Cigarette smoking causes
the largest human exposure to carbon monoxide. The COHb [C = carbon, O = oxygen,
CO = carbon monoxide, Hb = hemoglobin] content in an average nonsmoker is about 0.5%, while in a smoker it is ten time3s higher,
about 5% (but level up to 12% have been reported). Toxics A to Z, Jim Harte et al, U. of Cal. Press, 1991, p. 25.
Lowered level of hemoglobin
is minor compared to its effect upon the arteries. The formation of plack is primarily a healing response brought on
by reactive chemicals. What clogs the arties is not just cholesterol, but also includes cells from the artery wall. The principle reactive chemical from smoking is carbon monoxide. Carbon monoxide
is the principle culprit that accounts for why a person who averages a pack or more a day is over two-and-one half times more likely in any
given year to die of a coronary disease. Given the prevalence early from tobacco
because of coronary problems than they do from cancer.
was in April of 1979 in Scientific American that an article presented the evidence in an organized way on the link to carbon
monoxide with coronary disease. That evidence still stands.--JK
Study Finds Carbon Monoxide can Trigger Brain-Damage Attack by Immune System
JAMA, October 6, 2004—Vol.
292, No. 13
Tracy Hampton, PhD
REPUTATION as a stealth toxin goes beyond its odorless, colorless
properties. The gas can also surreptitiously cause delayed permanent brain damage, an effect that scientists have been
unable to explain. But now they are no longer in the dark. A new study reveals
that the damage arises from over activation of immune cells that attack proteins that help insulate nerves.
The findings were
published in the September 1 online issue of the Proceedings of the National Academy of Science (vvvvw.pnas.org).
Annually in the
United Stales, about 40,000 individuals are
treated for carbon monoxide poisoning,
the leading agent of injury and death by poisoning worldwide. The gas' initial
effect on the body is a result of its high affinity for hemoglobin. This
causes hypoxic stress, and affected patients are generally treated with oxygen.
Stephen Thorn, MD,
PhD, of the University of Pennsylvania in Philadelphia, has been studying carbon monoxide’s second effect—permanent brain damage, which can become evident between
4 days and 3 weeks following exposure.
Thorn and colleagues have found that this effect occurs because carbon monoxide exposure modifies myelin basic protein,
found in the insulating cells around neurons. "It turns out that the altered
myelin basic protein is now recognized by the body as an invader or a foreign substance," said Thorn. "The big surprise
in our findings vas that once the immune system is turned on, the lymphocytes also recognize normal myelin basic protein
as abnormal. As
these immune cells continue to lash out against normal myelin basic protein, permanent brain damage can result. Thorn and the
research learn carne to their conclusions when they found that rats engineered to be incapable of mounting an immune response
against myelin basic protein did not develop brain damage following carbon monoxide exposure. These rats also performed normally
in a maze test that measures cognitive and motor function.
Control rats did not fare as well. Their
brain cells exhibited measurable biochemical damage and the animals performed poorly in the maze test. "We think that that's also a clinical correlate—that is to say, patients who suffer serious carbon
monoxide poisoning and don't get early treatment, they have perhaps as much as a 50% chance of suffering what is called
delayed neurological sequelae." said Thorn. "So it's a clinically very important problem," one that can result in impaired
learning and concentration problems, he said.
The study's findings
suggest potential therapies. "One of the next steps is to go back to the animal model and say, now that we have this pathway
figured out, what can we what can we do to disturb it," said Thorn. Obvious candidates an immunosuppressants. It they prove
effective in animal studies, then "we rather quickly could be going to clinical trials to see if we can do something
for patients," said Thorn. D
This ties in well with the fact that an active immune system will stimulate healing response, which in turn results
in the build up of plaque—see above article.--JK
Relationship Between Homocysteine and Superoxide Dismutase in Homocystinuria
Possible Relevance to Cardiovascular Risk
David E. L. Wilcken; Xing Li Wang; Tetsuo Adachi; Hirokazu Hara; Natalia Duarte; Kathryn Green; Bridget
From the Department of Cardiovascular Medicine (D.E.L.W., X.L.W., N.D.), Prince of Wales
Hospital, and University of New South Wales Centre for Thrombosis and Vascular Research, Sydney, Australia; the Laboratory
of Clinical Pharmaceutics (T.A., H.H.), Gifu Pharmaceutical University, Gifu, Japan; and the NSW Biochemical Genetics Service
(K.G., B.W.), the Royal Alexandra Hospital for Children, Sydney, Australia.
Correspondence to Professor David Wilcken, Cardiovascular Genetics Laboratory, Edmund Blacket
Building, Prince of Wales Hospital, Randwick, NSW 2031, Australia. E-mail email@example.com
AbstractA modest homocysteine elevation is associated with an increased cardiovascular risk.
Marked circulating homocysteine elevations occur in homocystinuria due to cystathionine ß-synthase (CßS) deficiency,
a disorder associated with a greatly enhanced cardiovascular risk. Lowering homocysteine levels reduces this risk
significantly. Because homocysteine-induced oxidative damage may contribute to vascular changes and
extracellular superoxide dismutase (EC-SOD) is an important antioxidant in vascular tissue, we assessed EC-SOD
and homocysteine in patients with homocystinuria. We measured circulating EC-SOD, total homocysteine (free plus
bound), and methionine levels during the treatment of 21 patients with homocystinuria, 18 due to CßS
deficiency, aged 8 to 59 years, and 3 with remethylating defects. We measured total homocysteine by immunoassay,
EC-SOD by ELISA, and methionine by amino acid analysis and assessed interindividual and intraindividual relationships.
There was a significant, positive relationship between EC-SOD and total homocysteine. For the interindividual
assessment, levels were highly correlated, r=0.746, N=21, P<0.0001. This relationship was
maintained after taking into account intraindividual patient variation (r=0.607, N=62, P<0.0001).
In 2 newly diagnosed CßS-deficient patients, treatment that lowered the markedly elevated pretreatment
homocysteine level (from 337 to 72 and from 298 to 50 µmol/L) reduced the associated elevated EC-SOD
in each by 50%. EC-SOD and methionine levels were unrelated (r=0.148, n=39, P=0.368). The positive
relationship between circulating EC-SOD and homocysteine could represent a protective antioxidant response
to homocysteine-induced oxidative damage and contribute to reducing cardiovascular risk in homocystinuric patients.
EC-SOD levels may be relevant to the pathogenesis of vascular disease in other patient groups.
Key Words: homocysteine superoxide dismutase oxidative stress vascular disease cystathionine