Abstract: A method for ameliorating the effects of hemorrhagic shock in a subject consists of locally administering to the gut of the subject, at a selected time during the period of from about 5 hours before blood loss to about 5 hours after blood loss, a therapeutic amount of a cytokine.

Abstract: Methods and materials for the treatment of human meningococcemia are provided in which therapeutically effective amounts of BPI protein products are administered.

Abstract: Compounds of the formula I ##STR1## are described in which at least one of the substituents R(1), R(2), R(3), R(4) and R(5) is a nitrogen-containing heterocyclic radical. They are outstanding cardiovascular therapeutic agents. They are obtained by reaction of a compound II ##STR2## with guanidine.

Abstract: This invention is directed to a pharmacologically acceptable composition for inhibiting or treating hemorrhagic shock in a mammal. The composition includes a K.sub.ATP inhibitor and a pharmacologically acceptable carrier, with the K.sub.ATP inhibitor being present in an amount sufficient to inhibit or treat hemorrhagic shock in the mammal. The invention is also directed to a method for inhibiting or treating hemorrhagic shock in a mammal. The method includes administering to the mammal an amount of a K.sub.ATP channel inhibitor sufficient to inhibit or treat hemorrhagic shock in the mammal. In a preferred form of the invention, the K.sub.

Abstract: Ortho-substituted benzoic acid derivatives of the formula I ##STR1## in which R.sup.1, R.sup.2 and R.sup.3 have the given meanings, and Q is guanidyl, and also their physiologically harmless salts, exhibit antiarrhythmic properties and act as inhibitors of the cellular Na.sup.+ /H.sup.+ antiporter. In addition, the compounds of the formula I, in which R.sup.1 to R.sup.3 and also Q have the given meanings, are suitable for use as valuable intermediates for the preparation of medicaments, in particular of inhibitors of the cellular Na.sup.+ /H.sup.+ antiporter.

Abstract: A method is provided for reducing an inflammatory response in a mammal comprising administering to a mammal at risk of developing or afflicted with an inflammatory response characterized by substantially elevated levels of IL-1.alpha., IL-1.beta., IL-6, IL-8 and TNF.alpha., an amount of IL-10 effective to substantially lower the levels of such cytokines.

Abstract: Disclosed are compounds, compositions and methods for inhibiting interleukin-1.beta. protease activity, the compounds having the formula A described herein.

Abstract: The pleiotropic effects of TNF alfa in a wide variety of mammalian cell types is decreased and treated by administering glucosaminylmuramyl peptides with D-amino acid residue in a second or third position from the proximal end. New methods for nonspecific oral, vaginal, and topic inhibition is proposed. Inhibition of cytotoxicity of TNF alfa is also achieved.

Abstract: There is disclosed a novel amino alcohol amine derivatives of L-N.sup.6 -(1-iminoethyl)lysine, pharmaceutical compositions containing these novel compounds, and to their use in therapy, in particular their use as nitric oxide synthase inhibitors.

Abstract: A therapeutical method for treating endotoxic shock which comprises administering to a patient in need thereof a (3-phthalidyliden) alkyl ester of carnitine or alkanoyl carnitine, is disclosed.

Abstract: Compositions and methods of making selectively O-desulfated heparin compositions, preferably 6-O-desulfated heparin compositions, wherein the methods permit regulating the degree of 6-O-desulfation. The compositions are useful for treating various diseases, including cancer, angiogenesis, shock, ischemia reperfusion injury, inflammation, and cardiovascular diseases including restenosis.

Abstract: The invention relates to methods and compositions for the prevention or treatment of patients suffering from respiratory distress syndrome and/or sepsis syndrome by administering directly into the lungs small or nicrocrystalline particles or droplets of at least one protease inhibitor alone or with an oxygen metabolite scavenger. The method can also include the treatment in combination with the monitoring of the urine desmosine level of the patients and the use of DNase.

