Abstract: Disclosed herein are methods for diagnosing a pregnancy related hypertensive disorder or a predisposition to a pregnancy related hypertensive disorder by measuring the level or biological activity of soluble endoglin. Also disclosed herein are methods for treating a pregnancy related hypertensive disorder, such as pre-eclampsia and eclampsia, using compounds that alter soluble endoglin levels or biological activity.

Abstract: Provided herein is a pharmaceutical composition or a kit comprising a combination of a carbonic anhydrase inhibitor analog and an adenosine A1 receptor agonist. Also provided herein is a method of reducing intraocular pressure (IOP) in a subject using such a combination or kit. In a particular embodiment, provided herein is a combination of dorzolamide marketed under the brand Trusopt™ and Compound A.

Abstract: The present invention is directed to a benzyloxy cyclopentyladenosine (BCPA) compounds and to their use as selective A1 adenosine receptor agonists. The compounds of the invention are particularly directed to use in subjects for reducing and/or controlling elevated or abnormally fluctuating IOPs in the treatment of glaucoma or ocular hypertension (OHT).

Abstract: The present invention provides a method of optimizing therapeutic efficacy and reducing toxicity associated with 6-mercaptopurine drug treatment of an immune-mediated gastrointestinal disorder such as inflammatory bowel disease. The method of the invention includes the step of determining the level of one or more 6-mercaptopurine metabolites in the patient having an immune-mediated gastrointestinal disorder.

Abstract: The invention provides methods for treating or preventing psychiatric and substance abuse disorders, involving administration of a therapeutically-effective amount of a cytosine-containing or cytidine-containing compound, creatine-containing compound, adenosine-containing, or adenosine-elevating compound to a mammal.

Abstract: A method of supplementing a diet and ameliorating oxidative stress in a mammal includes administering a pharmaceutically effective amount of lipid soluble, hydrophobic active compounds having a chemical structure: wherein R1 is an aromatic backbone and R2 is a sulfur containing ligand. Through formation of disulfide linkages other moieties can be attached to R2 converting the hydrophobic base into a water soluble entity, for ease of delivery, which can be reconverted back to the original compound by biochemical reduction in the blood stream.

Abstract: Formulations for systemic buccal delivery, in particular chewing gums, chewable tablets, orodispersible tablets, oromucosal preparations comprising sulpho-adenosyl-L-methionine (SAMe) which allows the absorption of the active principle through the oral mucosa are described.

Abstract: Described herein are assays, kits and methods for treating mood disorders by testing for one or more polymorphisms in a specific group of genes and for analyzing the results of polymorphism testing; the genes included may converge in one or more signaling pathways, and may be epigenetic. The genes are included based on the relationships of the proteins encoded by the genes in the context of particular signaling pathways and provide a diagnostically relevant nexus. Also described herein are methods of presenting the data collected by the screen, including methods of delivering interpretive comments and/or treatment guidance based on the results of the genetic screening either individually or based on the genetic composition of particular clusters of genes which may be related to each other. Importantly, drugs which modulate these genetic disturbances are described for targeted therapeutic use based upon companion diagnostic method.

Abstract: The present invention provides antioxidant compositions comprising S-adenosylmethionine (SAMe), vitamin E and vitamin C and uses thereof for the treatment of liver injury and insulin resistance.

Abstract: The invention provides methods for, and compositions effective for, treating obesity, inhibiting weight gain, treating diabetes mellitus, inhibiting atherosclerosis and treating related disorders and conditions comprising administering a pharmaceutically effective amount of at least one compound capable of inhibiting AC5 to a patient. The compound capable of inhibiting AC5 may be administered singly or in combination with another agent. In some embodiments, the AC5 inhibiting compound is 9-?-D-arabinofuranosyladenine (AraAde). The compounds may be administered in an amount of about 1 to about 200 mg/kg/day, about 1 to about 100 mg/kg/day, about 10 to about 80 mg/kg/day, about 12 to about 40 mg/kg/day or about 15 to about 25 mg/kg/day. In some embodiments, the compound is administered orally.

Abstract: The invention provides compositions comprising a therapeutically effective amount of a compound of general formula (I): wherein R1, R2 and R3 may be independently selected from H, OH and OMe; wherein X is C1 or C2 and wherein for C2 each carbon is linked by a single or multiple bond (preferably a double bond) and is substituted with one or more H or OH; for use as a medicament for treating or preventing the development of medical conditions characterised by inappropriate platelet aggregation.

