Abstract: A system and method for assisting in a determination of one or more maladies associated with a human voice anatomy utilizes voice information acquired over at least two temporally displaced acquisitions. Acquired voice samples, including plural vowel sounds, are digitized and passed through one or more bandpass filters to isolate one or more frequency ranges. Curve fitting of acquired data is completed in accordance with a plurality of parameter weights applied in either a time domain or frequency domain model of the voice. This process is repeated a second, later time, for the same human, and the same process is completed for the subsequently-acquired voice information. A difference between the curve information in the respective data sets is analyzed relative to the weights, and corresponding changes are correlated to maladies of various areas of the human voice anatomy.

Abstract: The invention provides methods, compositions, and kits featuring a ribonucleoside chain terminator for use in preventing or inhibiting a retrovirus infection.

Abstract: Provided herein is a method of reducing intraocular pressure (IOP) in humans using N6-cyclopentyladenosine (CPA), CPA derivatives or prodrugs or enhanced cornea permeability formulations of CPA. In one embodiment, the invention is directed to CPA derivatives or prodrugs that are permeable to the cornea. In another embodiment, the invention is directed to uses of certain compounds in human subjects for reducing and/or controlling elevated or abnormally fluctuating IOPs in the treatment of glaucoma or ocular hypertension (OHT).

Abstract: A myocardial imaging method that is accomplished by administering one or more adenosine A2A adenosine receptor agonist to a human undergoing myocardial imaging as well as pharmaceutical compositions comprising at least one A2a receptor agonist, at least one liquid carrier, and at least one co-solvent.

Abstract: The present invention discloses methods for treating eye disorders. The methods include the step of administering an effective amount of a topically-administered dipyridamole. Preferably, the topically-administered dipyridamole is formulated as a solution. Preferably, the topically-administered dipyridamole is at least one agent selected from the group consisting of: dipyridamole, and a pharmaceutically-acceptable salt thereof. Preferably, the effective amount corresponds to a concentration of at least about 10?5 molarity. Preferably, the effective amount is based on a treatment administration of at least once every other day.

Abstract: The present invention relates to compositions and methods for modulating melanin production, secretion and/or accumulation in human skin cells. In particular, the present invention relates to the use of A3 adenosine receptor antagonists in compositions and methods for the treatment and amelioration of hyper-pigmentation conditions and for the lightening of skin, and to the use of A3 adenosine receptor agonists in compositions and methods for the treatment and amelioration of hypo-pigmentation conditions and for the tanning of skin.

Abstract: The present invention provides an efficient process for the synthesis of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol and hydrates thereof and methods for treating disorders in which DOT1-mediated protein methylation plays a part, such as cancer and neurological disorders, by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also provides novel crystalline forms of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol and hydrates thereof (Form A, Form B, and Form C), characterized by a unique X-ray diffraction pattern and Differential Scanning Calorimetry profile, as well as a unique crystalline structure.

Abstract: The present invention provides a method of myocardial perfusion imaging using reduced doses of (1-{9-[(4S,2R,3R,5R)3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-aminopurin-2-yl}pyrazol-4-yl)-N-methylcarboxamide.

Abstract: The present invention relates to substituted purine and 7-deazapurine compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating disorders in which DOT1-mediated protein methylation plays a part, such as cancer and neurological disorders, by administering these compounds and pharmaceutical compositions to subjects in need thereof.

Abstract: Disclosed is a synthesis suitable for large scale manufacture of an A2A-adenosine receptor agonist, and also relates to polymorphs of that compound, and to methods of isolating a specific polymorph.

Abstract: The present disclosure provides a process for the preparation of 2-adenosine N-pyrazole compounds exemplified by the structure shown below that are potent and selective agonists for A2A adenosine receptor, compositions comprising these compounds, and methods for using these compound to stimulate mammalian coronary vasodilatation for imaging the heart.