Abstract: A magnesium-taurine compound and its method of synthesis. The compound is synthesized by reacting taurine and magnesium in a 2:1 molar ratio. The resulting mixture is diluted with methanol and the remaining clear filtrate is crystallized from methanol. This compound may be administered orally as a nutritional supplement or may be administered orally or intravenously for the therapeutic or prophylactic treatment of pre-eclampsia/eclampsia and acute cardiac conditions.

Abstract: The present invention is directed to products containing G-CSF and a TNF binding protein and compositions of G-CSF and TNF-BP, and methods of treating and/or preventing septic shock by administering the products and compositions of the invention.

Abstract: The use of dsRNA for use in the reactivation of natural defense systems within human cells, tissues and organs reduced to inadequate function subsequent to injury. Specific treatments for various clinical phases of the biological continuous of an acquired immune deficient state are described. Protection from the toxic effects associated with increased TNF levels is described.

Abstract: The present invention provides compositions and methods for inactivating thrombin bound to fibrin within a thrombus or clot, whereby the ability of clot-bound thrombin to catalytically promote further clot accretion is substantially diminished or eliminated. The compositions and methods of the present invention are particularly useful for preventing thrombosis in the circuit of cardiac bypass apparatus and in patients undergoing renal dialysis, and for treating patients suffering from or at risk of suffering from thrombus-related cardiovascular conditions, such as unstable angina, acute myocardial infarction (heart attack), cerebrovascular accidents (stroke), pulmonary embolism, deep vein thrombosis, arterial thrombosis, etc.

Abstract: Methods and materials for the treatment of humans suffering from hemorrhage due to trauma are provided, in which therapeutically effective amounts of BPI protein products are administered.

Abstract: Disclosed are methods for treatment of humans exposed to bacterial endotoxin in circulation by administration of bactericidal/permeability-increasing (BPI) protein products. Serologically and hematologically verifiable alleviation of endotoxin mediated increases in circulating cytokines, fibrinolysis and coagulation factors and changes in lymphocyte counts are observed upon such treatment. Also observed is alleviation of endotoxin mediated decreases in systemic vascular resistance index (SVRI) and concomitant increases in cardiac index (CI).

Abstract: The present invention is directed to products containing G-CSF and a TNF binding protein and compositions of G-CSF and TNF-BP, and methods of treating and/or preventing septic shock by administering the products and compositions of the invention.

Abstract: The present invention provides compositions and methods for inactivating thrombin bound to fibrin within a thrombus or clot, whereby the ability of clot-bound thrombin to catalytically promote further clot accretion is substantially diminished or eliminated. The compositions and methods of the present invention are particularly useful for preventing thrombosis in the circuit of cardiac bypass apparatus and in patients undergoing renal dialysis, and for treating patients suffering from or at risk of suffering from thrombus-related cardiovascular conditions, such as unstable angina, acute myocardial infarction (heart attack), cerebrovascular accidents (stroke), pulmonary embolism, deep vein thrombosis, arterial thrombosis, etc.

Abstract: 2,5-Diaryl tetrahydrofurans, 2,5-diaryl tetrahydrothiophenes, 1,3-diaryl cyclopentanes are disclosed that reduce the chemotaxis and respiratory burst leading to the formation of damaging oxygen radicals of polymorphonuclear leukocytes during an inflammatory or immune response. The compounds exhibit this biological activity by acting as PAF receptor antagonists, by inhibiting the enzyme 5-lipoxygenase, or by exhibiting dual activity, i.e., by acting as both a PAF receptor antagonist and inhibitor of 5-lipoxygenase. Also disclosed is a method to treat disorders mediated by PAF and/or leukotrienes that includes administering an effective amount of one or more of the above-identified compounds or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable carrier, to a patient in need of such therapy.

