Abstract: The invention relates to control of biofilm development. Specifically, some embodiments of the present invention relate to control of bacterial biofilm formation through addition or breakdown of signal(s) that induce biofilm formation. More specifically, some embodiments of the present invention relate to control (e.g., promotion, prevention) of biofilm development by application or hydrolysis of adenosine triphospate (ATP), deoxyadenosine triphosphate (dATP), or derivatives or analogs thereof (e.g., through application or administration of an agent that hydrolyzes ATP, dATP, or derivatives or analogs thereof (e.g., apyrase)).

Abstract: Compounds having the formula I or II, wherein R1, R2, B, and V are as defined herein, are Hepatitis C virus NS5b polymerase inhibitors. Also disclosed are compositions and methods for treating an HCV infection and inhibiting HCV replication.

Abstract: A method and preparation for the stimulation of tear secretion in a subject in need of such treatment is disclosed. The method comprises administering to the ocular surfaces of the subject a purinergic receptor agonist such as uridine 5?-triphosphate (UTP), dinucleotides, cytidine 5?-triphosphate (CTP), adenosine 5?-triphosphate (ATP), or their therapeutically useful analogs and derivatives, in an amount effective to stimulate tear fluid secretion and enhance drainage of the lacrimal system. Pharmaceutical formulations and methods of making the same are also disclosed. Methods of administering the same would include: topical administration via a liquid, gel, cream, or as part of a contact lens or selective release membrane; or systemic administration via nasal drops or spray, inhalation by nebulizer or other device, oral form (liquid or pill), injectable, intra-operative instillation or suppository form.

Abstract: Embodiments of the invention include nucleotide and nucleoside monomers protected at the 5?- or 3?-hydroxyls with thioether substituted aryl carbonate protecting groups. In certain cases, the carbonate protecting groups include an aryl moiety, e.g., a phenyl group, attached to the carbonate, where the aryl moiety further includes a thioether group, e.g., an alkyl or aryl thioether group, bound directly to the aryl ring. Aspects of the invention further include methods of synthesizing nucleic acids, e.g., oligonucleotides, using such protected nucleoside monomer monomers, as well as nucleic acids produced using methods of the invention and compositions thereof.

Abstract: A lipid vesicle comprising a phospholipid which is a stable vesicle former and at least one unstable vesicle forming member, wherein the unstable vesicle forming member is selected from the group consisting of a polar lipid which is not a stable vesicle former, a PEG, a raft former and a fusion protein is provided. The vesicle can further comprise a biomolecule, such as for example ATP. Methods of using the vesicle for delivery of biomolecules are also provided.

Abstract: The present invention provides methods and compositions for the prophylaxis of blood cell disorders such as neutropenia, thrombocytopenia, lymphocytopenia, and anaemia. The invention provides methods wherein compositions comprising at least one cytokinin compound are administered either therapeutically or prophylactically. The invention further has utility in methods of DNA repair.

Abstract: Provided herein are methods of reducing adhesion formation in a subject, for example, post-surgical abdominal and pelvic adhesions. The methods comprise administering to the subject a compound chosen from one or both of 2?,3? cyclic adenosine monophosphate, or an analogue or pharmaceutically acceptable salt thereof, able to reduce the formation of adhesions in a subject as compared to adenosine monophosphate, wherein the 2?,3? cyclic adenosine monophosphate, or analogue or pharmaceutically acceptable salt thereof, is administered to the subject in an amount effective to reduce adhesions in the subject.

Abstract: The present invention relates to the use of oxidized nicotinamide adenine dinucleotide (NAD+) or of its reduced form, NADH, as sodium channel modulators. The present invention also relates to the use of compositions containing NAD+ or NADH to treat conditions associated with sodium channel current, such as arrhythmia. NAD+ is found to increase sodium channel current, while NADH is found to decrease sodium channel current. Thus, conditions that are associated with decreased sodium channel current can be treated with NAD+, while conditions that is associated with increased sodium channel current can be treated with NADH.

Abstract: A method of treating or preventing a disease or condition in a subject that was previously treated with at least one thienopyhdine is described. The method includes administering to the subject an effective amount of at least one reversible, short-acting P2Yi2 inhibitor. The described method can be used for subjects diagnosed with symptoms such as stable or unstable angina, vascular ischemic events, atherosclerosis, acute coronary syndrome, as well as STEMi or N-STEMI. The described method can also be used for patients having previously received a stent, such as a bare metal stent or a drug-eluting stent, and the treatment or prevention of stent thrombosis. The method can be used prior to, during, or after an invasive procedure such as coronary artery bypass grafting, percutaneous coronary intervention, or other genera! surgical procedure.

