Abstract: An automated electronic impact platform provides sustainable funding for socially responsible endeavors using investment returns from an impact fund. A first portion of a philanthropic contribution is used to fund charitable activity related to a socially responsible endeavor, while a second portion of a philanthropic contribution is used to invest in an impact fund that invests in commercial activity related to the socially responsible endeavor. As the impact fund generates a financial return, the financial return is recycled back to the contribution stage, whereby the financial return contribution, similarly as the initial philanthropy contribution, is divided into a first portion used to fund charitable activity and a second portion used to re-invest in the impact fund to fund commercial activity.

Abstract: A method of treating disorders associated with NO/SNO deficiency or benefiting from increased SNO in a subject in need thereof includes administering to the subject an ADH inhibitor, AKR inhibitor, SNO-CoAR inhibitor, and/or SNO-CoA at an amount(s) effective to promote S-nitrosylation of proteins in the subject.

Abstract: A method of treating disorders associated with NO/SNO deficiency or benefiting from increased SNO in a subject in need thereof includes administering to the subject an ADH inhibitor, AKR inhibitor, SNO-CoAR inhibitor, and/or SNO-CoA at an amount(s) effective to promote S-nitrosylation of proteins in the subject.

Abstract: A method of treating disorders associated with NO/SNO deficiency or benefiting from increased SNO in a subject in need thereof includes administering to the subject an ADH inhibitor, AKR inhibitor, SNO-CoAR inhibitor, and/or SNO-CoA at an amount(s) effective to promote S-nitrosylation of proteins in the subject.

Abstract: Provided herein are methods for ameliorating the pathophysiology cysteine protease exotoxin comprising the step of administering to said individual an effective dose of an S-nitrosylating agent and an inositol phosphate or analog thereof.

Abstract: A resin connected by amide bond to pyridyl sulfide or methylthiosulfonate can be conjugated to a post traditionally modified protein/peptide to allow determination of presence and kind and optionally location of cysteine modification(s).

Abstract: Provided herein are methods for ameliorating the pathophysiology cysteine protease exotoxin comprising the step of administering to said individual an effective dose of an S-nitrosylating agent and an inositol phosphate or analog thereof.

Abstract: A resin connected by amide bond to pyridyl sulfide or methylthiosulfonate can be conjugated to a post traditionally modified protein/peptide to allow determination of presence and kind and optionally location of cysteine modification(s).

Abstract: The presently disclosed subject matter provides methods for increasing perfusion in hypoxic regions of tissues in subjects. Also provided are methods for treating diseases and/or disorders associated with hypoxia in subjects, methods for increasing sensitivity of tumors to radiation and/or chemotherapy treatments, methods for delaying tumor growth in subjects, and methods for inhibiting tumor blood vessel growth in subjects. In some embodiments, the presently disclosed methods involve administering to subjects in need thereof a first composition selected from the group consisting of a nitrosylated hemoglobin and an agent that induces nitrosylation of endogenous hemoglobin in the subject and a second composition comprising a hyperoxic gas. In some embodiments, the presently disclosed methods also include treating a tumor with radiation therapy, chemotherapy, photodynamic therapy, immunotherapy, or combinations thereof. Also provided are inhalable gases that can be employed in the presently disclosed methods.

Abstract: The presently disclosed subject matter provides methods for increasing perfusion in hypoxic regions of tissues in subjects. Also provided are methods for treating diseases and/or disorders associated with hypoxia in subjects, methods for increasing sensitivity of tumors to radiation and/or chemotherapy treatments, methods for delaying tumor growth in subjects, and methods for inhibiting tumor blood vessel growth in subjects. In some embodiments, the presently disclosed methods involve administering to subjects in need thereof a first composition selected from the group consisting of a nitrosylated hemoglobin and an agent that induces nitrosylation of endogenous hemoglobin in the subject and a second composition comprising a hyperoxic gas. In some embodiments, the presently disclosed methods also include treating a tumor with radiation therapy, chemotherapy, photodynamic therapy, immunotherapy, or combinations thereof. Also provided are inhalable gases that can be employed in the presently disclosed methods.

Abstract: The present invention provides compositions comprising a gas and a gastrointestinal smooth muscle relaxing agent comprising ethyl nitrite in a therapeutically effective amount. The present invention also provides methods of relaxing gastrointestinal smooth muscle, alleviating contraction or spasm of gastrointestinal smooth muscle to facilitate a diagnostic medical procedure and treating or preventing a gastrointestinal disorder using the compositions of the invention.

