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Haemostasis

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https://www.readbyqxmd.com/read/11910198/identification-of-anticoagulant-activities-in-salivary-gland-extracts-of-four-horsefly-species-diptera-tabanidae
#1
M Kazimírová, M Sulanová, M Kozánek, P Takác, M Labuda, P A Nuttall
Anticoagulant activities against the extrinsic and intrinsic coagulation pathways were identified in salivary gland extracts (SGE) prepared from four tabanids (Hybomitra muehlfeldi, Tabanus autumnalis, Haematopota pluvialis, Heptatoma pellucens). All extracts prolonged human plasma clotting time in a dose-dependent manner and inhibited thrombin activity in the chromogenic substrate assay. Horsefly SGE did not inhibit factor Xa. Partial purification of SGE proteins using reversed-phase high-performance liquid chromatography revealed species-specific differences in the elution profiles and range of fractions with anticoagulant activities...
May 2001: Haemostasis
https://www.readbyqxmd.com/read/11910197/lonomia-genus-caterpillar-envenomation-clinical-and-biological-aspects
#2
REVIEW
C L Arocha-Piñango, B Guerrero
Persons who have been in contact with Lonomia achelous or Lonomia obliqua caterpillars present external and internal bleeding and opening of recently healed wounds. Hematological tests show normal platelet count, prolonged prothrombin time, activated partial thromboplastin time and thrombin time, totally corrected by normal plasma. Decreased fibrinogen (Fg), factor (F) V, FXIII, plasminogen and alpha(2)-antiplasmin with increased FVIII: C, von Willebrand factor, Fg degradation products and D dimers. Tissue plasminogen activator, plasminogen activator inhibitor and protein C varied...
May 2001: Haemostasis
https://www.readbyqxmd.com/read/11910196/anticoagulant-venom-and-mammalian-secreted-phospholipases-a-2-protein-versus-phospholipid-dependent-mechanism-of-action
#3
REVIEW
C M Mounier, C Bon, R M Kini
Some venom and mammalian-secreted phospholipases A(2) (sPLA(2)) have been described to exert an anticoagulant effect. This review will discuss and compare phospholipid-dependent versus protein-dependent mechanisms of action of these sPLA(2) on the coagulation cascade. The importance of venom proteins, and of the study of their pharmacological effects, to explore the physiological functions of homologous mammalian proteins is also pointed out.
May 2001: Haemostasis
https://www.readbyqxmd.com/read/11910195/interaction-of-bothrojaracin-with-prothrombin
#4
REVIEW
R B Zingali, M L Bianconi, R Q Monteiro
Bothrojaracin (BJC) is a 27-kD protein from Bothrops jararaca venom that interacts with alpha-thrombin (K(D) = 0.7 nM) through both anion-binding exosites I and II. Recently, it has been shown that BJC interacts with the exosite I precursor (proexosite I) on human prothrombin (K(D) = 75 nM), forming a 1:1 Ca(2+)-independent noncovalent complex with the zymogen. Complex formation was associated with inhibition of zymogen activation by Oxyuranus scutellatus venom. In addition, BJC strongly decreased the prothrombin activation by factor Xa only in the presence of factor Va...
May 2001: Haemostasis
https://www.readbyqxmd.com/read/11910194/protein-c-activators-from-snake-venoms-and-their-diagnostic-use
#5
REVIEW
P M Gempeler-Messina, K Volz, B Bühler, C Müller
Proteinases converting the zymogen protein C (PC) of vertebrates into activated PC have been detected in several snake venoms. Most PC activators have been purified from venom of snake species belonging to the genera of the Agkistrodon complex. Unlike the physiological, thrombin-catalyzed PC activation reaction which requires thrombomodulin as a cofactor, most snake venom activators directly convert the zymogen PC into the catalytically active form which can easily be determined by means of coagulation or chromogenic substrate techniques...
May 2001: Haemostasis
https://www.readbyqxmd.com/read/11910193/effects-of-lopap-on-human-endothelial-cells-and-platelets
#6
A M Chudzinski-Tavassi, M Schattner, M Fritzen, R G Pozner, C V Reis, D Lourenço, M A Lazzari
Severe consumption coagulopathy has been detected in rats after Lopap (a prothrombin activator from Lonomia obliqua caterpillar bristles) infusion and in humans after accidental contact with L. obliqua bristles. However, platelet count and antithrombin (AT) levels were only modestly affected, suggesting that a different form of blood coagulation activation may be involved in this hemorrhagic syndrome. Here we describe that Lopap had no effect on aggregation of washed human platelets induced by several agonists, suggesting that it might not impair platelet function in vivo...
May 2001: Haemostasis
https://www.readbyqxmd.com/read/11910192/molecular-basis-for-the-partition-of-the-essential-functions-of-thrombin-among-snake-venom-serine-proteinases-the-case-of-thrombin-like-enzymes
#7
R C Maroun
Thrombin is a mammalian serine proteinase that plays a prominent role in the maintenance and regulation of hemostasis through its interaction with various substrates and/or ligands. The venoms of several snakes contain glycosylated serine proteinases that have been recognized to possess one or more of the essential activities of thrombin on fibrinogen (Fg) and/or platelets. These proteinases share about 60% sequence identity. One class of snake venom serine proteinases are those known as thrombin-like (TLE), named after their ability to directly clot Fg in order to preferentially produce fibrinopeptide A, fibrinopeptide B or both...
