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Sauron
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@O3, thanks, I will look back into this. Meanwhile you might want to see a two volume study from the Natl Academy of Sciences called SOLDIERS AT RISK.
This is available online for free.
Clinton, having been blinsided by the Agent Orange controversy and settlement, wanted to make sure there were no other similar situations lurking, and
this report concerns possible claims resulting from voluntary testing on military personnel. It covers lethal and nonlethal agents, and a lot of
chemical, biochemical and medical background is provided. I am not sure whether it helps or hurts my position on lewisite, as it has been a few years
since I looked at it. I have it in hardcopy at my office where I rarely go these days.
Later
@O3, looks like you nailed it. From National Academy Press, (1999)
Review of the U.S. Army's Health Risk Assessments for Oral Exposure to Six Chemical-Warfare Agents (1999)
Board on Environmental Studies and Toxicology p.282
"MECHANISM OF ACTION
The toxicological effects of lewisite are ultimately due to its interaction with thiol groups of biologically active proteins such as enzymes. The
interaction with sulfhydryl groups of enzymes may result in inhibition of enzyme function by the formation of stable cyclic structures with arsenic
(As+3) as a result of the reaction of the arsenic with the sulfhydryl groups of organic compounds such as those occurring in dihydrolipoic acid and in
reduced keratin (De Bruin 1976). Dihydrolipoic acid is a dithiol cofactor active in several important enzyme systems (required for cellular
respiration) including alphaketoacid oxidases such as pyruvate oxidase, 2-oxoglutarate oxidase, and aldehyde dehydrogenase. Lewisite combines with the
dihydrolipoic acid to form stable six-member ring structures (cyclic thioarsenite
complexes), thereby inactivating the enzymes. Overall, the end result of these interactions and the ultimate mechanism of lewisite toxicity appear to
be energy depletion which, in turn, results in cell death. Organochloroarsines, of which lewisite is an example, are also potent alkylating agents;
this feature suggests carcinogenic potential."
Compare with Sulfur Mustard: p.243
"2 MECHANISM OF ACTION
The acute toxic effects of mustard vesicants are usually attributed to the consequences of alkylation reactions with organic compounds including
nucleoproteins such as DNA. Alkylation reactions can result in physiological and metabolic disturbances as well as genotoxic effects. Several
hypotheses have been advanced concerning the primary cause of cell death following acute exposures. As reviewed by Papirmeister et al. (1991), the
three major hypotheses are:
Poly(ADP-ribose) polymerase (PADPRP) hypothesis. - In this theory DNA is the initial target of the mustard agent. Alkylated DNA purines undergo
spontaneous and enzymatic depurination, leading to the production of apurinic sites which are cleaved by apurinic endonucleases to yield DNA breaks.
Accumulation of DNA breaks leads to activation of the chromosomal enzyme PADPRP, which utilizes nicotinamide adenine dinucleotide (NAD+) as a
substrate to ADP-ribosylate and a variety of nuclear proteins, causing severe lowering of cellular NAD+. Depletion of NAD+ results in the inhibition
of glycolysis, and stimulation of the nicotinamide adenine dinucleotide phosphate (NADP+)-dependent hexose monophosphate shunt (HMS) pathway follows
as a result of the accumulation of glucose-6-phosphate, a common precursor for both glycolysis and the HMS. Induction and secretion of proteases is
stimulated as a result of enhanced HMS activity, and this leads to pathological changes in the cell.
Thiol-Ca+2 peroxidation hypothesis. The first step in this process is thought to be the alkylation of glutathione (GSH) by the mustard agent.
Depletion of GSH subjects protein sulfhydryl groups to damage from the agent or from reactive cellular oxidants. Proteins most susceptible to damage
include Ca2+ translocases (Ca2+-stimulated, Mg2+-dependent ATPase) which are dependent on thiol groups to maintain cellular Ca2+ homeostasis, and
microfilamentous proteins, where loss of sulfhydryl groups could result in disruptions of the cytoskeletal and structural integrity of the plasma
membrane.
Lipid peroxidation hypothesis. According to this hypothesis the mustard agent causes depletion of GSH which, in turn leads to the buildup of highly
toxic oxidants, usually through H2O2-dependent reaction sequences. The oxidizing agents react with membrane phospholipids to form lipid peroxides,
initiating a chain reaction of lipid peroxidation which can lead to alterations in membrane fluidity, loss of membrane protein function, and loss of
membrane integrity."
[Edited on 21-1-2007 by Sauron]
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Ozone
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Thanks! That's a great reference, top-shelf for sure!
