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Anti-Radiation Antidote: Immunologically-based Prophylaxis and Treatment of Acute Toxic Radiation Syndromes Associated with Long-term Space Flight to Mars

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1. Dmitri Popov. PhD. Radiobiology. (Advanced Medical Technologies and Systems, Canada); Jeffrey Jones. Prof. (Baylor School of Medicine, USA); Anti-Radiation Antidote: Immunologically-based Prophylaxis and Treatment of Acute Toxic Radiation Syndromes Associated with Long-term Space Flight to Mars. 2. Immunologically-based Prophylaxis and Treatment of Acute Toxic Radiation Syndromes Associated with Long-term Space Flight to Mars. Protecting crew from ionizing radiation is a key life sciences problem for long-duration space missions. 3. Immunologically-based Prophylaxis and Treatment of Acute Toxic Radiation Syndromes Associated with Long-term Space Flight to Mars. The three major sources/types of radiation are found in space: galactic cosmic rays, trapped Van Allen belt radiation, and solar particle events. All present varying degrees of hazard to crews; however, exposure to high doses of any of these types of radiation ultimately induce both acute and long-term biological effects. 4. Immunologically-based Prophylaxis and Treatment of Acute Toxic Radiation Syndromes Associated with Long-term Space Flight to Mars. High doses of space radiation can lead to the development of toxicity associated with the acute radiation syndrome (ARS) which will have significant mission impact, and even render the crew incapable of performing flight duties. 5. Immunologically-based Prophylaxis and Treatment of Acute Toxic Radiation Syndromes Associated with Long-term Space Flight to Mars. The creation of efficient radiation protection technologies is considered an important target in space radiobiology, immunology, biochemistry and pharmacology. 6. Immunologically-based Prophylaxis and Treatment of Acute Toxic Radiation Syndromes Associated with Long-term Space Flight to Mars. Three major mechanisms of cellular, organelle, and molecular destruction as a result of radiation exposure have been identified: 1) Damage induced directly by incident radiation on the macromolecules they encounter. 2) Radiolysis of water and generation of secondary free radicals and reactive oxygen species (ROS). 3) Activation of hydrolytic enzymes which induce chemical bond breakage, molecular substitutions, and damage to biological molecules such as DNA, and proteins, and membranes. 7. Immunologically-based Prophylaxis and Treatment of Acute Toxic Radiation Syndromes Associated with Long-term Space Flight to Mars. Enzyme activation after irradiation: Phospholipases increase cell and organelle membrane permeability; proteases damage cytoskeleton and organelles; Endonucleases cause fading of chromatin and DNA breaks; ATPases destroy ATP, hydrolytic enzymes such as Phosphodiesterases and enzymes that hydrolysis of phosphodiester bonds in ATP and important substrates. 8. Immunologically-based Prophylaxis and Treatment of Acute Toxic Radiation Syndromes Associated with Long-term Space Flight to Mars. Important consequence of this toxicity is altered metabolism of endothelial cells, which leads to vascular and circulatory effects cerebrovascular, cardiovascular, GI systems vascular insufficiency. Changes in molecular structures initiate autoimmune reactions with auto-antibodies production and cell mediated immune-toxic reactions. 9. Immunologically-based Prophylaxis and Treatment of Acute Toxic Radiation Syndromes Associated with Long-term Space Flight to Mars. Hemolysis and autoimmune hemolytic anemia develop at high doses of radiation. Vasculitis, tissue specific hypoxia and development Acute Radiation Cerebrovascular Syndrome, Acute Radiation Cardiovascular Syndrome, Acute Radiation Bowel (GI) Syndrome and Acute Radiation Hematopoietic Syndrome. 10. Immunologically-based Prophylaxis and Treatment of Acute Toxic Radiation Syndromes Associated with Long-term Space Flight to Mars. Two types of radiation-induced cellular lethality that ultimately develops, apoptosis or necrosis, depends on the spectrum of incident radiation, dose, dose rate, and functional conditions of impacted cells/organisms. 