Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.6 (thromboplastin)
13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Known allyl 4,6-O-benzylidene-alpha-D-glucopyranoside was first converted into methyl (prop-1-enyl 2,3-di-O-benzyl-4-O-chloroacetyl-alpha-D-glucopyranosid)-uronate. Acid hydrolysis, followed by treatment with (bromomethylene)dimethyl-ammonium bromide, gave methyl (2,3-di-O-benzyl-4-O-chloroacetyl-alpha-D-glucopyranosyl bromide)uronate. Condensation of this bromide with 3-O-acetyl-1,6-anhydro-2-azido-2-deoxy-4-O-(methyl 2,3-di-O-benzyl-4-O-chloroacetyl-beta-D-glucopyranosyluronate)-bet a-D-glucopyranose. Acetolysis, followed by treatment with titanium tetrabromide, then gave 3,6-di-O-acetyl-2-azido-2-deoxy-4-O-(methyl 2,3-di-O-benzyl-4-O-chloroacetyl-beta-D-glucopyranosyluronate)-alp ha-D-glucopyranosyl bromide. Condensation of this bromide with benzyl 6-O-acetyl-3-O-benzyl-2-benzyloxy- carbonylamino-2-deoxy-4-O-(methyl 2-O-acetyl-3-O-benzyl-alpha-L- idopyranosyluronate)-alpha-D-glucopyranoside provided benzyl O-(methyl 2,3-di-O-benzyl-4-O-chloroacetyl-beta-D-glucopyranosyluronate)-(1- ---4)-O-(3,6-di-O-acetyl- -2-azido-2-deoxy-alpha-D-glucopyranosyl)-(1----4)-O-(methyl 2-O-acetyl-3-O-benzyl-alpha-L-idopyranosyluronate)-(1----4)-6-O-ac etyl-3-O- acetyl-3-O-benzyl-2-benzyloxycarbonylamino-2-deoxy-alpha-D-gluc opyranoside. O-Dechloroacetylation followed by condensation with 6-O-acetyl-2-azido-3,4-di-O-benzyl-2-deoxy-alpha-D-glucopyranosyl bromide provided benzyl O-(6-O-acetyl-2-azido-3,4-di-O-benzyl-2-deoxy-beta-D-glucopyranosyl)- (1----4)-O-(methyl 2,3-di-O-benzyl-beta-D-glucopyranosyluronate)-(1----4)- O-(3,6-di-O-acetyl-2-azido-2-deoxy-alpha-D-glucopyranosyl)-(1----4)-O-(m ethyl 2-O-acetyl-3-O-benzyl-alpha-L-idopyranosyluronate)-(1----4)-6-O-ac etyl-3-O- benzyl-2-benzyloxycarbonylamino-2-deoxy-alpha-D-glucopyranoside in 70% yield. O-Deacetylation followed by re-esterification, O-sulfation, saponification, catalytic hydrogenolysis, and N-sulfation gave the decasodium salt of O-(2-deoxy-2-sulfamido-6-O-sulfo-alpha-D- glucopyranosyl)-(1----4)-O-(beta-D-glucopyranosyluronic acid)-(1----4)-O-(2-deoxy-2-sulfamido-3,6-di-O-sulfo-alpha-D-gl ucopyranosyl)-(1----4)-O-(2-O-sulfo-alpha-L-idopyranosyluronic+ ++ acid)-(1----4)-2-deoxy-2-sulfamido-6-O-sulfo-D-glucopyranose. This synthetic pentasaccharide binds to antithrombin III with an association constant similar to that of high-affinity heparin and elicits a potent anti-factor Xa activity in plasma.
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PMID:Synthesis of heparin fragments. A chemical synthesis of the pentasaccharide O-(2-deoxy-2-sulfamido-6-O-sulfo-alpha-D-glucopyranosyl)-(1-4 )-O-(beta-D-glucopyranosyluronic acid)-(1-4)-O-(2-deoxy-2-sulfamido-3,6-di-O-sulfo-alpha-D-glu copyranosyl)-(1-4)-O-(2-O-sulfo-alpha-L-idopyranosyluronic acid)-(1-4)-2-deoxy-2-sulfamido-6-O-sulfo-D-glucopyranose decasodium salt, a heparin fragment having high affinity for antithrombin III. 370 27

