Abstract: The present invention provides methods and compositions for promoting healing of damaged tissue that result in an increased level of nitric oxide in the vicinity of the damaged tissue. Also provided are methods and compositions for inhibiting unwanted wound healing by inhibiting the activity of nitric oxide in the tissue.

Abstract: The invention concerns the association of an antagonist of &agr;-adrenergic receptors, for instance yohimbine, and a nitrogen monoxide donor, for instance arginine, with synergistic effect and useful for fighting against female sexual dysfunction.

Abstract: This invention provides methods of preventing neurotoxicity by activated microglia. A method of treating a medical condition in a subject is provided, wherein said condition is affected by the presence of neurotoxins such as peroxynitrite or TNF-&agr;, said method comprising administering to the subject a compound that decomposes peroxynitrite or inhibits TNF-&agr; secretion but does not affect normal activity of microglia, wherein the decomposition of peroxynitrite alone is sufficient to alleviate the pathology of said condition.

Abstract: The present invention relates to anti-adhesion barriers which prevents an adhesion between tissues at an operated legion and have various shapes, comprising sodium carboxymethyl cellulose (NaCMC) and gellan gum in 1:(0.1˜10) of weight ratio.

Abstract: A method and a pharmaceutical composition for inhibiting premature rupture of the fetal membranes, ripening of the uterine cervix and preterm labor of female mammals including human. The method includes the step of administering compounds for reversing at least two biochemical conditions being associated with the above processes. The pharmaceutical composition includes compounds for reversing at least two biochemical conditions being associated with the above processes.

Abstract: Inhalation of low levels of nitric oxide can rapidly and safely decrease pulmonary hypertension in mammals. Precise delivery of nitric oxide at therapeutic levels of 20 to 100 ppm and inhibition of reaction of nitric oxide with oxygen to form toxic impurities such as nitrogen dioxide can provide effective inhalation therapy for pulmonary hypertension.

Abstract: A two-part disinfecting systems, as well as disinfecting compositions and methods for making and using the same. The two-part disinfecting system contains a first part and a second part adapted to be mixed to yield an aqueous disinfecting composition, wherein the first part comprises a chlorite and the second part comprises an acid and an optional oxidizable colorant, and wherein the first part, the second part, or both the first and second parts comprise an alpha olefin sulfonate.

Abstract: A method is provided for enhancing the solubility of an ionizable compound in a lipophilic medium by admixing the compound with an effective solubility-enhancing amount of an N,N-dinitramide salt. The ionizable compound, upon ionization, gives rise to a biologically active cationic species that ionically associates with the N,N-dinitramide anion N(NO2)2− following admixture with the N,N-dinitramide salt. The biologically active cationic species may be a pharmacologically active cation, in which case the method is useful for enhancing the penetration of the blood-brain barrier by the pharmacologically active cation. In other embodiments, the ionizable compounds are medical imaging or diagnostic agents, or agricultural agents such as pesticides. Salts of biologically active cations and N,N-dinitramide ion are also provided as novel compositions of matter.

Abstract: Pharmaceutical compositions for the therapy and the prevention of ulcer and dyspepsia relapses comprising as essential components the following components a) and b): component a): one or more components selected from the conventional anti-ulcer products; component b): organic compounds containing the —ONO2 function, or inorganic compounds containing the —NO group, characterized in that they are NO nitric oxide donors.

Abstract: An oxidizing species is described herein as a reaction product through an in situ preparation combining a protonizable phosphorus or sulfur compound, and a halide source at controlled proportions in an aqueous, non-aqueous, gel, aerosol, solid-phase or powdered media. The oxidizing species can be used to reduce microbial and viral populations on a surface or object or in a body or stream of water. The invention thus finds applications as a bleach, sanitizer, oxidant, or in any other application in which an oxidizing agent can be beneficially used alone or in a formulation.

