatives of sulfated polysaccharides. Various biological activities of heparin/HS are attributed to their specific interaction and regulation with various heparin-binding cytokines, antithrombin (AT), and extracellular matrix (ECM) biomolecules. Specific domains with distinct saccharide sequences in heparin/HS mediate these interactions are mediated and require different highly sulfated saccharide sequences with different combinations of sulfated groups. Multivalent and cluster effects of the specific sulfated sequences in heparinoids are also important factors that control their interactions and biological activities. This review provides an overview of heparinoid-based biomaterials that offer novel means of engineering of various heparin-binding cytokine-delivery systems for biomedical applications and it focuses on our original studies on non-anticoagulant heparin-carrying polystyrene (NAC-HCPS) and polyelectrolyte complex-nano/microparticles (N/MPs), in addition to heparin-coating devices.
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&NA;. "Heparin/heparinoid." Reactions Weekly &NA;, no. 1405 (June 2012): 20–21. http://dx.doi.org/10.2165/00128415-201214050-00070.
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Mimura, Wataru, and Manabu Akazawa. "The Association Between Internet Searches and Moisturizer Prescription in Japan: Retrospective Observational Study." JMIR Public Health and Surveillance 5, no. 4 (October 8, 2019): e13212. http://dx.doi.org/10.2196/13212.
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Background Heparinoid is a medication prescribed in Japan for skin diseases, such as atopic dermatitis and dry skin. Heparinoid prescription has increased with instances of internet blogs recommending its use as a cosmetic. Objective This study aimed to examine the prescription trends in moisturizer use and analyze their association with internet searches. Methods We used a claims database to identify pharmacy claims of heparinoid-only prescriptions in Japan. Additionally, we used Google Trends to obtain internet search data for the period between October 1, 2007, and September 31, 2017. To analyze the association between heparinoid prescriptions and internet searches, we performed an autoregressive integrated moving average approach for each time series. Results We identified 155,733 patients who had been prescribed heparinoid. The number of prescriptions increased from 2011 onward, and related internet searches increased from 2012 onward. Internet searches were significantly correlated with total heparinoid prescription (correlation coefficient=.25, P=.005). In addition, internet searches were significantly correlated with heparinoid prescription in those aged 20-59 years at –1-month lag in Google Trends (correlation coefficient=.30, P=.001). Conclusions Google searches related to heparinoid prescriptions showed a seasonal pattern and increased gradually over the preceding several years. Google searches were positively correlated with prescription trends. In addition, in a particular age group (20-59 years), prescriptions increased with the increase in internet searches. These results suggest that people obtained health-related information on the internet and that this affected their behavior and prescription requests.
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ARGE, E. "Heparinoid and Heparin." Acta Medica Scandinavica 155, no. 6 (April 24, 2009): 469–74. http://dx.doi.org/10.1111/j.0954-6820.1956.tb14396.x.
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Preissner, K. T. "Heparinoids and cellular interactions in the vascular system." Hämostaseologie 16, no. 01 (January 1996): 28–34. http://dx.doi.org/10.1055/s-0038-1656635.
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SummaryHeparin and related polysaccharides have long been used for therapautic intervention in different disease states related to thromboembolic complications. The localization and functional availability of heparin-like components in the body is mostly confined to cell surfaces and extracellular matrix/basement membranes. Their strategic position particularly in the vascular system enables heparinoids linked to various core proteins (designated as heparan sulfate proteoglycans) to interact with a variety of heparin-binding proteins such as apolipoproteins, lipases, proteases and protease inhibitors, matrix proteins as well as surface receptors on other cells and microorganisms. The variety in gene expression of respective core proteins and differences in glycosaminoglycan side chains are relevant factors for the selectivity of these interactions. Heparinoid-associated core proteins serve as co-receptors for a number of metabolic properties of vascular cells as well as for the regulation of cellular processes, particular as they relate to cell growth and differentiation in angiogenesis. Moreover, heparan sulfate proteoglycans contribute to the process of lipoprotein retention in the vessel wall and the onset of atherosclerosis. Elucidation of molecular properties, functions and their role in vascular diseases can lead to valuable information for the design of heparinoid analogues to be used for pharmacological intervention.
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Muhl, Lars, Etty Zwang, Neta Ilan, Yair Herishanu, Varda Deutsch, Elizabeth Naparstek, Israel Vlodavsky, Klaus Preissner, and Ben-Zion Katz. "Heparanase modulates heparinoids anticoagulant activities via non-enzymatic mechanisms." Thrombosis and Haemostasis 98, no. 12 (2007): 1193–99. http://dx.doi.org/10.1160/th07-04-0256.
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SummaryA key element for the physiological restriction of blood coagulation at the endothelial cell surface is its non-thrombogenic property, mainly attributed to cell surface heparan sulfate proteoglycans. Heparanase is an endo-β-D-glucuronidase with specific heparan sulfate degrading activity, which is produced and stored in platelets, and is released upon their activation. We examined the effects of heparanase pro-enzyme on coagulation functions, predominantly under physiological conditions. While heparanase pro-enzyme does not directly affect coagulation protein activities, it has profound effects on heparinoid-mediated regulation of coagulation responses, apparently via mechanisms that do not involve its enzymatic activity. Heparanase pro-enzyme reverses the anti-coagulant activity of unfractionated heparin on the coagulation pathway as well as on thrombin activity. In addition, heparanase pro-enzyme abrogated the factor X inhibitory activity of low-molecular-weight heparin (LMWH). The pro-coagulant effects of the non-active heparanase were also exerted by its major functional heparin-binding peptide. Finally, the effects of heparanase on the activity of factor VII activating protease that is auto-activated by heparinoids indicated a complete antagonistic action of heparanase in this system. Altogether, heparanase pro-coagulant activities that were also demonstrated in plasma samples from patients under LMWH treatment,point to a possible use of this molecule as antagonist for heparinoid treatment.
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Du, ZhenXing, XueJing Jia, Jing Chen, SiYi Zhou, JianPing Chen, XiaoFei Liu, XiaoHuang Cao, SaiYi Zhong, and PengZhi Hong. "Isolation and Characterization of a Heparin-Like Compound with Potent Anticoagulant and Fibrinolytic Activity from the Clam Coelomactra antiquata." Marine Drugs 18, no. 1 (December 19, 2019): 6. http://dx.doi.org/10.3390/md18010006.
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Heparin from mollusks with unique sulfated glycosaminoglycan exhibits strong anti-thrombotic activities. This study reports on a purified heparinoid from Coelomactra antiquata, which shows potent anticoagulant and fibrinolytic abilities. Its structure was characterized by infrared spectroscopy, high-performance liquid chromatography, and one-dimensional and two-dimensional nuclear magnetic resonance spectroscopy. Its fibrinolytic activity was determined in vitro and in vivo. Its anticoagulant activity was determined by activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). The results indicated that clam heparinoid was a homogeneous glycosaminoglycan with a molecular weight of 30.99 kDa, mainly composed of →4)-α-IdoA2S-(1→4)-α-GlcNS3S6S (or GlcNS6S)-(1→4)-β-GlcA-(1→4)-α-GlcNS6S (or GlcNAC)-(1→. Furthermore, this heparinoid showed a highly anticoagulant titer and fibrinolytic value of 149.63 IU/mg and 1.96 IU/mg, respectively. In summary, clam heparinoid shows great potential for application in the clinic and antithrombotic drugs industry.