May 2001: Haemostasis
https://www.readbyqxmd.com/read/11910191/factor-v-activation-and-inactivation-by-venom-proteases
#8
REVIEW
J Rosing, J W Govers-Riemslag, L Yukelson, G Tans
Blood coagulation factor V is a single-chain glycoprotein with M(r) = 330,000 which plays an important role in the procoagulant and anticoagulant pathways. Thrombin activates factor V into factor Va, a two-chain molecule which is composed of a heavy (M(r) = 105,000) and a light chain (M(r) = 71,000/74,000). Factor Va accelerates factor Xa-catalysed prothrombin activation more than 1,000-fold and under physiological conditions the cofactor activity of factor Va in prothrombin activation is down-regulated by activated protein C...
May 2001: Haemostasis
https://www.readbyqxmd.com/read/11910190/snake-venom-prothrombin-activators-homologous-to-blood-coagulation-factor-xa
#9
REVIEW
J S Joseph, R M Kini
We have recently determined the complete amino acid sequence of trocarin, a group D prothrombin activator from the venom of Tropidechis carinatus (Australian rough-scaled snake). This proteinase is both functionally and structurally similar to mammalian blood coagulation factor Xa. It shows approximately 70% homology and possesses the characteristic Gla domain, two EGF domains and serine proteinase domain. To examine structure-function relationships, we generated a molecular model of trocarin based on a human factor Xa des-Gla crystal structure (1xka) as template...
May 2001: Haemostasis
https://www.readbyqxmd.com/read/11910189/snake-venom-activators-of-factor-x-an-overview
#10
REVIEW
G Tans, J Rosing
Activators of blood coagulation factor X have been described in the venom of many snake species belonging to the genus Viperidae and Crotalidae as well as from a few Elapid species. Based on the structural and functional properties of purified activating principles, factor X activators are either metalloproteases or serine proteases. The best known activator is RVV-X from Russell's viper (Daboia russelli), a metalloprotease consisting of a heavy chain containing the catalytic domain and two light chains which share homology with C-type lectins and which are thought to exert a regulatory function in the Ca(2+)-dependent activation of factor X...
May 2001: Haemostasis
https://www.readbyqxmd.com/read/11910188/procoagulant-proteins-from-snake-venoms
#11
REVIEW
R M Kini, V S Rao, J S Joseph
Several procoagulant proteins from snake venoms have been isolated and characterized. They are either serine proteinases or metalloproteinases, which activate specific zymogens of coagulation factors and initiate the coagulation cascade. These procoagulant proteins are useful in treating various thrombotic and hemostatic conditions and contribute to our understanding of molecular details in the activation of specific coagulation factors. Recent studies have shown that the prothrombin activators with serine proteinase activity are structurally and functionally similar to mammalian coagulation factors...
May 2001: Haemostasis
https://www.readbyqxmd.com/read/11910187/diagnostic-uses-of-snake-venom
#12
REVIEW
N A Marsh
Snake venom toxins are invaluable for the assay of coagulation factors and for the study of haemostasis generally. Thrombin-like enzymes (SVTLE) are used for fibrinogen and fibrinogen breakdown product assays as well as detecting dysfibrinogenaemias. Since SVTLE are not inhibited by heparin, they can be used for assaying antithrombin III in samples containing heparin. Snake venom prothrombin activators are utilised in prothrombin assays, whilst Russell's viper venom (RVV) can be used to assay clotting factors V, VII, X and lupus anticoagulants (LA)...
May 2001: Haemostasis
https://www.readbyqxmd.com/read/11910186/lebetin-peptides-potent-platelet-aggregation-inhibitors
#13
REVIEW
N Marrakchi, K Mabrouk, I Regaya, S Sarray, M Fathallah, H Rochat, M El Ayeb
Lebetins from Macrovipera lebetina snake venom constitute a new class of inhibitors of platelet aggregation. There are two groups of peptides: lebetin 1 (L1; 11- to 13-mer) and lebetin 2 (L2; 37- to 38-mer). The short lebetins are identical to the N-terminal segments of the longer ones. They inhibit platelet aggregation induced by various agonists (e.g. thrombin, PAF-acether or collagen). The shortest lebetin (11-mer) shows potent inhibition of rabbit (IC(50) = 7 nM) and human (IC(50) = 5 nM) platelets. They prevent collagen-induced thrombocytopenia in rats...
May 2001: Haemostasis
https://www.readbyqxmd.com/read/11910185/viper-venom-components-affecting-angiogenesis
#14
T F Huang, C H Yeh, W B Wu
Angiogenesis is a complex process consisting of the proliferation, migration and differentiation of endothelial cells, and it is essential for the progression of malignant solid tumors. In this report, we examine the effects of disintegrins (e.g. rhodostomin and accutin) and glycoprotein-lb-binding proteins (e.g. agkistin) on each step in angiogenesis using in vitro and in vivo models. Rhodostomin (but not agkistin) inhibited the viability of human umbilical vein endothelial cells (HUVECs) and capillary tube formation of HUVECs...