11. Radiation Inflammation. local and general vasculitis, tissue specific hypoxia and development Acute Radiation Cerebrovascular Syndrome, Acute Radiation Cardiovascular Syndrome, Acute Radiation Bowel (GI) Syndrome and Acute Radiation Hematopoietic Syndrome. 12. Immunologically-based Prophylaxis and Treatment of Acute Toxic Radiation Syndromes Associated with Long-term Space Flight to Mars. 1. Free-radical scavengers and antioxidants, which neutralize the damaging activities of ROS, are effective in reducing the impact of small to moderate doses of radiation. However, antioxidants playing only adaptive role in the case of high doses of radiation. Antioxidants alone may be inadequate as a radioprotective therapy. However, it remains a valuable component of a more holistic strategy of prophylaxis and therapy. 13. Immunologically-based Prophylaxis and Treatment of Acute Toxic Radiation Syndromes Associated with Long-term Space Flight to Mars. 2. Inhibitors of proteases. ( very efficient treatment). 14. Immunologically-based Prophylaxis and Treatment of Acute Toxic Radiation Syndromes Associated with Long-term Space Flight to Mars. 3. Antibody inhibitors of clinically important hydrolytic enzymes such as some Phosphodiesterases. 4. Phosphodiesterases can be isolate from mammals or from venom of rattle snakes ( research model) and antibodies to Phosphodiesterases were used as Antiradiation Antidote. 15. Immunologically-based Prophylaxis and Treatment of Acute Toxic Radiation Syndromes Associated with Long-term Space Flight to Mars. Who needs also in radiation protection prophylaxis and treatment ? Patients with cancer which undergo to radiation therapy. Astronauts, Cosmonauts, Taikonauts. Pilots and crew members. Military personnell 16. Immunologically-based Prophylaxis and Treatment of Acute Toxic Radiation Syndromes Associated with Long-term Space Flight to Mars. The administration of an experimental anti- radiation Antidote will provide an immunologically based, adjunct method of prevention or prophylaxis and treatment against clinical ARS. 17. Immunologically-based Prophylaxis and Treatment of Acute Toxic Radiation Syndromes Associated with Long-term Space Flight to Mars. The administration of experimental anti-radiation serum (ARS) and the use of the blood dialysis methods, such as immune plasma-sorption, assist in the clearance of radiation-specific toxins and may enhance established strategies for the mitigation of the biological effects leading to ARS, and should be evaluated for use on exploration- class space missions. 18. Immunologically-based Prophylaxis and Treatment of Acute Toxic Radiation Syndromes Associated with Long-term Space Flight to Mars. http://www.slideshare.net/dlpopov/toxicology-of- acute-cerebrovascular-radiation-syndrome-part-2 http://www.slideshare.net/dlpopov/toxicology-of- acute-cerebrovascular-radiation-syndrome http://www.slideshare.net/dlpopov/handrons- radiation-protection http://www.slideshare.net/dlpopov/novocain- blocade-vishnevsy http://www.slideshare.net/dlpopov/rad- toxhydrolyticenzymes 19. Immunologically-based Prophylaxis and Treatment of Acute Toxic Radiation Syndromes Associated with Long-term Space Flight to Mars. http://www.slideshare.net/dlpopov/radiation- toxicity-lipids-radiotoxins http://www.slideshare.net/dlpopov/acute- radiation-gastrointestinalsyndrome http://www.slideshare.net/dlpopov/radiation- toxicity-tolllike-receptors http://www.slideshare.net/dlpopov/acute- radiationdiseasecountermeasure-development http://www.slideshare.net/dlpopov/radiation-toxity- complement-system-activation 20. Immunologically-based Prophylaxis and Treatment of Acute Toxic Radiation Syndromes Associated with Long-term Space Flight to Mars. http://www.slideshare.net/dlpopov/radiation- toxicity-necrosis-apoptosis http://www.slideshare.net/dlpopov/rapid- bioassessment-protocol-for-acute-radiation- syndromes http://www.slideshare.net/dlpopov/radiation- toxicity-inflammation http://www.slideshare.net/dlpopov/histamine- toxicity-different-opinion http://www.slideshare.net/dlpopov/histamine- toxicity 21. Immunologically-based Prophylaxis and Treatment of Acute Toxic Radiation Syndromes Associated with Long-term Space Flight to Mars. http://www.intechopen.com/books/current-topics- in-ionizing-radiation-research/radiation-toxins- molecular-mechanisms-of-toxicity-and- radiomimetic-properties-