Dissertations / Theses on the topic "Heparinoid"
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Broberg, Karl Rufus. "Synthetic approaches towards heparinoid related saccharides and derivatives." Thesis, University of Manchester, 2011. https://www.research.manchester.ac.uk/portal/en/theses/synthetic-approaches-towards-heparinoid-related-saccharides-and-derivatives(6c1366ba-82dc-43b2-9af3-294ebed56639).html.
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Heparin glycosaminoglycans mediate a range of biological events, including anticoagulation as well as a diversity of cell proliferation and differentiation processes. Heparin saccharides have been shown to act as inhibitors against angiogenesis and metastasis of tumour cells. This thesis describes work developing chemistry towards varying length oligosaccharide sequences with potential to offer variable sulfation patterns. The main synthetic components to this work were contribution to developing scalable syntheses of an orthogonally protected L-Iduronic acid unit and a differentially protected D-glucosamine unit. The synthetic work also evaluated a recently reported diazo transfer reagent, which allowed for earlier placement of azide protection over that of previously developed routes within the group. This provided a cheaper, more atom efficient route towards protected D-glucosamine building blocks. Glycosylation of the developed D-GlcN donor units with the L-Ido acceptor allowed the production of key disaccharides which facilitated an efficient iterative glycosylation strategy towards longer oligosaccharides, ultimately providing a differentially protected pentasaccharide. The project evaluated methods towards generating various dimeric heparin type systems through forming new O4 ether linkages between GlcN residues across various short linker fragments. The most successful of these dimerisations used a methallyl dichloride core which allowed for further derivatisation towards dihydroxylated species, the analysis of which highlighted some interesting proton NMR data. The final aspect of this project began development of chemistry towards non-reducing end-labelled oligosaccharide sequences by implementation of a masked aldehyde unit on the C4 hydroxyl of GlcN synthesised from the allylated GlcN precursor via dihydroxylation chemistry. Incorporation of this moiety (protected as a 1,2-dibenzyl glycol) within both a trisaccharide and a pentasaccharide was achieved. Further development of this chemistry should allow for late step oxidative cleavage to reveal the reactive aldehyde, potentially allowing for attachment of various amine functionalised fluorophores via reductive amination. Radiolabelling of such a species should also be possible through sodium borotritide reduction for example.
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Brito, Adriana da Silva. "Potencial terap?utico de um heparin?ide isolado do invertebrado marinho Litopenaeus vannamei." Universidade Federal do Rio Grande do Norte, 2008. http://repositorio.ufrn.br:8080/jspui/handle/123456789/12521.
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The occurrence of bioactive compounds in marine organisms comes awaking the interest of the pharmaceutical industry. Heparin, a sulfated polysaccharide which presence was already identified in several marine invertebrates, is very attractive due its remarkable functional versatility. Besides to intervene in blood coagulation, this molecule has a great anti-inflammatory potential. However, its strong anticoagulant activity difficult the clinical exploitation of its anti-inflammatory properties. Thus, the aims of this work were to evaluate the effect of a heparin-like compound (heparinoid), isolated from the cephalotorax of the Litopenaeus vannamei shrimp, on the inflammatory response, hemostasia and synthesis of antithrombotic heparan sulfate by endothelial cells, besides studying some aspects concerning its structure. The purified heparinoid was structurally characterized following an analytical boarding, involving electrophoresis and chromatography. The structural analysis have shown that this compound possess a high content of glucuronic acid residues and disulfated disaccharide units. In contrast to mammalian heparin, the heparinoid was incapable to stimulate the synthesis of heparan sulfate by endothelial cells in the tested concentrations, beyond to show reduced anticoagulant activity and hemorrhagic effect. In a model of acute inflammation, the compound isolated from the shrimp reduced more than 50% of the cellular infiltration. Besides reduce the activity of MMP-9 and proMMP-2 of the peritoneal lavage of inflamed animals, the heparinoid also reduced the activity of MMP-9 secreted by activated human leukocytes. These results demonstrate the potential of heparinoid from L. vannamei to intervene in the inflammatory response. For possessing reduced anticoagulant activity and hemorrhagic effect, this compound can serve as a structural model to direct the development of more specific therapeutical agents to the treatment of inflammatory diseases
A ocorr?ncia de compostos bioativos em representantes da biodiversidade marinha vem despertando o interesse da ind?stria farmac?utica. Heparina, um polissacar?deo sulfatado cuja presen?a j? foi identificada em v?rios invertebrados marinhos, destaca-se por sua extraordin?ria versatilidade funcional. Al?m de interferir na coagula??o sangu?nea, essa mol?cula possui grande potencial antiinflamat?rio. No entanto, sua forte atividade anticoagulante dificulta o aproveitamento cl?nico de sua propriedade antiinflamat?ria, o que estimula a pesquisa por an?logos de heparina com efeitos colaterais reduzidos. Diante disso, este trabalho teve por objetivos avaliar o efeito de um composto semelhante ? heparina (heparin?ide), isolado do cefalot?rax do camar?o Litopenaeus vannamei, sobre a resposta inflamat?ria, hemostasia e s?ntese de heparam sulfato antitromb?tico pelas c?lulas endoteliais, al?m de estudar alguns aspectos relevantes a cerca de sua estrutura. O heparin?ide purificado foi estruturalmente caracterizado seguindo uma abordagem anal?tica, envolvendo eletroforeses e cromatografias. As an?lises estruturais mostraram que esse composto possui um elevado conte?do de res?duos de ?cido glucur?nico e de dissacar?deos dissulfatados. Ao contr?rio da heparina de mam?feros, o heparin?ide foi incapaz de estimular a s?ntese de heparam sulfato pelas c?lulas endoteliais nas concentra??es testadas, al?m de apresentar atividade anticoagulante in vitro e efeito hemorr?gico reduzidos. Em um modelo de inflama??o aguda, o composto isolado do camar?o reduziu mais de 50% da infiltra??o celular. Al?m de reduzir a atividade de MMP-9 e proMMP-2 no lavado peritoneal dos animais submetidos ao modelo de inflama??o, o heparin?ide tamb?m reduziu a atividade de MMP-9 secretada por leuc?citos humanos ativados. Esses resultados demonstram o potencial do heparin?ide de L. vannamei em interferir em v?rios eventos da resposta inflamat?ria. Por possuir atividade anticoagulante e efeito hemorr?gico reduzidos, esse composto pode servir como um modelo estrutural para direcionar o desenvolvimento de agentes terap?uticos mais espec?ficos para o tratamento de doen?as inflamat?rias
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Coelho, Luciana de Figueir?do. "Efeito anti-inflamat?rio do heparin?ide isolado do camar?o Litopenaeus vannamei sobre a peritonite aguda." Universidade Federal do Rio Grande do Norte, 2013. http://repositorio.ufrn.br:8080/jspui/handle/123456789/12611.
