Abstract: Provided, among other things, is a method of treating or ameliorating or preventing an indication of the invention in an animal, including a human comprising administering an effective amount of a compound of the formula I: 1

Abstract: The present invention relates to compositions and methods for inhibiting nonenzymatic cross-linking (protein aging). Accordingly, a composition is disclosed which comprises a substituted 1,2,4-triazine of the formula (I) and the biologically and pharmaceutically acceptable salts thereof; capable of inhibiting the formation of advanced glycosylation endproducts of target proteins. The method comprises contacting the target protein with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated.

Abstract: Provided are, among other things, lipid-lowering or glucose-lowering methods and compounds, particularly lipid-lowering or glucose-lowering compounds, with an A-B ring structure as follows: wherein the dotted line between carbons 5 and 6, the dotted line between carbon 4 and R2, and the dotted line between carbon 11 and R3 each independently represent an optional double bond from the respective numbered carbon to a linked carbon, and wherein X is hydroxy or, together with Y is oxy linking carbon 8 and carbon 12.

Abstract: The present invention relates to compositions and methods for reversing advanced glycosylation end product-mediated cross-linking and protein aging. Accordingly, compositions are described which comprise thiazolium compounds substituted with heterocyclic groups which are capable of reversing the formation of advanced glycosylation end product cross-links. Both industrial and therapeutic applications for the invention are disclosed, as food spoilage and animal protein aging can be treated. Such compounds have particular application in the treatment of protein aging such as is responsible for the complications of aging and diabetes.

Abstract: The present invention relates to compositions and methods for inhibiting nonenzymatic cross-linking (protein aging). Accordingly, a composition is disclosed which comprises a substituted 1,2,4-triazine of the formula (I) ##STR1## and the biologically and pharmaceutically acceptable salts thereof; capable of inhibiting the formation of advanced glycosylation endproducts of target proteins. The method comprises contacting the target protein with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated.

Abstract: The present invention relates to compositions and methods for inhibiting and reversing nonenzymatic cross-linking (protein aging). Accordingly, compositions are disclosed which comprise an agent capable of inhibiting the formation of advanced glycosylation endproducts of target proteins, and which additionally reverse pre-formed crosslinks in the advanced glycosylation endproducts by cleaving alpha-dicarbonyl-based protein crosslinks present in the advanced glycosylation endproducts. Certain agents useful are thiazolium salts. The method comprises contacting the target protein with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated. A novel immunoassay for detection of the reversal of the nonenzymatic crosslinking is also disclosed.

Abstract: The present invention relates to compositions and methods for inhibiting nonenzymatic cross-linking (protein aging). Accordingly, a composition is disclosed which comprises a substituted 1,2,4-triazine of the formula (I) ##STR1## and the biologically and pharmaceutically acceptable salts thereof; capable of inhibiting the formation of advanced glycosylation endproducts of target proteins. The method comprises contacting the target protein with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated.

Abstract: The present invention relates to monoclonal antibodies to advanced glycosylation endproducts formed in vivo and cross-reactive with advanced glycosylation endproducts formed in vitro, and to methods of diagnosis and therapy based thereon. More particularly, the invention is directed to a monoclonal antibody, or an antigen-binding fragment thereof, reactive with in vivo produced advanced glycosylation endproducts (AGEs), which monoclonal antibody or antigen binding fragment thereof demonstrates an immunological binding characteristic of monoclonal antibodies selected from the group consisting of 4G9 as produced by hybridoma 4G9, deposited with the American Type Culture Collection (ATCC) and assigned Accession Number CRL 11626, 2G6 as produced by hydridoma 2G6, deposited with the American Type Culture Collection (ATCC) on Dec. 19, 1995, and assigned Accession Number HB 12008, and BH4 as produced by hydridoma BH4, deposited with the American Type Culture Collection (ATCC) on Dec.

Abstract: The present invention relates to compositions and methods for inhibiting nonenzymatic cross-linking (protein aging) using compounds of the following formula I ##STR1## wherein alk is a straight or branched chain alkylene group containing from 2 to 8 carbon atoms, and R is a lower alkyl group containing from 1 to 6 carbon atoms; and their biologically or pharmaceutically acceptable acid addition salts. Accordingly, a compositions are disclosed which comprises these N-acylaminoalkylhydrazinecarboximidamides, which are capable of inhibiting the formation of advanced glycosylation endproducts of target proteins. The method comprises contacting the target protein with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated.

Abstract: Compounds useful in the production and analysis of monoclonal antibodies to advanced glycosylation endproducts are 6-(N-carboxymethylamino)caproates of the formulaXO.sub.2 C--(CH.sub.2).sub.5 --NH--CH.sub.2 CO.sub.2 X (I)wherein X is hydrogen or an alkali metal salt cation. These compounds can be used in the production of such monoclonal antibodies, and to assess the purity and reactivity of AGE-antibodies produced for diagnostic purposes.

Abstract: The present invention relates to a practical and facile synthesis of 2-(2-furoyl)-4(5)-(2-furanyl)-1H-imidazole (FFI) and analogs thereof. The synthesis utilized a novel hydrazinium salt as an intermediate reaction product which facilitates the isolation of purified product in high yields.