Abstract: The present invention provides methods to treat mood disorders and anxiety disorders using antagonists of the P2X7 receptor and pharmaceutical compositions thereof, or combinations.

Abstract: 8-quinolinol (8Q) and derivatives thereof for use in the treatment of proliferative diseases such as cancer, in particular slow metabolizing quiescent cancer stem cells.

Abstract: The present invention encompasses compositions and methods that activate P2Y receptors for the increased production of new synapses in the central nervous system. The formulations of the invention may be administered to a healthy subject or to a subject in need thereof to restore synapses.

Abstract: Methods of treating disorders such as neurofibromatosis-1 are provided, including methods in which catalytic antioxidants such as metalloporphyrins are administered. Methods of regulating longevity, and methods and systems for screening for modulators of aging or longevity, are also provided. In addition, related transgenic animals are described.

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: An object of the present invention is to provide a composition for external application that is applied to a part of the skin to more effectively elicit the useful effects of an adenine compound such as adenine, adenosine, and a phosphoric ester of adenosine, and that has long-lasting effects and enhanced skin-moisturizing effects. A gel composition for external application containing an adenine compound such as adenine, adenosine, and a phosphoric ester of adenosine is prepared by using agar as a gelling agent. The gel composition is further prepared in the form of a sheet-like adhesive patch. The gel composition in the form of a sheet-like adhesive patch is kept immersed in an aqueous solution containing the adenine compound.

Abstract: The invention provides methods for treating various conditions using derivatives of cyclopamine having the following formula:

Abstract: A method of treating an ocular surface disorder in a subject in need of such treatment is provided. The method includes exposing conjunctival tissue of the subject to an effective amount of a vasopermeability agent that increases conjunctival vascular permeability. In some embodiments, the agent is a nitric oxide donor, which may be in a sustained release form. A method of screening a substance for treating an ocular surface disorder is also provided.

Abstract: Inventors have discovered a method for inducing bone formation in a patient in need thereof comprising administering an effective amount of benzoyladenosine-3?,5?-cyclic monophosphate (6-Bnz-cAMP) to the patient. Systems for bone tissue engineering, comprising a polymer-based scaffold, such as a PLAGA scaffold and an effective amount of 6-Bnz-cAMP are also disclosed herein.

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 present invention provides compositions methods for treating susceptible viral infections, especially hepatitis C viral (HCV) infections as well as co infections of HCV with other viruses such as HBV and/or HIV. In one embodiment, the present invention provides compositions having the formula (I) and their use in treating viral infections: or a pharmaceutically acceptable salt, ester, stereoisomer, tautomers, solvate, prodrug, or combination thereof.

Abstract: Compositions are provided that contain a combination of a nitric oxide-cobalamin complex along with at least one cobalamin drug conjugate, together with methods for their use in the treatment of neoplastic disease.

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: Inhibitors of saporin-L1 are disclosed, as are related compositions and uses thereof, in particular in cancer therapy that employs saporin-L1-linked immunotoxins.

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 present invention provides a composition that can effectively improve melasma and a composition that can effectively reduce skin dullness. The composition for improving melasma comprises a purine nucleic acid-related substance and a pharmaceutically or cosmetically acceptable carrier, and exhibits an excellent melasma improving effect due to the action of the purine nucleic acid-related substance contained. The composition for reducing skin dullness comprises a purine nucleic acid-related substance and a pharmaceutically or cosmetically acceptable carrier, and exhibits an excellent effect of reducing skin dullness due to the action of the purine nucleic acid-related substance contained.

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: Methods and compositions for protecting and treating a muscarinic receptor in a subject in need thereof from dysfunction not resulting from oxidative stress, toxic actions of metals or metal ions, or infectious agents by administering a pyrophosphate analog.

Abstract: The present invention refers to active substance combinations comprising of a nucleoside analog or antimetabolic agent like Gemcitabine, and either a Nodal/Activin inhibitor or a SHH-Inhibitor and an mTOR-inhibitor, medicaments comprising the same and the use of the active substance combinations in the treatment of cancer, especially of epithelial cancer.

Abstract: The invention is related to salts of anti-viral compounds, compositions containing such salts, and therapeutic methods that include the administration of such salts, as well as to processes and intermediates useful for preparing such salts.