Abstract: The present invention provides a method of administration of an agent which acts to remodel neuronal or vascular pathways for the long term management of sexual dysfunction in both males and females. In a preferred embodiment, the invention provides a method of ameliorating or reversing pathogenic vascular degradative modeling in the ilio-hypogastric-pudendal arterial bed and genitalia comprising administering to a human patient in need of such treatment a therapeutically effective amount of an anti-pressor agent. The anti-pressor agent comprises one or more compounds selected from the therapeutic classes of direct vasodilators such as hydralazine and NO donors, ACE inhibitors, angiotensin-II receptor antagonists, &agr;1-adrenergic receptor antagonists, &bgr;-adrenergic receptor antagonists, calcium channel blockers, and phosphodiesterase inhibitors.

Abstract: Restenosis is inhibited through local delivery of anti-restenotic agents including angiotensin converting enzyme inhibitors; nicotine receptor agonists, agents that increase concentrations of nitric oxide, anti-angiogenic agents, agonists of the TGF-beta receptor; death domain receptor ligands; and thrombin inhibitors. In one embodiment of the invention, the localized delivery is effected through the use of a stent modified for delivery of the agent at the site of injury from balloon angioplasty.

Abstract: A new topical drug (ointment or eye drop) for treating glaucoma or ocular hypertension in a patient, which comprises a mixture of a nitric oxide (NO) donor such as nitrovasodilators like minoxidil, nitroglycerin, L-arginine, isosorbide dinitrate, or nitroprusside, and a cyclic guanosine 3′,5′-monophosphate (cGMP) specific phosphodiesterase type 5 (PDE5) inhibitor such as sildenafil citrate (ViagraRTM) in an ophthalmologically acceptable solution mix. In this manner there will be increased blood circulation to the optic nerve and the ocular hypotensive effect of the combined compounds is enhanced synergistically.

Abstract: The present invention relates to methods for prevention and/or treatment of diseases or conditions caused by deficiency in the adult isoform of a given protein wherein said method comprises administering to a patient in need thereof a composition containing NO or at least one compound able to release, induce and/or promote NO formation in cells, said administration resulting in augmenting or restoring the production of the fetal isoform of said protein in said patient.

Abstract: The invention provides a method and compositions for controlling food borne enteric bacterial pathogens in animals. Populations of enteropathogenic bacteria may be substantially reduced or eliminated by treatment of animals with an effective amount of the compound Xm(ClO3)n, wherein X is a cationic moiety and m and n are independently selected from integers necessary to provide a net valency of 0. The compounds may be administered orally, providing a reduction in the populations of the enteropathogenic bacteria in the alimentary tract of the animal, or they may be applied externally onto the animal to reduce the populations of any such bacteria which may be present as contaminants on the surface of the animal. The method and compositions are particularly useful for the control of Salmonella species, enteropathogenic Escherichia coli, and Clostridia species.

Abstract: A sanitizing composition comprising at least one aliphatic short chain antimicrobially effective C5 to C14 fatty acid or mixture thereof, at least one carboxylic weak acid and a strong mineral acid which may be nitric or a mixture of nitric and phosphoric acids.

Abstract: There is provided a method of promoting neurogenesis by administering a therapeutic amount of a nitric oxide donor compound to a patient in need of neurogenesis promotion. Also provided is a compound for providing neurogenesis having an effective amount of a nitric oxide donor sufficient to promote neurogenesis. A nitric oxide compound for promoting neurogenesis is also provided. Further, a method of augmenting the production of brain cells and facilitating cellular structural and receptor changes by administering an effective amount of a nitric oxide donor compound to a site in need of augmentation is provided. There is provided a method of increasing both neurological and cognitive function by administering an effective amount of a nitric oxide donor compound to a patient.

Abstract: The present invention provides a dosage form for the treatment of bacterial, viral or fungal conditions which comprises, a pharmaceutically acceptable acidifying agent in an amount sufficient to reduce the pH at an environment of use to below pH4, and a pharmaceutically acceptable source of nitrite ions or a nitrate precursor therefor; wherein said acidifying agent and said source of nitrite ions or nitrate precursor are separately disposed in respective pharmaceutically acceptable carriers for admixture at the intended environment of use to release NO or NO2 ions.

