WO1995018629A1 - Method for treatment and prevention of disease in animals - Google Patents
Method for treatment and prevention of disease in animals Download PDFInfo
- Publication number
- WO1995018629A1 WO1995018629A1 PCT/US1994/014839 US9414839W WO9518629A1 WO 1995018629 A1 WO1995018629 A1 WO 1995018629A1 US 9414839 W US9414839 W US 9414839W WO 9518629 A1 WO9518629 A1 WO 9518629A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- growth hormone
- animal
- melatonin
- effective amount
- increased
- Prior art date
Links
- 241001465754 Metazoa Species 0.000 title claims abstract description 41
- 238000000034 method Methods 0.000 title claims abstract description 27
- 230000006806 disease prevention Effects 0.000 title description 3
- 102000018997 Growth Hormone Human genes 0.000 claims abstract description 55
- 108010051696 Growth Hormone Proteins 0.000 claims abstract description 55
- 239000000122 growth hormone Substances 0.000 claims abstract description 54
- 230000000422 nocturnal effect Effects 0.000 claims abstract description 18
- 210000000987 immune system Anatomy 0.000 claims abstract description 15
- 238000005728 strengthening Methods 0.000 claims abstract description 4
- YJPIGAIKUZMOQA-UHFFFAOYSA-N Melatonin Natural products COC1=CC=C2N(C(C)=O)C=C(CCN)C2=C1 YJPIGAIKUZMOQA-UHFFFAOYSA-N 0.000 claims description 26
- 238000004519 manufacturing process Methods 0.000 claims description 26
- 229960003987 melatonin Drugs 0.000 claims description 26
- DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 claims description 26
- 239000000126 substance Substances 0.000 claims description 22
- 230000000694 effects Effects 0.000 claims description 15
- 230000002411 adverse Effects 0.000 claims description 12
- 230000000903 blocking effect Effects 0.000 claims description 7
- 239000002876 beta blocker Substances 0.000 claims description 5
- 230000028993 immune response Effects 0.000 description 14
- 201000010099 disease Diseases 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 230000000638 stimulation Effects 0.000 description 6
- 230000004936 stimulating effect Effects 0.000 description 4
- 102000038461 Growth Hormone-Releasing Hormone Human genes 0.000 description 3
- 239000000095 Growth Hormone-Releasing Hormone Substances 0.000 description 3
- 206010062767 Hypophysitis Diseases 0.000 description 3
- WVVXBPKOIZGVNS-UHFFFAOYSA-N N-[2-[2-(phenylmethyl)-1H-indol-3-yl]ethyl]acetamide Chemical compound N1C2=CC=CC=C2C(CCNC(=O)C)=C1CC1=CC=CC=C1 WVVXBPKOIZGVNS-UHFFFAOYSA-N 0.000 description 3
- 101710142969 Somatoliberin Proteins 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000003203 everyday effect Effects 0.000 description 3
- 210000004560 pineal gland Anatomy 0.000 description 3
- 210000003635 pituitary gland Anatomy 0.000 description 3
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol hydrochloride Natural products C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 3
- METKIMKYRPQLGS-GFCCVEGCSA-N (R)-atenolol Chemical compound CC(C)NC[C@@H](O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-GFCCVEGCSA-N 0.000 description 2
- NVUGEQAEQJTCIX-UHFFFAOYSA-N N-acetyltryptamine Chemical compound C1=CC=C2C(CCNC(=O)C)=CNC2=C1 NVUGEQAEQJTCIX-UHFFFAOYSA-N 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 230000003042 antagnostic effect Effects 0.000 description 2
- 229960002274 atenolol Drugs 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 238000002483 medication Methods 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 1
- MEAPRSDUXBHXGD-UHFFFAOYSA-N 3-chloro-n-(4-propan-2-ylphenyl)propanamide Chemical compound CC(C)C1=CC=C(NC(=O)CCCl)C=C1 MEAPRSDUXBHXGD-UHFFFAOYSA-N 0.000 description 1
- 102000001419 Melatonin receptor Human genes 0.000 description 1
- 108050009605 Melatonin receptor Proteins 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000002354 daily effect Effects 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 230000000459 effect on growth Effects 0.000 description 1
- 229960005309 estradiol Drugs 0.000 description 1
- 229930182833 estradiol Natural products 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 239000003668 hormone analog Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 229960003712 propranolol Drugs 0.000 description 1
- 229960004604 propranolol hydrochloride Drugs 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000000153 supplemental effect Effects 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 235000019195 vitamin supplement Nutrition 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0004—Homeopathy; Vitalisation; Resonance; Dynamisation, e.g. esoteric applications; Oxygenation of blood
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/25—Growth hormone-releasing factor [GH-RF], i.e. somatoliberin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/27—Growth hormone [GH], i.e. somatotropin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0023—Aggression treatment or altering
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Endocrinology (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Alternative & Traditional Medicine (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Methods of increasing the effective amount of growth hormone in an animal to stimulate the animal's immune system during the early stage of nocturnal sleep results in strengthening the animal's immunue sytem.
