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Blood Clotting (blood + clotting)
Selected AbstractsNovel MRI and fluorescent probes responsive to the Factor XIII transglutaminase activityCONTRAST MEDIA & MOLECULAR IMAGING, Issue 4 2010Lorenzo Tei Abstract Transglutaminases, including factor XIII and tissue transglutaminase, participate in multiple extracellular processes associated with remodeling of the extracellular matrix during wound repair, blood clotting, tumor progression and fibrosis of ischemic injuries. The aim of this work was to evaluate a novel substrate analog for transglutaminase optimized by molecular modeling calculations (DCCP16), which can serve for molecular imaging of transglutaminase activity by magnetic resonance imaging and by near-infrared imaging. Experimental data showed covalent binding of Gd,DCCP16 and DCCP16-IRIS Blue to human clots, to basement membrane components and to casein in purified systems as well as in three-dimensional multicellular spheroids. In vivo, DCCP16 showed enhancement with a prolonged retention in clots and tumors, demonstrating the ability to detect both factor XIII and tissue transglutaminase mediated covalent binding of the contrast material. Copyright © 2010 John Wiley & Sons, Ltd. [source] Effectiveness of Microporous Polysaccharide Hemospheres for Achieving Hemostasis in Mohs Micrographic SurgeryDERMATOLOGIC SURGERY, Issue 6 2004FRCPC, Stephen R. Tan MD Background. Microporous polysaccharide hemospheres consist of controlled-porosity spherical particles manufactured from bioinert plant polysaccharide. Microporous polysaccharide hemospheres facilitate hemostasis by rapidly absorbing the fluid component of blood, concentrating platelets and clotting factors to accelerate blood clotting. Objective. The objective was to compare a microporous polysaccharide hemosphere bandage and electrocautery in achieving hemostasis. Methods. Twenty-four patients with a total of 48 stages of Mohs micrographic surgery were included. Patients were stratified by whether or not they were taking anticoagulant medications. Within each group, patients were randomized to receive either the microporous polysaccharide hemosphere bandage or electrocautery. Outcomes included bleeding through the dressing (early time point) and active bleeding upon dressing removal (late time point). Results. Nineteen patients not taking anticoagulants had 40 stages, of which 18 received the study bandage and 22 received electrocautery. The remaining 5 patients on anticoagulants had 8 stages, of which 4 received the study bandage and 4 received electrocautery. In both total and subgroup analysis, there was a higher incidence of bleeding through the dressing with the study bandage (p<0.05), but no increase in the incidence of active bleeding upon dressing removal (p>0.05). Conclusion. The microporous polysaccharide hemosphere study bandage had an increased incidence of bleeding through the dressing compared to electrocautery, but did not have an increased incidence of active bleeding upon dressing removal. [source] Health economics of treating haemophilia A with inhibitorsHAEMOPHILIA, Issue 2005C. KNIGHT Summary., Haemophilia is a rare, inherited blood disorder in which blood clotting is impaired such that patients suffer from excessive internal and external bleeding. At present there is no cure for haemophilia A and patients require expensive, life-long treatment involving clotting factor replacement therapy. Treatment costs are perceived to be higher for patients who have developed inhibitory antibodies to factor VIII, the standard therapy for haemophilia A. However, initial cost analyses suggest that clotting factor therapy with alternative haemostatic agents, such as recombinant activated factor VII or activated prothrombin complex concentrate, is no more expensive for the majority of haemophilia A patients with inhibitors than for those without inhibitors. With the availability of effective alternative haemostatic agents, orthopaedic surgery for haemophilia A patients with inhibitors is now a clinical option, and initial cost analyses suggest this may be a cost-effective treatment strategy for patients with inhibitors whose quality of life (QoL) is severely impaired by joint arthropathy. In an era of finite healthcare resourcing it is important to determine whether new treatments justify higher unit costs compared with standard therapies and whether such higher costs are justified from an individual perspective in terms of improved QoL, and from a societal perspective in terms of improved productivity and reduced overall healthcare costs. This paper examines current data on the health economics of treating haemophilia A patients with inhibitors, focusing on the overall costs of clotting factor replacement therapy and the cost consequences of joint replacement. [source] A physical organic mechanistic approach to understanding the complex reaction network of hemostasis (blood clotting)JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 10 2007Christian J. Kastrup Abstract This review