Abstract: The present invention provides a dosage form for the treatment of bacterial, viral or fungal conditions which comprises, a pharmaceutically acceptable acidifying agent in an amount sufficient to reduce the pH at an environment of use to below pH4, and a pharmaceutically acceptable source of nitrite ions or a nitrate precursor therefor; wherein said acidifying agent and said source of nitrite ions or nitrate precursor are separately disposed in respective pharmaceutically acceptable carriers for admixture at the intended environment of use to release NO or NO2 ions.

Abstract: A wound dressing is provided that is formed in situ on the wound by spray application of a composition including a composition that gels in situ to form a hydrogel. The composition preferably includes macromers having water soluble regions and crosslinkable regions. Compositions for making a hydrogel wound dressing are also provided.

Abstract: Methods are provided for delivering nitric oxide to the vascular tissue of a patient to inhibit or prevent restenosis or improve vascular function following various surgical procedures or associated with various NO-related conditions. The disclosed methods comprise contacting the vascular tissue of a patient with a medical device coated with a coating comprising nitric oxide associated with and releaseable from a polyurea network formed from the reaction on said medical device of a polyisocyanate; an amine donor and/or hydroxyl donor; an isocyanatosilane adduct having terminal isocyanate groups and at least one hydrolyzable alkoxy group bonded to silicon; and optionally a polymer selected from the group consisting of polyethylene oxide, polyvinyl pyrrolidone, polyvinyl alcohol, polyethylene glycol, and polyacrylic acid.

Abstract: The use of acidified nitrate as an agent to produce local production of nitrate oxide at the skin surface is described in the treatment of peripheral ischaemia and associated conditions. The dosage form may be in any pharmaceutically acceptable carrier means and comprises an acidifying agent adapted to reduce the pH at the environment. A barrier consisting of a membrane allows diffusions of the nitrate ions while preventing direct contact of the skin and acidifying agent. Amongst the many potential applications for the invention is the management of chronic skin wounds, peripheral ischaemia conditions such as Raynaud's phenomenon. Compositions and methods of use for these applications are described.

Abstract: A polymeric composition capable of releasing nitric oxide under physiological conditions which includes a biopolymer, such as a peptide, polypeptide, protein, oligonucleotide or nucleic acid, to which is bound a nitric oxide-releasing N2O2− functional group; pharmaceutical compositions comprising the polymeric composition; and methods of treating biological disorders in which dosage with nitric oxide is therapeutic.

Abstract: A preparation is disclosed for producing enhanced blood flow in tissue thus causing beneficial effects such as promoting hair growth on scalp tissuelacking sufficient hair, restoring normal sexual function in males with erectile dysfunction. Specifically, this is a preparation which provides local delivery of the amino acid L-arginine, an important biological precursor to the main substance which is responsible for relaxation of blood vessels permitting enhancement of blood flow. In the preferred embodiments, the L-arginine is provided so that it can be topically applied to the scalp or penis. The preparation also contains an agent which aids in the transfer of L-arginine into the tissue. In the preferred embodiments this agent overcomes the resistance to transfer caused by the high charge density of L-arginine. In the preferred embodiments this means is high ionic strength created by addition of choline chloride, magnesium chloride and sodium chloride.

Abstract: A disinfecting composition which is bactericidal and effective to kill yeast includes (a) at least one a monocarboxylic acid of formula R—COOH, in which R a saturated or unsaturated, straight- or branched-chain alkyl radical comprising from 6 to 12 carbon atoms; (b) a strong inorganic acid; (c) at least one organic acid of formula R′CH2—CO2H, in which R′ is H or OH; (d) at least one anionic surfactant; (e) at least one solubilizing agent consisting of a compound of formula R″O(CH2CH2O)x—H, in which R″ represents a C2 to C6 alkyl radical, x represents an integer from 1 to 3; and (f) water.

Abstract: A method for protecting a ground plot of plants, a hydroponic system of plants, and the like from fungal infection by the application of a solution of nitrates to the plants, ground surface and other associated structures present on which fungus spores may be located in order to inhibit fungus spore germination upon the occurrence of conditions of darkness and humidity favorable therefor.