Abstract: Nitrosylhemoglobin can be produced by introducing gaseous NO into an aqueous solution of hemoglobin. It has been demonstrated that nitrosylhemoglobin in aqueous solution can be converted to SNO-hemoglobin upon introduction of oxygen to the solution, as is postulated to occur in the lungs. Nitrosylhemoglobin can be used in methods to produce the physiological effects of NO, for example, to reduce vasoconstriction and to inhibit platelet aggregation.

Abstract: A C-nitroso compound having a molecular weight ranging from 225 to 1,000 (from 225 to 600 for oral administration) on a monomeric basis wherein a nitroso group is attached to a tertiary carbon, which is obtained by nitrosylation of a carbon acid having a pKa less than about 25, is useful as an NO donor. When the compound is obtained from a carbon acid with a pKa less than about 10, it provides vascular relaxing effect when used at micromolar concentrations and this activity is potentiated by glutathione to be obtained at nanomolar concentrations. When the compound is obtained from a carbon acid with a pKa ranging from about 15 to about 20, vascular relaxing effect is obtained at nanomolar concentrations without ghitathione. In another embodiment, a biocompatible polymer incorporates a C-nitroso moiety.

Abstract: The invention provides a method for preventing adverse effects associated with the use of a medical device in a patient by introducing into the patient a device of which at least a portion includes a prophylactic or therapeutic amount of a nitric oxide adduct. The nitric oxide adduct can be present in a matrix coating on a surface of the medical device; coated per se on a surface of the medical device; directly or indirectly bound to reactive sites on a surface of the medical device; or at least a portion of the medical device can be formed of a material, such as a polymer, which includes the nitric oxide adduct. Also disclosed is a method for preventing adverse effects associated with the use of a medical device in a patient by locally administering a nitric oxide adduct to the site of contact of said device with any internal tissue.

Abstract: The invention provides stable S-nitrosothiol, such as S-nitrosoglutathione, formulations for long term storage and in vivo delivery of S-nitrosothiols. The invention provides stable aerosol formulations comprising S-nitrosothiol, such as S-nitrosoglutathione, and methods of treating patients in need of S-nitrosothiol, such as S-nitrosoglutathione, and/or nitric oxide treatment.

Abstract: This invention provides a modified yeast two-hybrid system in order to identify NO-dependent protein-protein interactions. Bait proteins implicated in apoptotic signaling pathways were used to identify NO-dependent interactions. The physiological relevance of these interactions is demonstrated by their occurrence and dependence on endogenous NO in mammalian cells, and by the functional interrelatedness of bait and prey.

Abstract: The combination of nitric oxide generating compounds which are not dependent upon aldehyde dehydrogenase for bioactivation, or are specifically targeted to nNOS or the sarcoplasmic reticulum of cardiac muscle cells, and xanthine oxidase inhibitors are effective in the treatment of heart disease, specifically congestive heart failure and ischemic coronary disease. This treatment is particularly effective in patients who have particularly heavy oxidative burdens, e.g. diabetics, patients with lung disorders, patients with sickle cell anemia and patients of Asian descent.

Abstract: Treatment of pulmonary disorders associated with hypoxemia and/or smooth muscle constriction and/or inflammation comprises administering into the lungs as a gas a compound with an NO group which does not form NO2/NOx in the presence of oxygen or reactive oxygen species at body temperature. Treatment of cardiac and blood disorders, e.g., angina, myocardial infarction, heart failure, hypertension, sickle cell disease and clotting disorders, comprises administering into the lungs as a gas, a compound which reacts with cysteine in hemoglobin and/or dissolves in blood and has an NO group which is bound in said compound so that it does not form NO2/NOx in the presence of oxygen or reactive oxygen species at body temperature. Exemplary of the compound administered in each case is ethyl nitrite. Treatment of patient in need of improved oxygenation, blood flow of and/or thinning of blood comprises providing in the patient a therapeutic amount of red blood cells loaded with nitrosylated hemoglobin.

Abstract: Those in need of nitroglycerin (GTN) therapy who have polymorphism in the mtALDH gene, e.g., those of Asian descent for whom this polymorphism is common, and/or who are being treated with or ingesting or exposed to mtALDH inhibitor are treated with GTN in combination with agent which converts GTN to product which is metabolized without mtALDH activity, e.g., N-acetylcysteine.

Abstract: Patients needing NO donor therapy or inhibition of pathologically proliferating cells or increased NO bioactivity are treated with a therapeutically effective amount of an inhibitor of glutathione-dependent formaldehyde dehydrogenase.