Abstract: According to the invention, a major role for the winged helix protein FKHL14/FOXC2 in regulating energy balance and adiposity is demonstrated. The invention relates to transgenic non-human mammalian animals being capable of expressing the human FKHL14/FOXC2 gene in its adipose tissue. The invention also relates to methods for identifying compounds useful for the treatment of medical conditions related to obesity or diabetes, said compounds being capable of stimulating expression of the human FKHL14/FOXC2 gene, or being capable of stimulating the biological activity of a polypeptide encoded by the human FKHL14/FOXC2 gene. The invention further relates to methods for identifying compounds useful for the treatment of medical conditions related to malnutrition, said compounds being capable of decreasing expression of the human FKHL14/FOXC2 gene, or being capable of decreasing the biological activity of a polypeptide encoded by the human FKHL14/FOXC2 gene.

Abstract: A device for dispensing at least two mutually reactive components, such as fibrinogen and thrombin, comprising a supplier (12A, 12B) having a primary channel for supplying a respective one of said at least two reactive components to a dispenser (14) having secondary channels (18A, 18B) for separately discharging said components at a distal end orifice thereof opening into a target area for external intimate mixing of the respective reactive components outside a distal tip end of said dispenser (14). A distributor (38, 40) is interposed between said supplier and said dispenser for multiplying the number of the respective primary channels with at least a factor 2. Adjacent ones of said secondary channels (18A, 18B) are adjoined to primary channels (32, 34) intended for supply of reactive components of different kind.

Abstract: A method of enhancing the transcription of a gene in a DNA construct incorporated into the genome of a eucaryotic host cell, wherein the DNA construct comprises a structural gene for a desired protein or polypeptide in a gene promoter upstream of the structural gene, comprises providing at least one enhancer element comprising the nucleotide sequence TTC TGA GAA upstream of the promoter, and exposing the DNA construct to lactogenic stimuli. An expression vector, a host cell and a transgenic mammal containing the vector are of interest.

Abstract: The invention relates to compounds of the general formula (I): wherein Ar is optionally substituted aryl or heteroaryl; A is (i) —O—, —S—, —SO2—, —NH—, (ii) a C1-4-alkyl- or C1-6-acyl-substituted nitrogen atom or (iii) a C1-8-alkylene chain or a heteroalkylene chain having 2 to 8 chain atoms, which optionally contains at least one unsaturation, and which may be substituted and/or contain a bridge to form a saturated or partially or fully unsaturated ring having 3-8 ring members; B is —C(R4)(R5)—, —OC(R4)(R5)—, —N(R6)C(R4)(R5)—, —N(R6)—, —O—, —S— or —SO2—; R is optionally substituted C3-8-cycloalkyl, aryl or heteroaryl; R1 is (i) a saturated or unsaturated azacyclic or aminoazacyclic ring, or a saturated diazacyclic or aminodiazacyclic ring, which has 4 to 7 ring members, or a saturated aminoazabicyclic, azabicyclic or diazabicyclic ring which has 7 to 10 ri

Abstract: The invention relates to compounds of the general formula (I) wherein R1, R2 and R3 are as described in the specification, which compounds are ligands to the serotonin 5-HT2c receptor.

Abstract: Novel proteins obtainable by mutagenesis of surface-exposed amino acids of domains of natural bacterial receptors, said proteins being obtained without substantial loss of basic structure and stability of said natural bacterial receptors; proteins which have been selected from a protein library embodying a repertoire of said novel proteins; and methods for the manufacture of artificial bacterial receptor structures.

Abstract: The present invention relates an isolated human Site-1 Protease promoter region. The invention also relates to screening methods for agents decreasing the expression of Site-1 protease and thereby being potentially useful for the treatment of medical conditions related to obesity and/or diabetes.

Abstract: According to the invention, a major role for the winged helix protein FKHL14/FOXC2 in regulating energy balance and adiposity is demonstrated. The invention relates to transgenic non-human mammalian animals being capable of expressing the human FKHL14/FOXC2 gene in its adipose tissue. The invention also relates to methods for identifying compounds useful for the treatment of medical conditions related to obesity or diabetes, said compounds being capable of stimulating expression of the human FKHL14/FOXC2 gene, or being capable of stimulating the biological activity of a polypeptide encoded by the human FKHL14/FOXC2 gene. The invention further relates to methods for identifying compounds useful for the treatment of medical conditions related to malnutrition, said compounds being capable of decreasing expression of the human FKHL14/FOXC2 gene, or being capable of decreasing the biological activity of a polypeptide encoded by the human FKHL14/FOXC2 gene.