Abstract: A dry composition of an ionophore antibiotic such as monensin comprising from 10 to 95% (when expressed as the sodium salt) of at least one crystalline ionophore antibiotic, from 0 to 10% antifoam agent(s), from 0.

Abstract: A method of treating liquid animal manure comprising contacting a manure slurry with a treatment composition comprising a treatment effective amount of AlCl3.nH2O or Al(NO3)3.mH2O, or the residue of AlCl3.nH2O or Al(NO3)3.mH2O, to form a resulting slurry, wherein n is from 0 to 10, and m is from 0 to 12. The treatment effective amount is effective to reduce phosphorus solubility in the manure; reduce phosphorus runoff and/or phosphorus leaching from fields fertilized with manure; inhibit ammonia volatilization from the manure; flocculate solids in the manure; reduce pathogens in the manure; increase the nitrogen content in the manure; and/or reduce acid rain and PM-10s associated with the manure.

Abstract: Wound healing is impaired in many diabetics, who suffer increased risk of chronic foot ulceration and amputation. Diabetic patients with poor healing ability were found to possess significantly lower fasting urinary nitrate levels than diabetic patients with normal healing ability or non-diabetic controls, implicating decreased endogenous nitric oxide activity as the mediator of diabetes-impaired wound healing. Methods and kits are provided for predicting the wound healing ability of diabetic patients and patients with venous stasis ulceration or another disease or condition characterized by chronically impaired cutaneous wound healing in some patients based on the levels of nitric oxide related products such as nitrate or nitrite in urine or other specimens. Methods are also provided for treating non-wound healing patients and monitoring diabetic ulcer treatment.

Abstract: The present intention provides superoxygenating compositions that comprise hemoglobin and guanosine 3′:5′-cyclic monophosphate (cyclic GMP) generating compounds, and methods for treatment of diseases or medical conditions which utilize the superoxygenating compositions as biocolloids, i.e. hemodiluents, blood substitutes, plasma expanders, or resuscitative fluids. The cardiac output-increasing compositions comprise a simple mixture of hemoglobin and the cyclic GMP generating compounds or hemoglobin physically or chemically coupled to the cyclic GMP generating compounds. The invention also provides time-controlled superoxygenating compositions of hemoglobin and cyclic GMP generating compounds that would be used for treatment of specific diseases or medical conditions requiring time-dependent use of biocolloids, i.e. hemodiluents, blood substitutes, plasma expanders, or resuscitative fluids.

Abstract: A method of treating pulmonary hypertension in a subject in need of such treatment comprises inhibiting EMAP II activity in the subject by an amount effective to treat the pulmonary hypertension in the subject (e.g., in the lungs and more particularly in the pulmonary vasculature). Pharmaceutical formulations useful for carrying out such methods (e.g., an antibody that specifically binds to EMAP II in a pharmaceutically acceptable carrier) and screening techniques useful for identifying additional compounds that can be used for carrying out such methods are also disclosed.

Abstract: Compositions and methods of the topical treatment of equine laminitis are disclosed. In particular, combinations of a fast acting nitric oxide (NO) donor, a sustained acting NO donor and an NSAID mixed in a lipid-based carrier are described. The application of such combinations to the affected areas, e.g., the hoofs and surrounding tissues, of an equine afflicted with laminitis provides relief from the debilitating effects of this painful, often life-threatening condition.

Abstract: A method for treating congestive heart failure (CHF) has been developed that restores kidney renal functions by artificial vasodilation of at least one kidney. A vasodilator drug is locally delivered to the kidney via a kidney perfusion catheter. The drug can be mixed with the patient's blood, saline or other suitable solvent and the mixture directly applied to the kidney through the catheter. The restoration of kidney function assists the heart by removing excess fluid, urine and toxin from the patient, and by normalizing the patient's renin-angiotensin system and other neurohormonal substances. The method is applicable to treat chronic and acute CHF.