Abstract: The invention provides formulations comprising adenosine in a silk fibroin-based, sustained-release delivery system. The formulations provide sustained, focal release of adenosine at therapeutic levels for the treatment of epilepsy and/or the prevention of epileptogenesis.

Abstract: The present invention relates to novel 1,2,3-triazolyl purine derivatives. The invention also relates to using the derivatives to treat cancer and various viral infections.

Abstract: Provided herein are compounds useful for the treatment of HBV infection in a subject in need thereof, pharmaceutical compositions thereof, and methods of inhibiting, suppressing, or preventing HBV infection in the subject.

Abstract: A human dietary supplement comprises theacrine and optionally other compounds that modulate the effects of theacrine. Uses for the theacrine-containing supplement include improvement of at least one of mood, energy, focus, concentration or sexual desire or a reduction of at least one of anxiety or fatigue.

Abstract: The disclosure provides linked purine pterin compounds and analogs thereof that are novel HPPK inhibitors. The HPPK inhibitors described herein are compounds and the pharmaceutically acceptable salts thereof of general Formula I The variables, e.g. A1 to A3, R1 to R4, L1, L2, B1, and B2 are described herein. Compounds and salts of Formula I bind to HPPK with high affinity and specificity. Pharmaceutical compositions containing an HPPK inhibitor of Formula I and methods of treating a bacterial infection in a patient by providing one or more HPPK inhibitors of Formula I to the patient are also provided. Processes and intermediates useful for preparing compounds of Formula I are also provided. Methods of using the disclosed compounds to guide the development of additional novel anti-bacterial agents are also provided.

Abstract: The present invention provides aqueous compositions comprising (a) at least one compound selected from the group consisting of adenosine and adenosine analogs, and (b) at least one hydrotrope in an amount effective to solubilize said at least one compound (a) in water, for cosmetic uses.

Abstract: Methods for treating diseases in humans and vertebrate animals are provided using competitive antagonists of cellular metabolites combined with a protective agent for protecting host cells from toxic effects of the drugs. Also provided are kits comprising competitive antagonists and suitable protective agents. In addition, screening methods for identifying competitive antagonists, protective agents and potentiating agents, for use according to the methods of the invention, are provided.

Abstract: Disclosed herein are nucleosides, nucleotides and nucleotide analogs, methods of synthesizing the same and methods of treating diseases and/or conditions such as a Picornavirus and/or Flaviviridae infection with one or more nucleosides, nucleotides and nucleotide analogs.

Abstract: The present invention provides novel heteroaryl compounds having a pyrimidine-containing core that is linked to a 4-trifluoromethoxyphenyl group via an amine linker. Such compounds are useful for the treatment of cancers.

Abstract: Clinical finding shows that twice daily administrations of 2 mg of 1-deoxy-1-[N6-(3-iodobenzyl)-adenin-9-yl]-N-methyl-?-D-ribofuronamide (IB-MECA) (total daily administration of 4 mg) to subjects having moderate to severe psoriasis, was significantly more effective in treatment of the psoriatic plaques than treatment of psoriasis at two administration doses of 1 mg or 4 mg (total daily doses of 2 or 8 mg, respectively). A pharmaceutical composition for the treatment of psoriasis includes as the active ingredient IB-MECA in an amount suitable for a total daily dose administration of about 4 mg. In one preferred embodiment, IB-MECA is administered twice a day to a subject in need of psoriasis treatment, the pharmaceutical composition including an administration dose of 2 mg.

Abstract: In one embodiment, the present application discloses synthetic LDL nanoparticles comprising mixtures of components selected from the group consisting of phospholipids, triglycerides, cholesterol ester and free cholesterol; optionally further comprising an agent selected from the group consisting of natural antioxidants, ubiquinol and vitamin E, and methods for preparing the synthetic nanoparticles. The disclosed synthetic LDL nanoparticles are capable of selectively delivering lipophilic drugs and prodrugs to cellular targets expressing LDL receptors after intra venous injection.