Abstract: A dispenser comprising at least two parallel, hollow cylinders for supplying different mutually reactive components to a mixing device located downstream of the cylinders. The dispenser comprises a respective first piston moveable in each of the cylinders and displaceable by a piston rod connected to the respective piston. A component for actuating the pistons rods to perform a forward stroke of the pistons in their respective cylinders for dispensing an amount of the reactive components to the mixing device comprises at least one rotatable member biased in a rotational direction by a torsion spring, and at least one flexible string attached to the rotatable member and to an element connected to the piston rods. A manually operable brake member is arranged to normally act on the rotatable member to hold it still, but, when deactivated, adapted to release the rotatable member thereby causing the pistons to dispense the reactive components to the mixing device.

Abstract: A compound of the general formula (I): 1

Abstract: A tissue treatment composition, especially an adhesive composition comprises (i) fibrin or fibrinogen and (ii) a biodegradable and biocompatible polymer capable of forming a viscous aqueous solution. In addition to glueing, the tissue adhesive composition may be used for slow-release of a drug incorporated into it or for anti-adherence purposes, for wound healing, etc.

Abstract: The present invention relates to modified polypeptide derivatives of the B domain or Z domain of staphylococcal protein A (SPA). The derivatives contain amino acid substitutions that result in the ability of the B domain or Z domain to interact with at least one domain of a human Factor VIII protein, without substantially disrupting the structure and stability of the B domain or Z domain.

Abstract: The present invention is directed to a novel Afx response element comprising the nucleotide sequence AACATGTT, said nucleotide sequence having a DNA binding site for the human fork head transkription factor Afx. The invention also relates to the use of the Afx response element in the screening for genes as diabetes drug targets and in the bioinformatic analysis of the human genome, said genes in turn being useful in other screening methods for compounds modifying the insulin receptor signaling pathway. A further aspect of the invention is a vector construct comprising the novel nucleotide sequence, a host cell transformed with said vector construct as well as the fusion protein expressed by said host cell.

Abstract: The present invention relates to a pharmaceutical composition comprising Factor VIII and the divalent metal ions Zn2+ and Cu2+, optionally in the presence of Ca2+ ions and/or Mn2+ ions, wherein said Factor VIII is stable without the addition of albumin. The invention also relates to a method for the production of recombinant Factor VIII from mammalian cells carrying the gene therefor, comprising culturing said mammalian cells in medium free of plasma-derived protein and supplemented with divalent metal ions, including Cu2+ and Zn2+, and optionally in the presence of Ca2+ and Mn2+ ions.

Abstract: According to the invention &bgr;-tubulin, as well as a 65 kDa polypeptide present in pancreatic &bgr;-cells, have been identified as molecular targets for sulfonylurea compounds. These findings enable for the identification of new insulin secretagogues. The invention thus relates to the use of sulfonylurea compounds, such as e.g. glibenclamide, in methods for identification of compounds binding the 65 kDa polypeptide or tubulin, or stimulating tubulin polymerization and/or turnover, thereby stimulating insulin secretion.

Abstract: The invention relates to a method of antagonizing GLP-1 activity in a mammalian patient, comprising administering to said patient an effective amount of a compound of the general formula I: wherein R1 and R2 independently of each other are C1-4alkyl, R3 is halogen, hydroxy, C1-4-alkoxy or trifluoromethoxy, R4 is hydrogen, hydroxy or C1-4-alkoxy, or a pharmacologically acceptable salt thereof. The invention also relates to a pharmaceutical composition comprising a compound of formula I.

Abstract: The invention relates to compounds of the general formula (I): 1

Abstract: The present invention relates to methods for purification of antithrombin-III (AT-III) by precipitation of impurities. The said methods comprise (a) adding, to a solution comprising antithrombin-III, a saccharide and citrate, in an amount sufficient for impurities to precipitate while antithrombin-III essentially remains in solution; (b) allowing impurities to precipitate; and (c) removing the precipitated impurities, thereby obtaining a solution comprising purified antithrombin-III. The invention also relates to pharmaceutical compositions, obtainable by the said methods, comprising purified antithrombin-III, as well as to reconstituted pharmaceutical compositions essentially free from visible particles.

Abstract: Novel proteins obtainable by mutagenesis of surface-exposed amino acids of domains of natural bacterial receptors, said proteins being obtained without substantial loss of basic structure and stability of said natural bacterial receptors; proteins which have been selected from a protein library embodying a repertoire of said novel proteins; and methods for the manufacture of artificial bacterial receptor structures.

Abstract: The present invention is directed to compounds of formula I, formula Ia, and formula Ib. wherein each of R1, R2, R3, R4, Ra, and Rb has been defined herein. The invention is also directed to a process for the preparation, the use and pharmaceutical compositions comprising the compounds described above. These novel compounds are useful in therapy, particularly for the treatment of type 2 diabetes.