Abstract: The present invention relates to biologically active peptides which specifically inhibit the Factor IX-dependent pathway of blood coagulation. These peptides are based on a specific motif which represents a sequence of Factor VIII (amino acid 1811-1818) involved in binding to activated Factor IX as well as to the intact Factor IX zymogen. Binding of said peptides to Factor IX or activated derivatives thereof effectively inhibits complex assembly with Factor VIII. These peptides thereby specifically interfere in the Factor IX-dependent pathway of thrombin formation, while leaving other haemostatic pathways unaffected. By virtue of this unique specificity, the peptides of this invention are particularly useful in novel pharmaceutical compositions for the treatment of thrombotic disorders.

Abstract: A method for isolating tissue repair promoting substances from human or animal blood, which method comprises collecting the human or animal blood from a single human or animal individual in a first container of a container system comprising at least first and second interconnected containers; centrifuging the container system containing said blood so as to separate the blood in various fractions including a plasma fraction; transferring at least part of the plasma fraction to said second container of the container system; subjecting the plasma fraction in said second container to a low temperature so as to obtain a precipitate comprising tissue repair promoting substances; concentrating said precipitate in said second container so as to obtain a first fraction comprising a major part of the non-precipitated material, and a second fraction comprising at least the major part of the precipitate and a minor part of the non-precipitated material; and separating said second fraction comprising the tissue repair pro

Abstract: The invention provides methods for drying platelets to obtain compositions which are storage stable over a wide range of temperatures and for an extended period of time. The invention also provides compositions obtained thereby and devices for use therein.

Abstract: System and methods treat plasma carrying contaminants and cellular matter that are capable of entraining contaminants. The systems and methods separate cellular matter from the plasma by filtration, thereby removing contaminants entrained within the cellular matter. The system and methods add to the plasma a photoactive material. The systems and methods emit radiation at a selected wavelength into the plasma to activate the photoactive material and thereby eradicate the contaminant that is free of entrainment by cellular matter.

Abstract: A method using diafiltration to prepare a blood product is described. The method removes contaminating plasma proteins from whole blood or blood products. Diafiltration may be used on paraformaldehyde-fixed platelets to remove formaldehyde to undetectable levels, and to suspend the platelets into a formulation buffer suitable for subsequent treatment, such as lyophilization. The manufacturing procedure can be divided into three steps, a first diafiltration, fixation, preferably with paraformaldehyde, and a second diafiltration. In the first step, plasma proteins are removed from fresh or stored platelets or blood cells. The technique is gentle to prevent the activation and aggregation of the platelets. Fixation stabilizes the platelets to withstand freezing, lyophilization and subsequent reconstitution, and also provides a viral and bacterial reduction.

Abstract: A multiple coagulation test system and method for determining an appropriate coagulation promoting substance for administration to a patient as a therapy for improving clotting function in said patient has at least three sample wells. One of the wells is for testing a baseline clotting indicator time of a patient's blood to serve as a control sample. Each of the other wells are for testing clotting indicator times of different coagulation promoting substances when mixed with the patient's blood. The coagulation promoting substances are agents or combination of agents capable of improving clotting function in the patient. An appropriate therapy for improving clotting function in the patient is determined by comparison of the baseline control clotting indicator time with the clotting indicator times of the coagulation promoting substances mixed with the patient's blood. Generally, the agent giving the lowest clotting indicator time is selected as an appropriate treatment for reducing hemorrhaging begun.

Abstract: Antithrombotic materials and methods are provided for the treatment of thrombotic disorders, in which therapeutically effective amounts of BPI protein products are administered.

Abstract: A method is provided for diagnosing Alzheimer's disease using human blood platelets wherein the presence or absence of functioning calcium-dependent potassium channels in blood platelets are determined by employing potassium channel blockers such as apamin or charybdotoxin, the absence of functioning calcium-dependent potassium channels indicating a positive diagnosis for Alzheimer's disease.