Abstract: Compounds and methods of making them having the following formula are described which bind to selectin receptors and thus modulate the course of inflammation, cancer and related diseases by modulating cell-cell adhesion events: ##STR1## wherein each R.sup.1 is independently H or lower alkyl (1-4C); R.sup.2 is H, OH or lower alkyl (1-4C), or a lipophilic group such as a higher alkyl group (5-15C), alkylaryl or one or more additional saccharide residues;R.sup.3 is a negatively charged moiety including SO.sub.4.sup.2-, PO.sub.4.sup.2-, or related group;Y is H or lower alkyl (1-4C); andX is H or --CHR.sup.4 (CHOR.sup.1).sub.2 CHR.sup.5 OR.sup.1 wherein R.sup.4 and R.sup.5 are each independently H, lower alkyl (1-4C), or taken together result in a five- or six-membered ring optionally containing a heteroatom selected from the group consisting of O, S, and NR.sup.1 ;said five- or six-membered ring optionally substituted with one substituent selected from the group consisting of R.sup.1, CH.sub.2 OR.sup.1, OR.sup.

Abstract: The present invention is directed to a new class of compound which are useful as inhibitors of the biosynthesis of nitric oxide.

Abstract: This invention provides a nitric oxide synthesis inhibitor composition comprising, as an active ingredient, at least one member of the group consisting of various phenanthrene derivatives, typically represented by the following general formula (1), and salts thereof. ##STR1## The nitric oxide synthesis inhibitor composition of this invention is useful for the prophylaxis and therapy of nitric oxide-associated diseases such as endotoxin shock.

Abstract: Coenzyme A-independent transacylase is required for the release of free arachidonic acid, and the production of arachidonic acid metabolites and platelet activation factor. Blocking of this enzyme inhibits the production of these inflammatory mediators and will be of therapeutic utility in a broad range of allergic and inflammatory diseases and disorders. Compounds are described herein which inhibit the action of CoA-IT and are therefore useful in the treatment of disease states caused thereby.

Abstract: Disclosed are methods for treatment of humans exposed to bacterial endotoxin in circulation by administration of bactericidal/permeability-increasing (BPI) protein products. Serologically and hematologically verifiable alleviation of endotoxin mediated increases in circulating cytokines, fibrinolysis and coagulation factors and changes in lymphocyte counts are observed upon such treatment. Also observed is alleviation of endotoxin mediated decreases in systemic vascular resistance index (SVRI) and concomitant increases in cardiac index (CI).

Abstract: There is disclosed compounds and pharmaceutical compositions that are a resolved R or S (preferably R) enantiomer of an .omega.-1 alcohol of a straight chain alkyl (C.sub.5-8) substituted at the 1-position of 3,7-disubstituted xanthine. The inventive compounds are effective in modulating cellular response to external or in situ primary stimuli, as well as to specific modes of administration of such compounds in effective amounts.

Abstract: A method of treating hypovolemic shock and related shock syndromes by the administration of substantially non-anticoagulant heparinoids without the hemorrhaging problems generally associated with heparin; such syndromes include degradation of the microvascular structure, immune and gastrointestinal tract dysfunction, and multiple organ failure.

Abstract: A method of treating a PAF-mediated pathology or for treating or preventing psoriasis, nephritis, asthma, inflammation or shock by administering an effective amount of a PAF antagonist of the formula ##STR1## wherein R.sup.1 and R.sup.2 are each --R.sup.5, --CH.dbd.CH--R.sup.5 or --C.tbd.C--R.sup.5 ; R.sup.5 is an unsubstituted or substituted C.sub.6 -C.sub.14 carbocyclic aryl of an aromatic heterocyclic having from 5 to 14 ring atoms, of which from 1 to 5 are hetero-atoms selected from the group consisting of nitrogen, oxygen and sulfur, the heterocyclic group being unsubstituted or substituted; R.sup.3 is hydrogen, a C.sub.1 -C.sub.6 alkyl, cyano, or --R.sup.5 ; X is oxygen or sulfur; A is a 1,4-piperazin-1,4-diyl or a 1,4-homopiperazin-1,4-diyl; B is a C.sub.1 -C.sub.6 alkylene, carbonyl, thiocarbonyl, sulfinyl or sulfonyl; and R.sup.4 is an unsubstituted or substituted phenyl group.

Abstract: The use of IGF-II for preparing a medicament for the regeneration of muscle tissue; and methods for medical treatment for the purpose of regenerating muscle tissue, for minimizing scar formation during healing of a wound or for preventing undesired tissue adhesion after injury, such as after surgery.

