Abstract: The present invention relates to mononucleoside phosphate compounds that have the benefits of a dinucleotide pharmaceutical. These mononucleoside phosphates can be made from a mononucleotide that has been modified by attaching a degradation-resistant substituent on the terminal phosphate of a polyphosphate mononucleotide. By attaching this degradation-resistant substituent, the stability from degradation matches or exceeds those of certain dinucleotides. The mononucleoside phosphate compounds of the present invention are useful in preventing and treating epithelial tissue diseases or diseases or disorders associated with platelet aggregation.

Abstract: The present invention relates to mononucleoside phosphate compounds that have the benefits of a dinucleotide pharmaceutical. These mononucleoside phosphates can be made from a mononucleotide that has been modified by attaching a degradation-resistant substituent on the terminal phosphate of a polyphosphate mononucleotide. By attaching this degradation-resistant substituent, the stability from degradation matches or exceeds those of certain dinucleotides. The mononucleoside phosphate compounds of the present invention are useful in preventing and treating epithelial tissue diseases or diseases or disorders associated with platelet aggregation.

Abstract: The present invention is directed to interactive training, and in particular, to methods and systems for computerized interactive skill training. An example embodiment provides a method and system for providing skill training using a computerized system. The computerized system receives a selection of a first training subject. A training challenge related to the first training subject is accessed from computer readable memory. The training challenge is provided to a user via a terminal, optionally in verbal form. A first score related to the correctness and/or completeness of a verbalized challenge response provided by the user is stored in memory. A second score related to how quickly the trainee provided the verbalized challenge response is stored in memory. A third challenge score related to the confidence and/or style with which the trainee verbalized the challenge response is stored in memory.

Abstract: The present invention are directed to P1, P4-di(uridine 5?-)tetraphosphate, tetra-alkali metal salts such as tetrasodium, tetralithium, tetrapotassium, and mixed tetra-alkali metal cations thereof. The tetra alkali metal salts of P1, P4-di(uridine 5?-)tetraphosphate are water-soluble, nontoxic, and easy to handle during manufacture. These tetra-monovalent alkali metal salts are more resistant to hydrolysis than the mono-, di-, or tri-acid salts, therefore, they provide an improved stability and a longer shelf life for storage. The present invention also provides methods for the synthesis of P1, P4-di(uridine 5?-)tetraphosphate, and its pharmaceutically acceptably acceptable salts thereof, and demonstrates the applicability to the production of large quantities. The methods substantially reduce the time required to synthesize diuridine tetraphosphate, for example, to three days or less.

Abstract: The present invention relates to mononucleoside phosphate compounds that have the benefits of a dinucleotide pharmaceutical. These mononucleoside phosphates can be made from a mononucleotide that has been modified by attaching a degradation resistant substituent on the terminal phosphate of a polyphosphate mononucleotide. By attaching this degradation resistant substituent, the stability from degradation matches or exceeds those of certain dinucleotides.

Abstract: The present invention is directed to a method of altering the amount or composition of synovial fluids secreted from joints in a subject in need of such treatment. The method comprises administering to a subject a pharmaceutical composition comprising a P2Y purinergic receptor agonist in an amount effective to alter the amount or composition of synovial fluids. The P2Y purinergic receptor agonist is administered in an amount effective to stimulate secretion of synovial fluid, lubricin, hyaluronic acid, or surface-active phospholipids; to enhance joint lubrication; or to treat osteoarthritis. The pharmaceutical compositions useful in the present invention comprise a P2Y purinergic receptor agonist of Formula I and include, but are not limited to: uridine-, adenosine-, cytidine-5?-di- or triphosphates, dinucleoside polyphosphates, and analogs thereof. The invention is useful for treating conditions associated with reduced joint lubrication and joint stiffness, such as osteoarthritis.

Abstract: The present invention is directed to a method of reducing intraocular pressure. The method comprises administering to a subject a pharmaceutical composition comprising an effective amount of a purinerginic receptor ligand, which is a mononucleoside polyphosphate or dinucleoside polyphosphate defined by general Formula I. The method of the present invention is useful in the treatment or prevention of ocular hypertension, such as glaucoma, including primary and secondary glaucoma. The method can be used alone to reduce intraocular pressure. The method can also be used in conjunction with other therapeutic agents or adjunctive therapy commonly used to treat glaucoma to enhance the therapeutic effect of reducing the intraocular pressure.