Design goals for a mechanical heart valve include duplicating the hemodynamic performance of the natural valve, eliminating the need for anticoagulants, and maintaining safety. The Lapeyre-Dassault (Dassault-Aviation, Paris, France) prosthetic valve, undergoing development, addresses these goals. The unique trileaflet design consists of a solid titanium ring and three leaflets. Prototypes of the valve fabricated with Delrin leaflets were implanted in the mitral position in six calves (70-90 kg). Four calves (Studies 1, 2, 3, 5) had long-term survival of 165, 158, 219, and 281 days, respectively. Two calves were killed, one on Day 37 and one on Day 39, after complications unrelated to the valve developed. In all calves heparin was given intravenously to maintain partial thromboplastin time at 1.5 to 2.0 x baseline for approximately 1 week. In Studies 1 and 2 full anticoagulation and antiplatelet therapy was given (orally administered sodium warfarin to maintain prothrombin time at 1.5 to 2.0 x baseline, along with aspirin (1 g/day) and dipyridamole 400 mg/day). In Study 3, all anticoagulation and antiplatelet therapy was discontinued at 1 month after implant. In Study 5, no anticoagulation therapy was given after the initial week of intravenous heparin; however, antiplatelet therapy was started on the fifth postoperative month and maintained until the study's end at 9 months. At 1, 2, 3, and 5 months, the mean plasma free hemoglobin level in the four long-term animals was 5.0 +/- 2.16, 6.0 +/- 3.83, 8.5 +/- 4.93, and 11.3 +/- 6.74 mg/dl, respectively. Hemolysis was not a problem. Valve performance during normal activity was excellent in all the calves, as evidenced by echocardiography and the overall appearance of good health. In the four completed long-term studies, left heart catheterization showed a mean valve pressure gradient of 11.57 +/- 1.26 mmHg and no apparent valvular regurgitation. Histopathologic examination of major organs showed no evidence of thromboembolic events. This study shows that the innovative design of this trileaflet valve performed well in initial in vivo testing, justifying further development.
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PMID:In vivo evaluation of a trileaflet mechanical heart valve. 855 6

The attachment and growth of vascular smooth muscle cells on biomaterials used as components of devices implanted in the vascular space may influence the biocompatibility of such materials. The nature of the materials may affect the attachment and/or the activation of these cells' procoagulant responses. Therefore, the main objective of this study was to measure the strength of adhesion of these vascular cells to potential biomaterials (titanium, zirconium alloys, and stainless steel) by exposing them to a range of shear stresses (50-300 dyn cm(-2)) in a parallel plate flow chamber. The procoagulant responses of the cells were evaluated by measuring the tissue factor (TF) activity promoted by the different materials under flow conditions. The materials supported distinctly different levels of initial cell adhesion in static culture. However, the fraction of adherent cells did not decline significantly with incrementally increasing shear stress within the range tested. TF expression, as measured by factor Xa (FXa) production. was material-dependent. For example, cells cultured on Ti1313 exhibited more FXa production (13.2 nM 10(-5) cells) than Ti1313(DH) (8.5 nM 10(-5) cells) or stainless steel (2 nM 10(-5) cells). Thus, our studies indicate that the level of adhesion, strength of attachment and the expression of procoagulant activity of adherent vascular cells depend strongly on the nature of the underlying biomaterial.
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PMID:Vascular cell attachment and procoagulant activity on metal alloys. 986 Jan 74

A biological evaluation is conducted for two types of nano-particle sols, hydroxyaptite(HAP) and titanium dioxide(TiO2). The results show that HAP sol significnatly prolongs the bleeding time and coagulation time of mice as well as the prothrombin time(PT) and partial thromboplastin time(PTT) of rats while TiO2 sol exhibits no such effects. Neither HAP sol nor TiO2 sol instigated in-vitro hemolysis of rabbit erythrocyte. However, both of the materials caused in-vitro aggregation of rabbit erythrocytes. The reason underlying the different results as to the two types of material is their specific stabilizer, heparin for HAP sol and PVC for TiO2 sol. We came to the conclusion that a biologically inert stablizer has no less significance than the nano-particle's very own nature in a nano-material's application prospect.
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PMID:[Studies on nano-particle sols of hydroxyaptite and titanium dioxide for haemo-compatibility]. 1254 61