Abstract: The invention provides a method of treating noise-induced hearing loss, the method including the step of administering an A1 adenosine receptor agonist to a patient in need thereof. In a particularly preferred embodiment the A1 adenosine receptor agonist is a selective A1 adenosine receptor agonist.

Abstract: Disclosed are a novel combination of specific therapeutics selected from S-adenosyl methionine or a salt thereof, folic acid or a metabolite or salt thereof, and one or more omega-3 fatty acids or salts thereof, useful for a variety of conditions, as discussed herein. Methods of treatment include the treatment of neuropsychiatric conditions, such as depression.

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: The present invention relates to the diagnosis and treatment of cancer, and in particular breast cancer. Specifically, in some embodiments the invention relates to methods of diagnosing cancer, and in particular breast cancer, using an antibody specific for a gene product that localizes selectively to the endoplasmic reticulum of the cancer cell(s). In some embodiments, the invention relates to methods of treating cancer, and in particular breast cancer, by administering a composition comprising an RNA interference sequence (e.g., shRNA, RNAi and/or siRNA molecule) characterized by an ability to inhibit an mRNA molecule, which mRNA molecule is encoded by the C43 gene (SEQ ID NO: 1). The invention additionally relates to methods for detecting cancer cells by detecting reduced methylation of the C43 promoter, and methods for reducing cancer metastasis by using demethylation inhibitors that result in increased methylation of the C43 promoter.

Abstract: A method and chemical composition for modifying and dissolving atherosclerotic plaques formed in a patient's blood vessels is provided. A chemical composition comprising one or more of an organic substance, an inorganic substance, and a bioactive substance is administered at sites of the plaques. The chemical composition comprises one or more of d-limonene, propylene glycol, octanoic acid, 2-octane, glycerine, acetylsalicylic acid, acetic acid, omega-3 fatty acids, ethanol, methanol, ezetimibe, rosuvastatin, resveratrol, lactic acid, gluconic acid, chloroform, carbon disulfide, dichloromethane, toluene, lauryldimethyl hydroxysultaine, and any combination thereof. The chemical composition enables modification of plaques by altering their composition. The modification comprises partial dissolution, complete dissolution, or elimination of the plaques, and makes the plaques amenable to different forms of plaque treatment. The modified plaques are eliminated from the patient's body.

Abstract: The present invention relates to new quinoline inhibitors of tyrosine kinases, pharmaceutical compositions thereof, and methods of use thereof.

Abstract: The present invention relates to phosphonate, nucleoside phosphonate or nucleoside phosphate compounds, compositions containing them, processes for obtaining them, and their use in treating a variety of medical disorders, in particular viral infections, cancers and the like.

Abstract: The invention provides for novel 2-Deoxyadenosine compounds, which can treat HIV infection at low cytotoxicity values. Substitution at the 4?-position provided compounds which demonstrated low cytotoxicity values in an ATP-based cytotoxicity assay.

Abstract: Drug eluting stents (DES) useful for the treatment of restenosis are described. The stents comprise biocompatible polymers and adenosine receptor modulators.

Abstract: Provided herein are methods for identifying a subject afflicted with chronic lymphocytic leukemia who is responsive to treatment with a chemotherapeutic agent by detecting the presence or absence of at least one APOE4 allele in the subject, the presence of an APOE4 allele identifying the subject as responsive to the treatment. Also provided are methods of treating a subject afflicted with chronic lymphocytic leukemia, including administering an estrogenic agent, an androgen withdrawal agent, an apoE4 peptide or mimetic thereof, and/or a chemotherapeutic agent in an amount effective to treat said chronic lymphocytic leukemia. Methods of determining a prognosis for a patient diagnosed with chronic lymphocytic leukemia are also provided. In addition, methods for stratifying a subject into a subgroup of a clinical trial and methods for identifying a patient in a clinical trial of a treatment for chronic lymphocytic leukemia are herein provided.

Abstract: Compositions and methods for modulating HSP70 function, particularly for the targeted killing of cancer cells, are disclosed.

Abstract: The invention provides compounds of formula (I) and salts thereof: R1-L-R2—B wherein R1, L, R2, and B have any of the values defined herein, as well as compositions comprising such compounds, and therapeutic methods comprising the administration of such compounds or salts. The compounds block siderophore production in bacteria and are useful as antibacterial agents.

Abstract: The invention provides compounds having the following general formula (I): wherein X, R1, R2, R7 and Z are as described herein.