Abstract: Product pseudodipeptide of general formula: ##STR1## in which A is: a) under the form: ##STR2## B represent an amine which nitrogen atom which is directly linked to the atom of carbon and chosen among the amines, the imines, the ammoniums,R is an atom of fluorine, a fluoro-alkyl radical, a functional group, an acyl radical, a linear alkyl chain, or an alkenyle or aryl radical,R' is an hydrogen atom, a fluorine atom, an alkyl radical, or fluoro-alkyl radical, andIm is an imidazole or an N-substituted imidazole ring;b) or the form of ##STR3## where R is an atom of hydrogen or a fluoro-alkyl or an acyl radical, or an hydrocarbon radical which can be substituted by one or several functional groups, and R" is a hydrocarbon radical or an acyle radical.

Abstract: The invention provides methods for treating cystic fibrosis and other pathological conditions in mammals using hepatocyte growth factor ("HGF"). The invention also provides articles of manufacture and kits containing HGF.

Abstract: The instant invention relates to a method and the apparatus for collecting a hyperconcentrated platelet product. A fluid containing platelets and other particles flows into a fluid chamber at a flow rate. The flow rate of the fluid is selected to retain the majority of the platelets in the fluid chamber in a saturated bed. The platelets are collected from the fluid chamber without collecting the other particles to form a hyperconcentrated other particle reduced platelet product.

Abstract: Fixed-dried human blood platelets and processes for preparing the same are disclosed. The platelets, upon reconstitution: adhere to thrombogenic surfaces; do not adhere to non-thrombogenic surfaces; undergo shape change (spreading) upon adhering to a thrombogenic surface; adhere to one another to form a hemostatic plug upon adhering to a thrombogenic surface; and release their granular contents. Pharmaceutical formulations containing the same are also disclosed. The platelets are preferably fixed by means of a fixative such as formaldehyde, paraformaldehyde, or glutaraldehyde, or fixed by means of a permanganate fixate. The platelets are preferably dried by lyophilization.

Abstract: Methods of photodecontamination are described which employ phosphate buffered aqueous solutions. Blood products comprising plasma are diluted with these solutions and treated with psoralen.

Abstract: The present invention provides a method for screening candidate agents to identify compounds that modulate the hemostatic system. The method of the invention involves a screening medium comprised of stored whole blood, preferably diluted with buffer, to which unrefrigerated platelets have been added. Candidate agents that may inhibit or activate clot formation or clot lysis are added to the screening medium and suitable compounds are identified. The assay provided is physiologically relevant, rapid, inexpensive and allows for large scale screening of candidate agents.

Abstract: Antithrombotic materials and methods are provided for the treatment of thrombotic disorders, in which therapeutically effective amounts of BPI protein products are administered.

Abstract: A process for the preparation of factor IX from a biological source by chromatography involves prior treatment with ammonium sulfate as a protein precipitant at a concentration of from 1.5-2.3 mol/l.

Abstract: Fixed-dried human blood platelets and processes for preparing them are disclosed. The platelets, upon reconstitution: adhere to thrombogenic surfaces; do not adhere to non-thrombogenic surfaces; undergo shape change (spreading) upon adhering to a thrombogenic surface; adhere to one another to form a hemostatic plug upon adhering to a thrombogenic surface; and release their granular contents. Surgical aids containing such platelets are also disclosed. The platelets are preferably fixed by a fixative such as formaldehyde, paraformaldehyde, or glutaraldehyde, or fixed by a permanganate fixate. The platelets are preferably dried by lyophilization.

Abstract: Methods and compositions for preserving platelets at cryogenic temperatures with retention of hemostatic activity are provided. The compositions include a first agent for inhibiting actin filament severing and a second agent for inhibiting actin polymerization. Contacting the platelets with the first and second agents prior to exposure to cold temperature prevents cold-induced platelet activation.

Abstract: The invention provides methods for treating cystic fibrosis and other pathological conditions in mammals using hepatocyte growth factor ("HGF"). The invention also provides articles of manufacture and kits containing HGF.

Abstract: Compositions of lactoferrin, ovotransferrin or serotransferrin in apo or iron-saturated form are provided which have bacterial anti-invasive properties against Streptococcus pyogenes and Staphylococcus aureus. Methods of treatment of epithelial calls and mucosal membranes are described.

