Abstract: Matrix metalloproteases (MMPs) play many important roles in normal and pathological remodeling processes including atherothrombotic disease, inflammation, angiogenesis and cancer. This invention relates to the activation of protease-activated receptor-1 (PAR-1) by endogenous platelet MMP-1 collagenase on the surface of platelets. Exposure of platelets to fibrillar collagen converts the surface-bound pro-MMP-1 zymogen to active MMP-1, which promotes aggregation through PAR-1, MMP-1 is shown to cleave the PAR-1 extracellular domain at a novel site, which then strongly activates Rho-GTP signaling pathways, cell shape change and motility, and MAPK signaling. Blockade of MMP-PAR 1 suppresses thrombogenesis under arterial flow conditions and inhibited thrombosis in animals. These studies provide a link between matrix-dependent activation of metalloproteases and platelet-G protein signaling and identify MMP-1/PAR-1 as a new target for the treatment and prevention of arterial thrombosis and other thrombotic diseases.

Abstract: The invention concerns a recombinant CBE gelatin and recombinant gelatins having multimers of the CBEmonomersequence that are of particular use in several applications involving cell attachment such as in cell culture work and applications involving cell cultures of anchor dependent cells and also in a variety of medical applications.

Abstract: The present invention relates to the use of at least one antibody and/or one inhibitor for inhibiting factor XII and preventing the formation and/or the stabilization of three-dimensional thrombi. It also relates to a pharmaceutical formulation and the use of factor XII as an anti-thrombotic target.

Abstract: The present invention provides anti-thrombotic agents, methods for screening for said anti-thrombotics agents and methods of treating thrombotic and other cardiovascular disorders.

Abstract: Disclosed is an adhesive hemostatic agent based on non-blood constituents including DOPA, able to strongly adhere to collagen fibers, and which comprises an antifibrinolytic agent in addition to an esterified atelocollagen which is non-immunogenic and may become positively charged thereon such that the adhesive hemostatic agent has no possibility of mediating particular diseases or viral infections (HIV, HCV, HBV, CMV, etc), unlike conventional agents comprising blood constituents, and readily binds to negatively charged platelets at high adhesive strength, thus inducing quick blood coagulation. Also, provided is a method for preparing the same.

Abstract: This invention relates to pharmaceutical compounds and nutritional supplements that are acetylated derivatives of naturally occurring amino acids and acetylated derivatives of peptides derived from naturally occurring amino acids containing hydroxyl groups. They are as useful as anti-platelet drugs, and as nutritional supplements.

Abstract: The present disclosure provides methods and uses of Slit proteins and nucleic acids for inhibiting platelet coagulation and related disorders. Further provided is a vascular device coated with Slit protein or a cell expressing a Slit protein.

Abstract: Compositions and Methods for the treatment of coagulation disorders using Factor V variants are provided. Preferred disorders include hemophilia A and B.

Abstract: This invention provides an agonist antibody to a human thrombopoietin receptor (alias: human c-Mpl).

Abstract: The present invention relates to the discovery of the Aegyptin gene and Aegyptin protein, a molecule that interacts with collagen and inhibits platelet adhesion, activation and aggregation. Novel biological tools, prophylactics, therapeutics, diagnostics, and methods of use of the foregoing are also disclosed.

Abstract: The present invention describes the design and development of new fibrinogen and fibrinogen derived products with significantly reduced binding to bacteria while retaining normal physiological functions by using modified fibrinogen amino acid sequences. The present invention describes modified sequences of Fg ?-chains and ?-chains with reduced binding to S. aureus ClfA and S. epidermidis SdrG respectively. Modified Fg with the described modifications will not bind other bacterial surface proteins that bind Fg using similar mechanisms as ClfA and SdrG. These new Fg and Fg derived products will therefore have less binding to bacteria and will be advantageous compared to normal human Fg in a number of different settings.