High strength oxide ceramic materials like alumina and zirconia are frequently used for artificial joints because of their biocompatibility and high wear resistance. Their suitability as materials for implants and biomedical devices with direct blood contact, such as cardiovascular implants or components for blood pumps and dialyzers, has not been confirmed to date. The objective of this study was to investigate whether oxide ceramics show sufficient hemocompatibility. Dense specimens were made out of alumina, zirconia, titanium oxide, and aluminum titanate. Polyvinylchloride and silicone were additionally tested as reference materials. Interactions of human blood with the surfaces were studied by investigating partial thromboplastin time (PTT), thrombin antithrombin III complex (TAT), free plasma hemoglobin concentration, complete blood count, complement factor 5a, and protein adsorption. The results from the PTT and TAT tests clearly indicated higher blood activation by the ceramic materials when compared to the two polymer materials. However, alumina and zirconia showed lower C5a concentrations and less protein adsorption than the reference materials. Our results revealed that oxide ceramic materials alone cannot be used for implants in direct blood contact without modification of the ceramic surface, for example, by made-to-measure inert nanocoatings.
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PMID:Hemocompatibility of high strength oxide ceramic materials: an in vitro study. 1725 52

Extracellular matrix (ECM)-like biomimetic surface modification of cardiovascular implants is a promising method for improving hemocompatibility. In the present work, collagen (Col) and sulfated chitosan (SCS) multilayers were coated on pure titanium using a layer-by-layer (LBL) self-assembly technique. The Col-SCS multilayer growth was carried out by first depositing a single layer of positively charged poly-L-lysine (PLL) on the NaOH-treated titanium substrate (negatively charged surface), followed by alternate deposition of negatively charged SCS and positively charged Col, and terminated by an outermost layer of SCS. Platelet adhesion in vitro, partial activated thromboplastin time (APTT) and prothrombin time (PT) assays were used to evaluate the hemocompatibility of the Col-SCS multilayer coated titanium. The multilayer processed surfaces displayed reduced platelet adhesion and activation, and prolonged clotting time of APTT and PT compared with untreated titanium. Thus, the approach described here may provide a basis for the preparation of modified titanium surfaces for application in cardiovascular implants.
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PMID:Anticoagulant surface modification of titanium via layer-by-layer assembly of collagen and sulfated chitosan multilayers. 1843 11

Coimmobilization as a versatile biomodification technique has been widely used in the development of biomimetic materials with superior mechanical and biological properties. In this study, a mixture of heparin and fibronectin (Hep/Fn) was tested for its hemocompatibility after either physisorption or covalent coimmobilization to a titanium (Ti) substrate. The process of substrate activation and film deposition was associated with an increase of roughness; successful immobilization in both cases was demonstrated by FTIR. The immobilized heparin amount was probed by toluidine blue O binding, fibronectin by immunochemistry. Both molecules had slightly higher concentrations on the physisorbed film than after covalent coimmobilization. Plasmatic coagulation activation, tested as activated partial thromboplastin time APTT, and platelet adhesion were significantly improved on the covalently coimmobilized samples than on the physisorbed or blank ones. All these results suggest that the covalent coimmobilization of heparin with fibronectin improved the anticoagulant activity of heparin and caused a favorable blood compatibility. We envisage that this method will provide a potential and effective selection for biomaterials surface modification.
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PMID:Coimmobilization of heparin/fibronectin mixture on titanium surfaces and their blood compatibility. 2069 34