Abstract: A process for reducing degradation of recombinant coagulation factor VIII caused by metal-dependent proteases requiring Zn.sup.2+ for activity or containing Zn.sup.2+ as an integral part of their structure comprises adding an inhibitor of Zn.sup.2+ dependent proteases to a recombinant factor VIII solution. The recombinant factor VIII solution is obtained after harvesting a conditioned medium from a cell culture used for producing the recombinant coagulation factor VIII. The inhibitor is selected from complexing agents with a stronger affinity for the Zn.sup.2+ ion of the protease than for the ion or ions stabilizing the factor VIII molecule, and compounds structurally related to the natural substrate of the protease and containing an electronegative moiety.

Abstract: The subject invention relates to the use of thrombin in a medical procedure in an animal. More specifically, the subject invention relates to such use of thrombin wherein the thrombin is a thrombin blood fraction is autologous to that animal.

Abstract: Autologous fibrinogen and chitosan containing hemostatic adhesive agents having strong hemostatic properties when applied to a bleeding wound or vessel. Fibrinogen is isolated and purified using ammonium sulphate precipitation in slow incremental portions.

Abstract: A simple, inexpensive, physiologically compatible, cryopreservation solution which includes the innocuous components of (i) glycerol, (ii) an alkali metal chloride salt, (iii) a monosaccharide, and (iv) serum albumin.

Abstract: A plasma-buffy coat concentrate that comprises plasma, platelets at a concentration of at least 1.0.times.10.sup.9 cells/ml, and fibrinogen at concentration of at least 5 mg/ml is described. The plasma-buffy coat concentrate can be combined with a fibrinogen activator to form a platelet glue wound sealant. A method for processing blood to produce the plasma-buffy coat concentrate is also provided. The method comprises centrifuging anticoagulated blood to remove red blood cells and produce a plasma-buffy coat mixture. Water is removed from the mixture to produce the plasma-buffy coat concentrate. A fibrinogen activator is mixed with the plasma-buffy coat concentrate to produce a wound sealant, which can then be applied to a wound to facilitate sealing and healing of the wound.

Abstract: The present invention relates to novel pharmaceutical composition for skin diseases, in particular to novel pharmaceutical composition useful for treatment of skin diseases; e.g. burns, wounds, general operative wounds, pernio, decubitus, folliculitis, impetigo, intertrigo, radiation ulcer, acne vulgaris or infectious eczematous dermatitis comprising deproteinized dialysate of calf's blood with tissue regenerative activity and aminoglycoside antibiotic with bacterial infection inhibitory activity as active ingredients.

Abstract: A protein isolated from crude extracts of Hirudo medicinalis is disclosed, which strongly inhibits the binding to collagen of platelets and their subsequent activation, which leads to platelet aggregation and thrombus formation. Additionally the protein prevents binding of von Willebrand factor to collagen. Described is a method for isolation and purification of the protein as well as its use for blocking collagen-stimulated platelet aggregation. The new protein (Brandinin) has a molweight of approximately 15 kD, binds to collagen but has no collagen-cleaving activity. The protein is useful in the prophylaxis, prevention and treatment of thrombotic diseaeses and for coating of blood-contacting materials, rendering them thromboresistant.

Abstract: Fixed-dried human blood platelets and processes for preparing the same are disclosed. The platelets, upon reconstitution: adhere to thrombogenic surfaces; do not adhere to non-thrombogenic surfaces; undergo shape change (spreading) upon adhering to a thrombogenic surface; adhere to one another to form a hemostatic plug upon adhering to a thrombogenic surface; and release their granular contents. Pharmaceutical formulations containing the same are also disclosed. The platelets are preferably fixed by means of a fixative such as formaldehyde, paraformaldehyde, or glutaraldehyde, or fixed by means of a permanganate fixate. The platelets are preferably dried by lyophilization.