Abstract: The present invention is directed to a method of reducing intraocular pressure. The method comprises administering to a subject a pharmaceutical composition comprising an effective amount of a nucleoside 5?-pyrophosphate pyranoside or analogue, which is defined by general Formula I. The method of the present invention is useful in the treatment or prevention of ocular hypertension, such as found in glaucoma, including primary and secondary glaucoma. The method can be used alone to reduce intraocular pressure. The method can also be used in conjunction with another therapeutic agent or adjunctive therapy commonly used to treat glaucoma to enhance the therapeutic effect of reducing the intraocular pressure. The present invention also provides a novel composition comprising a nucleoside 5?-pyrophosphate pyranoside or analogues.

Abstract: The present invention is directed to P1, P4-di(uridine 5?)-tetraphosphate, tetra-alkali metal salts such as tetrasodium, tetralithium, tetrapotassium, and mixed tetra-alkali metal cations thereof. The tetra alkali metal salts of P1, P4-di(uridine 5?)-tetraphosphate are water-soluble, nontoxic, and easy to handle during manufacture. These tetra-monovalent alkali metal salts are more resistant to hydrolysis than the mono-, di-, or tri-acid salts, therefore, they provide an improved stability and a longer shelf life for storage. The present invention also provides methods for the synthesis of P1, P4-di(uridine 5?)-tetraphosphate, and its pharmaceutically acceptably acceptable salts thereof, and demonstrates the applicability to the production of large quantities. The methods substantially reduce the time required to synthesize diuridine tetraphosphate, for example, to three days or less.

Abstract: The present invention provides a method of reducing intraocular pressure by administering pharmaceutical compositions comprising indole derivatives. The pharmaceutical compositions useful in this invention comprise indole derivatives and melatonin analogs of Formulae I-IV. A preferred embodiment is a method of lowering intraocular pressure using 5-(methoxycarbonylamino)-N-acetyltryptamine (5-MCA-NAT), also known as GR 135531, which has a prolonged duration of action and greater efficacy in lowering intraocular pressure compared to melatonin. The present invention further provides a method of treating disorders associated with ocular hypertension, and a method of treating various forms of glaucoma; the method comprises administering an effective dose of a pharmacuetical composition comprising an indole derivative with or without agents commonly used to treat such disorders.

Abstract: The present invention provides a method of reducing intraocular pressure by administering pharmaceutical compositions comprising indole derivatives. The pharmaceutical compositions useful in this invention comprise indole derivatives and melatonin analogs of Formulae I-IV. A preferred embodiment is a method of lowering intraocular pressure using 5-(methoxycarbonylamino)-N-acetyltryptamine (5-MCA-NAT), also known as GR 135531, which has a prolonged duration of action and greater efficacy in lowering intraocular pressure compared to melatonin. The present invention further provides a method of treating disorders associated with ocular hypertension, and a method of treating various forms of glaucoma; the method comprises administering an effective dose of a pharmacuetical composition comprising an indole derivative with or without agents commonly used to treat such disorders.

Abstract: The present invention are directed to P1, P4-di(uridine 5′)-tetraphosphate, tetra-alkali metal salts such as tetrasodium, tetralithium, tetrapotassium, and mixed tetra-alkali metal cations thereof. The tetra alkali metal salts of P1, P4-di(uridine 5′)-tetraphosphate are water-soluble, nontoxic, and easy to handle during manufacture. These tetra-monovalent alkali metal salts are more resistant to hydrolysis than the mono-, di-, or tri-acid salts, therefore, they provide an improved stability and a longer shelf life for storage. The present invention also provides methods for the synthesis of P1, P4-di(uridine 5′)-tetraphosphate, and its pharmaceutically acceptably acceptable salts thereof, and demonstrates the applicability to the production of large quantities. The methods substantially reduce the time required to synthesize diuridine tetraphosphate, for example, to three days or less.

Abstract: The present invention is directed to a method of reducing intraocular pressure. The method comprises administering to a subject a pharmaceutical composition comprising an effective amount of a purinerginic receptor ligand, which is a mononucleoside polyphosphate or dinucleoside polyphosphate defined by general Formula I. The method of the present invention is useful in the treatment or prevention of ocular hypertension, such as glaucoma, including primary and secondary glaucoma. The method can be used alone to reduce intraocular pressure. The method can also be used in conjunction with other therapeutic agents or adjunctive therapy commonly used to treat glaucoma to enhance the therapeutic effect of reducing the intraocular pressure.

