Abstract: The present invention provides an apoptosis inducer comprising, as active ingredients, a compound selected from the group consisting of di(alkylcarbonyl) phosphatidylcholine, di(alkylcarbonyl) phosphatidylalkanolamine, di(alkylcarbonyl) phosphatidylinositol and di(alkylcarbonyl) phosphatidylserine.

Abstract: The present invention discloses a method for therapeutically treating an animal, including a human, for psychosomatic, depressive and neuropsychiatric diseases, such as anxiety, depression, insomnia, schizophrenia, epilepsy, spasm and chronic pain. Administration of a suitable attractin inhibitor causes the reduction of activity in the enzyme attraction or in isoforms thereof in the brain of mammals and leads as a causal consequence to a reduced degradation of the neuropeptide Y (NPY) and similar substrates. Such treatment will result in a reduction or delay in the decrease of the concentration of functionally active neuronal NPY (1-36). As a consequence of the resulting enhanced stability of the endogenous NPY (1-36), NPY activity is prolonged thereby resulting among other things in functionally active NPY Y1 receptor activity thereby facilitating antidepressive, anxiolytic, analgesic, t antihypertension and other neurological effects.

Abstract: Novel methods are provided for the treatment or prevention of T cell mediated conditions in a mammal that comprise administering to said mammal a therapeutically effective amount of a pharmaceutical composition comprising at least one DR6 agonist or DR6 antagonist.

Abstract: The present invention relates to methods of treating obesity, diabetes, sexual dysfunction, atherosclerosis, insulin resistance, impaired glucose tolerance, hypercholesterolemia or hypertrigylceridemia using a neurotensin receptor ligand. The present invention also relates to pharmaceutical compositions and kits that comprise a neurotensin receptor ligand.

Abstract: Compounds that are vancomycin analogs bearing terminal carboxyl group modifications as well as modifications to the vancosamine nitrogen and, optionally, modifications to the C6 position of the glucose residue attached to the amino acid four of the vancomycin heptapeptide chain are disclosed. Methods of making the compounds and methods of using the compounds to treat a bacterial infection in a host are also disclosed.

Abstract: The present invention relates to a method of inhibiting desensitization of a cell to the effects of a compound. The method comprises contacting the cell with an agent capable of inhibiting phosphorylation, by a protein kinase, of a receptor for the compound present on the surface of the cell. The present invention also relates to a method of screening a compound for its ability to inhibit desensitization.

Abstract: This invention provides an isolated nucleic acid encoding a human MCH1 receptor, a purified human MCH1 receptor, vectors comprising isolated nucleic acid encoding a human MCH1 receptor, cells comprising such vectors, antibodies directed to a human MCH1 receptor, nucleic acid probes useful for detecting nucleic acid encoding human MCH1 receptors, antisense oligonucleotides complementary to unique sequences of nucleic acid encoding human MCH1 receptors, transgenic, nonhuman animals which express DNA encoding a normal or mutant human MCH1 receptor, methods of isolating a human MCH1 receptor, methods of treating an abnormality that is linked to the activity of a human MCH1 receptor, as well as methods of determining binding of compounds to mammalian MCH1 receptors. This invention further provides a method of treating a subject suffering from urinary incontinence which comprises administering to the subject an amount of an MCH1 antagonist effective to treat the subject's urinary incontinence.

Abstract: A method of inhibiting the release of a proinflammatory cytokine in a cell is disclosed. The method comprises treating the cell with a cholinergic agonist. The method is useful in patients at risk for, or suffering from, a condition mediated by an inflammatory cytokine cascade, for example endotoxic shock. The cholinergic agonist treatment can be effected by stimulation of an efferent vagus nerve fiber, or the entire vagus nerve.

Abstract: The present invention discloses an artificial skin formation promoting agent and skin basement membrane stabilizing agent comprising matrix metalloproteinase inhibitor or matrix metalloproteinase inhibitor and matrix protein production promoting agent; as well as a production method of artificial skin comprising adding matrix metalloproteinase inhibitor or matrix metalloproteinase inhibitor and matrix protein production promoting agent to an artificial skin formation medium.