Abstract: This invention provides a method for prolonging the preservation of human blood platelets at reduced temperatures. The method uses an inhibitor system that enables blood platelets to maintain their discoid shape and retain their functional integrity during storage. This is accomplished by interrupting normal platelet function during storage, so as to help keep platelets from activating and losing their shape. Before using the platelets in a transfusion, they are returned to their normal functional level by washing the inhibitor system away from the platelets.

Abstract: Intravenous administration of 8-methoxypsoralen is disclosed, and more specifically intravenous administration of 8-methoxypsoralen-blood preparations, including platelets. Random donor platelet bags are treated, stored and pooled prior to transfusion.

Abstract: A method of making a platelet releasate product is disclosed involving performing an assay on a platelet releasate sample for a component of the releasate and forming platelet releasate product by comparing the assay results to a predetermined range of amounts of the component to be contained in the product. A method of treatment of tissue is disclosed involving the topical application of such product.

Abstract: A simple, inexpensive, physiologically compatible, cryopreservation solution which includes the innocuous components of (i) glycerol, (ii) an alkali metal chloride salt, (iii) a monosaccharide, and (iv) serum albumin.

Abstract: The present invention relates to a method for inducing myocardial cell proliferation. It is based, at least in part, on the discovery that adult human myocardial cells may be induced to proliferate in culture by exposure to a platelet freeze/thaw extract. The present invention provides for a method for inducing myocardial cell proliferation in vitro, as well as for myocardial cell cultures produced by this method. In a preferred embodiment, the invention provides for human myocardial cell cultures. The myocardial cell cultures of the invention may be used to study the physiology of cardiac muscle. In addition, they may be used to identify pharmaceutical agents that may be useful in the treatment of heart disease or, alternatively, agents that are cardiotoxic. Furthermore, the cultures of the invention may be used to provide myocardial cells that may be transplanted or implanted in a patient that suffers from a cardiac disorder.

Abstract: A method for isolating tissue repair promoting substances from human or animal blood, which method comprises collecting the human or animal blood from a single human or animal individual in a first container of a container system comprising at least first and second interconnected containers; centrifuging the container system containing the blood so as to separate the blood in various fractions including a plasma fraction; transferring at least part of the plasma fraction to the second container of the container system; subjecting the plasma fraction in the second container to a low temperature so as to obtain a precipitate comprising tissue repair promoting substances; concentrating the precipitate in the second container so as to obtain a first fraction comprising a major part of the non-precipitated material, and a second fraction comprising at least the major part of the precipitate and a minor part of the non-precipitated material; and separating the second fraction comprising the tissue repair promoting

Abstract: A reconstituted platelet membrane vesicle preparation is provided. The preparation, directed at promoting hemostasis, may be prepared from proteins and lipids derived from either synthetic sources or from mammalian platelet membranes. The product may be used for transfusions or may be topically applied. Methods for forming the vesicles and products for storing and dispensing the vesicles also are provided.

Abstract: Methods and compositions for preserving platelets at cryogenic temperatures with retention of hemostatic activity are provided. The compositions include a first agent for inhibiting actin filament severing and a second agent for inhibiting actin polymerization. Contacting the platelets with the first and second agents prior to exposure to cold temperature prevents cold-induced platelet activation.

Abstract: Synthetic-based platelet storage media are provided along with methods of using the media for the storage of platelets for an extended period of time. The synthetic-based media contain phosphate and a substrate for oxidative phosphorylation and for providing buffering in the media upon oxidation selected from the group including pyruvate, butyrate, C.sub.3-8 fatty acid anions, acetate, acetoacetate, acetone, and beta-hydroxybutyrate.

Abstract: This invention provides methods for inactivating pathogenic contaminants in whole blood, plasma, cellular blood components, or in any combination thereof, by adding a phenthiazin-5-ium dye(s) thereto and irradiating said dye-containing composition for an effective length of time with light of wavelengths from 560 to 800 nm or red light, of an effective intensity, whereby the irradiation in conjunction with the dye(s) inactivate substantially all pathogenic contaminants contained therein. The methods of this invention inactivate pathogenic contaminants, such as viruses, bacteria and parasites, without substantially altering the whole blood, plasma, cellular blood components, or combinations thereof, such that they are suitable for transfusion.

