Abstract: Disclosed herein is a sulfated octasacchande of formula (I), a pharmaceutically acceptable salt, solvate or ester thereof: wherein R1 is —NHAc or —NHSO3H; and R2 and R3 are independently H, or —SO3H. Also encompasses herein is a method of treating neuron injury and/or diseases associated with a disrupted autophagy flux. The method includes administering an effective amount of the sulfated octasaccharide of formula (I) to a subject in need of such treatment.

Abstract: Disclosed herein is a sulfated octasacchande of formula (I), a pharmaceutically acceptable salt, solvate or ester thereof: wherein R1 is —NHAc or —NHSO3H; and R2 and R3 are independently H, or —SO3H. Also encompasses herein is a method of treating neuron injury and/or diseases associated with a autophagy flux. The method includes administering an effective amount of the sulfated octasaccharide of formula (I) to a subject in need of such treatment.

Abstract: A monoclonal antibody, which recognizes at least two amino acids among amino acids located at position 69, position 79, position 81 and position 102 of human midkine, has been found to have excellent reactivity with and excellent neutralizing activity against human midkine. Moreover, the activity of suppressing the proliferation of tumor has been observed in the antibody having excellent neutralizing activity. The use of the antibody of the present invention makes it possible to treat cancer effectively and to detect or purify midkine efficiently.

Abstract: An object of the present invention is to provide a substance which can be used as an active ingredient for improving neuropathic pain having a mechanism of action different from those of currently available agents and, therefore, provide an improving agent for neuropathic pain which rarely interacts with currently available agents and also does not have adverse reactions similar to those of currently available agents. An improving agent for neuropathic pain due to a hyperalgesic response of the present invention for resolution is characterized by comprising, as an active ingredient, a lyase (an elimination enzyme) which has an activity of degrading a chondroitin sulfate chain of a chondroitin sulfate proteoglycan, and is typified by chondroitinase ABC which selectively removes chondroitin sulfate and dermatan sulfate of a proteoglycan.

Abstract: The present invention provides an aptamer binding to midkine and capable of forming a potential secondary structure represented by the formula (I): wherein X1, X2, X5 and X6 are the same or different and each is one or two nucleotides selected from the group consisting of A, G, C, U and T, or a bond, X1 and X6, and X2 and X5 each form a Watson-Crick base pairs, and X3 and X4 are the same or different and each is a nucleotide selected from A, G, C, U and T.

Abstract: The present invention provides an aptamer binding to midkine and capable of forming a potential secondary structure represented by the formula (I): wherein X1, X2, X5 and X6 are the same or different and each is one or two nucleotides selected from the group consisting of A, G, C, U and T, or a bond, X1 and X6, and X2 and X5 each form a Watson-Crick base pairs, and X3 and X4 are the same or different and each is a nucleotide selected from A, G, C, U and T.

Abstract: A monoclonal antibody, which recognizes at least two amino acids among amino acids located at position 69, position 79, position 81 and position 102 of human midkine, has been found to have excellent reactivity with and excellent neutralizing activity against human midkine. Moreover, the activity of suppressing the proliferation of tumor has been observed in the antibody having excellent neutralizing activity. The use of the antibody of the present invention makes it possible to treat cancer effectively and to detect or purify midkine efficiently.

Abstract: A method to treat the chronic stage of heart injury after ischemia or reperfusion by administering Midkine to a subject in need of such treatment is described.

Abstract: An object of the present invention is to provide a substance which is able to be an active ingredient for the improvement of dysfunction caused by nerve damage. An improving agent for dysfunction due to nerve damage of the present invention as a means for resolution thereof is characterized in that it comprises an endo-?-N-acetylglucosaminidase type enzyme which hydrolyzes an N-acetylglucosamide bond in a keratan sulfate backbone as an active ingredient. When the improving agent of the present invention is administered, clinical improvement is achieved in motor neuron dysfunction and sensory neuron dysfunction such as neuropathic pain represented by a pain caused by allodynia and hyperalgesic reaction of the object to be treated.

Abstract: An object of the present invention is to provide a substance which can be used as an active ingredient for improving neuropathic pain having a novel mechanism of action different from those of currently available agents and, therefore, provide an improving agent for neuropathic pain which rarely interacts with currently available agents and also does not have adverse reactions similar to those of currently available agents. An improving agent for neuropathic pain due to a hyperalgesic response of the present invention as a means for resolution is characterized by comprising, as an active ingredient, a lyase (an elimination enzyme) which has an activity of degrading a chondroitin sulfate chain of a chondroitin sulfate proteoglycan, and is typified by chondroitinase ABC which selectively removes chondroitin sulfate and dermatan sulfate of a proteoglycan.