Abstract: Provided herein is a method of reducing intraocular pressure (IOP) in humans using N6-cyclopentyladenosine (CPA), CPA derivatives or prodrugs or enhanced cornea permeability formulations of CPA. In one embodiment, the invention is directed to CPA derivatives or prodrugs that are permeable to the cornea. In another embodiment, the invention is directed to uses of certain compounds in human subjects for reducing and/or controlling elevated or abnormally fluctuating IOPs in the treatment of glaucoma or ocular hypertension (OHT).

Abstract: Provided herein are compositions and formulations comprising S-adenosyl-L-methionine (“SAM-e” or “SAMe”) and one or more gallic acid esters. Also provided herein are methods for improving the delivery of SAMe. Compositions and formulations provided herein increase SAMe plasma concentrations and area under the curve (AUC) values. Also provided herein are methods of treating a disease or disorder in a subject by administering compositions or formulations comprising exogenous SAMe and one or more gallic acid esters.

Abstract: The invention includes compositions and methods of treatment of cancers susceptible to treatment with nucleotide analog chemotherapeutic agent, including cancers in which nucleotide analog resistant tumors have developed, including identifying a subject having cancer susceptible to treatment with a nucleotide analog chemotherapeutic agent and a mitotic disruptor/polo-like kinase (Plk) pathway inhibitor to a subject; and monitoring the subject for a reduction or stabilization of at least one sign or symptom of cancer.

Abstract: A method for preventing stroke in a patient suffering from atrial fibrillation, wherein the patient has at least one risk factor for major bleeding events, the method comprising administering to the patient 110 mg b.i.d. of dabigatran etexilate, optionally in the form of a pharmaceutically acceptable salt thereof.

Abstract: The present invention is directed to novel treatment of controlling hippocampal neural circuit hyperexcitability occurring in a neurological disease or disorder associated with epileptogenesis in a subject in need of such treatment, comprising the step of contacting the hippocampus in said subject with a compound effective to restore excitatory/inhibitor balance thereby controlling the neural circuit hyperexcitability. Further provided is a method of treating a neurological disease or disorder associated with epileptogenesis in a subject in need of such treatment, comprising the step of administering an amount of an adenosine A1 receptor agonist pharmacologically effective to block epileptogenetic activities without blocking excitatory synaptic transmission.

Abstract: In various embodiments, the present invention describes materials and methods for the local reprogramming of cells in a location where the treatment is applied. The invention can be used to replace lost cells or to restore function to tissue damaged due to disease, injury or genetic defect. In various embodiments, the treatment includes a semisolid hydrogel embedded with liposomes. The liposomes can contain an effector molecule or molecules. When phagocytic cells such as monocytes infiltrate the hydrogel, they encounter the liposomes and incorporate the liposomes carrying the effector molecules into the cells. In some embodiments, the effector molecules can be genetic material encoding the expression of specific proteins such as transcription factors, the expression of which can initiate the reprogramming of the cells. In other embodiments, the effector molecules can induce angiogenesis. In other embodiments, the effector molecules are tumor antigens.

Abstract: Provided herein are compounds, compositions and methods for the treatment of liver disorders, including HCV infections. In one embodiment, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents.

Abstract: The present disclosure relates to compositions and methods for treating retinal damage and/or retinal degradation. More specifically, this disclosure relates to methods for treating degradation of the retinal pigment epithelium by administering compositions comprising a nucleoside and/or a nucleoside or nucleotide reverse transcriptase inhibitor.

Abstract: The present invention is directed to a combination or a kit comprising a prostaglandin analog and an adenosine receptor A1 agonist and to a method of reducing intraocular pressure (IOP) in a subject using such combination or kit. The invention is particularly directed to a combination of latanoprost marketed under the brand Xalatan™ and Compound A.