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In recent years the heparin has been the subject of several studies that aim to expand its use as a therapeutic agent, due to its ability to modulate the activity of various proteins that play important roles in the regulation of pathophysiological processes. In several experiments and preclinical trials, heparin has demonstrated an anti-inflammatory role. However, its clinical use is limited, due to its strong anticoagulant activity and hemorrhagic complications. For this reason, considerable efforts have been employed in discovery of heparin analogous (heparinoid) with reduced side effects, that retain the anti-inflammatory properties of heparin. In this context, a heparinoid obtained from the head of Litopenaeus vannamei shrimp, which presents a structural similarity to heparin, showed, in previous studies, anti-inflammatory activity in a model of acute peritonitis with reduced anticoagulant effect in vitro and low hemorrhagic activity. Thus, the present work had as objective to evaluate the effect the heparinoid of the cephalothorax of gray shrimp on the acute inflammatory response in different times (3 or 6 hours after the induction of inflammatory stimulus), using the model of acute peritonitis induced in mice. It was also analyzed the HL effect over the activity of elastase, an enzyme involved in leukocyte recruitment. Furthermore to check if the different doses of heparin and heparinoid change the hemostatic balance in vivo, was assessed the effect of these compounds on the plasma clotting time in animals submitted to inflammation. The results show that in 3 hours, all doses of heparinoid were able to prevent efficiently in the acute inflammatory process without any anticoagulant effects, unlike the extrapolation dose of heparin, which has induced a large hemorrhage due its high anticoagulant activity. However, 6 hours after induction of inflammation, only the dosages of 0.1 and 1.0 μg/Kg of heparin and 1.0 μg/Kg of heparinoid kept anti-migratory effect, without changing of the hemostatic balance. These results indicate that the anti-migratory effect of theses compounds depends on the dosage and time of inflammatory stimulus. The HL and heparin were also able to inhibit the activity of the enzyme elastase. The discovery of this bioactive compound in the cephalothorax of shrimps can arouse great interest in biotechnology, since this compound could be useful as a structural model interesting for the development of new therapeutic agents for peritonitis
Nos ?ltimos anos a heparina tem sido alvo de diversos estudos que visam ampliar seu uso como agente terap?utico, devido ? sua habilidade de modular a atividade de v?rias prote?nas que desempenham pap?is importantes na regula??o de processos fisiopatol?gicos. Em diversos experimentos e ensaios pr?-cl?nicos, a heparina tem demonstrado papel anti-inflamat?rio. Entretanto, seu uso cl?nico ? limitado, devido ? sua forte atividade anticoagulante e complica??es hemorr?gicas. Por essa raz?o, consider?vel esfor?o tem sido empregado na descoberta de an?logos da heparina (heparin?ide) com reduzidos efeitos colaterais, que retenham as propriedades anti-inflamat?rias da heparina. Nesse contexto, um heparin?ide (HL) obtido da cabe?a do camar?o Litopenaeus vannamei, de semelhan?a estrutural ? heparina, apresentou em estudos pr?vios atividade anti-inflamat?ria em modelo de peritonite aguda, com reduzido efeito anticoagulante in vitro e baixa atividade hemorr?gica. Assim, o presente trabalho teve como objetivo avaliar o efeito deste heparin?ide sobre a resposta inflamat?ria aguda em diferentes tempos (3 ou 6 horas ap?s a indu??o do est?mulo inflamat?rio), utilizando o modelo de peritonite aguda induzida em camundongos. Foi analisado tamb?m o efeito do HL sobre a atividade da elastase, uma enzima envolvida no recrutamento de leuc?citos. Al?m disso, para verificar se as diferentes doses do heparin?ide e da heparina alteram o equil?brio hemost?tico in vivo, foi avaliado o efeito desses compostos sobre o tempo de coagula??o do plasma nos animais submetidos ? inflama??o. Os resultados revelam que em 3 horas, todas as doses do heparin?ide foram capazes de interferir de forma eficiente no processo inflamat?rio agudo sem apresentar efeito anticoagulante e interfer?ncia no equil?brio hemost?tico, ao contr?rio da dose de extrapola??o da heparina que induziu forte hemorragia, al?m de apresentar alta atividade anticoagulante. Entretanto, no tempo de 6 horas ap?s a indu??o da inflama??o, apenas as doses de 0,1 e 1,0 μg/Kg da heparina e 1,0 μg/Kg do heparin?ide mantiveram o efeito antimigrat?rio, sem alterar o equil?brio hemost?tico. Esses resultados indicam que o efeito antimigrat?rio depende do tempo e da dose administrada. O HL e a heparina tamb?m foram capazes de inibir a atividade da enzima elastase. A descoberta desse composto bioativo no cefalot?rax do camar?o poder? despertar grande interesse biotecnol?gico, pois este composto poderia servir como um modelo estrutural interessante para o desenvolvimento de novos agentes terap?uticos espec?ficos para a peritonite
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Newman, Peter Michael Pathology UNSW. "Antibody and Antigen in Heparin-Induced Thrombocytopenia." Awarded by:University of New South Wales. Pathology, 2000. http://handle.unsw.edu.au/1959.4/17485.
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Immune heparin-induced thrombocytopenia (HIT) is a potentially serious complication of heparin therapy and is associated with antibodies directed against a complex of platelet factor 4 (PF4) and heparin. Early diagnosis of HIT is important to reduce morbidity and mortality. I developed an enzyme immunoassay that detects the binding of HIT IgG to PF4-heparin in the fluid phase. This required techniques to purify and biotinylate PF4. The fluid phase assay produces consistently low background and can detect low levels of anti-PF4-heparin. It is suited to testing alternative anticoagulants because, unlike in an ELISA, a clearly defined amount of antigen is available for antibody binding. I was able to detect anti-PF4-heparin IgG in 93% of HIT patients. I also investigated cross-reactivity of anti-PF4-heparin antibodies with PF4 complexed to alternative heparin-like anticoagulants. Low molecular weight heparins cross-reacted with 88% of the sera from HIT patients while half of the HIT sera weakly cross-reacted with PF4-danaparoid (Orgaran). The thrombocytopenia and thrombosis of most of these patients resolved during danaparoid therapy, indicating that detection of low affinity antibodies to PF4-danaparoid by immunoassay may not be an absolute contraindication for danaparoid administration. While HIT patients possess antibodies to PF4-heparin, I observed that HIT antibodies will also bind to PF4 alone adsorbed on polystyrene ELISA wells but not to soluble PF4 in the absence of heparin. Having developed a technique to affinity-purify anti-PF4-heparin HIT IgG, I provide the first estimates of the avidity of HIT IgG. HIT IgG displayed relatively high functional affinity for both PF4-heparin (Kd=7-30nM) and polystyrene adsorbed PF4 alone (Kd=20-70nM). Furthermore, agarose beads coated with PF4 alone were almost as effective as beads coated with PF4 plus heparin in depleting HIT plasmas of anti-PF4-heparin antibodies. I conclude that the HIT antibodies which bind to polystyrene adsorbed PF4 without heparin are largely the same IgG molecules that bind PF4-heparin and thus most HIT antibodies bind epitope(s) on PF4 and not epitope(s) formed by part of a PF4 molecule and part of a heparin molecule. Binding of PF4 to heparin (optimal) or polystyrene/agarose (sub-optimal) promotes recognition of this epitope. Under conditions that are more physiological and sensitive than previous studies, I observed that affinity-purified HIT IgG will cause platelet aggregation upon the addition of heparin. Platelets activated with HIT IgG increased their release and surface expression of PF4. I quantitated the binding of affinity-purified HIT 125I-IgG to platelets as they activate in a plasma milieu. Binding of the HIT IgG was dependent upon heparin and some degree of platelet activation. Blocking the platelet Fc??? receptor-II with the monoclonal antibody IV.3 did not prevent HIT IgG binding to activated platelets. I conclude that anti-PF4-heparin IgG is the only component specific to HIT plasma that is required to induce platelet aggregation. The Fab region of HIT IgG binds to PF4-heparin that is on the surface of activated platelets. I propose that only then does the Fc portion of the bound IgG activate other platelets via the Fc receptor. My data support a dynamic model of platelet activation where released PF4 enhances further antibody binding and more release.
