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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Anti-Radiation Antidote: Immunologically-based Prophylaxis and Treatment of Acute Toxic Radiation Syndromes Associated with Long-term Space Flight to Mars.
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.
ο 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.
ο The three major sources/types of radiation are
found in space: galactic cosmic rays, trapped Van
Allen belt radiation, and solar particle events.
ο 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.
ο 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.
ο 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.
ο 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.
ο 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.
ο Important consequence of this toxicity is altered
metabolism of endothelial cells, which leads to
vascular and circulatory effects β
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.
ο Hemolysis and autoimmune hemolytic anemia
develop at high doses of radiation.
ο 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.
ο 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. ο 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.
ο 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.
ο 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.
ο 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.
ο Who needs also in radiation protection β
prophylaxis and treatment ?
ο Patients with cancer which undergo to radiation
therapy.
ο Astronauts, Cosmonauts, Taikonauts.
ο Pilots and crew members.
ο Military personnell
16. Immunologically-based Prophylaxis and Treatment of
Acute Toxic Radiation Syndromes Associated with
Long-term Space Flight to Mars.
ο 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.
ο 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.
ο http://www.slideshare.net/dlpopov/toxicology-of-
acute-cerebrovascular-radiation-syndrome-part-2
ο http://www.slideshare.net/dlpopov/toxicology-of-
acute-cerebrovascular-radiation-syndrome
ο http://www.slideshare.net/dlpopov/handrons-
radiation-protection
ο http://www.slideshare.net/dlpopov/novocain-
blocade-vishnevsy
ο 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.
ο http://www.slideshare.net/dlpopov/radiation-
toxicity-lipids-radiotoxins
ο http://www.slideshare.net/dlpopov/acute-
radiation-gastrointestinalsyndrome
ο http://www.slideshare.net/dlpopov/radiation-
toxicity-tolllike-receptors
ο http://www.slideshare.net/dlpopov/acute-
radiationdiseasecountermeasure-development
ο 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.
ο http://www.slideshare.net/dlpopov/radiation-
toxicity-necrosis-apoptosis
ο http://www.slideshare.net/dlpopov/rapid-
bioassessment-protocol-for-acute-radiation-
syndromes
ο http://www.slideshare.net/dlpopov/radiation-
toxicity-inflammation
ο http://www.slideshare.net/dlpopov/histamine-
toxicity-different-opinion
ο 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.
ο http://www.intechopen.com/books/current-topics-
in-ionizing-radiation-research/radiation-toxins-
molecular-mechanisms-of-toxicity-and-
radiomimetic-properties-