Abstract: The present invention relates to the use of suppressive macrophage or dendritic cells (activated with C-reactive protein or CRP-related compounds), for the treatment of various disease states and conditions associated with immune thrombocytopenic purpura (ITP) and/or systemic lupus erythematosus (SLE), including lupus of the skin (discoid), systemic lupus of the joints, lungs and kidneys, hematological conditions including hemolytic anemia and low lymphocyte counts, lymphadenopathy and CNS effects, including memory loss, seizures and psychosis, among numerous others as otherwise disclosed herein. In another aspect of the invention, the reduction in the likelihood that a patient who is at risk for an outbreak of a disease state or condition associated with systemic lupus erythematosus or ITP will have an outbreak is an additional aspect of the present invention. In the case of ITP, methods of the present invention are used to increase platelet counts in the treated patient.

Abstract: Disclosed are peptides having a cystine knot structural motif and comprising a sequence engineered for specificity against ?IIb?3 integrin, found on platelets, and a method of using the same in anti-thrombotic therapies. The present peptides utilize a cystine knot scaffold derived from modified agouti-related protein or agatoxin, An alternate library screening strategy was used to isolate variants of peptides that selectively bound to ?IIb?3 integrin or to both ?IIb?3 and ?V?3 integrins. Unique consensus sequences were identified within the identified peptides suggesting alternative molecular recognition events that dictate different integrin binding specificities. In addition, the engineered peptides prevented human platelet aggregation in a plasma-based assay and showed high binding affinity for ?IIb?3 integrin.

Abstract: The present invention relates generally to methods and compositions for treating a disease or condition by administering a first therapeutic protocol comprising targeting and delivering solid-phase platelet-dependent vascular occlusion agents, and administering at least one second therapeutic composition or method.

Abstract: The present invention relates, in general, to receptors and to platelet aggregation and, in particular, to a method of inhibiting platelet aggregation using an aptamer that binds to and inhibits the activity of a receptor, such as glycoprotein IIb/IIIa (gpIIb/IIIa), and to aptamers suitable for use in such a method. The invention also relates to antidotes to antiplatelet agents and to methods of using such antidotes to reverse aptamer-induced platelet inhibition. The invention further relates to von Willebrand Factor (VWF) inhibitors, and antidotes therefore, and to methods of using same.

Abstract: The instant invention provides methods and compositions for the treatment, prevention and diagnosis of for example, platelet aggregation or clot formation in a subject. The invention inhibits the activity of decreases the amount of neutrophils in the subject by inhibiting the activity or production of IL-6, interferon-gamma, STAT1, or cathepsin D. The invention addresses decreasing the amount of neutrophils in an attempt to treat subjects that have or are at risk of developing a vascular occlusive disease, an ischemia or reperfusion injury, an acute or chronic inflammatory state, autoimmune disease, myelodysplastic syndrome, tissue injury from surgery or accidental trauma, acute bacterial or viral infection, has undergone a microvascular surgical reconstructive procedure, is receiving granulocyte colony stimulating factor therapy, receiving stem cell therapy, or has sickle cell anemia.

Abstract: Disclosed are peptide ligands for G-protein coupled receptors that are useful for treating disorders associated with G-protein coupled receptor activation.

Abstract: This invention relates to methods of expressing eukaryotic proteins in prokaryotic hosts, particularly eukaryotic proteins that require formation of disulfide bridges for biological activity. Various approaches are used including fusion to thioredoxin, cytoplasmic expression of disulfide isomerases, deficiencies in thioredoxin and/or glutathione reductases, deficiencies in proteases, and the like. The method is applicable to express monomeric and dimeric forms of the eukaryotic protein with biological activity such as monomeric and dimeric forms of a disintegrin or a disintegrin domain. Included are the vectors, host cells expressing the proteins, the expressed proteins and methods of using the proteins.

Abstract: Disclosed herein are compositions, methods, uses, and devices having antiseptic and anticoagulation properties in a mammal. The compositions, methods, uses, and devices are based on a therapeutically effective amount of one or more N-halogenated or N,N-dihalogenated amines, analogues or derivatives thereof, or pharmaceutically acceptable salts and esters. The preferred compound is N-chlorotaurine.