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Kibondo, Aimee. "Evaluation of the role of heparinoids as immune modulators of organ perfusion solutions." Thesis, University of Sunderland, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.556572.
Full textAbstract:
Kidney transplantation is the only therapy for patients with end-stage kidney failure. There is a shortage of suitable organs from living donors and heart-beating donors (HBDs) leading to an increased use of marginal organs, including those from non- heart-beating donors (NHBD) to expand the donor pool. However, such kidneys are exposed to periods of warm and cold ischaemia plus reperfusion (IR) injury which can be associated with acute tubular necrosis leading to primary non function (PNF), delayed graft failure (DGF) with an increased risk of acute and chronic allograft rejection. Therefore, minimising ischaemic injury will be beneficial to improve immediate allograft function and reduce the incidence of PNF and DGF. Perfusate solutions can ameliorate the damage caused by IR injury. This study examined the possible protective effect of heparinoids, low molecular weight (LMW) sodium heparin (HS-3400) and sodium pentosan polysulfate (NaP PS), as supplements in perfusate solutions. An in vivo rodent surgical model of NHB kidney donation was used to investigate the effects of heparinoids as immune modulators during kidney preservation. It was demonstrated that heparinoids significantly reduced oedema but did not have any effects on pressure, intra-renal vascular resistance (I RVR) or osmolarity of the perfusate solution. Microarray and qPCR analysis revealed that many genes involved in IR injury were differentially expressed after warm oxygenated perfusion. Network analysis revealed that the pro-inflammatory cytokine TNF-a was the common denominator and a potential key regulator of IR injury. Data obtained strongly demonstrate that these networks were removed by the addition of heparinoids. In vitro biological assays investigated the effects of heparinoids on class 11 MHC antigen expression on primary endothelial cells (ECs) treated with IFN-y. It was found that NaPPS and the majority of its derivatives were more efficient in antagonising IFN-y activity. In addition, NaPPS and its derivatives significantly inhibited transendothelial migration of leukocytes across an IFN-y-activated endothelial monolayer. The anti-inflammatory properties of heparinoids can be exploited for better preservation of NHBD organs to improve short and long-term allograft survival and function. Significantly, this is the first study to reveal the potential of heparinoids as TNF-a antagonists and additives to perfusate solutions.
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Lukoševičiūtė, Kristina. "Filtracijos efektyvumo ir progesterono, estradiolio, heparino poveikio bulių spermatozoidų kokybiniams rodikliams, įvertinimas." Doctoral thesis, Lithuanian Academic Libraries Network (LABT), 2005. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2005~D_20050919_152311-37566.
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It is the first time in Lithuania that practical application of semen filtration by Sephadex G-15 for the needs of artificial insemination industry was assessed. The efficacy of semen filtration was assessed applying a battery of sperm quality assays to study bovine spermatozoa quality before and after filtration, as well as after cryopreservation. The estimation of effect of different concentrations of progesterone, oestradiol, heparin separately or in combination, on different functional parameters of bull spermatozoa after thawing was performed. These are the first published studies applying integrated approach to study the effects of sperm challenge with several biologically active substances.
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Pranckevičienė, Gabrielė. "Pharmacoepidemiologic assessment of low-molecular-weight heparins utilization in Lithuania and development of pharmacoeconomic model." Doctoral thesis, Lithuanian Academic Libraries Network (LABT), 2014. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2014~D_20140305_141832-70667.
Full textAbstract:
In recent years, many countries have struggled with the fact that expenditures on health care are growing much faster than the overall level of wealth. Research objectives: 1) to conduct a meta-analysis of heparins by the means of their efficacy, safety parameters and treatment outcomes; 2) to conduct pharmacoepidemiological assessment of long-term heparins utilization in Lithuania; 3) to develop a pharmacoeconomic cost-minimization model for low-molecular-weight heparins based on reference pricing methodology; 4) to investigate heparins prescribing trends and to evaluate heparins prescription adherence to international clinical guidelines at a secondary level clinical hospital. Meta-analysis results showed that low-molecular-weight heparins could be considered interchangeable due to similar therapeutic profiles in some indications. In Lithuania consumption of heparins and corresponding costs were constantly increasing during the period of investigation; therefore it would be relevant to implement modern pharmacoeconomic methodologies to regulate costs. Cost-minimization model suggested that expenditures on this group of medicines could be decreased by nearly 70 percent. Analysis of pharmacoepidemiological study data confirmed that heparins prescription practices at the clinical hospital were insufficiently regulated. In addition this study conducted at the clinical hospital revealed non-compliance of heparins safety monitoring practices with clinical guidelines.Pastaraisiais metais daugelyje šalių sveikatos priežiūros išlaidos augo daug greičiau nei bendras gerovės lygis, todėl yra nuolat diskutuojama, kaip šį išlaidų augimą reikėtų kontroliuoti. Darbo uždaviniai: 1) atlikti heparinų preparatų meta-analizę, palyginant jų efektyvumo ir saugumo parametrus bei gydymo baigtis; 2) atlikti heparinų preparatų ilgalaikio suvartojimo Lietuvoje farmakoepidemiologinį tyrimą; 3) suformuluoti farmakoekonominį kaštų mažinimo sprendimų modelį mažos molekulinės masės heparinų preparatų grupei, remiantis referentinės kainos metodika; 4) ištirti heparinų preparatų skyrimo tendencijas antrinio lygio klinikinėje ligoninėje ir palyginti heparinų preparatų skyrimo atitikimą tarptautinėms gairėms. Meta-analizės rezultatai parodė, jog mažos molekulinės masės heparinai gali būti tarpusavyje pa¬keičiami dėl analogiškų terapinių savybių tam tikrose indikacijose. Heparinų preparatų suvartojimas ir atitinkamos išlaidos tiriamuoju laikotarpiu Lietuvoje nuolat didėjo, todėl būtų aktualu taikyti šiuolaikines farmakoekonomines išlaidų reguliavimo metodikas. Pritaikius kaštų mažinimo modelį heparinų preparatų grupei, būtų galima sumažinti išlaidas šios grupės preparatams beveik 70 procentų. Farmakoepidemiologinio tyrimo rezultatai atskleidė, jog heparinų preparatų skyrimo praktika klinikinėje ligoninėje buvo nepakankamai reglamentuota. Taip pat heparinų preparatų saugumo parametrų stebėjimo praktika ligoninėje neatitiko tarptautinių rekomendacijų.