Abstract: The present invention is directed to a method of altering the amount or composition of synovial fluids secreted from joints in a subject in need of such treatment. The method comprises administering to a subject a pharmaceutical composition comprising a P2Y purinergic receptor agonist in an amount effective to alter the amount or composition of synovial fluids. The P2Y purinergic receptor agonist is administered in an amount effective to stimulate secretion of synovial fluid, lubricin, hyaluronic acid, or surface-active phospholipids; to enhance joint lubrication; or to treat osteoarthritis. The pharmaceutical compositions useful in the present invention comprise a P2Y purinergic receptor agonist of Formula I and include, but are not limited to: uridine-, adenosine-, cytidine-5′-di- or triphosphates, dinucleoside polyphosphates, and analogs thereof. The invention is useful for treating conditions associated with reduced joint lubrication and joint stiffness, such as osteoarthritis.

Abstract: The present invention relates to mononucleoside phosphate compounds that have the benefits of a dinucleotide pharmaceutical. These mononucleoside phosphates can be made from a mononucleotide that has been modified by attaching a degradation resistant substituent on the terminal phosphate of a polyphosphate mononucleotide. By attaching this degradation resistant substituent, the stability from degradation matches or exceeds those of certain dinucleotides.

Abstract: The present invention is directed to a method of reducing intraocular pressure. The method comprises administering to a subject a pharmaceutical composition comprising an effective amount of a nucleoside 5′-pyrophosphate pyranoside or analogue, which is defined by general Formula I. The method of the present invention is useful in the treatment or prevention of ocular hypertension, such as found in glaucoma, including primary and secondary glaucoma. The method can be used alone to reduce intraocular pressure. The method can also be used in conjunction with another therapeutic agent or adjunctive therapy commonly used to treat glaucoma to enhance the therapeutic effect of reducing the intraocular pressure. The present invention also provides a novel composition comprising a nucleoside 5′-pyrophosphate pyranoside or analogues.

Abstract: The present invention provides a method of reducing intraocular pressure by administering pharmaceutical compositions comprising indole derivatives. The pharmaceutical compositions useful in this invention comprise indole derivatives and melatonin analogs of Formulae I-IV. A preferred embodiment is a method of lowering intraocular pressure using 5-(methoxycarbonylamino)-N-acetyltryptamine (5-MCA-NAT), also known as GR 135531, which has a prolonged duration of action and greater efficacy in lowering intraocular pressure compared to melatonin. The present invention further provides a method of treating disorders associated with ocular hypertension, and a method of treating various forms of glaucoma; the method comprises administering an effective dose of a pharmacuetical composition comprising an indole derivative with or without agents commonly used to treat such disorders.

Abstract: The invention relates to libraries of cyclic organic compounds and method of producing and assaying such libraries. According to the invention, each cyclic organic compound is constructed from a starting material in the form of a solid surface derivatized with a starting resin. Compounds are reacted with the resin to add or to form a cyclic group. The reactions are preferable carried out using a split resin procedure so that different compounds can be reacted with a plurality of subamounts so as to increase the size of the library. For example, compounds are reacted with a solid support bound starting resin to obtain a compound which includes an aldehyde functional group wherein the aldehyde compound or compounds reacted with it have substituents which are varied such that a mixture of products is obtained.

Abstract: Methods for solid phase synthesis of N-alkyl amides comprise reductive amination of carbonyl compounds using a reducing agent and an amine-containing linker bound to a solid support. The methods afford high yields of linker-bound, monoalkylated amines, and subsequent coupling with acid derivatives provide derivatized N-substituted amides in excellent yields after cleavage from the solid-phase. Compositions useful in solid phase synthesis are also described.

Abstract: An attachment device is described that is fittable on a variety of lace-closable shoes for use with a lace-substitute hand-actuable shoe-closure system. The device is used with conventional shoes that include dual flaps positioned on opposing sides of a tongue, with each flap having plural, spaced openings formed in it for receiving a shoe lace. The attachment device includes buckle-like structure or plates positionable adjacent at least one opening in each flap, and constructed for handling via gross-motor hand movement. Also included is peg-like structure such as a threaded bolt associated with each buckle plate, and having a preselected length which allows it to extend through at least the one opening in each such flap. Fastener structure such as a tee nut is usable with the bolt to effect releasable, hand-actuable attachment of the buckle plate to each flap.