Abstract: A method of treating a mammal exposed to endotoxin in order to reduce the detrimental effects of said endotoxin, comprising administering to said mammal a therapeutically effective amount of a 2-halo-adenosine nucleotide analog. 2-Cloro-ATP is the preferred species of the 2-halo-adenosine nucleotide. The nucleotide used in this treatment inhibits lipo-polysaccharide-induced GTPase activity.

Abstract: Administration of metabotropic glutamate receptor agonists protect neuronal cells from death from cerebral ischemia. Examples of agents are L(+)-2-amino-4-phosphonobutyric acid, trans-amino cyclopentane dicarboxylic acid, (1S,3R)-amino cyclopentane dicarboxylic acid and quisqualic acid.

Abstract: Compositions and methods for prevention of adhesion formation, whereby an effective amount of at least one compound selected from dipyridamole and analogs thereof is administered as active agent for a period of time sufficient to permit tissue repair. The active agent is preferably administered in conjunction with a delivery vehicle (e.g., microcapsules, microspheres, lipid-based systems, viscous instillates and absorbable mechanical barriers) useful for maintaining local concentrations of the compound at an effective level.

Abstract: A method of treating mammals to reduce the deleterious effects of endotoxin and endotoxic shock mediators comprising administering a therapeutic amount of a 2-alkylthio-adenosine-5'-nucleotide. The preferred compound is 2-methylthio-adenosine-5'-triphosphate. The nucleotide used in this treatment inhibits lipopolysaccharide-induced GTPase activity.

Abstract: The present invention relates to a method for enhancing white blood cell functioning and metabolism on a mucosal surface of a mammal. The present invention also relates to a method for treating or preventing a condition in a mammal caused by the presence of a disease-causing agent on a mucosal surface or a cutaneous surface wherein the disease-causing agent can be diminished by the actions of the white blood cells. The present invention yet also relates to a method for healing a wound of a mucosal or cutaneous surface. The present invention also relates to compositions for use in such methods.

Abstract: A method is provided for treatment of neuronal insult, such as caused by lack of oxygen, which neurons are prone to Parkinsonian degeneration by administering an ATP-sensitive potassium channel blocker, such as a sulfonyl urea, for example, tolbutamide.

Abstract: This invention discloses a rapid-diffusion injectable formulation, comprising disulfiram or a suitable salt or analog of disulfiram. Unlike slow-release injectable formulations designed to ensure that chronic alcoholics have significant quantities of disulfiram in their blood at all time, the rapid-diffusion injectable formulation disclosed herein is designed to reduce the hypoxic or ischemic damage caused by crisis events such as stroke, heart attack, cardiac arrest, or asphyxiation. A rapid-diffusion injectable formulation can contain disulfiram mixed with water, an organic compound having a plurality of hydroxyl groups (such as pharmaceutically acceptable glycols or polysaccharides; propylene glycol, dextrans, and cyclodextrins are often used for such purposes), and a buffer.

Abstract: Methods for treatment of free-radical-mediated tissue injury, particularly sepsis, are provided wherein compositions containing at least one keto analog of a branched-chain amino acid are administered. The composition is administered orally or parenterally, preferably in frequent or continuous dosages. Preferred forms of the keto analogs are their ornithine, arginine, or sodium salts.

Abstract: A treatment modality for infectious diseases and pulmonary conditions that result from the inflammatory responses by tissues to infections by microorganisms, including but not limited to viruses, retroviruses, bacteria, or other microorganisms, or toxins that arise from microorganisms comprises administering an effective amount of histidine to the affected subject to combat the disease or the distress condition resulting therefrom.

Abstract: A therapeutic process for treating septic shock comprising the administration of a polyhydroxy-substituted benzamide or phenylacetamide derivative to a human suffering from, or in danger of contracting, septic shock.

Abstract: The present invention is a method of treating hypotension and shock using select ornithine or N.sup.G -arginine derivatives.