Blood compatibility is the most important aspect for blood-contacting medical devices including cardiovascular stents. In this study, the surface of nickel-titanium (TiNi) stent was coated with diamond-like carbon (DLC) and then subsequently grafted by using zwitterion (N(+) and SO(3) (-))-linked poly(ethylene glycol) (PEG). We hypothesize that this coupling of zwitterion and PEG may significantly improve blood compatibility of DLC-coated TiNi stent. The surface modified TiNi stents, including PEG-grafted stent (DLC-PEG) and zwitterionic PEG-grafted one (DLC-PEG-N-S) were the main focus on the tests of surface characteristics and blood compatibility. The zwitterionic PEG derivatives were obtained from a series of chemical reactions at room temperature. The results exhibited that as compared to the DLC-PEG, the hydrophilicity was much better with DLC-PEG-N-S and significantly increased atomic percentage of oxygen and nitrogen proved the entity of zwitterions on the surface of DLC-PEG-N-S. Meanwhile, the adsorption of blood proteins such as, human serum albumin (HSA) and fibrinogen was found considerably down-regulated in DLC-PEG-N-S, due mainly to the protein-repellent effect of PEG and zwitterion. Microscopic observation also revealed that as compared with the other substrates without zwitterion, the degree of platelet adhesion was the lowest with DLC-PEG-N-S. In addition, DLC-PEG-N-S retained an extended blood coagulation time as measured by activated partial thromboplastin time (APTT). The present results suggested that surface grafting of zwitterionic PEG derivatives could substantially enhance the blood compatibility of TiNi-DLC stent. In conclusion, anti-fouling properties of PEG and zwitterions are expected to be very useful in advancing overall stent performance.
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PMID:Surface grafting of blood compatible zwitterionic poly(ethylene glycol) on diamond-like carbon-coated stent. 2127 72

Magnesium and its alloys have been used in the recent development of lightweight, biodegradeable implant materials. However, the corrosion properties of magnesium limit its usefulness. In a previous study, a micro-arc oxidation (MAO) method was used to modify a Mg-1.0 wt % Zn-1.0 wt % Ca alloy surface, with the purpose of improving the corrosion resistance of Mg alloys. However, the blood compatibility of MAO-treated Mg alloy is unknown. Results of cytotoxicity assays with bone marrow-derived mesenchymal stem cells showed that extracts of MAO-treated alloy significantly decreased cytotoxicity compared to titanium alloy extract. Results of blood compatibility tests showed that the MAO group had a decreased hemolytic ratio (2.25%) compared to the untreated Mg alloy group (24.58%) (p < 0.001). The MAO group showed significantly shorter prothrombin and thrombin times and significantly longer activated partial thromboplastin time than the untreated Mg alloy group. Arachidonic acid- and adenosine diphosphate-induced platelet aggregations were significantly decreased by the untreated Mg alloy extract, and they were less affected by extract of MAO-treated Mg alloy. In conclusion, MAO-treated Mg-1.0 wt % Zn-1.0 wt % Ca alloy exhibits favorable blood compatibility characteristics and may be useful in the development of magnesium implant materials.
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PMID:Improved blood compatibility of Mg-1.0Zn-1.0Ca alloy by micro-arc oxidation. 2197 41

The endothelialization of the metal surface of vascular stents came into focus as a new method for improving the biocompatibility of intravascular stents. This article has its focus on building a biofunctional layer on the activated titanium surface with anti-CD34 antibody, vascular endothelial growth factor (VEGF), and heparin by a layer-by-layer (LBL) self-assembly technique, to promote the endothelialization of the surface. When compared with titanium surface, the number of adhered endothelial progenitor cells (EPCs) on LBLs increased 47.1% after 5 days culture, meanwhile the proliferation rate of EPCs on LBLs during 5 days culture also exhibit significantly improvement. The results of blood compatibility evaluation clearly show that the LBLs reduce the number of adhered and activated blood platelets (adhered: Ti 83% vs. LBL <20% and activated: Ti 57% vs. LBL 19%), and the activated partial thromboplastin time of the LBL surface prolonged about 20 s in compared with platelet-poor plasma. The assembled LBL thus improves the thromboresistance of the titanium surface. The presented biofunctional multilayer of anti-CD34, VEGF, and heparin on titanium can significantly improve the blood compatibility and the endothelialization of a medical device. The biofunctional layer supports generation of a new endothelium onto titanium surface by capturing EPCs and oriented differentiation.
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PMID:Influence of a layer-by-layer-assembled multilayer of anti-CD34 antibody, vascular endothelial growth factor, and heparin on the endothelialization and anticoagulation of titanium surface. 2304 61


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