focuses on how the mechanistic approach of physical organic chemistry can be used to elucidate the mechanisms behind complex biochemical networks. The dynamics of biochemical reaction networks is difficult to describe by considering their individual reactions, just as the dynamics of organic reactions is difficult to describe by considering individual electrons and atomic nuclei. Physical organic chemists have developed a useful set of tools to predict the outcome of organic reactions by separating the interacting molecules into modules (functional groups), and defining general rules for how these modules interact (mechanisms). This review shows how these tools of physical organic chemistry may be used to describe reaction networks. In addition, it describes the application of these tools to develop a mechanistic understanding of the dynamics of the complex network of hemostasis, which regulates blood clotting. Copyright © 2007 John Wiley & Sons, Ltd. [source] Protein,membrane interactions: blood clotting on nanoscale bilayersJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2009J. H. MORRISSEY Summary., The clotting cascade requires the assembly of protease,cofactor complexes on membranes with exposed anionic phospholipids. Despite their importance, protein,membrane interactions in clotting remain relatively poorly understood. Calcium ions are known to induce anionic phospholipids to cluster, and we propose that clotting proteins assemble preferentially on such anionic lipid-rich microdomains. Until recently, there was no way to control the partitioning of clotting proteins into or out of specific membrane microdomains, so experimenters only knew the average contributions of phospholipids to blood clotting. The development of nanoscale membrane bilayers (Nanodiscs) has now allowed us to probe, with nanometer resolution, how local variations in phospholipid composition regulate the activity of key protease,cofactor complexes in blood clotting. Furthermore, exciting new progress in solid-state NMR and large-scale molecular dynamics simulations allow structural insights into interactions between proteins and membrane surfaces with atomic resolution. [source] Metallocene based polyolefin: a potential candidate for the replacement of flexible poly (vinyl chloride) in the medical fieldPOLYMERS FOR ADVANCED TECHNOLOGIES, Issue 9 2010M. C. Sunny Abstract A comparative assessment of the performance properties of metallocene polyolefin (m-PO) with those of plasticized poly (vinyl chloride) (pPVC) and ethylene vinyl acetate (EVA) copolymer having 18% vinyl acetate content (EVA-18), the two common polymers used for flexible medical products, is carried out. The preliminary evaluation of the processability, mechanical properties, and thermal stability of the new material, m-PO is described. The processability parameters like mixing torque and melt viscosity of m-PO are found to be comparable with those of pPVC and EVA-18. Mechanical properties such as tensile strength, elongation at break, and tear strength (TS) of m-PO are much higher than that of pPVC and EVA-18. Thermo gravimetric analysis (TGA) indicates that the thermal degradation of m-PO takes place only at temperatures above 340°C and can be processed at 170°C without much damage. Oxygen and carbon dioxide permeabilities of m-PO at three different temperatures (10, 25, and 40°C) are evaluated and compared with those of pPVC and EVA-18. It could be seen that the permeabilities of both the gases for m-PO at three temperatures were lower than those of pPVC and EVA. Biological evaluation of m-PO is carried out by assessing its cytotoxicity, hemolytic property, and blood clotting initiation. The cytotoxicity studies indicate that m-PO is non-toxic to the monolayer of L929 mammalian fibroblast cell lines on direct contact or the exposure of its extract. Non-hemolytic property of m-PO by direct contact as well as test on extract is revealed both in static and in dynamic conditions. Blood clotting time experiments indicate that the initiation of blood clotting due to m-PO is faster than that of pPVC and EVA-18. Copyright © 2009 John Wiley & Sons, Ltd. [source] Unconventional serine proteases: Variations on the catalytic Ser/His/Asp triad configurationPROTEIN SCIENCE, Issue 12 2008an Ekici, Özlem Do Abstract Serine proteases comprise nearly one-third of all known proteases identified to date and play crucial roles in a wide variety of cellular as well as extracellular functions, including the process of blood clotting, protein digestion, cell signaling, inflammation, and protein processing. Their hallmark is that they contain the so-called "classical" catalytic Ser/His/Asp triad. Although the classical serine proteases are the most widespread in nature, there exist a variety of "nonclassical" serine proteases where variations to the catalytic triad are observed. Such variations include the triads Ser/His/Glu, Ser/His/His, and Ser/Glu/Asp, and include the dyads Ser/Lys and Ser/His. Other variations are seen with certain serine and threonine peptidases of the