May 2001: Haemostasis
https://www.readbyqxmd.com/read/11910184/a-novel-snake-venom-disintegrin-that-inhibits-human-ovarian-cancer-dissemination-and-angiogenesis-in-an-orthotopic-nude-mouse-model
#15
F S Markland, K Shieh, Q Zhou, V Golubkov, R P Sherwin, V Richters, R Sposto
OVCAR-5 is a human epithelial carcinoma cell line of the ovary, established from the ascitic fluid of a patient with progressive ovarian adenocarcinoma without prior cytotoxic treatment. The unique growth pattern of ovarian carcinoma makes it an ideal model for examining the anticancer activity of contortrostatin (CN), a homodimeric disintegrin from southern copperhead venom. FACS analysis revealed that OVCAR-5 is integrin alphavbeta3 negative, but alphavbeta5 positive. CN effectively blocks the adhesion of OVCAR-5 cells to several extracellular matrix proteins and inhibits tumor cell invasion through an artificial basement membrane...
May 2001: Haemostasis
https://www.readbyqxmd.com/read/11910183/new-insights-on-disintegrin-receptor-interactions-eristostatin-and-melanoma-cells
#16
M A McLane, M A Kuchar, C Brando, D Santoli, C A Paquette-Straub, M E Miele
Viper venom disintegrins have been used frequently to study the cellular receptors which characterize various types of cells, including platelets, endothelial cells and cancer cells. While the majority of such analyses have pointed to involvement of integrin receptors alphavbeta3, alpha5beta1 or alphaIIbbeta3, this may not always be so. Eristostatin, from Eristocophis macmahoni, is a potent inhibitor of ADP-induced platelet aggregation as well as of human and murine melanoma metastases in mouse model systems...
May 2001: Haemostasis
https://www.readbyqxmd.com/read/11910182/lebecetin-a-c-lectin-protein-from-the-venom-of-macrovipera-lebetina-that-inhibits-platelet-aggregation-and-adhesion-of-cancerous-cells
#17
S Sarray, N Srairi, J Luis, J Marvaldi, M El Ayeb, N Marrakchi
A novel C-lectin protein, lebecetin, was purified and characterized from the venom of Macrovipera lebetina. It is a disulfide-linked heterodimer of 15 and 16 kD. The subunits are homologous to each other and to the other snake venom proteins of the C-type (Ca(2+)-dependent) lectin superfamily. Lebecetin shows a potent inhibitory effect on whole blood and washed platelets induced by different agonists. It inhibits the agglutination of human fixed platelets in the presence of ristocetin. Lebecetin also interferes with the adhesion of IGR39 melanoma and HT29D4 adenocarcinoma cells...
May 2001: Haemostasis
https://www.readbyqxmd.com/read/11910181/the-use-of-snake-venom-toxins-as-tools-to-study-platelet-receptors-for-collagen-and-von-willebrand-factor
#18
REVIEW
R K Andrews, A S Kamiguti, O Berlanga, M Leduc, R D Theakston, S P Watson
A large proportion of the biologically active proteins and peptides present within snake venoms interact with components of the haemostatic system to promote or inhibit the normal sequence of events that lead to clot formation. The venom proteins achieve their effects through interaction with various components of the coagulation cascade, endothelial matrix and platelets. Within the latter group, a number of venom proteins target the interaction of platelets with the major adhesive proteins, von Willebrand factor and collagen...
May 2001: Haemostasis
https://www.readbyqxmd.com/read/11910180/multifunctional-snake-c-type-lectins-affecting-platelets
#19
REVIEW
K J Clemetson, A Navdaev, D Dörmann, X Y Du, J M Clemetson
Snake venoms contain a wide range of components, many of which affect haemostasis by activation or inhibition of platelets or coagulation factors. They can be classified into groups based on structure and mode of action. One group is the snake C-type lectins, so called because of the typical folding which closely resembles that found in classical C-type lectins, such as selectins and mannose-binding proteins. Unlike the classic C-type lectins, those from snakes are generally heterodimeric with two subunits, alpha and beta...
May 2001: Haemostasis
https://www.readbyqxmd.com/read/11910179/alfimeprase-pharmacology-of-a-novel-fibrinolytic-metalloproteinase-for-thrombolysis
#20
REVIEW
C F Toombs
Alfimeprase is a recombinantly produced, truncated form of fibrolase, a known directly fibrinolytic zinc metalloproteinase that was first isolated from the venom of the southern copperhead snake (Agkistrodon contortrix contortrix). Both fibrolase and alfimeprase have been shown to have direct proteolytic activity against the fibrinogen Aalpha chain. In vivo pharmacology studies have shown that thrombolysis with alfimeprase is up to 6 times more rapid than with plasminogen activators. Alfimeprase can be bound and neutralized by serum alpha(2)-macroglobulin, a prevalent mammalian protease inhibitor which is capable of forming a macromolecular complex with alfimeprase...
May 2001: Haemostasis
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