Abstract: The invention is a sterile, plasma-free storage medium for blood components including red blood cells and for platelets processed separately or together. The red cell storage medium includes adenine and a physiologically compatible, aqueous electrolyte solution. In one liter of this electrolyte solution there is between about 3.0 grams and about 25.0 grams of dextrose, between about 3.0 grams and about 6.0 grams of sodium citrate, and between about 2.0 grams and about 4.2 grams of sodium bicarbonate. The red cell storage medium is isotonic and has a pH in a range of between about 6.8 and about 7.4. The red cell storage medium is capable of storing and preserving red cells for at least 49 days.

Abstract: The present invention provides a composition and method for improving the storage of platelets and optimizing the viability of stored platelets. The present invention allows platelets to be stored in plasma for extended periods, without the addition of buffer, by adding storage extension additives, which include acetate, pyruvate, acetoacetate, .beta.-hydroxybutyrate, acetone, .alpha.-ketoglutarate, succinate, fumarate, malate, oxaloacetate, C.sub.3-8 fatty acid anions, triose phosphates and mixtures thereof, to a platelet concentrate.

Abstract: The invention is an improved platelet storage method and composition. Medium for the storage of platelets for transfusion comprising acetate or an acetate-like compound and phosphate is disclosed.

Abstract: Methods for inhibiting the attachment of platelets to a site of an injury are provided. The methods involve administering to a subject that has sustained an injury an effective amount of a platelet binding-site agent. Preferred platelet binding-site agents are platelets that are substantially free of platelet substances contained in lysosomes, dense granules or alpha granules.

Abstract: Synthetic media formulations are disclosed for use with blood preparations intended for in vivo use, including synthetic media formulations to be employed in conjunction with the photodecontamination of platelets using 8-methoxypsoralen.

Abstract: A reconstituted platelet membrane vesicle or micellar structure preparation is provided. The preparation, directed at promoting hemostasis, may be prepared from proteins and lipids derived from either synthetic sources or from mammalian platelet membranes. The product may be used for transfusions or may be topically applied. Methods for forming the vesicles or micellar structures and products for storing and dispensing the vesicles or micellar structures also are disclosed.

Abstract: A method is provided for inactivating viral and/or bacterial contamination in blood cellular matter, such as erythrocytes and platelets, or protein fractions. The cells or protein fractions are mixed with chemical sensitizers and irradiated with, for example, UV, visible, gamma or X-ray radiation. In particular, quaternary ammonium or phosphonium substituted, halo-psoralen compounds are described as being useful.

Abstract: The invention provides a method and composition for preserving platelets which is based on the use of a composition which includes apyrase and an antioxidant. Preferred compositions will also include a protease inhibitor and optionally a solvent.

Abstract: The invention is an improved platelet storage method and composition. Medium for the storage of platelets for transfusion comprising acetate or an acetate-like compound and phosphate is disclosed.

Abstract: A multiple coagulation test device has a plurality of tubes, each tube having associated coagulation detection means, and containing a treatment dosage of a coagulation enhancing agent. Whole blood samples are placed in the tubes which are mixed and warmed to 37.degree. C., with the time to coagulation determined. The agent giving the lowest clotting time is selected as the most effective treatment for reducing hemorrhaging within a few minutes and the selected treatment begun. Utilizing the inventive device eliminates the need to use a multiple agent approach, by identifying the most effective course of action.

Abstract: Methods for preserving platelets at temperatures of less than about 15.degree.C. with retention of hemostatic activity are provided. The method uses a first agent for inhibiting actin filament severing and a second agent for inhibiting actin polymerization. Contacting the platelets with the first and second agents prior to exposure to cold temperature prevents cold-induced platelet activation.

Abstract: The present invention provides a composition and method for improving the storage of platelets and optimizing the viability of stored platelets. The present invention allows platelets to be stored in plasma for extended periods, without the addition of buffer, by adding storage extension additives to a platelet concentrate.