Abstract: Pulmonary disorders in which the GSNO pool or glutathione pool in the lung is depleted and where reactive oxygen species in lung are increased, are treated by delivering into the lung as a gas, agent causing repletion or increase of the GSNO pool or protection against toxicity and does so independently of reaction with oxygen. Agents include ethyl nitrite, NOCl, NOBr, NOF, NOCN, N2O3, HNO, and H2S. Optionally, N-acetylcysteine, ascorbate, H2S or HNO is administered in addition to other GSNO repleting agent to potentiate the effect of said agent.

Abstract: Biocompatible metallic medical devices having silanized surfaces coupled to nucleophile residues that release sustained, therapeutic amounts of nitric oxide to specific sites within a mammalian body are provided. Additionally, the biocompatible metallic medical devices can also be provided with anti-thrombogenic, lubricious coatings that release sustained, therapeutic amounts of nitric oxide. Moreover, the silanized metallic devices are surprisingly durable when exposed to harsh chemical methods often needed to bind nitric oxide-releasing functional groups to nucleophile residues. Furthermore, methods are provided for producing stable, silanized, sustained nitric oxide-releasing metallic medical devices.

Abstract: Paraquat has been found to accept electrons from nitric oxide synthase (NOS) whereupon the reduced paraquat generates toxic O2− and prevents NOS from giving electrons to arginine and thereby inhibits NO production. This is generalized for compounds with a redox potential greater than nitric oxide synthase. The compounds inhibit nitric oxide synthase and kill cells including NOS by generating O2− and also by depriving the cells of the NO which they need. Applications include treating paraquat-induced injury and pathologically proliferating cells (tumors, restenosis benign prostatic hypertrophy, pulmonary hypertension, infective pathogens).

Abstract: Metal amino acid chelates for animals are beneficial for facilitating and promoting growth by increasing desired metallic ion uptake. The present invention is directed to a process for providing an animal fed additive by preparing metal amino acid chelates, and the metal amino acid chelate growth facilitator, promoter and enhancer prepared by the process.

Abstract: The present invention provides methods and compositions for promoting healing of damaged tissue that result in an increased level of nitric oxide in the vicinity of the damaged tissues. Also provided are methods and compositions for inhibiting unwanted wound healing by inhibiting the activity of nitric oxide in the tissue.

Abstract: A method is disclosed for treating and preventing diseases, wherein at least one of the causes of the disease is .beta.-amyloid peptide induced change in free radical production resulting in vascular endothelial dysfunction and vasoactivity, by antagonizing vascular free radicals in excess of functional equilibrium.

Abstract: A stabilized two-part disinfecting system comprising a first part and a second part adapted to be mixed to yield an aqueous disinfecting composition. The first part contains a non-esterifying acid and an alcohol-containing humectant or antifreeze, while the second part contains a salt of an organic acid and an optional metal chlorite. Methods for making a disinfecting composition by mixing the two-part disinfecting system, as well as for disinfecting substrates by contact therewith, are also disclosed.

Abstract: A simple, biocompatible system and procedure for generating nitric oxide (NO) is described. A mixture of powdered sodium nitrite, ascorbic acid, and maleic acid (or another organic acid of adequate strength) immediately generates nitric oxide (NO) on treatment with water. To slow down the NO generation, one may prepare an ointment from a nonaqueous medium (petrolatum, vaseline) and the three powdered ingredients, which on being applied topically on the skin will release NO as water permeates through this medium; alternatively, one may convert the aqueous sodium nitrite solution into a gel with hydroxyethylcellulose (or other gel-forming compound) and combine this gel with another gel obtained from aqueous ascorbic and maleic acids with hydroxyethylcellulose for topical application (on intact skin, burns, intra-cavity, etc.).

Abstract: A chemical agent for use in binding to and insolubilizing the solubilized products of fat digestion in order to prevent absorption of fat from the diet.