Sulfhydryl compounds can readily stabilize radical species (they can also then re-initiate radical sequences). This is a feasible mechanism so long as
there is an external radical source (such as H2O2 and Fe). The interesting thing is that propagation via chain transfer is not susceptable to O2
poisoning (as is most other propagating radical regimes). The main products of the catalyzed decomposition of H2O2 are .OH and -OH. Hydroxyl radicals
are right up there with fluorine, in terms of oxidative potential; these would be quite likely to disprupt phospholipid bilayers (causing cells to
leak).
Interesting, and, once again,
Thanks,
O3
-Anyone who never made a mistake never tried anything new.
--Albert Einstein
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Sauron
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Phosgene oxime is a really strange one, its effects are slow to heal and reportedly recur many times. I believe it was principally a Soviet agent. I
do not regard it as a structural analog of any of these others.
[Edited on 21-1-2007 by Sauron]
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franklyn
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| Quote: | Originally posted by Sauron
Now entirely different countermeasures are employed. These I will not discuss.
I believe we mostly rely on prophylactic compounds (premedication of troops)
There has been some controversy about some of these compounds supposedly
interacting with insect repellants but I have not paid much attention to the
resolution of this pissing contest. |
The interaction of PYRIDOSTIGMINE BROMIDE with DEET
caused far more casualties in the Irag Desert Storm affair than can be counted.
Epidemialogical statistical methods have identified 3 distinct syndromes _
Syndrome 1 ("impaired cognition") is characterized by distractibility, difficulty
remembering, depression, middle and terminal insomnia, fatigue, slurring of speech,
confused thought process, and migrainelike headaches.
Syndrome 2 ("confused-ataxia") is characterized by problems with thinking,
reasoning and getting confused or disorientated and problems with impotence and
a high frequency of occupational disability. This is associated with testing
abnormalities characteristic of brain and spinal cord damage and possibly peripheral
neuropathy (Haley, et al., 1997a).
Syndrome 3 ("neuro-myo-arthropathy") is characterized by generalized joint and
muscle pains, muscle weakness and fatigability, and stocking-glove paresthesias.
This is different from the other two in that it has definite neurologic abnormalities
that could be from dysfunction of either the central of peripheral nervous system
(Haley, et al., 1997a).
The body of knowledge which has emerged can only be called a pissing contest
if infinitive proof is required. On that vein there are philosophies which assert
that we really do not exist, but then , that is not science.
FOR REASONS I CANNOT FATHOM THE LINKS I PROVIDE REFERENCING THIS
ISSUE , CANNOT BE PARSED BY THE FORUM BOARD , SO INSTEAD THEY ARE
ACTIVE LINKS IN THE ATTACHED *.PDF FILE.
| Quote: | Originally posted by Sauron
Phosgene oxime is a really strange one, its effects are slow to heal and reportedly
recur many times. I believe it was principally a Soviet agent. I do not regard it as
a structural analog of any of these others. |
The premiere vessicant ( blister agent ) is phosgene oxime ( CBW nomenclature , CX )
this causes immediate stinging pain to all exposed tissue. Methyl isocyanate is similar
in effect but not as potent, accidental industrial release of this caused a few
thousand casualties in Bhopal India over 20 years ago.
.
[Edited on 9-2-2007 by franklyn]
Attachment: Resource Links.pdf (13kB)
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Sauron
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Phosgene oxime is inferior to some other vesicants precisely because its effects are immediate rather than delayed. With delayed effects you get
casualties from individuals remaining unmasked because they are unaware they are being exposed.
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franklyn
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| Quote: | Originally posted by Sauron
Phosgene oxime is inferior to some other vesicants precisely because its effects are immediate rather than delayed. With delayed effects you get
casualties from individuals remaining unmasked because they are unaware they are being exposed. |
Field commander's call, the maimimg and crippling of soldiers has always been
preferable in protracted attrition conflicts, regardless of the modality , because
caring for the wounded diverts resources that can othwerwise be employed to
the battle. The Iraq Iran war being the most recent example. At low concentration
more time is needed for cumulative harm to result , so in this regard only , against
poorly trained combatants or more often civilians , is a stealthy application even
realistic. Curious that the same argument was made AGAINST enhanced radiation ,
neutron bombs , which were specifically designed to counter a massed Soviet tank
offensive and minimize colateral damage in the congested european geography.
Terminal effects to the crews from induced free radical poisoning i.e. radiation
sickness only results many hours to as much as a day after exposure to the
detonation. This just proves that lawyers can argue both sides of any question.
See here middle paragraph _
http://www.sciencemadness.org/talk/viewthread.php?tid=1216&a...
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