Abstract: There are disclosed skin treatment compositions containing cell signaling compounds, which induce and promote the biosynthesis and/or bioactivity of endogenous chemicals that mediate cell to cell communication in the skin between keratinocytes, fibroblasts and other cell types present in the skin. The cell signaling compound is selected from the group consisting of: andrographolide and its derivatives; adenosine cyclic phosphate and its derivatives; hydrolyzed milk proteins; sunflower seed extract; plankton extract; phytol and its derivatives; and mixtures thereof.

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: Phosphoramidate derivatives of nucleoside compounds of formula I derived from bases such as adenine and guanine have enhanced therapeutic potency, in particular, enhanced potency with respect to the prophylaxis or treatment of a viral infection such as hepatitis C virus. The glycoside moiety of the nucleoside compound is suitably substituted at the ?-2? position with methyl and the phosphoramidate group, suitably comprises 1-naphthyl linked by —O— to the P atom.

Abstract: A nutritional composition is proposed, such as an infant formula composition or an enteral composition for children 3-17 years, that is especially targeted as patients having food allergies or impairments of intestinal absorption. The composition comprises structured lipids. The composition is based on free amino acids and contains a very low amount of peptides or proteins, if any. The composition comprises a source of carbohydrate and has a particular caloric density. The composition can comprise arachidonic acid (ARA) and/or docosahexaenoic acid (DHA). The composition delivers specific nutritional benefits to the patients.

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

Abstract: A major object of the present invention is to provide a creamy O/W emulsion composition containing an adenosine phosphate ester, more specifically, to provide a creamy O/W emulsion composition containing an adenosine phosphate ester, which ensures emulsification stability and a superior feel during use. Specifically, the present invention provides a creamy O/W emulsion composition containing the following Components (A) to (F) at the following proportions based on its total amount: (A) not less than 0.1 wt. % of adenosine phosphate ester selected from at least one member selected from the group consisting of cyclic adenosine 3?,5?-monophosphate, adenosine monophosphate, adenosine diphosphate, adenosine triphosphate, and salts thereof; (B) 0.5 to 6 wt. % of polyglycerin fatty acid ester; (C) 0.05 to 0.7 wt. % of acrylic acid-alkyl methacrylate copolymer; (D) 0.5 to 10 wt. % of amphiphilic lipid; (E) 0.5 to 20 wt. % of polyhydric alcohol; and (F) 0.3 to 5 wt.

Abstract: The instant invention provides methods and compositions for the treatment, prevention and diagnosis of for example, platelet aggregation or clot formation in a subject. The invention inhibits the activity of decreases the amount of neutrophils in the subject by inhibiting the activity or production of IL-6, interferon-gamma, STAT1, or cathepsin D. The invention addresses decreasing the amount of neutrophils in an attempt to treat subjects that have or are at risk of developing a vascular occlusive disease, an ischemia or reperfusion injury, an acute or chronic inflammatory state, autoimmune disease, myelodysplastic syndrome, tissue injury from surgery or accidental trauma, acute bacterial or viral infection, has undergone a microvascular surgical reconstructive procedure, is receiving granulocyte colony stimulating factor therapy, receiving stem cell therapy, or has sickle cell anemia.

Abstract: Aortic valve stenosis (AS) is a chronic process related to a progressive mineralization of the aortic root and valve cusps. We found in human AS valves a high level of expression and enzymatic activity of ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP-1), which correlated to the degree of mineralization. In vitro, inhibition of ENPP activity with ARL 67156 significantly reduced calcification of isolated valve interstitial cells. In a rat model of cardiovascular calcification, ARL 67156 significantly reduced calcification of the aortic root and valve cusps. This is the first study to demonstrate that increased expression and activity of ENPP-1 promotes the mineralization process in AS valves. Hence, inhibition of ectonucleotidase may represent a novel target of therapy for this frequent and serious cardiovascular disease.

Abstract: Provided herein are methods of improving one or more symptoms of a dermatological condition in a patient. The methods comprise topically administering a topical composition to the patient comprising a branched chain amino acid, and an enzyme activator. Also provided are kits comprising the topical composition and optionally a topical steroid.

Abstract: The present invention is directed to a method of treating a subject with acute spinal cord injury by administering a purine receptor antagonist to the subject under conditions effective to treat spinal cord injury. The purine receptor antagonist inhibits P2X purine receptor activation. The inhibition of P2X purine receptor activation can also be used in conjunction with methods of treating a subject with spinal cord ischemia resulting from stroke or vascular insult, interruption, or mechanical injury, treating a subject with ischemic or traumatic insults of brain tissue in regions expressing P2X receptors, and for inhibiting ATP-triggered brain or spinal cord cell death.