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Kildonavičiūtė, Gabrielė. "Farmakoepidemiologinė/farmakoekonominė vaistų suvartojimo analizė KMUK 2001-2005 metais." Master's thesis, Lithuanian Academic Libraries Network (LABT), 2006. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2006~D_20060704_153514-84940.
Full textAbstract:
Background and Objectives: To perform the analysis of medicines consumption in HKUM from 2001 to 2005; to analyze more comprehensively the usage of Heparins and Antibiotics.
Design and Setting: The data about medicines consumption was taken from the hospital pharmacy database in Hospital of Kaunas University of Medicine.
Main Outcome Measures: The consumption of medicines was evaluated from the financial stand-point and by the mean of DDD methodology. Also the Meta-analysis of Heparins was performed. In the end, the usage of Antibiotics was evaluated from the financial and DDD stand-points.
Results: The total drug expenses in HKUM increased dramatically during the five year period i.e. more than 46%, from 5.261 thousand Lt in 2001 to 9.804 thousand Lt in 2005. The mostly consumed medicines by the means of the number of DDDs per 1000 hospitalization days managed to remain almost the same during the mentioned period. After the performed Meta-analysis of heparins, the price of Dalteparinum natricum was set as the reference one. It was done, because UFH showed significantly lower efficacy in comparison with different LMWHs. The further calculations demonstrated that it could be possible to rationalize the usage of 93-144 thousand Lt yearly, if the reference pricing methodology for heparins were adopted. Besides, total expenses of Antibiotics increased more than 70% during the five-year period, from 1.229 thousand Lt in 2001 to 2.112 thousand Lt in 2005. This is extremely... [to full text]
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LELIEVRE, SOPHIE. "Implications des adn topoisomerases dans le mecanisme d'action cytotoxique de la suramine, un medicament antitumoral : developpement et caracterisation de cellules resistantes a cet heparinoide." Paris 6, 1994. http://www.theses.fr/1994PA066625.
Full textAbstract:
La suramine est un compose polyanionique et polyaromatique, possedant des proprietes heparinoides. Sa puissante activite antitumorale, en particulier sur les cancers prostatiques, a inscite au developpement d'etudes pour mettre en evidence ses mecanismes d'action antitumoraux, ce qui permettrait le developpement de derives plus cibles et moins toxiques pour l'organisme. Il semble que les proprietes heparinoides de ce compose soient a l'origine de son interaction avec des composants aussi bien extracellulaires que cytoplasmiques et nucleaires. Ainsi, les effets de la suramine sur certains facteurs de croissance, des recepteurs membranaires, des enzymes lysosomales et des enzymes nucleaires (impliquees dans la regulation de l'expression de l'adn) ont ete decrits sans pouvoir avec certitude correler ces interactions aux effets cytostatiques, differenciants, cytotoxiques et antimetastatiques de cet heparinoide. Nous avons recemment montre que la suramine est un puissant inhibiteur de topoisomerase ii in vitro et sur culture cellulaire (dc-3f) et qu'elle agit sans induire la formation de complexes clivables adn-topoisomerase ii. Cet effet est le premier pouvant expliquer l'action cytotoxique de la suramine sur certaines lignees de cellules tumorales ; il indique egalement que ce compose, stable dans les cellules, pourrait servir d'outil pour l'etude de l'effet des heparinoides (impliques dans la regulation de la proliferation cellulaire et du phenotype metastatique) au niveau des topoisomerases, fondamentales pour la regulation de la topologie de l'adn et de l'expression genique. Les cellules de fibrosarcome, dc-3f/su 1000, 10 fois resistantes a l'action cytotoxique de la suramine, developpees et etudiees au cours du travail de these montrent des caracteristiques uniques pour des cellules resistantes a un inhibiteur de topoisomerase ii: (1) ces cellules ont augmente leur potentiel invasif et metastatique par rapport aux cellules dc-3f parentales. (2) l'evolution de la resistance a l'action cytotoxique de la suramine peut etre mise en parallele avec l'evolution du potentiel metastatique. Cette modification phenotypique particuliere confirme que la suramine intervient au niveau du potentiel metastatique des cellules tumorales. (3) les cellules dc-3f/su 1000 sont 2 fois resistantes aux inhibiteurs classiques de topoisomerase ii tels que l'etoposide, l'amsacrine et la doxorubicine (technique de clonage en continu) et elles possedent effectivement un fonctionnement altere de leur topoisomerase ii. En particulier, la topoisomerase ii des cellules resistantes montre une activite catalytique accrue associee a une diminution d'induction de formation des complexes adn-topoisomerase ii, sans que cela puisse s'expliquer par une alteration quantitative de l'enzyme. L'augmentation d'activite enzymatique semble etre due a une augmentation de phosphorylation (environ 4 fois) de l'isoforme 180 kda de la topoisomerase ii. Ces resultats confirment l'implication de cette enzyme nucleaire dans le mecanisme d'action cytotoxique de la suramine. (4) les cellules dc-3f/su 1000 presentent une modification de leur structure dans tous les compartiments associes a la transmission des signaux: la matrice extracellulaire, le cytosquelette et l'organisation chromatinienne dans laquelle la topoisomerase ii est fortement impliquee. Finalement, nous suggerons que ces cellules pourraient etre utilisees comme modele pour l'etude de l'effet des heparinoides sur la topoisomerase ii. Nos resultats laissent en effet esperer que l'exploration du role de la topoisomerase ii au niveau de la matrice nucleaire qui est le cur du systeme de regulation de la replication et de la transcription de l'adn, pourrait ouvrir la voie au developpement d'antitumoraux particuliers
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COUZI, JEROME. "Thrombopenies immuno-allergiques graves induites par un heparinoide de synthese : le polysulfate de pentosane, a propos de cinq observations du service de cardiologie de nice." Nice, 1988. http://www.theses.fr/1988NICE6501.
Full textBook chapters on the topic "Heparinoid"
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Harr, Jeffrey N., Philip F. Stahel, Phillip D. Levy, Antoine Vieillard-Baron, Yang Xue, Muhammad N. Iqbal, Jeffrey Chan, et al. "Heparinoid." In Encyclopedia of Intensive Care Medicine, 1080. Berlin, Heidelberg: Springer Berlin Heidelberg, 2012. http://dx.doi.org/10.1007/978-3-642-00418-6_1693.
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Wessel, Hans Peter. "Heparinoid mimetics." In Glycoscience Synthesis of Substrate Analogs and Mimetics, 215–39. Berlin, Heidelberg: Springer Berlin Heidelberg, 1997. http://dx.doi.org/10.1007/bfb0119258.