Abstract: This invention encompasses methods of preserving protein function by contacting a protein with a composition comprising one or more purine nucleosides (such as e.g., adenosine or uridine) and an antioxidant (such as e.g., manganese). In addition, the invention encompasses methods of treating and/or preventing a side effect of radiation exposure and methods of preventing a side effect of radiotherapy comprising administration of a pharmaceutically effective amount of a composition comprising one or more purine nucleosides (such as e.g., adenosine or uridine) and an antioxidant (such as e.g., manganese) to a subject in need thereof. The compositions may comprise D. radiodurans extracts.

Abstract: The invention provides novel compounds which are agonists of the adenosine 2A receptor along with pharmaceutical compositions thereof, and methods of administering such compounds.

Abstract: Methods and compositions are provided for treating a urinary tract infection (UTI). The methods involve administering to a subject in need thereof a cAMP elevator or agent that mimics cAMP, particularly a labdane diterpene such as forskolin or a derivative or analog thereof in a therapeutically effective amount to treat a UTI. The methods may further include administration of at least one cAMP elevator in combination with one or more additional active compounds from other classes of therapeutic agents, such as antimicrobial agents or cholesterol lowering drugs. Compositions of the invention include pharmaceutical compositions and kits for treating a UTI in a subject in need thereof that include therapeutically effective amounts of at least two cAMP elevators, particularly where one of the cAMP elevators is a labdane diterpene such as forskolin or a derivative or analog thereof.

Abstract: The present invention relates to taurine or taurine-like substances for the prevention of brain oedema, particularly brain intramyelinic oedema and more particularly brain intramyelinic oedema induced by an anti-convulsive drug such as vigabatrin. The invention relates to a substance selected from the group consisting of taurine, a taurine precursor, a taurine metabolite, a taurine derivative, a taurine analog and a substance required for the taurine biosynthesis for the prevention of brain oedema.

Abstract: The present invention relates to a pharmaceutical combination for the treatment of diseases which involves cell proliferation, migration or apoptosis of myeloma cells, or angiogenesis. The invention also relates to a method for the treatment of said diseases, comprising co-administration of effective amounts of specific active compounds and/or co-treatment with radiation therapy, in a ratio which provides an additive and synergistic effect, and to the combined use of these specific compounds and/or radiotherapy for the manufacture of corresponding pharmaceutical combination preparations.

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: Novel adenine derivatives of the formula (I), in which R1, R2, R3, X and Y have the meanings indicated in Claim 1, are HSP90 inhibitors and can be used for the preparation of a medicament for the treatment of diseases in which the inhibition, regulation and/or modulation of HSP90 plays a role.

Abstract: Use of compounds of formula: (I) wherein R is C1-4 alkoxy and X is H or OH; for the prevention, treatment, or amelioration of cancer, inflammation, auto-immune disease, ischemia-reperfusion injury, epilepsy, sepsis, septic shock, neurodegeneration (including Alzheimer's Disease), muscle fatigue or muscle cramp is described. The compounds are effective at very low doses, and so can be administered at doses at which serious side effects are not observed.

Abstract: The present invention relates to a method for treating recurrent tumor metastases following liver resection that includes administration of an effective amount of an agonist of A2A adenosine receptors (ARs).

Abstract: It has been discovered that certain natural mRNAs serve as metabolite-sensitive genetic switches wherein the RNA directly binds a small organic molecule. This binding process changes the conformation of the mRNA, which causes a change in gene expression by a variety of different mechanisms. Modified versions of these natural “riboswitches” (created by using various nucleic acid engineering strategies) can be employed as designer genetic switches that are controlled by specific effector compounds. Such effector compounds that activate a riboswitch are referred to herein as trigger molecules. The natural switches are targets for antibiotics and other small molecule therapies.

Abstract: This invention relates to sustained release formulations comprising silk fibroin biopolymer and adenosine, that provide for sustained, focal release of adenosine at therapeutic levels for the treatment of epilepsy and/or the prevention of epileptogenesis. An embodiment provides for a silk-based, adeno sine-releasing implant that alleviates seizures or prevents epileptogenesis. Another embodiment provides for a method of treating epilepsy or preventing epileptogenesis comprising focally administering adenosine in a sustained-release, silk-based adenosine delivery system.

Abstract: A method for determining a therapeutically effective amount of suramin for administering to a patient, who is to receive a cytotoxic agent, which comprises the steps of determining the circulating suramin concentration in the patient; administering suramin, if required, to establish a low circulating concentration of suramin in the patient of below about 200 ?M; and administering the chemotherapeutic agent to the patient when the low circulating concentration of suramin is present in the patient. Conveniently a nomogram can be constructed for use in clinical settings with the suramin.

