Abstract: Methods of preventing tissue damage associated with decreased blood flow in a human by administering AICA riboside or a prodrug thereof in an amount which provides a blood plasma concentration of between 1 .mu.g/ml and 20 .mu.g/ml of AICA riboside for a time sufficient to reduce the risk of said tissue damage in said human. Methods of preventing an adverse clinical outcome, such as an adverse cardiovascular and/or cerebrovascular event, in a patient at risk for such outcome by administering AICA riboside or a prodrug thereof in an amount which provides a blood plasma concentration of between 1 .mu.g/ml and 20 .mu.g/ml of AICA riboside for a time sufficient to reduce the risk for said patient.

Abstract: A closed-loop drug delivery system uses patient response and rule based decision making methods to achieve operator specified responses for diagnostic purposes. In the preferred embodiment, cardiac diagnosis is performed by pharmacologically stressing the heart by administration of an exercise simulating agent drug. In the preferred method, a protocol is defined, which preferably includes a target for a physiologic variable, such as heart rate, and a plan to achieve that target value. Preferably, the plan includes a specification of the desired rate of increase in that variable, such as the rate of increase in the heart rate per minute. The plan comprises the desired changes in the physiologic variable as a function of time. While any desired function may be used, the more common modes include RAMP, HOLD, LEVEL and TARGET mode. In one aspect of this invention, the protocol may be varied by the operator after drug administration has begun.

Abstract: AICA riboside and prodrugs of AICA riboside are provided which lower blood glucose for the treatment of various pathologic conditions, including hypoglycemia, insulin deficiency, insulin resistance diabetes and Syndrome X. Prodrugs of AICA riboside provide AICA riboside in an orally bioavailable form. The use of adenosine kinase inhibition and ZMP enhancement for lowering blood glucose are also described.

Abstract: Methods and devices for the diagnosis, evaluation and treatment of coronary artery disease (CAD) by means of a closed-loop drug delivery system that delivers an exercise simulating agent, including novel exercise simulating agents which elicit both acute and adaptive cardiovascular responses similar to those elicited by aerobic activity are provided. The acute responses to the exercise simulating agent are used to diagnose and evaluate CAD in lieu of the acute responses to aerobic exercise. Due to their adaptive responses these compounds may be used to treat CAD in lieu of the adaptive responses caused by aerobic exercise training or to treat other conditions where the adaptive responses caused by aerobic exercise are desirable.

Abstract: Methods and devices for the diagnosis, evaluation and treatment of coronary artery disease (CAD) by means of a closed-loop drug delivery system that delivers an exercise simulating agent, including novel exercise simulating agents which elicit both acute and adaptive cardiovascular responses similar to those elicited by aerobic activity are provided. The acute responses to the exercise simulating agent are used to diagnose and evaluate CAD in lieu of the acute responses to aerobic exercise. Due to their adaptive responses these compounds may be used to treat CAD in lieu of the adaptive responses caused by aerobic exercise training or to treat other conditions where the adaptive responses caused by aerobic exercise are desirable.

Abstract: The invention provides methods for preventing neural tissue damage caused by injury to the central nervous system (CNS) by the administration of a therapeutically effective amount of an adenosinergic agent. One aspect of the invention is directed toward continuous administration of a therapeutically effective amount of an adenosinergic agent for a period of time sufficient to prevent neural tissue damage. In another aspect of the present invention, the adenosinergic agents may be administered on several occasions during the prolonged period of treatment, so long as the doses of adenosinergic agents are spaced in time so that a therapeutically effective concentration of adenosinergic agent is maintained for a period of time sufficient to prevent neural tissue damage.

Abstract: Methods and devices for the diagnosis, evaluation and treatment of coronary artery disease (CAD) by means of a closed-loop drug delivery system that delivers an exercise simulating agent, including novel exercise simulating agents which elicit both acute and adaptive cardiovascular responses similar to those elicited by aerobic activity are provided. The acute responses to the exercise simulating agent are used to diagnose and evaluate CAD in lieu of the acute responses to aerobic exercise. Due to their adaptive responses these compounds may be used to treat CAD in lieu of the adaptive responses caused by aerobic exercise training or to treat other conditions where the adaptive responses caused by aerobic exercise are desirable.

Abstract: A test method for identifying for and evaluating anti-seizure activity of candidate compounds is provided which shows superior sensitivity for adenosinergic activity and which is believed to be predictive of other adenosine releasing activities for the candidate compounds.

Abstract: Methods of preventing neural tissue damage caused by excitotoxicity due to increased release of excitatory amino acids by increasing extracellular concentrations of adenosine in and around the neural tissue are provided. These methods are especially useful in treating neurodegenerative diseases such as Parkinson's Disease, Alzheimer's Disease, Amyotrophic Lateral Sclerosis or Huntington's Disease.

Abstract: A drug dispenser comprising a drug vial to whose neck a hollow spike is attached for insertion into a diluent container, with a jaw around the spike grasping the inlet port of the container. A stopper seals the vial's throat, and a two-way value covers its mouth. The valve is opened, and the stopper is blown from the vial's throat by squeezing the diluent container, thereby sending diluent under pressure through the hollow spike, the open valve, and the unobstructed throat into the vial.

Abstract: Antiviral purine nucleosides, purine nucleoside analogs and prodrugs of both are provided. Also provided are methods of enhancing the antiviral activity of AZT by administering AZT in combination with such purine compounds.

Abstract: Methods and devices for the diagnosis, evaluation and treatment of coronary artery disease (CAD) by means of a closed-loop drug delivery system that delivers an exercise simulating agent, including novel exercise simulating agents which elicit both acute and adaptive cardiovascular responses similar to those elicited by aerobic activity are provided. The acute responses to the exercise simulating agent are used to diagnose and evaluate CAD in lieu of the acute responses to aerobic exercise. Due to their adaptive responses these compounds may be used to treat CAD in lieu of the adaptive responses caused by aerobic exercise training or to treat other conditions where the adaptive responses caused by aerobic exercise are desirable.

Abstract: An apparatus and method for iontophoretic transdermal delivery of exercise simulating agents includes an electrode having disposed therein a drug reservoir comprising a viscosity-control agent comprising an aqueous sol with an antioxidant, a preservative, a chelator and a buffer. A silver/silver chloride conducive element is preferably situated in the electrode adjacent the drug reservoir to conduct an electric charge across the reservoir.

Abstract: Prodrugs of AICA riboside are provided which increase the bioavailability of AICA riboside and thereby increase extracellular concentrations of the prophylactic and affirmative treatment of various pathologic conditions, including ischemia. Also provided are methods of using AICA riboside prodrugs in treating such conditions.