Abstract: Disclosed herein are formulations, methods, and kits of increasing GLP-1 levels. Some embodiments of the formulations are useful for inhibiting, ameliorating, delaying the onset of, reducing the likelihood of, treating, and/or preventing obesity. The formulations are also useful for inhibiting, ameliorating, delaying the onset of, reducing the likelihood of, treating, and/or preventing diabetes. The formulations have at least one extract from a tart cherry, resveratrol, and L-arginine. Also disclosed are methods of making the formulations.

Abstract: Disclosed herein are formulations, methods, and kits of formulations for inhibiting, ameliorating, delaying the onset of, reducing the likelihood of, treating, and/or preventing metabolic syndrome, and/or increasing energy levels. The formulations have at least one extract from a tart cherry, at least one antioxidant vitamin, at least one polyphenolic compound, and at least one prebiotic. Also disclosed are methods of making the formulations.

Abstract: Disclosed herein are formulations, methods, and kits of formulations for inhibiting, ameliorating, delaying the onset of, reducing the likelihood of, treating, and/or preventing metabolic syndrome, and/or increasing energy levels. The formulations have at least one extract from a tart cherry, at least one antioxidant vitamin, at least one polyphenolic compound, and at least one prebiotic. Also disclosed are methods of making the formulations.

Abstract: Disclosed herein are formulations, methods, and kits of formulations for inhibiting, ameliorating, delaying the onset of, reducing the likelihood of, treating, and/or preventing metabolic syndrome, and/or increasing energy levels. The formulations have at least one extract from a tart cherry, at least one antioxidant vitamin, at least one polyphenolic compound, and at least one prebiotic. Also disclosed are methods of making the formulations.

Abstract: Methods and compositions are provided for generating and applying long-lasting therapeutic nitric oxide (NO) gas from the reaction of a least one microencapsulated nitrite salt and an activating volume of an aqueous acidified gel that has sufficient acidity to convert the nitrite salt to a nitric oxide (NO) and further provides a reducing property that retains the NO in bioactive form

Abstract: Methods and compositions are provided for generating and applying long-lasting therapeutic nitric oxide (NO) gas from the reaction of a least one microencapsulated nitrite salt and an activating volume of an aqueous acidified gel that has sufficient acidity to convert the nitrite salt to a nitric oxide (NO) and further provides a reducing property that retains the NO in bioactive form.

Abstract: Methods and compositions are provided for generating and applying long-lasting therapeutic nitric oxide (NO) gas from the reaction of water-soluble chemical reactants microencapsulated in polymer matrices. In some applications the microencapsulated reactants are introduced in an aqueous gel, and in other applications they are introduced to the area of therapy either directly or in a medical device such as a therapeutic pad or dressing. In some applications, the microencapsulated chemical precursors are maintained in close physical proximity to one another in a limited volume, and using a limited amount of solvent residing within that same volume to extract and process the chemical precursors to form NO.

Abstract: Methods and compositions are provided for generating and applying long-lasting therapeutic nitric oxide (NO) gas from the reaction of a least one microencapsulated nitrite salt and an activating volume of an aqueous acidified gel that has sufficient acidity to convert the nitrite salt to a nitric oxide (NO) and further provides a reducing property that retains the NO in bioactive form

Abstract: Methods and compositions are provided for generating and applying long-lasting therapeutic nitric oxide (NO) gas from the reaction of water-soluble chemical reactants microencapsulated in polymer matrices. In some applications the microencapsulated reactants are introduced in an aqueous gel, and in other applications they are introduced to the area of therapy either directly or in a medical device such as a therapeutic pad or dressing. In some applications, the microencapsulated chemical precursors are maintained in close physical proximity to one another in a limited volume, and using a limited amount of solvent residing within that same volume to extract and process the chemical precursors to form NO.

Abstract: We disclose a method of activating soluble guanylyl cyclase (sGC) in a patient, comprising administering to the patient a composition comprising a corrin and a pharmaceutically-acceptable carrier. We also disclose a composition, comprising a corrin, an NO-independent sGC activator selected from the group consisting of BAY 41-2272, BAY 58-2667, HMR1766, YC-I, and S3448, and a pharmaceutically-acceptable carrier.

Abstract: We disclose a method of inhibiting activity of adenylyl cyclase or guanylyl cyclase in a mammal by administering to the mammal an amount of a composition effective to inhibit the activity, wherein the composition contains at least one compound selected from the group consisting of structural formulae (Ia) and (Ib) and salts thereof, wherein R1 is —H or has the structure —C(?O)R8; R2 is ?O or has the structure —OC(?O)R9; and R3, R4, R5, R6, and R7 are each independently selected from the group consisting of —H, —NO2, formula (I), -halogen, —OC(?O)R9, —OR9, —OH, —R8OH, —CH3, —OC(?O)CH2Ph, formulae (II), (III), (IV), —OPh, —CF3, —R8, —C(?O)OR9, -Ph, —R8Ph, formulae (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX), (XX), and (XXI), wherein each R8 is independently a linear or branched hydrocarbon group having from 1 to 4 carbon atoms and each R9 is independently a hydrocarbon group having from 1 to 2 carbon atoms.