Abstract: The invention provides a physiologically acceptable solution for treating circulatory shock in mammals which is hyperosmotic as compared to blood plasma. The solution contains a reabsorbable solute and sodium salt in a concentration having an osmolarity in excess of about 1000 mOsms. The physiologically acceptable solution can be easily administered by rapid infusion of 4-6 ml/kg body weight and results in rapid normalization of circulatory function.

Abstract: A method of inhibiting tissue damage in warm blooded animals related to reperfusion of tissues after extended periods of ischemia is presented. The method comprises treatment prior to a planned ischemic event or up to six hours after an unplanned ischemic event with an effective amount of monophosphoryl lipid A or 3-deacylated monophosphoryl lipid A. Pharmaceutical compositions for the treatment are also disclosed.

Abstract: An anti-hypotensive formulation comprising an essentially arginine-free or low arginine (less than about 0.1%, most preferably, about 0.01%) containing mixture of amino acids is provided. The invention in particular embodiments of the anti-hypotensive formulation includes ornithine, citrulline or both. A method for prophylaxis and treatment of systemic hypotension in an animal is provided. Most particularly, a method for treating hypotension caused by nitric oxide synthesis through administering a low or essentially arginine-free parenteral formulation to an animal, so as to reduce or eliminate nitric oxide synthesis is described. A method for treating an animal in septic shock is also disclosed, comprising administering to the animal an anti-hypotensive formulation comprising a mixture of amino acids, which is essentially arginine free.

Abstract: A method is provided for treatment of neuronal insult, such as caused by lack of oxygen, which neurons are prone to Parkinsonian degeneration by administering an ATP-sensitive potassium channel blocker, such as a sulfonyl urea, for example, tolbutamide.

Abstract: A method of preparing TPN solutions, which is particularly well adaptable to computerized control, has been developed. These methods can assist the pharmacist or physician in the preparation of three-in-one TPN solutions containing lipid, dextrose and amino acids. The method includes a series of criteria for concentrations of lipid, dextrose, amino acids, and ions as well as eliminating the possibility of certain deleterious interactions.

Abstract: The present invention provides compositions and methods for decreasing tissue breakdown in mammals. Specifically, tissue breakdown in a mammal can be decreased by the administration of composition, wherein said composition comprises from about 35% to 50% essential amino acids of which from about 18% to 30% are branched chain amino acids, and from about 50% to 65% non-essential amino acids, wherein the non-essential amino acids comprise from about 5% to 15% ALA and from about 15% to 45% GLN. In addition, the present invention provides methods of preparing compositions which are capable of meeting the specific metabolic needs of a patient experiencing catabolic tissue breakdown.

Abstract: New N,N-di-alkyl- or alkenyl-substituted derivatives of oxamic acid of which the two alkyl or alkenyl groups are different from each other are now produced and found to exhibit the cerebral protective effect against cerebral anoxia in the brain of a mammalian animal, including human, and to be useful as an agent for improving or ameliorating the damaged or disturbed functions of the brain. Some known N,N-di-alkyl-substituted derivatives of oxamic acid or which the two alkyl groups are identical to each other are now also found to have similar, cerebral protective effect against cerebral anoxia and to be useful as an agent for improving the damaged functions of the brain.

Abstract: A liquid nutritional product for trauma and surgery patients has a caloric density of about 1.2 to 1.5 Kcal/mL and a calorie to nitrogen ratio of about 112:1 to 145:1. A portion of the protein system comprises partially digested protein, and supplemental L-arginine provides about 1-3% of the total calories in the product. The lipid system has a ratio of linoleic acid to alpha linoleic acid in the range of about 3.5:1 to about 5.5:1.

Abstract: An agent and treatment for a subject susceptible to septic shock. The subject is treated with a PKC inhibitor, preferably wit a PKC inhibitor selected from the group consisting of lipid analogues. Preferred among the lipid analogues are sphingosine and its analogues. The inhibitors of this invention are administered, preferably by infusion in a suitable pharmaceutical carrier, in a range of 0.1 to 50 mg/Kg body weight preferably in the range of 0.5 to 25 mg/Kg body weight and most preferably in the range of 1 to 5 mg/Kg body weight.