Abstract: The disclosure provides a new use of adenosine analogs for the treatment of pain through activation of neurokinin 1 (NK1) receptor signaling pathway, thereby inducing the activation of M-type potassium channel to induce outward currents. A method and pharmaceutical composition for treating pain comprising an adenonsine analog that activates NK1 receptor signaling, thereby inducing outward current are also provided.

Abstract: This application describes compositions, methods of treatment, and methods of manufacturing a medicament for reducing injury or damage to cells, tissues or organs during ischemia, reperfusion, or following ischemia or trauma. The methods for reducing damage to a cell, tissue or organ comprise administering an effective amount of a composition including (i) a potassium channel opener or agonist and/or adenosine receptor agonist; and (ii) an antiarrhythmic agent. The methods may further include postconditioning the cell, tissue or organ.

Abstract: Many pathogens, including Mycobacterium tuberculosis and Yersinia pestis, rely on an iron acquisition system based on siderophores, secreted iron-chelating compounds with extremely high Fe(III) affinity. The compounds of the invention are inhibitors of domain salicylation enzymes, which catalyze the salicylation of an aroyl carrier protein (ArCP) domain to form a salicyl-ArCP domain thioester intermediate via a two-step reaction. The compounds include the intermediate mimic 5?-O—[N-(salicyl)sulfamoyl]-adenosine (salicyl-AMS) and analogs thereof. These compounds are inhibitors of the salicylate activity of MbtA, YbtE, PchD, and other domain salicylation enzymes involved in the biosynthesis of siderophores. Therefore, these compounds may be used in the treatment of infection caused by microorganisms which rely on siderphore-based iron acquisition systems.

Abstract: The present invention relates to a method of reducing injury to cells, a tissue or organ to be explanted from a body and upon implantation into a body by administering a composition to the cell, tissue or organ, including: (i) a potassium channel opener or agonist and/or an adenosine receptor agonist; and (ii) an antiarrhythmic agent. The invention also provides a composition for reducing injury to vasculature ex vivo including: (i) a potassium channel opener or agonist and/or an adenosine receptor agonist; and (ii) an antiarrhythmic agent.

Abstract: The present invention provides a method of myocardial perfusion imaging using reduced doses of (1-{9-[(4S,2R,3R,5R)3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-aminopurin-2-yl}pyrazol-4-yl)-N-methylcarboxamide.

Abstract: The present invention relates to novel compositions having anti-viral activity and in particular it relates to synergistic compositions active against Hepatitis C virus (HCV). The invention also relates to methods for retarding, reducing or otherwise inhibiting HCV growth and/or functional activity.

Abstract: Compounds for use in the treatment of human immunodeficiency virus (HIV) infection are disclosed. The compounds have the following Formula (I): including stereoisomers and pharmaceutically acceptable salts thereof, wherein R1, X, Y1, Y2, or L are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

Abstract: The present disclosure concerns the A3 adenosine receptor agonist, 2-Chloro-N6-(3-iodobenzyl)-adenosine-5?-N-methyluronamide (Cl-IB-MECA) in an amount of at least about 10 mg/day, for use in treatment of hepatocellular carcinoma (HCC). The present invention also provides Cl-IB-MECA for use in maintenance of liver function in a subject having a chronic liver disease, such as cirrhosis. The liver function is considered as maintained if level of at least one physiological parameter indicative of liver function is essentially constant between two or more time points, i.e. the difference between the two time points does not exceed a medically acceptable tolerance.

Abstract: 2? and/or 3? prodrugs of 1?, 2?, 3? or 4?-branched nucleosides, and their pharmaceutically acceptable salts and derivatives are described. These prodrugs are useful in the prevention and treatment of Flaviviridae infections, including HCV infection, and other related conditions. Compounds and compositions of the prodrugs of the present invention are described. Methods and uses are also provided that include the administration of an effective amount of the prodrugs of the present invention, or their pharmaceutically acceptable salts or derivatives. These drugs may optionally be administered in combination or alteration with further anti-viral agents to prevent or treat Flaviviridae infections and other related conditions.