Abstract: Methods and compositions are disclosed for quantifying and/or identifying a nitroderivative compound, or a residue thereof, and are applicable for assessing in vivo nitrative stress and for aiding in diagnosis of mammalian pathologies such as asthma, atherosclerosis, Alzheimer's disease, inflammation, ischemia, Parkinson's disease, and cancer. A preferred method comprises a) providing a sample containing the nitroderivative compound, or residue thereof, in the form of a diazo compound or residue thereof; b) azo-coupling the diazo compound, or residue thereof, to a target compound capable of producing a signal, to yield an azo-coupled compound; c) isolating the nitroderivative compound, or residue thereof, or the azo-coupled compound; d) quantitating and/or detecting the signal, to yield a quantitation and/or detection result; and e) determining from the quantitation and/or detection result the identity and/or concentration of the nitroderivative compound, or residue thereof, in the sample.

Abstract: A method of screening a substance of interest for heme independent modulation of enzymatic activity of soluble guanylyl cyclase (sGC) is disclosed, comprising (a) obtaining ??Cys105 mutant sGC enzyme; (b) determining activity of the mutant enzyme for forming cGMP from GTP in the presence of the substance of interest in a reaction medium; (c) determining activity as in step (b), except in the absence of the substance of interest; optionally, (d) including an activator other than the substance of interest in steps b) and c); e) comparing results of (b)–(d) to yield a comparison result; and f) from that value of that result, assessing activity of the substance of interest for modulating cGMP production by the mutant enzyme. Increased or decreased formation of cGMP in the presence of the substance of interest indicates activity of the substance for modulating heme independent cGMP production.

Abstract: Methods and compositions are disclosed for quantifying and/or identifying a nitroderivative compound, or a residue thereof, and are applicable for assessing in vivo nitrative stress and for aiding in diagnosis of mammalian pathologies such as asthma, atherosclerosis, Alzheimer's disease, inflammation, ischemia, Parkinson's disease, and cancer. A preferred method comprises a) providing a sample containing the nitroderivative compound, or residue thereof, in the form of a diazo compound or residue thereof; b) azo-coupling the diazo compound, or residue thereof, to a target compound capable of producing a signal, to yield an azo-coupled compound; c) isolating the nitroderivative compound, or residue thereof, or the azo-coupled compound; d) quantitating and/or detecting the signal, to yield a quantitation and/or detection result; and e) determining from the quantitation and/or detection result the identity and/or concentration of the nitroderivative compound, or residue thereof, in the sample.

Abstract: Murine cDNA encoding the alpha1 subunit of soluble guanylyl cyclase (sGC) and additional sequence to the known 3? noncoding part of beta1 subunit of soluble guanylyl cyclase are identified herein. The new genes are further used for expression of encoded proteins. The new part of the beta1 cDNA sequences is further used for screening of regulatory factors associated with modulation of the expression of the beta1 sGC subunit.

Abstract: Methods of using a heme-deficient mutant sGC with a substituted His105 residue, which has a high basal specific activity and displays properties similar to NO-stimulated wild type sGC, are disclosed. Preferred embodiments aid in the prevention and treatment of cyclic GMP-dependent pathophysiologies, and are useful in the development of drugs that inhibit or activate sGC. Certain embodiments provide a method of treating angina and other chronic heart diseases comprising delivery of a constitutively active &agr;&bgr;Cys105 mutant gene or enzyme to an in vivo cell are described.

Abstract: Murine cDNA encoding the alpha 1 subunit of soluble guanylyl cyclase (sGC) and additional sequence to the known 3′ noncoding part of beta1 subunit of soluble guanylyl cyclase are identified herein. The new genes are further used for expression of encoded proteins. The new part of the beta1 cDNA sequences is further used for screening of regulatory factors associated with modulation of the expression of the beta1 sGC subunit.

Abstract: Compounds of the formula: ##STR1## useful as regulators of nitric oxide synthase that indirectly modulate cyclic guanosine monophosphate (cGMP), pharmaceutical compositions thereof, for treating disorders of vascular smooth muscles, macrophages, neurons, platelets, bronchial smooth muscles, optic muscles and gastrointestinal smooth muscles, sickle cell anemia and diabetes.

Abstract: Compounds of the formula: ##STR1## useful as regulators of nitric oxide synthase that indirectly modulate cyclic guanosine monophosphate (cGMP), pharmaceutical compositions thereof, for treating disorders of vascular smooth muscles, macrophages, neurons, platelets, bronchial smooth muscles, optic muscles and gastrointestinal smooth muscles, sickle cell anemia and diabetes.

Abstract: Two-site immunometric assays for multideterminant antigens are described in which the antigen is reacted with an immobilized monoclonal antibody directed against one antigen determinant and a second monoclonal antibody that is directed against a distinct antigenic determinant and is of a different class or subclass than the immobilized monoclonal antibody. The second monoclonal antibody is labeled in direct versions of the assay and is reacted with a labeled antibody against it in indirect versions of the assay. The immobilizing medium and classes (subclasses) of the antibodies may be selected so as to reduce the likelihood of nonspecific binding enhance sensitivity and/or permit signal amplification.