Description
METHOD FOR TREATMENT AND PREVENTION OF DISEASE IN ANIMALS The present invention relates generally to the treatment and prevention of disease. More particularly, it relates to methods for strengthening the immune system of an animal, including a human. Disease in animals is primarily overcome by the animal's immune system. It is known that growth hormone (also known as somatotropin) has a stimulative effect on the immune system. This is a result of its effect on T-cells, macrophages and other parts of the immune system. It would be advantageous to have methods of increasing the production of growth hormone so that the stimulation of an animal's immune system is increased. It is an object of the present invention to disclose methods of increasing the effective amount of growth hormone in an animal so that the stimulation of the animal's immune system is increased. I have discovered that the immune system of an animal can be stimulated if the effective amount of growth hormone in the animal is increased during the early stage of nocturnal sleep (i. e. approximately the first 90 minutes). More specifically, I have discovered that if during the early nocturnal sleep of an animal, such as a human, the effective amount of growth hormone in the animal is increased, the immune response of the animal is increased and the production of T-cells, macrophages and other parts of the immune system are optimized to create an optimal immune response in the animal. The effective amount of growth hormone may be increased by either administering to the animal substances that directly increase the growth hormone or by methods which block the adverse effects of melatonin on the animal's own growth hormone production. Methods of directly increasing the amount of growth hormone include the following: (1) By Growth Hormone Supplementation In this embodiment of the method the levels of growth hormone in an animal are increased by administering growth hormone itself to the animal before the onset of the early stage of nocturnal sleep so that increased growth hormone is available during that early stage of nocturnal sleep. (2) By Administering Growth Hormone Stimulating Chemicals In this embodiment of the invention the effective amount of growth hormone in an animal is increased by administering to the animal a substance that stimulates growth hormone production in the body during the early stage of nocturnal sleep so that increased growth hormone is available during that early stage of nocturnal sleep. The adverse effects of melatonin production on growth hormone production can be blocked until after the early stage of nocturnal sleep by one of the following embodiments of the methods of the present invention: (1) By The Chemical Blocking Of The Production Of Melatonin In this embodiment of the method the patient is administered a safe and effective amount of a substance that blocks the production of melatonin until after the early stages of nocturnal sleep (i. e., approximately the first 90 minutes of human sleep). The substance is given to the patient daily before sunset at a time sufficiently prior to sunset for the substance to be absorbed by the body and to begin the blocking of the production of melatonin at about the time of sunset and to continue the blocking until the onset of sleep and during the early stage of nocturnal sleep. (2) By The Use Of Light To Block The Production Of Melatonin. In this embodiment of the method, the patient is exposed to a bright light (1,500 Lux to 12,000 Lux) for intermittent periods of time between the time of sunset and the onset of sleep every day in order to suppress production of melatonin by the pineal gland until after the onset of sleep. In either of the above embodiments of the method, the adverse effects of melatonin on the production of growth hormone in an animal, such as a human, are blocked until after the early stage of nocturnal sleep so that the stimulation of the body's immune response to disease by growth hormone is increased. When melatonin production is suppressed or its effects offset by greater amounts of growth hormone during approximately the first 90 minutes of sleep, the animal's immune response to disease is optimized. Description of the Preferred Embodiments In the preferred embodiments of the method of the present invention, the effective amount of growth hormone in the animal's body during the early stage of nocturnal sleep is increased by blocking the adverse effects of melatonin on growth hormone production by either the administration of a safe and effective amount of a substance or by the exposure of the animal to bright light for an effective period of time. Although a variety of substances can be used to block the adverse effects of melatonin, the presently preferred substances are beta-adrenergic antagonists. These substances are believed to act by blocking receptors in the pineal gland from receiving neural signals from the eyes. By blocking these neural signals the beta-adrenergic antagonists prevent the synthesis of melatonin in the pineal gland. Representative of the beta-adrenergic antagonists which can be used are propranolol hydrochloride and atenolol. Both of these products can be administered orally about one to seven hours prior to the onset of nocturnal sleep. Atenolol is administered in oral dosages of from 0.1 mg to 50 mg. The oral dosage for propranolol is from 0.1 mg to 60 mg. The production of melatonin is believed to be suppressed by the beta-adrenergic blockers for sufficient time to allow optimal production of growth hormone in the pituitary gland. As a result, the optimal production of growth hormone yields optimum stimulation of the immune system resulting in