Yicks!!  That's the clinic from hell.  Damn.

~Ray~

Baillieres Clin Haematol. 1994 Dec;7(4):965-1000.  Related Articles, Links  

Control of disease by selective iron depletion: a novel therapeutic strategy
utilizing iron chelators.

Hershko C.

Department of Medicine, Shaare Zedek Medical Center, Jerusalem, Israel.

Recognition of the central role of iron in the generation of toxic,
oxygen-derived species through the Haber-Weiss reaction, the ability of
desferrioxamine (DFX) to prevent the damage associated with free radical
generation in reperfusion injury, and its inhibitory effect on cell
proliferation by inactivation of the iron dependent enzyme ribonucleotide
reductase, resulted in an increasing number of studies exploring the novel
therapeutic applications of iron chelating drugs: (a) Animal models of
reperfusion injury have shown that DFX is able to decrease post-anoxic damage
to the brain and heart as manifested in decreased infarct size and improved
functional recovery. Iron chelators may be particularly useful in improving the
preservation of organs intended for transplantation such as the heart, lung or
kidney. (b) Anthracycline cardiotoxicity is aggravated by iron and inhibited by
iron chelators. Because the mechanism of its antineoplastic effect differs from
its cardiotoxic effect, it is possible to inhibit anthracycline cardiotoxicity
without interfering with therapeutic efficacy. In vivo and in vitro animal
studies have yielded encouraging results but much additional experimental work
is still required before iron chelating therapy may be advocated for use in
patients on anthracycline therapy. (c) Cell proliferation can be inhibited by
iron chelators through the reversible inhibition of ribonucleotide reductase, a
rate-limiting enzyme in DNA synthesis. This may be exploited for the treatment
of malignant disease, and preliminary studies have already shown that DFX in
combination with multidrug chemotherapy is effective in controlling
neuroblastoma and other tumours. However, the contribution of DF to the overall
clinical effect is unclear. Prospective controlled clinical studies are
required in order to establish whether the antiproliferative, or cell
synchronizing properties of DFX may be of practical usefulness in the control
of malignant disease. (d) Control of protozoal infection: Experimental in vivo
and in vitro models have shown that malarial infection may be inhibited by iron
chelating therapy. This useful effect of DFX and other iron chelators is most
probably related to ribonucleotide reductase inhibition. Clinical studies of
asymptomatic P. falciparum malaria and of cerebral malaria have shown both an
accelerated rate of parasite clearance and earlier recovery from coma. These
observations lend new meaning to the term 'nutritional immunity' and open new
channels for exploring the possibility of controlling infection by means of
selective intracellular iron deprivation. Experimental models for studying the
effect of iron chelators on other intracellular pathogens such as Toxoplasma
gondii, Chlamydia psittaci, or Mycobacterium tuberculosis should be
established.(ABSTRACT TRUNCATED AT 400 WORDS)

Publication Types:
Review
Review, Academic

PMID: 7881162 [PubMed - indexed for MEDLINE]

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Who loves ya.
Tom

Wow, thanks.  I have not heard of a few of these, but they are worth looking
into.

~Ray~