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Harr, Jeffrey N., Philip F. Stahel, Phillip D. Levy, Antoine Vieillard-Baron, Yang Xue, Muhammad N. Iqbal, Jeffrey Chan, et al. "Heparinoids and Synthetic Heparinoids." In Encyclopedia of Intensive Care Medicine, 1080–82. Berlin, Heidelberg: Springer Berlin Heidelberg, 2012. http://dx.doi.org/10.1007/978-3-642-00418-6_717.
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Stief, T., and P. Kiefer. "Heparin und Heparinoide." In Springer Reference Medizin, 1088–89. Berlin, Heidelberg: Springer Berlin Heidelberg, 2019. http://dx.doi.org/10.1007/978-3-662-48986-4_1419.
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Stief, T., and P. Kiefer. "Heparin und Heparinoide." In Lexikon der Medizinischen Laboratoriumsdiagnostik, 1–2. Berlin, Heidelberg: Springer Berlin Heidelberg, 2017. http://dx.doi.org/10.1007/978-3-662-49054-9_1419-1.
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Oreste, P., and G. Zoppetti. "Semi-synthetic Heparinoids." In Heparin - A Century of Progress, 403–22. Berlin, Heidelberg: Springer Berlin Heidelberg, 2011. http://dx.doi.org/10.1007/978-3-642-23056-1_18.
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Harenberg, J., G. Huhle, and U. Hoffmann. "Pharmakologie der Heparine und Heparinoide." In Hämostaseologie, 684–97. Berlin, Heidelberg: Springer Berlin Heidelberg, 1999. http://dx.doi.org/10.1007/978-3-662-07673-6_95.
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Regelson, William. "Heparin, Heparinoids, Synthetic Polyanions, and Anionic Dyes." In ACS Symposium Series, 367–93. Washington, DC: American Chemical Society, 1991. http://dx.doi.org/10.1021/bk-1991-0467.ch024.
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Linhardt, Robert J., and Duraikkannu Loganathan. "Heparin, Heparinoids and Heparin Oligosaccharides: Structure and Biological Activities." In Biomimetic Polymers, 135–73. Boston, MA: Springer US, 1990. http://dx.doi.org/10.1007/978-1-4613-0657-3_8.
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Edward Conrad, H. "Heparinoid/Protein Interactions." In Heparin-Binding Proteins, 183–202. Elsevier, 1998. http://dx.doi.org/10.1016/b978-012186060-8/50007-3.
Full textConference papers on the topic "Heparinoid"
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Sternberger, A., S. Haas, K. Breddin, and G. Blümel. "COMPARISON OF VARIOUS AMI DOLYTIC HEPARIN ASSAYS: REPORT OF A COLLABORATIVE STUDY." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644169.
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The authors performed a controlled study to compare commercially available amidolytic heparin assays based on anti-Xa or anti-I la systems. All participants (see below) were provided with the same batch of all heparin preparations and reagents including homogenous plasma preparation. In addition plasma was spiked with the various unfractionated (n=2) as well as lmwh- (n=5) and heparinoid preparation (n=l). The four university laboratories analyzed all heparin preparations that are registered or used in clinical trials in FRG (n=8). The two testkit producers analyzed registered heparin preparations and the heparin producer their brand only. The study was recently completed and the data analysed and collected. The first evaluation revealed that the amidolytic anti-I la assay is insensitive for lmwh and heparinoids. Determination of unfractionated heparins is not accurate below 0.5 units of the corresponding standard. The Xa-methods are more sensitive for lmwh and heparinoids, however these methods also reveal a high standard deviation. Estimation of concentrations below 0.5 units of all tested heparin preparations is questionable.The authors are indented for active cooperation to Prof. Dr. K. Andrassy (Med. Univ. Heidelberg), Dr. M. Biegholdt (MIDY LABAZ), Dr. G. Dertinger (Sandoz AG), Dr. VJ. Feller (Braun Melsungen AG), Dr. P. Friberger (Kabi Vitrum Stockholm), Dr. P. Hell stern (Univ. Klinik Homburg), Dr. D. G. Meulemann (Organon Scientific Development Group), Dr. X. Muller (Nordmarkwerke), Dr. Zimmer (Boehringer Mannheim GmbH).
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Chong, B. H., F. Ismail, J. Cade, A. S. Gallus, S. Gordon, and C. N. Chesterman. "HEPARIN-INDUCED THROMBOCYTOPENIA: IN VITRO STUDIES WITH LOW MOLECULAR WEIGHT HEPARINOID, ORG 10172." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643926.
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Heparin-induced thrombocytopenia (HIT), an adverse effect of heparin therapy, may be associated with serious thrombosis resulting in severe disability or death. An IgG heparin-dependent antibody may be demonstrated in HIT by platelet aggregation studies with patient serum/plasma and standard (s) heparin. A recent study showed high cross-reactivity of the antibody with low molecular weight (LMW) heparins as most of the 22 patient sera tested gave a positive reaction with various LMW heparins including CY222, CY216, PK10169 and Kabi 2165 (Messmore HL et al, Blood 64(5), 1984 suppl). However, cross-reactivity rate with Org 10172, a LMW heparinoid which has strong anti-Xa but negligible antithrombin activity, is unknown. We tested the plasma of 17 patients with HIT for cross-reactivity with Org 10172. Although all 17 patient plasmas reacted positively with s.heparin (0.2 1.0 IU/ml), only 3 patient plasmas gave a positive but weaker reaction with Org 10172 (0.2-1.0 IU/ml).Further studies were performed to investigate the effect of adding Org 10172 (0.2 to 2.0 anti-Xa U/ml) to a reaction mixture of normal platelet-rich plasma, patient plasma and s.heparin (0.2 IU/ml). With 7 patient plasmas which showed no cross-reactivity with Org 10172, the antibody-induced platelet aggregation was inhibited when the concentration of Org 10172 exceeded 0.5 to 1.0 anti-Xa U/ml. When the study was repeated with other s.heparin concentrations (0.05, 0.1, 0.4 IU/ml), this inhibitory effect was again present provided the ratio of Org 10172 concentration (anti-Xa U/ml) to heparin concentration (IU/ml) exceeds 2.5 to 5. However, this inhibitory effect was not observed with the 3 patient plasmas which showed cross-reactivity with the heparinoid whqp. the same concentrations of Org 10172 were added. This inhibitory effect appeared to be specific for platelet aggregation induced by the heparin-dependent antibody as Org 10172 (<10 anti-Xa U/ml) did not affect platelet aggregation induced by collagen (2 ug/ml) and ADP (2.5 uM). These findings together with our experience of 3 cases of HIT successfully treated with Org 10172 suggest that this LMW heparinoid may be a useful drug for the treatment of HIT.
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Sakuragawa, N., S. Saitoh, and K. Takahashi. "INTERACTION BETWEEN CULTURED ENDOTHELIAL CELLS AND ABNORMAL ANTITHROMBIN III "TOYAMA"." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644366.