Abstract: The object is to find a nitric oxide synthase activator, a method for the administration of the activator, and the amount of the activator to be administered. Disclosed is a nitric oxide synthase activator comprising a midkine family protein or a midkine derivative as an active ingredient. Specifically disclosed is a nitric oxide synthase activator which is intended to be administered through the blood, a coronary artery or a vein and which comprises a midkine family protein or a midkine derivative as an active ingredient.

Abstract: An object of the present invention is to provide a substance which can be used as an active ingredient for improving neuropathic pain having a novel mechanism of action different from those of currently available agents and, therefore, provide an improving agent for neuropathic pain which rarely interacts with currently available agents and also does not have adverse reactions similar to those of currently available agents. An improving agent for neuropathic pain due to a hyperalgesic response of the present invention as a means for resolution is characterized by comprising, as an active ingredient, a lyase (an elimination enzyme) which has an activity of degrading a chondroitin sulfate chain of a chondroitin sulfate proteoglycan, and is typified by chondroitinase ABC which selectively removes chondroitin sulfate and dermatan sulfate of a proteoglycan.

Abstract: A method for controlling an electroporation apparatus for use in an animal such as human and a non-human animal, the method comprising a step of applying a voltage to an electrode of the electroporation apparatus placed in/on a biological sample of the animal in the presence of a nucleic acid construct capable of inhibiting the expression of a gene in the animal. In this manner, a nucleic acid construct can be introduced into a cell of a living body with good efficiency.

Abstract: To provide a novel biomarker that is useful for prediction of early onset of acute kidney injury, estimation of prognosis associated with a renal function, and differentiation of acute kidney injury. Furthermore, to provide use of the novel biomarker. Midkine is used as a biomarker. The determination of a possibility of the onset of acute kidney injury, estimation of prognosis associated with a renal function or differentiation of an acute kidney injury are carried out based on the detection result of the urinary midkine.

Abstract: Provided is a therapeutic method targeting midkine for treating mammalian kidney disorders, primary kidney disorders, hypertension that follows secondary kidney disorders such as diabetic nephropathy, and hypertension secondary to chronic kidney disease.

Abstract: An object of the present invention is to provide a substance which is able to be an active ingredient for the improvement of dysfunction caused by nerve damage. An improving agent for dysfunction due to nerve damage of the present invention as a means for resolution thereof is characterized in that it comprises an endo-?-N-acetylglucosaminidase type enzyme which hydrolyzes an N-acetylglucosamide bond in a keratan sulfate backbone as an active ingredient. When the improving agent of the present invention is administered, clinical improvement is achieved in motor neuron dysfunction and sensory neuron dysfunction such as neuropathic pain represented by a pain caused by allodynia and hyperalgesic reaction of the object to be treated.

Abstract: The present invention provides a pharmaceutical composition for the prevention or treatment of angiostenosis, comprising a compound inhibiting the function of midkine (MK) in blood vessel tissues as an effective ingredient. The present invention is useful for the prevention or treatment of angiostenosis attributed to arteriosclerosis or restenosis after percutaneous transluminal coronary angioplasty (PTCA). As compounds inhibiting the function of MK, antisense oligonucleotides that bind to a segment of a single-stranded mRNA transcribed from the MK gene to inhibit the synthesis of MK protein in cells, antibodies against the MK protein, and such can be used.

Abstract: The object is to find a nitric oxide synthase activator, a method for the administration of the activator, and the amount of the activator to be administered. Disclosed is a nitric oxide synthase activator comprising a midkine family protein or a midkine derivative as an active ingredient. Specifically disclosed is a nitric oxide synthase activator which is intended to be administered through the blood, a coronary artery or a vein and which comprises a midkine family protein or a midkine derivative as an active ingredient.

Abstract: A polypeptide of N-acetylglucosamine-6-O-sulfotransferase and a DNA encoding the peptide are provided. The polypeptide is (a) or (b) below: (a) a polypeptide having the amino acid sequence represented by SEQ ID NO: 2; or (b) a polypeptide which includes an amino acid sequence including substitution, deletion, insertion or transposition of one or a few amino acids in the amino acid sequence of (a) and which has an enzymatic activity to transfer a sulfate group from a sulfate group donor to a hydroxyl group at 6 position of an N-acetylglucosamine residue located at a non-reducing end of an oligosaccharide represented the formula I: GlcNAc?1-3Gal?1-4GlcNAc??(I) where GlcNAc represents an N-acetyl-glucosamine residue, Gal represents a galactose residue, ? 1-3 represents a ? 1-3 glycosidic linkage, and ? 1-4 represents a ? 1-4 glycosidic linkage.

Abstract: A study was made on the therapeutic effect of midkine on an occlusive peripheral vascular disease, and it was found that midkine has an activity of promoting neovascularization and that a blood vessel can be proliferated and the blood flow in the upper and lower limbs can be improved (in other words, the condition of an ischemic disease in the upper and lower limbs can be ameliorated) by introducing midkine into a site affected by the occlusive peripheral vascular disease.