Abstract: The present invention is directed to a method of inhibiting the growth of disease organisms on and in plants by directly applying an aqueous solution comprising urea and at least one water-soluble salt of a divalent cation and a monovalent anion to the seeds, stems, bark, leaves, seed heads or sub-surface root zones of said plants. The weight percent ratio of urea to divalent cation in these solutions should be from about 0.25-10.0 to 1.0. Preferred divalent cations include those of the alkaline earth metals and the transition metals. Most preferred are calcium, magnesium, zinc, manganese, copper, iron, cobalt, nickel and mixtures thereof. Preferred anions include nitrate, chloride, bromide and mixtures thereof. In more preferred solutions, the ratio of urea to divalent cation is from about 2.0-7.0 to 1.0. Particularly preferred solutions include calcium chloride as the water-soluble salt. Optionally, a second water-soluble salt of a divalent cation and a monovalent anion may be included.

Abstract: Disclosed are methods of treating, inhibiting or preventing vascular thrombosis or arterial restenosis in a mammal. The disclosed methods include causing the mammal to inhale a therapeutically-effective concentration of gaseous nitric oxide (NO). Also disclosed are methods that include the administration of the following types of agents in conjunction with inhaled nitric oxide: compounds that potentiate the beneficial effects of inhaled nitric oxide, and antithrombotic agents that complement or supplement the beneficial effects of inhaled nitric oxide.

Abstract: Compositions and methods of the topical treatment of equine laminitis are disclosed. In particular, combinations of a fast acting nitric oxide (NO) donor, a sustained acting NO donor and an NSAID mixed in a lipid-based carrier are described. The application of such combinations to the affected areas, e.g., the hoofs and surrounding tissues, of an equine afflicted with laminitis provides relief from the debilitating effects of this painful, often life-threatening condition.

Abstract: A method is disclosed for treating and preventing diseases, wherein at least one of the causes of the disease is .beta.-amyloid peptide induced change in free radical production resulting in vascular endothelial dysfunction and vasoactivity, by antagonizing vascular free radicals in excess of functional equilibrium. An animal model for the disease is also disclosed.

Abstract: Disclosed are methods of treating, inhibiting or preventing vascular thrombosis or arterial restenosis in a mammal. The disclosed methods include causing the mammal to inhale a therapeutically-effective concentration of gaseous nitric oxide (NO). Also disclosed are methods that include the administration of the following types of agents in conjunction with inhaled nitric oxide: compounds that potentiate the beneficial effects of inhaled nitric oxide, and antithrombotic agents that complement or supplement the beneficial effects of inhaled nitric oxide.

Abstract: Cosmetic/dermatological/pharmaceutical compositions, well suited for the treatment of a variety of mammalian disorders of, for example, the skin, hair and/or mucous membranes, a manifestation of which is an excess in the synthesis and/or in the release of substance P, e.g., for the treatment of cutaneous disorders and sensitive skin, comprise an effective substance P antagonist amount of at least one salt of yttrium, lanthanum, cerium, praseodymium, neodymium, promethium, samarium, europium, gadolinium, terbium, dysprosium, holmium, erbium, thulium, ytterbium, lutetium, tin, manganese, or mixture thereof, in a cosmetically/pharmaceutically acceptable medium therefor.

Abstract: Disclosed are methods for treating a patient identified as having a hemoglobinopathy that is characterized by a reduced affinity of hemoglobin for oxygen. The methods involve providing gaseous nitric oxide and/or carbon monoxide for (i) inhalation by the patient or (ii) ex vivo treatment of the patient's erythrocytes. Alternatively, a nitric-oxide-releasing compound can be administered to the patient.

Abstract: The present invention involves perfluoro compound emulsions including nitric oxide, their preparation and their use. These emulsions provide a new source of nitric oxide. Such nitric oxide-containing emulsions may be used for the administration of nitric oxide to individuals in need thereof. Individuals in need of nitric oxide administration can include those suffering from hypertension, preeclampsia and a number of other situations where an increased blood flow, for example, is desirable. In addition, given the long use of perfluoro compound emulsions as blood substitutes, the present invention provides a relatively safe mode for administering and distributing nitric oxide-without potential negative side effects such as toxicities due to drug metabolites.