Abstract: The invention concerns methods of treating fibroproliferative disorders associated with TGF-&bgr; signaling, by administering non-peptide small molecule inhibitors of TGF-&bgr; specifically binding to the type I TGF-&bgr; receptor (TGF&bgr;-R1). Preferably, the inhibitors are quinazoline derivatives. The invention also concerns methods for reversing the effect of TGF-&bgr;-mediated cell activation on the expression of a gene associated with fibrosis, comprising contacting a cell or tissue in which the expression of such gene is altered as a result of TGF-&bgr;-mediated cell activation, with a non-peptide small molecule inhibitor of TGF-&bgr;, specifically binding a TGF&bgr;-R1 receptor kinase present in the cell or tissue.

Abstract: Compounds of the formula (I), in which the variables have the following meaning, D is phenyl or pyridyl, each of which is unsubstituted or monosubstituted or polysubstituted by Hal, A, OR2, N(R2)2, NO2, CN, COOR2 or CON(R2)2; R1 is H, Ar, Het, cycloalkyl or A, which may be substituted by OR2, SR2, N(R2)2, Ar, Het, cycloalkyl, CN, COOR2 or CON(R2)2; R2 is H or A; E is phenylene, which may be monosubstituted or polysubstituted by Hal, A, OR2, N(R2)2, NO2, CN, COOR2 or CON(R2)2, or is piperidine-1,4-diyl; W is AR, Het or N(R2)2 and, if E=piperidine-1,4-diyl, is alternatively R2 or cycloalkyl, X is NH or O, are inhibitors of coagulation factor Xa and can be employed for the prophylaxis and/or therapy of thromboembolic diseases and for the treatment of tumours.

Abstract: The invention regards a screening method for screening for modulators of the expression of hnf4&agr; from the hnf4&agr; P2 promoter region, which method comprises the steps of obtaining a transcription reporter system comprising a nucleotide construct comprising a reporter gene under control of the hnf4&agr; P2 promoter region corresponding to nucleotide 1 to 1447 of the sequence shown in the Sequence listing as SEQ ID No. 1 or a fragment thereof, contacting the transcription reporter system with a putative modulator and assaying for a change in the level of expression of the reporter gene.

Abstract: The present invention is directed to the novel use of an IL-8 receptor antagonist for the treatment of human virus infections and the exacerbation of symptoms associated therewith.

Abstract: The present invention relates to nanogel networks having at least one cross-linked polyionic polymer fragment and at least one nonionic water-soluble polymer fragment, and compositions thereof, having at least one suitable biological agent.

Abstract: The present invention provides methods of modulating neurotrophic factor-associated activity, especially CNTF-associated levels and activity, using aldose reductase inhibitors. These methods are especially useful in individuals suffering from, or at risk of developing, neurological disorders, including neurodegenerative disorders. The invention also provides methods of palliating neurological disorders and delaying development of neurological disorders using aldose reductase inhibitors.

Abstract: Vascular damage has proven to be dose limiting in administering immunotoxins into the brain to treat brain tumors. Vascular toxicity of immunotoxins which rely in part on exposure to lowered pH in cellular endosomes and lysosomes can be avoided by administering an endosome pH-raising agent systemically during some or all of the time that the immunotoxin is present in the brain of the organism. Suitable endosome pH-raising agents include lysosomotrophic amines, proton ionophores, and vacuolar H+ ATPase inhibitors. The invention increases the therapeutic window of the immunotoxins and increases the likelihood the treatment will have an effect on the course of the tumor.

Abstract: Disclosed herein is a pharmacophore model for antimalarial activity and methods of making and using thereof. The pharmacophore comprises two hydrogen bond acceptor (lipid) functions and two hydrophobic (aromatic) functions. The pharmacophore model was made using a test set of tryptanthrin compounds which exhibit antimalarial activity. Also disclosed are tryptanthrin compounds having greater solubility and bioactivity as compared to prior art tryptanthrin compounds and methods of making and using thereof. Also disclosed are methods of treating malaria in a subject.

