Patent EA-003232-B1 (EA)
Title: Treatment of stress and preconditioning against stress
Inventor: HAMET PAVEL
IPC: A61K41/00
Filed: 1998-09-11
Abstract: 1. Use, in the treatment of a mammalian patient, to reduce symptoms of stress in the patient, or to precondition the patient's body so as to result in reduced manifestations of symptoms of strew resulting from the patient's encountering stress subsequent to the treatment, the symptoms being increase in heart rate, increase in body temperature and/or increase in blood pressure of the patient, or in decreasing infarct size, or in protecting mammalian donor organs destined for transplantation from a mammalian donor to a mammalian recipient, or in preconditioning a mammalian patient to better withstand the adverse effects of ischemic stress to be encountered as a result of subsequent ischemia-reperfusion of a body organ of the patient, characterized by using of an aliquot of compatible mammalian blood which has been subjected extracorporeally to at least two stressors selected from oxidative environment, UV radiation and elevated temperature up to about 45 degree C or which has been subjected extracorporeally to infra-red radiation, optionally in combination with an oxidative environment and/or UV radiation, or which has been subjected extracorporeally to at least two stressors known to be effective in inducing a stress response, commonly indicated by activation of the SAP kinase pathway in blood cells when applied to mammalian blood. 2. Use according to claim 1 wherein the blood aliquot is the patient's own blood. 3. Use according to claim 1 or claim 2 wherein the blood aliquot is of volume about 0.1 ml to 400 ml. 4. Use according to any preceding claim wherein the oxidative environment stressor to which the blood aliquot is subjected is a mixture of medical grade oxygen and ozone, with an ozone content from about 0.1-100 mug/ml. 5. Use according to any preceding claim wherein the ultraviolet radiation stressors is ultraviolet radiation from UV lamps emitting primarily at wavelengths of 280 nm or shorter. 6. Use according to any preceding claim wherein the elevated temperature stressor is a temperature in the range from about 38-43 degree C. 7. Use according to any preceding claim wherein the chosen combination of stressors is applied to the blood aliquot for a period of time in the range 0.5-60 minutes. 8. Use according to any of claims 1-5 and 7 wherein the aliquot of blood is subjected to the oxidative environment stressor and the UV radiation stressor simultaneously. 9. Use according to any of claims 1-4, 6 or 7 wherein the aliquot of blood is subjected to the oxidative stressor and the elevated temperature stressor simultaneously. 10. Use according to any of claims 1-3 or 5-8, wherein the aliquot of blood is subjected to the UV radiation stresses and the heat stressor simultaneously. 11. Use according to any of claims 1-8 wherein the blood aliquot is subjected to all three said stressors simultaneously. 12. Use according to any of claims 1-7 and 9-11 wherein the heat stressor is applied by infra-red radiation. 13. Use according to claim 1 wherein the ischemia stress ischemia-reperfusion of the patient's kidney, heart, liver, intestine or brain. 14. Use according to claim 1 wherein the ischemic stress is ischemia-reperfusion of the kidney. 15. Use according to claim 1 wherein the aliquot of blood is an aliquot of the patient's own blood, of volume about 0.1 ml-400 ml, which has been subjected to all three said stressors simultaneously, or to any two of the said stressors simultaneously. 16. Use according to claim 15 wherein the oxidative environment stressor to which the blood aliquot is subjected is a mixture of medical grade oxygen and ozone, with an ozone content of from about 0.1-100 mug/ml, the ultraviolet radiation stressors is ultraviolet radiation from UV lamps emitting primarily an wavelengths of 280 nm or shorter, the elevated temperature stressor is a temperature in the range from about 38-43 degree C, and each said stressor is applied to the blood aliquot from a period of time in the range 0.5-60 minutes. 17. Use according to claim 1 in which the patient suffers from atherosclerosis and is scheduled for general anaesthesia prior to ischemia of a vital organ in a surgical procedure. 18. Use according to claim 1 in which the patient is scheduled to undergo open-heart surgery with cardio-pulmonary bypass. 19. Use according to any preceding claim, of a plurality of said treated blood aliquots, administered at intervals of at least 1 day.