Abstract: The present invention relates to pharmaceutical compositions and methods for promoting wound healing. The invention also relates to methods of making pharmaceutical compositions disclosed herein. Pharmaceutical compositions are disclosed comprising an effective amount of a 2-alkoxyadenosine or 2-aralkoxyadenosine, about 10% to about 70% w/w propylene glycol and a thickening agent.

Abstract: The present invention relates to the use of S-adenosyl-L-methionine or its salts for preparing a composition for the regulation of behavioral problems in pets.

Abstract: The present invention provides isolated or substantially purified polypeptides, nucleic acids, and virus-like particles (VLPs) derived from a Merkel cell carcinoma virus (MCV), which is a newly-discovered virus. The invention further provides monoclonal antibody molecules that bind to MCV polypeptides. The invention further provides diagnostic, prophylactic, and therapeutic methods relating to the identification, prevention, and treatment of MCV-related diseases.

Abstract: The invention provides compounds having the following general formula (I): wherein X, R1, R2, R7 and Z are as described herein.

Abstract: The invention relates to methods for transdifferentiation of body tissues which can be used to generate specific cell types needed for regenerating organs or body parts, following cellular degeneration, injury or amputation. The present invention also describes the use of tissue transdifferentiation for treating cancer and autoimmune diseases.

Abstract: A pharmaceutical composition for induction therapy which has a hypomethylating agent and a histone deacetylase inhibitor (“HDAC inhibitor”); wherein the hypomethylating agent is a DNA and histone methylation inhibitor such as cladribine and the HDAC inhibitor is, for example, entinostat, panobinostat, vorinostat, and/or romedepsin; further wherein the hypomethylating agent and the HDAC inhibitor are combined in formulations for various administrations including e.g., a continuous delivery system such as a transdermal patch of at least one reservoir or a plurality of reservoirs, oral, a fixed-dose oral combination, intravenous, and combinations thereof. This pharmaceutical composition for induction therapy is used with a monoclonal antibody in the treatment of various cancers, sarcomas, and other malignancies.

Abstract: The present invention is directed to method of modulating a heat shock response in a first cell of a multicellular organism comprising stimulating or inhibiting an HSR signaling activity of a second cell, wherein the second cell is a neuronal cell that regulates heat shock response activation in the first cell and that does not directly innervate the first cell.

Abstract: The present invention concerns nitrogenated derivatives of narciclasine and pancratistatin of the following general formula (I) as well their pharmaceutically acceptable salts. The present invention also concerns the use of these compounds in cancer therapy as well as a method for their preparation.

Abstract: Provided herein is an ophthalmic formulation that comprises a fine particle of an A1 agonist in an aqueous suspension and a manufacturing process thereof. More specifically, provided herein is a topically applied ophthalmic aqueous suspension which is obtainable by suspending a fine particle of an A1 agonist in a surfactant and preservative; a method of reduction of intraocular pressure using the formulation and a manufacturing process of the aqueous suspension thereof.

Abstract: This invention is directed to a method of preventing or treating diseases or conditions associated with platelet aggregation. The method is also directed to a method of treating thrombosis or related disorders. The method comprises administering to a subject a pharmaceutical composition comprising an effective amount of a non-nucleotide compound, preferably a P2Y12 receptor antagonist compound, wherein said amount is effective to inhibit platelet aggregation. The compounds useful for this invention include compounds of general Formulae I and III-XII, or salts, hydrates, and solvates thereof. The present invention also provides novel compounds of Formulae I and III-XII.

Abstract: The invention is directed to 3-?-D-ribofuranosylthiazolo[4,5-d]pyrimidine nucleosides and pharmaceutical compositions containing such compounds that have immunomodulatory activity. The invention is also directed to the therapeutic or prophylactic use of such compounds and compositions, and to methods of treating diseases and disorders described herein, by administering effective amounts of such compounds.

Abstract: The present disclosure provides methods of treating a hepatitis C virus infection. The methods generally involve administering to an individual in need thereof an effective amount of an active agent that inhibits a RAS-RAF-MEK-ERK signal transduction pathway.

Abstract: Methods and formulations for treating oncological disorders in humans using epimetabolic shifters, multidimensional intracellular molecules or environmental influencers are described.

Abstract: The invention pertains to methods for treating ectopic pregnancy. More particularly, the present invention relates to methods for treating unruptured ectopic pregnancy using a non-surgical method comprising the administration of an EGFR inhibitor alone or in combination with an anti-metabolite e.g. methotrexate (MTX). The methodology is potentially applicable to treatment of unruptured ectopic pregnancies of all sizes.