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Purpose: Abnormal antithrombin III(AT-III)Toyama showed non-affinity to heparin and heparinoid to show loss of immediate antithrombin activity. On the endothelial cells, there are heparinoids including heparan sulfate. We investigated on the interaction between cultured endothelial cells and abnormal AT-III"Toyama" from the viewpoint of antithrombin activity.Materials and methods: (1) Endothelial cell culture:^125I-labelled normal and abnormal AT-III were placed on the washed endothelial cultured cells in 0.2 ml of RPMI-1640 medium for 15 min at 37°C. The medium was suctioned off and the cell layer was washed with Hank's balanced salt solution. The cells were incubated with 1 ml of heparin(3 ug/ml) for 15 min at 4°C. The radioactivity in the supernatant was counted, and represented AT-III which bound to the cells surface. (2) Antithrombin activity: 0.23 ml of thrombin solution^ U/ml) and 0.03 ml of normal or abnormal AT-III plasma were mixed, and incubated on the cultured cell surface for 5 min at room temperature. The residual thrombin activity was assayed by 0.3 ml of the substrate (S-2238) solution(0.8mM)for 5 min. After these procedures,2 ml of 2% citric acid solution was added to stop the reaction, and 0D(405 nm) was recorded.Results: Abnormal AT-III showed reduced binding-activity to cultured cells to one fifth compared with normal AT-III, and the residual thrombin activity in the abnormal was higher compared with that in normal plasma.Conclusion: Abnormal AT-III showed less binding activity to the cultured endothelial cells, and less thrombin neutralizing activity to show thrombogenic tendency.
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Turple, A. G. G., M. N. Levin, J. Hirish, C. J. Carter, R. M. Jay, P. J. Powers, M. Andrew, H. N. Magnani, R. D. Hull, and M. Gent. "A DOUBLE BLIND RANDOMIZED TRIAL OF ORG 10172 LOW MOLECULAR WEIGHT HEPARINOID IN THE PREVENTION OF DEEP VEIN THROMBOSIS IN PATIENTS WITH THROMBOTIC STROKE." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643239.
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The optimal method of venous thrombosis prophylaxis in patients with stroke is uncertain. ORG 10172 is a low molecular weight heparinoid consisting principally of heparan and dermatan sulphates. In animal studies, ORG 10172 is as effective as unfractionated heparin in preventing venous thrombosis but produces less bleeding. There have been a limited number of descriptive studies on its use in humans, but to date randomized efficacy trials of ORG 10172 in the prevention of venous thrombosis have not been reported. A double blind randomized trial was carried out to compare ORG 10172 with placebo in the prevention of deep vein thrombosis in patients with thrombotic stroke. Seventy-five patients were randomized to receive ORG 10172 (50 patients) in a loading dose of 1,000 anti-Xa units intravenously followed by 750 anti-Xa units subcutaneously 12 hourly or placebo (25 patients). Prophylaxis was commenced within 7 days of stroke onset, continued for 14 days or until discharge from hospital, if earlier. Venous thrombosis surveillance was carried out with 125-1 fibrinogen leg scanning and impedance plethysmography. Venous thrombosis was confirmed by venography which occurred in 2 of 50 (4%) in the ORG 10172 group and 7 of 25 (28%) in the placebo group (p=0.005). The corresponding rates for proximal vein thrombosis were 0% and 16%, respectively (p=0.01). There was one major haemorrhage in the treated group and one minor haemorrhage in the placebo group. The anti-factor Xa levels (units/ml; mean ± SE) gradually rose from 0.18 ± 0.001 and 0.06 ± 0.01 six and 12 hours after injection on the first day to 0.24 ± 0.02 and 0.12 ± 0.01 after 11 days treatment. The results of this study indicate that ORG 10172 heparinoid is effective prophylaxis against deep vein thrombosis in patients with acute thrombotic stroke.
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Wester, J., F. W. J. Van Mensvoort, D. G. Meuleman, H. ten Cate, C. P. Henny, and J. W. ten Cate. "EFFECTS OF ORG 10172, A NOVEL LMW HEPARINOID ON PRIMARY HAEMOSTASIS IN RATS AND HUMANS. A MORPHOLOGICAL STUDY." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643238.
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Org 10172 is a novel low molecular weight heparinoid isolated from animal mucosa with a higher anti-thrombotic/bleeding risk ratio than standard heparin. The effects of Org 10172 and heparin on primary haemostasis in rats and humans have been studied by light and electron microscopy (LM&EM).In rat ears bleeding wounds were inflicted. The wound areas were excised 5, 15 or 30 min. after bleeding induction, and processed for LM and EM. Org 10172 and heparin have been administered in doses of 300 or 600 anti-Xa U/kg i.v., 5 or 1 min. prior to bleeding induction. Bleeding wounds of drug treated animals have been compared with those of placebo animals. Heparin inhibited degranulation as well as fibrin deposition and groups of not aggregated, sometimes even discoidal platelets could be found after heparin treatment. Org 10172 inhibited degranulation to some extent but less than heparin and Org 10172 hardly inhibited fibrin deposition.In six human volunteers SimplateR bleeding time wounds were excised by punch biopsy, 20 min. after bleeding induction and processed for LM and EM. Org 10172 was administered as single bolus injection of either 3200 or 6400 anti-Xa U i.v., 10 min. prior to bleeding induction. Heparin was given in a dosis of 10.000 anti-Xa U i.v. All biopsies from post-drug bleeding time wounds were compared with biopsies taken from pre-drug bleeding time wounds in the same volunteer. As in the rat studies, heparin inhibited degranulation and fibrin deposition whereas after Org 10172 treatment these effects were hardly detectable. In general the effects of both drugs on haemostasis in the human volunteer study were less distinct than in the rat study. This may be attributed to the lower dose levels used.In conclusion, primary haemostasis after Org 10172 treatment is somewhat retarded, but essentially normal, whereas haemostasis after heparin treatment is more severely disturbed.
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Gerhart, T., H. Yett, A. Donovan, M. A. Lee, M. Smith, and E. W. Salzman. "ORGANON 10172 VS. WARFARINTO PREVENT VENOUS THROMBOSIS AFTER HIP FRACTURE." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643686.
Full textAbstract:
Deep venous thrombosis (DVT) remains a serious and frequent complication after fracture of the hip, and even the mostefficacious prophylactic agents, e.g., warfarin, may fail to prevent DVT in up to 2056 of cases. There is evidence that low molecular weight heparin or heparin-like agents may have advantages in antithrombotic prophylaxis with reduced hemorrhagic sideeffects in patients at risk of DVT. We are engaged in a randomized prospective trial comparing the antithrombotic effect ofwarfarin (PT 1.5x control)with that of Organon 10172, a mixture ofsulfated low molecular weight glycosamioglycans (750 anti-Xa u b.i.d. sc., begunpreop and continued 9 days, followe by warfarin). Diagnosis is by 125-1 fibrinogen scan and impedence plethysmography with confirmatory phlebography. At present71 patients have been admitted, and patient groups are comparable in age, sex, type of fracture, and all other significant respects. DVT has been diagnosed in 7of 36 patients given warfarin an in 1 of35 patients who received Organon10172. Pulmonary embolism has not beenencountered. GI bleeding has occurred twice on warfarin and once on Organon 10172 There has been no difference in estimated operative blood loss, transfusion requirements, or other major bleeding complications.One patient on warfarin died ofmyocardial infarction and pneumonia. There were no other adverse reactions.The study is still in progress. The present trend in the results suggests that the heparinoid Organon 10172 may be a promising new agent to prevent DVT in high risk patients, such as those with fractures of the hip.