optimal immune response. Another type of compound that can be used to block the adverse effects of melatonin is N-acetyltryptamine 2benzyl-N-acetyltryptamine (Luzindole). It is believed to suppress melatonin by antagonizing melatonin receptors in the body. By antagonizing these receptors, the compound prevents melatonin from acting on the pituitary gland and thus preventing melatonin's suppression of growth hormone. The oral dosage for Luzindole is 200 mg to 1000 mg. Other substances that block the adverse effects of melatonin can also be used. For example, estradiol and progesterone have also been shown to suppress melatonin in the body. The administration of a substance that blocks the adverse effects of melatonin is continued every day before sunset. The treatment is continued until all evidence of the disease is gone from the body. In another preferred embodiment of the method of the present invention the adverse effects of melatonin in the animal are blocked by exposing the animal to a bright light (1,500 Lux to about 12,000 Lux) for effective intermittent periods of time from sunset to the onset of the early stage of nocturnal sleep to optimize the production of growth hormone resulting in optimal immune response. In the preferred embodiment of the method of the invention in which the effective amount of growth hormone in the animal's body is directly increased, growth hormone is administered to the animal shortly before the onset of the first stage of nocturnal sleep. The growth hormone is administered orally in dosages of 1 mg to 20 mg before the onset of sleep each day so that it is absorbed by the body within 30 to 60 minutes after the onset of sleep. The growth hormone supplements the body's own production of growth hormone during the first stage of nocturnal sleep when the pituitary gland is producing the greatest quantity of the hormone. The presence of the supplemental growth hormone increases the total growth hormone level above the normal level produced by the body, thus resulting in an increased stimulation of the immune response. In still another embodiment, the effective amount of growth hormone is increased by administering to the animal a substance that stimulates growth hormone production during the early stage of nocturnal sleep. Representative of such substances are growth hormone releasing factor and analogs of growth hormone releasing factor. Growth hormone releasing factor is administered orally before the onset of sleep every day in dosages of 0.1 mg to 100 mg. The growth hormone production stimulating substance is given to the patient shortly before the onset of sleep each day. The substance is given at a time that will allow the body to absorb it and synthesize additional growth hormone within approximately 30 to 60 minutes of the onset of sleep. The growth hormone stimulating substance may act by offsetting the adverse effects of melatonin on growth hormone production. The substance can also be used to raise the growth hormone level above the level normally produced in the body. Optimal production of growth hormone can then be achieved during approximately the first 90 minutes of sleep each day. This results in optimal stimulation of the immune system and optimal immune response. With any of the above described embodiments of the method of the present invention, additional measures can be taken to help optimize the immune response in the animal: (1) The patient can be instructed not to nap. This will result in making the onset of sleep come more easily and quickly when the patient goes to bed. (2) The patient can be instructed not to eat or drink anything (except water) for several hours before going to bed. Sugar has been shown to suppress growth hormone. By not eating or drinking for several hours, all sugar in the body will be metabolized before the onset of sleep. (3) The patient can be taken off all medications that have a suppressant effect on growth hormone or the immune system. (4) The patient can be taken off all medication during the treatment. There may be some unknown suppressant effects of the medications the patient is taking. These could prevent optimizing the intended immune response. (5) The patient can be given vitamin supplements. Studies have shown that some vitamins may help stimulate immune response. (6) The patient can be instructed to go to bed at the same time every night. This in combination with the suppression of melatonin can help entrain the body to delay melatonin production until after the onset of sleep. The methods described with or without the additional measures can be continued beyond the time disease is gone from the body. By extending the treatment, the immune response may be improved to prevent future recurrences of the disease. The methods also can be combined with one or more of the other described treatment procedures to increase immune response. It will be apparent to those skilled in the art that the method of the present invention can also be used to strengthen the body's immune response to prevent the occurrence of disease. Example 1 A white, male patient, age 20, is exposed to the bright light (10,000 Lux) of a light fixture (Natural Illuminator 10,000 Model) from the Hughes Lighting Technologics Company for intermittent periods of time (of about 15 minutes to 60 minutes each) between sunset and the onset of sleep each night for 30 days. At the end of that time an analysis shows that the patient's immune system has been stimulated. It will be apparent to those skilled in the art that a number of modifications and changes can be made without departing from the spirit and scope of the invention. Therefore, it is intended that the invention only be limited by the claims.