Abstract: The present invention provides an efficient process for the synthesis of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol and hydrates thereof and methods for treating disorders in which DOT1-mediated protein methylation plays a part, such as cancer and neurological disorders, by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also provides novel crystalline forms of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol and hydrates thereof (Form A, Form B, and Form C), characterized by a unique X-ray diffraction pattern and Differential Scanning Calorimetry profile, as well as a unique crystalline structure.

Abstract: The invention provides methods and compositions for stimulating or promoting bone regeneration or repairing bone fracture or for stimulating or increasing differentiation or activation of osteoblasts by administering to a subject a therapeutically effective amount of an adenosine receptor agonist, or an analog, derivative or combination thereof, an adenosine receptor antagonist, or an analog, derivative or combination thereof, or adenosine or a compound that upregulates, increases the amount of or increases the biological activity of adenosine. The invention also extends to pharmaceutical compositions such as those comprising an agent that modulates an adenosine receptor such as an adenosine A2A agonist or A1 antagonist.

Abstract: Methods for detecting the presence and/or assessing the severity of myocardial ischemia during pharmacologic stress tests by administration of a pharmaceutical composition comprising adenosine and dipyridamole are described. The methods allow for the combined administration of dipyridamole administered as a bolus with adenosine given as an infusion, where the dosages of each of these compounds are below their respective dosages when the compounds are used as a single agent. The methods are useful for exploiting the vasodilating abilities of adenosine at doses at which side effects related to adenosine are substantially reduced while optimal coronary artery perfusion is achieved. Also presented, are compositions, unit dosage forms, and kits that are useful in performing the methods.

Abstract: This invention relates to a method of treating B cell malignancies, which involves administering to a subject a compound having a structure of formula (I) to cause cell death of a B cell malignancy, thereby treating the B cell malignancy in the subject. Also disclosed are a method of causing cell death of malignant B cells, pharmaceutical compositions and therapeutic systems comprising a compound having a structure of formula (I), and a compound having a structure of formula (I).

Abstract: Disclosed herein are nucleosides, nucleotides and analogs thereof, pharmaceutical compositions that include one or more of nucleosides, nucleotides and analogs thereof, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a disease and/or a condition, including an infection from a norovirus, with a nucleoside, a nucleotide and an analog thereof.

Abstract: The present invention relates to compounds of formula (I): wherein Rj, R2, R3, R4, Xi, X2, X3 and Z are as defined in claim 1. The compounds are useful in the prevention and/or treatment of bacterial infections.

Abstract: Disclosed herein are nucleosides, nucleotides and analogs thereof, pharmaceutical compositions that include one or more of nucleosides, nucleotides and analogs thereof, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a paramyxovirus viral infection, with a nucleoside, a nucleotide and an analog thereof.

Abstract: The present invention provides novel heteroaryl compounds of formula (I) having a pyrimidine-containing core that is linked to a 4-trifluoromethoxyphenyl group via an amine linker. Such compounds are useful for the treatment of cancers.

Abstract: The invention relates to the therapeutic uses of 2?,5?-oligoadenylate derivative compounds, more particularly for the treatment of chronic fatigue syndrome (CFS) and in the treatment of infection by a gamma-retrovirus.

Abstract: Compositions and methods to improve the pharmacokinetic profile of S-Adenosylmethionine (SAMe) are provided, as are methods of treating various disorders using SAMe formulations with improved pharmacokinetic profiles. More specifically, the invention is directed to methods of treating a disease or disorder in a subject and/or improving the nutritional status of a subject by administering formulations exhibiting improved pharmacokinetic profiles of exogenous SAMe. The method also includes the step of orally administering compositions of the invention to the subject once per day after overnight fast; that is prior to food intake in the morning.