Abstract: The invention concerns a novel nucleic acid fragment of the genome of rice pathogenic fungus Magnaporthe grisea comprising a gene coding for a protein (hereafter referred to as gene 763) whereof the presence and integrity are indispensable for pathogenesis of said fungus with respect to rice and barley. The invention also concerns the promoter of said gene, the gene coding for protein 763, protein 763 and uses thereof for identifying potential biological targets for novel fungicide molecules and for isolating genes coding for proteins controlling biochemical functions essential to the pathogenesis of the fungus Magnaporthe grisea with respect to rice and barley. The invention further concerns compounds inhibiting pathogenesis of fungi related to the expression of gene 763.

Abstract: The present invention provides a compound having a steroid C17,20-lyase-inhibitory activity and useful for the therapy and prophylaxis of tumor such as prostatism, breast cancer and the like, and a method for efficiently separating an optically active compound of this compound from a mixture of optical isomers thereof, a compound of the formula: 1

Abstract: The present invention provides compositions containing herbal extracts for preventing and treating arthritis and a manufacturing method of the same. Particularly, pharmaceutical compositions extracted from Achyranthis roots and Atractylodes japonica roots are very effective against arthritis, and further, fermentative by-products of the compositions have excellent effects in treating and preventing arthritis in contrast to the existing artificial chemical treatment materials.

Abstract: The invention discloses a catalog of targets of the myc oncogene family identified by Serial Analysis of Gene Expression. The invention also discloses a method for analyzing myc downstream targets in view of the full context of myc induced changes in gene expression. The invention further discloses a method for the treatment of cancer comprising modulating a myc-dependent downstream gene capable of supporting an essentially neoplastic characteristic of the cancer. The invention additionally discloses a method of screening to identify drugs that interfere with myc downstream effects.

Abstract: The invention provides methods of treating erectile dysfunction comprising the step of placing within the fossa navicularis of the patient an effective erection-inducing amount of a prostaglandin E1 composition of a semi-solid consistency, as well as suitable applicators. The composition comprises prostaglandin E1, a penetration enhancer, a polysaccharide gum, a lipophilic compound, and an acidic buffer system. The penetration enhancer is an alkyl-2-(N,N-disubstituted amino)-alkanoate ester, an (N,N-disubstituted amino)-alkanol alkanoate, or a mixture of these. The lipophilic compound may be an aliphatic C1 to C8 alcohol, aliphatic C2 to C30 ester, an aliphatic C8 to C30 ester, or a mixture of these. The composition includes a buffer system capable of providing a buffered pH value for said composition in the range of about 3 to about 7.4.

Abstract: The invention relates to a program controlled stirrer for producing pharmaceutical or cosmetic recipes, comprising a stirring unit which consists of a stirring tool which engages with a mixing receptacle. According to the invention, the stirring unit is coupled to a micro-processor which determines the length of stirring time and stirring speed at the stirring unit in a program-controlled manner. The micro-processor executes a data-processing program with the following steps: input of variable data; input of constant data; determination of the length of stirring time and stirring speed in order to produce the desired amount of the recipe by combining the variable and constant data; conversion of the determined length of stirring time and stirring speed into corresponding first current or voltage values; control of the stirring unit with said first current or voltage values.

Abstract: This invention relates to the use of compounds able to decrease potassium ion flow through intermediate conductance calcium activated potassium channels for treatment of diseases related to increased intraocular pressure modulated by intermediate conductance calcium activated potassium channels.

Abstract: Pharmaceutical preparations and methods of treating a human afflicted with bipolar disorder, particularly the manic phase thereof. The preparations and methods involve 1-EBIO.

Abstract: The present invention provides methods and compositions for drug screens to identify and characterize agents that are agonistic or antagonistic to activation of the promoter region of the NAG-1 gene. Activation of the NAG-1 gene is associated with the apoptotic elimination of cancer cells both in vitro and in vivo. The invention also provides novel promoter region sequences of the NAG-1 gene.

Abstract: A biocompatible polymer constituted by a sequence of identical or different components of the general formula (I): AaXxYy, in which A represents a monomer, X represents a carboxyl group fixed on a monomer A, Y represents a sulfate or sulfonate group fixed on a monomer A; a represents the number of monomers A, x represents the substitution rate of the set of monomers A by the groups X, y represents the substitution rate of the set of monomers A by the groups Y. The invention also pertains to the pharmaceutical or diagnostic compositions containing at least one polymer of general formula (I).