Abstract: Methods are disclosed for measuring the accumulation of advanced glycosylation endproducts (AGEs), which are predicated on the discovery that such AGEs are present in tobacco and its byproducts. More particularly, the methods focus on the observation that individuals who smoke or otherwise use tobacco have increased levels of AGEs over non-smoking individuals. The present methods relate to the measurement of AGE levels in both individuals and in tobacco and its byproduct, smoke. Methods are also disclosed for the evaluation of the tobacco products to determine their storage status and organoleptic capacity and potential, as well as for the treatment of the ambient to lower AGE levels. For example, air or other samples may be taken and evaluated by a dosimeter or like device, to determine whether AGE levels exceed normal, after which measures could be implemented to remediate the ambient condition. All such methods and corresponding materials are contemplated and included.

Abstract: The present invention relates to compositions and methods for inhibiting and reversing nonenzymatic cross-linking (protein aging). Accordingly, compositions are disclosed which comprise an agent capable of inhibiting the formation of advanced glycosylation endproducts of target proteins, and which additionally reverse pre-formed crosslinks in the advanced glycosylation endproducts by cleaving alpha-dicarbonyl-based protein crosslinks present in the advanced glycosylation endproducts. Certain agents useful are thiazolium salts. The method comprises contacting the target protein with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated. A novel immunoassay for detection of the reversal of the nonenzymatic crosslinking is also disclosed.

Abstract: Methods are provided for measuring the accumulation of advanced glycosylation endproducts (AGEs), and for lowering the accumulation of advanced glycosylation endproducts, which are predicated on the discovery that such AGEs and their precedent glycotoxins are present in tobacco and its byproducts. More particularly, the methods focus on the observation that individuals who smoke or otherwise use tobacco have increased levels of AGEs relative to non-smoking individuals. The present methods relate to the measurement of AGE levels in both individuals and in tobacco and its byproduct, smoke, and to the treatment of such individuals with agents capable of reacting with glycosylation products to either avert or diminish the accretion of AGEs in the body.

Abstract: The present invention relates to monoclonal antibodies to advanced glycosylation endproducts formed in vivo and cross-reactive with advanced glycosylation endproducts formed in vitro, and to methods of diagnosis and therapy based thereon. More particularly, the invention is directed to a monoclonal antibody, or an antigen-binding fragment thereof, reactive with in vivo produced advanced glycosylation endproducts (AGEs), which monoclonal antibody or antigen binding fragment thereof demonstrates an immunological binding characteristic of monoclonal antibody 4G9 as produced by hybridoma 4G9, deposited with the American Type Culture Collection (ATCC) and assigned Accession Number CRL 11626. In a specific embodiment, the 4G9 antibody is used in a sandwich ELISA to detect ApoB-AGE, IgG-AGE, collagen-AGE, serum-AGE peptides and proteins and urinary-AGE peptides and proteins.

Abstract: The present invention relates to monoclonal antibodies to advanced glycosylation endproducts formed in vivo and cross-reactive with advanced glycosylation endproducts formed in vitro, and to methods of diagnosis and therapy based thereon. More particularly, the invention is directed to a monoclonal antibody, or an antigen-binding fragment thereof, reactive with in vivo produced advanced glycosylation endproducts (AGEs), which monoclonal antibody or antigen binding fragment thereof demonstrates an immunological binding characteristic of monoclonal antibody 4G9 as produced by hybridoma 4G9, deposited with the American Type Culture Collection (ATCC) and assigned Accession Number CRL 11626. In a specific embodiment, the 4G9 antibody is used in a sandwich ELISA to detect ApoB-AGE, IgG-AGE, collagen-AGE, serum-AGE peptides and proteins and urinary-AGE peptides and proteins.

Abstract: The present invention relates to monoclonal antibodies to advanced glycosylation endproducts formed in vivo and cross-reactive with advanced glycosylation endproducts formed in vitro, and to methods of diagnosis and therapy based thereon. More particularly, the invention is directed to a monoclonal antibody, or an antigen-binding fragment thereof, reactive with in vivo produced advanced glycosylation endproducts (AGEs), which monoclonal antibody or antigen binding fragment thereof demonstrates an immunological binding characteristic of monoclonal antibody 4G9 as produced by hybridoma 4G9, deposited with the American Type Culture Collection (ATCC) and assigned Accession Number CRL 11626, on Apr. 27, 1994. In a specific embodiment, the 4G9 antibody is used in a sandwich ELISA to detect ApoB-AGE, IgG-AGE, collagen-AGE, serum-AGE peptides and proteins and urinary-AGE peptides and proteins.

Abstract: The present invention relates to compositions and methods for inhibiting nonenzymatic cross-linking (protein aging). Accordingly, a composition is disclosed which comprises bis(guanylhydrazone) of the formula ##STR1## capable of inhibiting the formation of advanced glycosylation endproducts of target proteins by reacting with the carbonyl moiety of the early glycosylation product of such target proteins formed by their initial glycosylation. The method comprises contacting the target protein with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated.

Abstract: The present invention relates to compositions and methods for inhibiting nonenzymatic cross-linking (protein aging). Accordingly, a composition is disclosed which comprises a bis-(2-aryl)hydrazone capable of inhibiting the formation of advanced glycosylation endproducts of target proteins. The method comprises contacting the target protein with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated.

Abstract: The present invention relates to compositions and methods for inhibiting and reversing nonenzymatic cross-linking (protein aging). Accordingly, a composition is disclosed which comprises a thiazolium compound capable of inhibiting, and to some extent reversing, the formation of advanced glycosylation endproducts of target proteins by reacting with the carbonyl moiety of the early glycosylation product of such target proteins formed by their initial glycosylation. The method comprises contacting the target protein with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated. A novel immunoassay for detection of the reversal of the nonenzymatic crosslinking is also disclosed.