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van Dinther, T. G., F. Hol, and D. G. Meuleman. "EFFECT OF VARIOUS HEPARIN(OID)S ON HEPARIN COFACTOR II MEDIATED ANTI-THROMBIN ACTIVITY AND INHIBITION OF THROMBIN GENERATION IN VITRO." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644353.
Full textAbstract:
The effects of various heparin(oid)s, standard heparin VII (SH), dermatan sulphate (DS), a low molecular weight fraction of heparin (UMW-H), FragminR (FRA), Org 10172 = low molecular weight heparinoid, the fraction of Org 10172 with high affinity for AT-III (HA-10172) and the low affinity fraction (LA-10172) respectively were examined on in vitro thrombin generation and inactivation.Thrombin inactivation in the presence of either heparin cofactor II (HC-II) or anti-thrombin III (AT-III) was assessed with two newly developed assays using the purified cofactors, thrombin and chromogenic substrate S2238 on microtiterplates. Thrombin generation in the presence of HC-II and AT-III was studied using purified factor Xa, prothrombin and blood platelet lysate and the residual thrombin activity was assessed amidolytically.The inhibition of the compounds on thrombin activity are summarized in the tableThe following conclusions can be drawn:- SH, LMW-H, HA-10172 and FRA potentiate the AT-III mediated inactivation of Ha more strongly than the HC-II mediated inactivation.- DS and LA-10172 show the reverse pattern of inactivation, while Org 10172 potentiates both inactivaton pathways to a similar extent.Thrombin generation in the presence of HC-II is inhibited by mw-heparin(oid)s at approx. 2-5 times lower concentrations than the HC-II mediated thrombin inactivation, while the inhibiting effect of SH in both assays is comparable.AT-III mediated thrombin generation inhibition and AT-III mediated thrombin inactivation is comparable as well for SH, LMW-H and FRA. In contrast, Org 10172 and its subfractions are approx. 10 times more potent on AT-III mediated thrombin generation inhibition than on AT-III mediated thrombin inactivation.Org 10172 shows low anti-thrombin activity and this activity is mainly mediated via FC-II.
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Kısa, Alperen. "Heparinin İndüklediği Trombositopeni: Olgu sunumu." In 4th International Symposium on Innovative Approaches in Health and Sports Sciences. SETSCI, 2019. http://dx.doi.org/10.36287/setsci.4.9.076.
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Messmore, H., B. Griffin, J. Seghatchian, and E. Coyne. "HIGH CONCENTRATIONS OF HEPARIN ARE MORE INHIBITORY TO PLATE- AGGREGATION IN-VITRO THAN ARE LOW MOLECULAR WEIGHT HEPARINS AND HEPARINOIDS AT THE SAME CONCENTRATION." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644186.
Full textAbstract:
Other investigators have shown that heparin in the usual therapeutic range (0.1-0.5 units/ml) has an enhancing effect on ADP aggregation and an inhibitory effect on collagen and thrombin induced aggregation. The effects of low molecular weight heparin (LMWH)and heparinoids (dermatan sulfate, heparan sulfate) on platelet aggregation have not been as extensivelystudied. We have utilized citrated platelet rich plasma (3.2%citrate-whole blood 1:9) drawn in plastic and adjusted to a final platelet count of 250,000/ul. A Bio-Data 4 channgl aggregometer was utilized with constantstirring at 37 C. The reaction was allowed to run for 20 minutes. Platelet rich plasma was supplemented 1:9 with saline or heparin and various agonists were then added ifno aggregation occurred. ADP, collagen, thrombin, ristocetin and serum from patients with heparin inudced thrombocytopenia (HIT) were utilized as agonists. Heparin was substituted at concentrations of 0.1 to 500 units per ml and various LMWH and heparinoids were substituted in equivalent anti-Xa or gravimetric concentrations. At low concentrations no inhibitory effect on any ofthe agonists was observed with any of the heparins or heparinoids. At concentrations of heparin of 100 u/ml or greater, all agonists were inhibited. At equivalent concentrations of five different LMWH (Cy 216, Cy 222, Pk 10169, Kabi 2165 and pentasaccharide) inhibition did notoccur at all or at very high concentions only. Dermatan sulfate and heparan sulfate inhibited only at high concentrations. HIT serum could not aggregate platelets with dermatan sulfate or pentasaccharide atany concentrations, but it was a good agonist with the other heparins and heparinoids.
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Haglund, O., L. Wibell, and T. Saldeen. "EFFECTS OF PENTOSAN POLYSULPHATE (EXMLRON) ON FIBRINOLYSIS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644864.
Full textAbstract:
Decreased fibrinolytic capacity is thought to be an important ccnponent in the pathqgenesis of different thrombotic states. There is a need for agents improving the fibrinolytic capacity, especially perorally (p.o.) active drugs. Since long the semi-synthetic heparinoid Pentosan Polysulphate (PPS) has been shown to have a stimulating effect on fibrinlysis when given parenterally. Alsop.o. administered drug has been claimedto improve fibrinolysis. However, the degree of gastrointestinal resorption has not been thoroughly assessed and the mechanism behind the effect of PPS cn fibrinolysis is not known.8 healthy male volcnteers and 14 patients with a history of venous thrombosis were studied. Before and after administration of PPS blood samples were taken and plasminogen activator activity (tPA-act), antigen (tPA-ag) and plasminogen activator inhibitor (PAI) were determined. The volonteers were given 50 ng PPS i.v. and blood was sanpled before and after 30 minutes. In a second experiment they received 400 rrg PPS p.o. follwed by blood sarrpling after 2 hours. They also received 400 ng of PPS daily p.o. for 25 days. The patient group were given 500 ng PPS p.o. 8 a.m. and blood was collected 6 hours later. To exclude influence of diumal variation blood was also taken 2 p.m. the day before. The plasma level of PPS after p.o. administration was determined by a sensitive modified radioassay for heparin.30 minutes after i.v. injection of PPS PAI was essentially unchanged, tPA-ac-tivity was slightly increased but tPA-ag showed a strongly significant decrease. 400 ng PPS p.o. resulted in an increase in tPA-ag after 2 hours. 400 ng PPS durirg 25 days resulted in a significant decrease of PAI with no charges in tPA-act and tPA-ag. 500 ng FEB given as a single dose in the morning did not cause greater charges of PAI than expected from the diumal variation. The uptake of PPS following p.o. administration is lav with a bioavailability of only 0,5 − 1 %.The low bioavailability of p.o. adninistrered PPS suggest that some of the ad-vantagous effects of PPS on fibrinolysis migjnt be caused through local effects in the intestine. The strong decrease of tPA-ag without significant changes in the other parameters may reflect an accelerated elimination of tPA-PAI-ccnplex. The mechanism of the inproved fibrinlysis following adninistration of PPS is still unsettled but our resluts may indicate that PPS initially facilitates the elimination of the tPA-PAI complex with a secondary increase of the tPA-ag. The tPA-ag may bind to PAI with a secondary decrease of the active component of this inhibitor. However, a more direct effect of PPS cn PAI cannot be excluded.