Abstract: An agent for the prophylaxis or treatment of an emotional disorder, which contains the NK-1 receptor antagonist having particular properties of (1) having no serotonin uptake inhibitory effect, (2) being capable of migrating into the hypothalamus, or (3) having an inhibitory effect on micturition reflex, an agent for the prophylaxis or treatment of depression accompanied by urinary frequency, urinary incontinence and/or irritable bowel syndrome, which contains an NK-1 receptor antagonist, an agent for the prophylaxis or treatment of a mood disorder of patients with urinary frequency and urinary incontinence, and a circadian rhythm controller for the hypothalamic endocrine system are provided.

Abstract: This invention describes a novel method for rapid screening of formulations for drug delivery, which uses a high throughput array to screen multiple samples. This method monitors the depletion of a test substance from a donor well, the migration of the substance into a test membrane, and/or the migration of the substance through a membrane into a receptor well. It can be used to discover new formulations as well as to optimize the existing formulations for delivering drugs via transdermal, oral, or injectable routes.

Abstract: Novel multi-binding compounds are disclosed that modulate enzymatic processes. The compounds of the invention comprise from 2-10 ligands covalently connected, each of said ligands being capable of binding to an enzyme, enzyme substrate or enzyme cofactor thereby modulating the biological processes/functions thereof.

Abstract: The invention relates to a combination of at least two therapeutic combination components selected from the group consisting of (i) an AT1-receptor antagonist or an AT1 receptor antagonist combined with a diuretic or, in each case, a pharmaceutically acceptable salt thereof, (ii) a HMG-Co-A reductase inhibitor or a pharmaceutically acceptable salt thereof and (iii) an ACE inhibitor or a pharmaceutically acceptable salt thereof for use in the prevention of, delay of progression of, treatment of selected diseases and conditions.

Abstract: Methods and devices for administration of substances into at least two compartments of skin for systemic absorption and improved pharmacokinetics, based on biphasic or bimodel kinetic profiling.

Abstract: Biocompatible crosslinked polymers, and methods for their preparation and use, are disclosed in which the biocompatible crosslinked polymers are formed from water soluble precursors having electrophilic and nucleophilic groups capable of reacting and crosslinking in situ. Methods for making the resulting biocompatible crosslinked polymers biodegradable or not are provided, as are methods for controlling the rate of degradation. The crosslinking reactions may be carried out in situ on organs or tissues or outside the body. Applications for such biocompatible crosslinked polymers and their precursors include controlled delivery of drugs, prevention of post-operative adhesions, coating of medical devices such as vascular grafts, wound dressings and surgical sealants.

Abstract: The present invention relates to the use of an assay that measures receptor residence time of a ligand on its receptor in vitro for the identification of a ligand for that receptor predicted to be efficacious in vivo in the treatment of a disease that responds to modulation of that receptor's natural function.

Abstract: The invention provides methods and compositions for modulating angiogenesis in a subject. The methods of modulating angiogenesis in a subject include administering to the subject a modulator of N-terminal cysteine oxygenase activity. The invention also provides a method of identifying such a modulator and a method of in vitro screening for modulators of N-terminal cysteine oxygenase activity. Additionally, the invention provides a method of treating an angiogenesis-related disorder.

Abstract: The invention relates to a crystal comprising P13K and Ras, and to the use of such crystals in modelling the Ras-P13K interaction and in the design and/or screening of ligands capable of modulating this interaction

Abstract: The invention concerns a nucleotide sequence derived from Listeria inocua corresponding to a sequence selected among SEQ ID NO: 1 to SEQ ID NO: 11 and the comparative analysis of said genome with that of Listeria monocytogenes.

Abstract: New aporphine derivatives are disclosed which have formula (I) and the physiologically acceptable salts thereof. Said derivatives may be used for the treatment of Parkinson's disease, hemicrania, restless legs syndrome (RLS), sexual dysfunction in men and women, hyperprolactemia and psychotic disorders, and/or evaluation of Parkinson's disease. Processes for the preparation of such derivatives are also disclosed.