Abstract: The invention relates to Glycoprotein VI (GPVI), its isolation, purification, and methods for recombinant production. Especially, the invention relates to the use of GPVI, preferably recombinant GPVI, in the treatment of disorders and pathological events correlated directly or indirectly to blood coagulation disorders such as thrombotic and cardiovascular diseases. The extracellular recombinant protein can also be used for establishing screening assays to find potential inhibitors of the membrane bound GPVI in order to inhibit binding of thrombocytes and platelets, respectively, to collagen. Changes in GPIV can be used to monitor platelet age and exposure to thrombiotic and cardiovascular diseases.

Abstract: The present invention provides a benzazepine compound that can maintain for a long period of time the blood level of tolvaptan enabling to provide the desired pharmaceutical effects. The benzazepine compound of the present invention is represented by general formula (1) wherein R1 represents a —CO—(CH2)n—COR2 group (wherein n is an integer of 1 to 4, and R2 is (2-1) a hydroxy group; (2-2) a lower alkoxy group optionally substituted with a hydroxy group, a lower alkanoyl group, a lower alkanoyloxy group, a lower alkoxycarbonyloxy group, a cycloalkyloxycarbonyloxy group, or 5-methyl-2-oxo-1,3-dioxo-4-yl; or (2-3) an amino group optionally substituted with a hydroxy-lower alkyl group), or the like.

Abstract: The present invention provides compositions and methods for treating or preventing vascular-associated disorders.

Abstract: Active agents, compositions, and methods for inhibiting and reversing platelet function are provided herein. In particular embodiments, the active agents provided herein inhibit or reverse platelet function. In particular embodiments, the compositions described herein are pharmaceutical formulations. Methods of inhibiting and reversing platelet function are also provided herein. In particular embodiments, methods as described herein include administration of a Sema3E polypeptide. Further, methods of treating pathologic conditions associated with platelet function (i.e., platelet activation) and methods of screening active agent candidates are also provided.

Abstract: The present invention is directed to methods for the prevention, treatment and/or diagnosis of a medical condition, such as sepsis, systemic inflammatory reaction syndrome, and/or thrombosis, for example. In particular, the method employs part or all of the A2 domain of von Willebrand factor. In certain cases, a recombinant A2 domain is utilized for the treatment of sepsis, systemic inflammatory reaction syndrome, and/or thrombosis, for example.

Abstract: This invention relates to collagen-binding synthetic peptidoglycans and engineered collagen matrices comprising a collagen matrix and a collagen-binding synthetic peptidoglycan where the collagen-binding synthetic peptidoglycan can be aberrant or can have amino acid homology with a portion of the amino acid sequence of a protein or a proteoglycan that regulates collagen fibrillogenesis. The invention also relates to kits, compounds, compositions, and engineered graft constructs comprising such collagen-binding synthetic peptidoglycans or engineered collagen matrices and methods for their preparation and use.

Abstract: Provided is a rapamycin analog composition including a crystalline form of a rapamycin analog. The crystal can be a hydrate. dehydrate, solvate, or desolvate.

Abstract: The present invention provides integrin ?IIb?3 specific antibodies and peptides. The antibodies and peptides demonstrate little or no immunoreactivity with other integrins. Methods for inhibiting platelet aggregation using the antibodies and peptides are also provided.

Abstract: Methods and compositions for inhibition of platelet cell aggregation are described. In particular, compositions comprising cell permeant RGT peptides, such as RGT bound to a lipid moiety are provided. Compositions may be used in the treatment and prevention of clot related diseases such as stroke and myocardial infarction.

Abstract: Novel serotonin reuptake inhibitor compounds which are designed to exert serotonin uptake inhibitory activity in the peripheral system while being devoid of CNS activity, and a process of preparing same are disclosed. Further disclosed are pharmaceutical compositions containing same and uses thereof in the treatment of medical conditions associated with peripheral serotonin levels and/or activity, and/or platelet aggregation.