Abstract: The present invention provides an externally applied composition capable of enhancing a stimulatory effect of an essential oil on IGF-1 secretion, the composition including (A) essential oil; and (B) at least one member selected from the group consisting of purine substances and salts thereof. Further, the present invention provides an externally applied composition capable of increasing the stratum corneum water content of the skin and maintaining transepidermal water loss at an appropriate level.

Abstract: The present invention provides methods and compositions for modulating at least one T cell-dependent immune response using an inhibitor of ATP-mediated T cell activation, such as oxidized ATP, for therapeutic and research purposes.

Abstract: The present invention relates to the use of nucleoside derivatives of formula Ia wherein the symbols are as defined in the specification, and of pharmaceutically acceptable salts thereof which inhibit HCV polymerase and are useful for treating a patient suffering from a HCV infection and to pharmaceutical compositions containing such compounds.

Abstract: The invention relates to methods for detecting and characterizing enzymatic modifications of oligosaccharides, such as heparan sulfate, and their interaction with binding partners, such as proteins, using an oligosaccharide-binding partner binding assay, such as a gel mobility shift assay. The instant invention relates to a rapid, convenient, sensitive and inexpensive method for identifying or studying oligosaccharide-binding partner interactions, identifying and characterizing structural features on oligosaccharides, identifying and characterizing binding partners, identifying agents capable of interfering with, enhancing, or facilitating the binding of an oligosaccharide to its binding partner, diagnosing conditions associated with altered oligosaccharide-binding partner binding, and generating oligosaccharide libraries and kits therefor.

Abstract: The present invention relates to novel compounds for modulating the activity of exchange proteins directly activated by cAMP (Epacs). In particular, the present invention relates to cAMP analogues that specifically modulate the activity of Epacs. Examples of the compounds of the invention are substituted deoxyadenosine-cyclic monosphosphates. The invention further relates to pharmaceutical compositions comprising the novel compounds, and the use of the compounds in the treatment of diseases like cancer, chronic inflammation, thrombosis and/or type-2 diabetes mellitus in humans and/or animals.

Abstract: The present invention relates to the discovery the 5?-AMP and analogues thereof can be used to induce a state of torpor or suspended animation in subjects, as exemplified by studies carried out in laboratory mice. In these studies; mice were injected with high doses of 5?-AMP, which was found to result in a decoupling of the animals' body temperature regulation mechanism accompanied by a reduction in the animals' core body temperature, which tended to lower towards the ambient environmental temperature. It was further discovered that the introduction of high levels of 5?-AMP resulted in an induction of fat regulation genes such as procolipase (Clps) in tissues and organs that do not normally express Clps, this in turn was accompanied by a shift in metabolism from a primarily glycolytic energy metabolism (which is inhibited at lower temperatures) to one that relied primarily on the liberation and metabolism of free fatty acids.

Abstract: The present invention provides a regeneration promoter for regenerating tissue with the use of somatic stem cells. The invention also provides a cell fusion promoter comprising ATP or its metabolite which is safely usable in vivo, a method of producing fused cells in the presence of ATP or its metabolite and a related pharmaceutical composition for regenerating or improving the function of a tissue or an organ in a subject suffering from dysfunction or hypofunction due to injury or denaturation.

Abstract: The invention described herein features methods, compositions, and kits for the use of activators of PKM2 for the treatment, prevention, or amelioration of diseases related to PKM2 function, including, e.g., cancer, diabetes, atherosclerosis, restenosis, obesity, autoimmune disorders, and proliferative disorders.

Abstract: A2A agonists of formula (I) is provided, wherein R1, R2, R4, R5, X, Y, Z, n, p, and q are as described herein. Also provided are compositions comprising and methods of using compounds of formula (I).

Abstract: The invention relates to the use of alkylphosphocholines in combination with antimetabolites for the treatment of multiple myeloma, colon cancer or renal cancer. Preferred alkylphosphocholines are described by the Formula II. A particularly effective treatment includes administering a combination of perifosine and capecitabine.

Abstract: The invention relates to a combination which comprises (a) a DNA damaging agent; and (b) 4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]-N-[5-(4-methyl-1H-imidazol-1-yl)-3-(trifluoromethyl)phenyl]benzamide (“nilotinib”); a pharmaceutical composition comprising such a combination and optionally at least one pharmaceutically acceptable carrier for simultaneous, separate or sequential use, in particular for the treatment chronic lymphocytic leukemia (CLL); the use of such a combination for the preparation of a medicament for the treatment of CLL; a commercial package or product comprising such a combination; and to a method of treatment of a warm-blooded animal, especially a human.