Ntn hydrolase superfamily that carry out catalysis with a single active site residue. This work discusses the structure and function of these novel serine proteases and threonine proteases and how their catalytic machinery differs from the prototypic serine protease class. [source] ORIGINAL ARTICLE: Isolation of Non-Activated Monocytes from Human Umbilical Cord BloodAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2010Erik Normann Problem, Methods for monocyte purification are common but few work with umbilical cord monocytes that do not activate the cell for subsequent culture analysis. Methods of study, The collection procedure avoids use of needles and procedures that variably activate blood clotting and uses a purification procedure that involves diluted Ficoll, autologous serum to remove platelets and 42% and 51% Percoll step gradients for the final purification. The resulting monocytes were stimulated with bacterial lipopolysaccharide and formalin-treated bacteria Escherichia coli and group B streptococci (GBS) to secrete TNF-, and IL-1,, measured by ELISA. Results, The purification procedure results in non-active but stimulation-competent monocytes with high yields (2.3,9 × 107 cells) and purity (from 70% to 98%). Conclusion, We describe a procedure that is easy, uses common reagents and provides a uniformly high yield and purity of non-activated fetal monocytes for studies of innate defense responses. [source] Different Evolutionary Histories of the Coagulation Factor VII Gene in Human Populations?ANNALS OF HUMAN GENETICS, Issue 1 2010Georgios Athanasiadis Summary Immoderate blood clotting constitutes a risk factor for cardiovascular disease in modern industrialised societies, but is believed to have conferred a survival advantage, i.e. faster recovery from bleeding, on our ancestors. Here, we investigate the evolutionary history of the Coagulation Factor VII gene (F7) by analysing five cardiovascular-risk-associated mutations from the F7 promoter and nine neutral polymorphisms (six SNPs and three microsatellites) from the flanking region in 16 populations from the broader Mediterranean region, South Saharan Africa and Bolivia (687 individuals in total). Population differentiation and selection tests were performed and linkage disequilibrium patterns were investigated. In all samples, no linkage disequilibrium between adjacent F7 promoter mutations ,402 and ,401 was observed. No selection signals were detected in any of the samples from the broader Mediterranean region and South Saharan Africa, while some of the data suggested a potential signal of positive selection for the F7 promoter in the Native American samples from Bolivia. In conclusion, our data suggest, although do not prove, different evolutionary histories in the F7 promoter region between Mediterraneans and Amerindians. [source] Is It Possible to Create a "Mechanical" Arteriovenous Fistula in Hemodialysis Patients?ARTIFICIAL ORGANS, Issue 3 2010Attilio Ignazio Lo Monte Abstract Manual suturing still remains the best technique for the creation of vascular anastomoses on uremic patients with excellent results, despite being time consuming, difficult to perform with small vessels, and associated with a significant learning curve. We created a full mechanical arteriovenous fistula on a 65-year-old uremic patient with a new device already used in cardiac bypass surgery. The fistula was created automatically and rapidly, without the need for temporary occlusion of the artery, reducing the risk of blood clotting. We believe that mechanical devices may be useful to produce precise and fast anastomoses requiring minimal training for the surgeon. [source] Experimental Evaluation of the V-Point Heparin-Bonding System Applied to a Dense-Membrane Artificial Lung During 24-Hour Extracorporeal Circulation in BeaglesARTIFICIAL ORGANS, Issue 8 2001Masafumi Tashiro Abstract: Heparin was covalently bonded to a hollow-fiber dense-membrane artificial lung and circuit using a silane coupling agent and polyethyleneimine as a spacer. This study investigated whether the novel artificial lung could sustain prolonged extracorporeal lung assist (ECLA) by venoarterial bypass in beagles using minimal anticoagulants. We maintained ECLA for 24 h in 3 groups of minimal systemic heparinization, heparinization with the new anticoagulant nafamostat mesilate, and without any systemic anticoagulant. The results were assessed from the functional performance of the artificial lung and by macroscopic and microscopic examination after the experiments. Artificial lung function, hemodynamics, hemogram, and platelet aggregation activity were well maintained in all groups. There was no plasma leakage from the artificial lung. Although several clots were observed in stagnant areas of the artificial lungs and circuits, there was no clot formation inside the artificial lung in any group. This highly biocompatible, heparin-bonded dense-membrane artificial lung performed well and safely during prolonged ECLA with blood clotting times less than 120 s. [source] | |||||||||||||