Abstract: Methods of diagnosing and/or of treating tumors by administering a nucleoside analog which is activated by thymidylate synthase and/or thymidine kinase enzyme into a diagnostic or toxic metabolite, and uridine analog compounds, and compositions of same having a pharmaceutically acceptable carrier. For diagnostic applications, compounds containing a label and methods of use of such compounds are described.

Abstract: Methods of diagnosing and/or of treating tumors by administering a nucleoside analogue which is activated by thymidylate synthase and/or thymidine kinase enzyme into a diagnostic or toxic metabolite, and uridine analogue compounds, and compositions of same having a pharmaceutically acceptable carrier. For diagnostic applications, compounds containing a label and methods of use of such compounds are described.

Abstract: The present invention relates generally to a method of modulating the growth of cells and, more particularly, to a method of down-regulating the growth of neoplastic cells. The present invention is useful, inter alia, in the therapeutic and/or prophylactic treatment of cancers such as, but not limited to, solid cancers such as cancers of the colon, stomach, lung, brain, bone, oesophagus, pancreas, breast, ovary or uterus.

Abstract: The present invention relates to a method for the treatment of Type II Diabetes Mellitus patients, which comprises administering an acidotropic agent to the patient in an amount sufficient for neutralizing intraendosomal pH or preventing lowering of intraendosomal pH; thereby activating insulin receptor kinase of the patient and preventing insulin resistance. The present invention also relates to a method for the screening of an acidotropic agent suitable for the treatment of Type II Diabetes Mellitus.

Abstract: The invention provides thieno[2,3-d]pyrimidinediones of general formula (I), wherein R, R1, R2 and R3 are as defined in the specification, processes for their production, pharmaceutical compositions containing them and their use in therapy.

Abstract: The present invention is based on the discovery that the metalloproteinase, ADAMTS-1 (A Disintegrin And Metalloproteinase), is associated with obesity, atherosclerosis, insulin resistance syndrome and non-insulin dependent diabetes. The application is directed to methods for screening for specidic modulators of ADAMS-1 activity, and the use of said modulators for treating the above-mentioned diseases.

Abstract: The invention is based on the discovery that angiogenic vessels have heterogeneous surface charge and that cationic liposomes actually target human tumor blood vessels only in irregularly shaped patches. The invention thus features methods for delivering therapeutic compounds to angiogenic vascular endothelial surfaces using a mixture, or “cocktail”, of positively charged and neutral liposomes. The new methods can be used to target multiple regions on the same tumor vessel and/or clusters of vessels within the same tumor. Liposomes with different chemical and/or physical properties (e.g., charge, stability, solubility, diameter) can be delivered simultaneously, and can target tumor vessels and other angiogenic vessels with greater efficiency compared to cationic liposomes alone.

Abstract: The invention features a method of designing broad spectrum inhibitors using structural data, compositions having broad spectrum activity, and methods for treating disease using those compositions.

Abstract: Methods and compositions are provided for modulating fat storage of animals by targeting the gene and gene products of cathepsins, particularly cathepsins L, K, and S, and especially cathepsin L. The method comprises: administering to the animal an agent that reduces an in vivo level of cathepsin L activity such that fat storage by the animal is reduced. The methods of the present invention can be used to diagnose obesity, diabetes and related diseases such as hyperinsulinmia, hyperglycermia, hypertension, cardiovascular diseases, muscular dystrophy and infertility, as well as to screen for agents that can be used therapeutics for these diseases.

Abstract: The invention provides methods and compositions for modulating angiogenesis in a subject. The methods of modulating angiogenesis in a subject include administering to the subject a modulator of N-terminal arginylation activity. The invention also provides a method of identifying such a modulator and a method of in vitro screening for modulators of N-terminal arginylation activity. Additionally, the invention provides a method of treating an angiogenesis-related disorder.

Abstract: Methods of diagnosing and/or of treating tumors by administering a nucleoside analogue which is activated by thymidylate synthase and/or thymidine kinase enzyme into a diagnostic or toxic metabolite, and uridine analogue compounds, and compositions of same having a pharmaceutically acceptable carrier.

Abstract: Compositions and methods are provided which may be used to advantage for the treatment of HIV infection. More specifically, neurokinin receptor antagonists and methods for administration to inhibit HIV invention are disclosed.