Claims
Claims
1. A method for strengthening the immune system of an animal needing immune system strengthening which comprises increasing the effective amount of growth hormone in such an animal during the early stage of nocturnal sleep.
2. A method of claim 1 in which the effective amount of growth hormone is increased by administering to the animal a substance that suppresses the adverse effects of melatonin on growth hormone in the animal.
3. A method of claim 2 in which the substance is a beta-adrenergic antagonist.
4. A method of claim 1 in which the effective amount of growth hormone is increased by administering to the animal growth hormone.
5. A method of claim 1 in which the effective amount of growth hormone is increased by administering to the animal a chemical substance that stimulates the increased production of growth hormone in the body.
6. A method of claim 1 in which the effective amount of growth hormone in an animal is increased by blocking the adverse effects of melatonin on growth hormone production by exposing the animal to a safe and effective amount of visible light.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU15542/95A AU1554295A (en) | 1994-01-05 | 1994-12-29 | Method for treatment and prevention of disease in animals |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US17766694A | 1994-01-05 | 1994-01-05 | |
| US08/177,666 | 1994-01-05 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1995018629A1 true WO1995018629A1 (en) | 1995-07-13 |
Family
ID=22649485
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1994/014839 WO1995018629A1 (en) | 1994-01-05 | 1994-12-29 | Method for treatment and prevention of disease in animals |
Country Status (2)
| Country | Link |
|---|---|
| AU (1) | AU1554295A (en) |
| WO (1) | WO1995018629A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004067719A3 (en) * | 2003-01-28 | 2005-03-31 | Advisys Inc | Growth hormone releasing hormone (ghrh) for use in reducing culling in herd animals |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4837202A (en) * | 1987-09-14 | 1989-06-06 | Pitman-Moore, Inc. | Method for stimulating the immune system |
| WO1993000109A1 (en) * | 1991-06-28 | 1993-01-07 | Genentech, Inc. | Method of stimulating immune response using growth hormone |
-
1994
- 1994-12-29 AU AU15542/95A patent/AU1554295A/en not_active Abandoned
- 1994-12-29 WO PCT/US1994/014839 patent/WO1995018629A1/en active Application Filing
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4837202A (en) * | 1987-09-14 | 1989-06-06 | Pitman-Moore, Inc. | Method for stimulating the immune system |
| WO1993000109A1 (en) * | 1991-06-28 | 1993-01-07 | Genentech, Inc. | Method of stimulating immune response using growth hormone |
Non-Patent Citations (5)
| Title |
|---|
| ACTA ENDOCRINOLOGICA (COPENH), Volume 123, issued 1990, P. FRANCO et al., "Influence of Growth Hormone on the Immunosuppressive Effect of Prednisolone in Mice", pages 339-344. * |
| BIOCHEMICAL PHARMACOLOGY, Volume 38, Number 5, issued 01 March 1989, K. KELLEY, "Growth Hormone, Lymphocytes and Marcrophages", pages 705-713. * |
| CLIN. EXP. IMMUNOL., Volume 68, issued 1987, B. LAWLER GOFF et al., "Growth Hormone Treatment Stimulates Thymulin Production in Aged Dogs", pages 580-587. * |
| PROGRESS IN NEUROENDOCRINIMMUNOLOGY, Volume 3, Number 4, issued 1990, D. WEIGENT et al., "Growth Hormone and the Immune System", pages 231-241. * |
| SCIENCE, Volume 239, issued 12 February 1988, C. EDWARDS et al., "A Newly Defined Property of Somatotropin: Priming of Macrophages for Production of Superoxide Anion", pages 769-771. * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004067719A3 (en) * | 2003-01-28 | 2005-03-31 | Advisys Inc | Growth hormone releasing hormone (ghrh) for use in reducing culling in herd animals |
Also Published As
| Publication number | Publication date |
|---|---|
| AU1554295A (en) | 1995-08-01 |
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