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Subject: iron/bacteria
Microbios 1996;87(351):77-87
Role of iron in the pathogenesis of Mycobacterium avium infection in mice.
Dhople AM, Ibanez MA, Poirier TC
Department of Biological Sciences, Florida Institute of Technology,
Melbourne 32901, USA.
Mycobacterial infections are of serious concern to HIV-infected
patients, and take a heavy toll of such patients. Mycobacterium avium
is the most common opportunistic bacterial infection in patients with
AIDS. The overload of iron in serum has been implicated in the
pathogenicity of a number of bacterial infections. Since iron storage
in cells such as macrophages is increased in AIDS, the role of iron as
a possible factor in the pathogenesis of M. avium infection was
examined. Supplementing iron to normal laboratory chow resulted in
accelerated M. avium infection in mice inoculated earlier with the
same organism. The bacterial loads in liver, spleen and lungs were
approximately 12-fold higher in mice receiving iron supplementation
compared with control groups. This is attributed to an increased
percentage saturation of iron in the sera of the mice, thus making
more iron available for the replication of bacteria. The addition of
beef fat to the diet, together with high iron supplementation, further
enhanced the infection. Using smaller inocula, mice receiving chow
supplemented with high iron and fat developed disseminated M. avium
infection faster than control mice. The results provide strong
evidence that iron may play a major role in the pathogenesis of M.
avium infection.
PMID: 9032957, UI: 97185223
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Subject: aids/hiv/chelators
J Infect Dis 2000 Feb;181(2):484-90
Inhibition of human immunodeficiency virus type 1 replication in human
mononuclear blood cells by the iron chelators deferoxamine, deferiprone, and
bleomycin.
Georgiou NA, van der Bruggen T, Oudshoorn M, Nottet HS, Marx JJ, van Asbeck
BS
Department of Internal Medicine, University Medical Center Utrecht,
Utrecht, The Netherlands. n.georgiou@lab.azu.nl
Replication of human immunodeficiency virus type 1 (HIV-1) can be
influenced by iron. Hence, decreasing the availability of iron may
inhibit HIV-1 replication. Deferoxamine and deferiprone, both forming
catalytically inactive iron-chelator complexes, and bleomycin, by use
of which iron catalyzes oxidative nucleic acid destruction, were
investigated. Expression of p24 antigen in human monocyte-derived
macrophages and peripheral blood lymphocytes (PBL) was reduced by all
3 iron chelators. In PBL, p24 reduction was mirrored by a decrease in
proliferation after incubation with deferoxamine or deferiprone,
suggesting that viral inhibition is closely linked to a decrease in
cellular proliferation. In contrast, clinically relevant bleomycin
concentrations reduced p24 levels by approximately 50% without
affecting proliferation. When deferoxamine and the nucleoside analogue
dideoxyinosine were used in combination, they acted synergistically in
inhibiting HIV-1 replication. These observations suggest that iron
chelators with different mechanisms of action could be of additional
benefit in antiretroviral combination therapy.
PMID: 10669330, UI: 20134572
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Subject: acidosis/iron
J Clin Invest 1997 Sep 15;100(6):1640-1646
Chloroquine induces human mononuclear phagocytes to inhibit and kill
Cryptococcus neoformans by a mechanism independent of iron deprivation.
Levitz SM, Harrison TS, Tabuni A, Liu X
The Evans Memorial Department of Clinical Research and the Department
of Medicine, Boston Medical Center, Boston, Massachusetts 02118, USA.
slevitz@med-med1.bu.edu
Infections due to Cryptococcus neoformans are common in AIDS patients.
We investigated the effect of chloroquine, which raises the pH of
phagolysosomes, on the anticryptococcal activity of mononuclear
phagocytes. C. neoformans multiplied within monocyte-derived
macrophages (MDM) in the absence of chloroquine but were killed with
the addition of chloroquine. Ammonium chloride was also beneficial,
suggesting that effects were mediated by alkalinizing the
phagolysosome. Chloroquine inhibits growth of other intracellular
pathogens by limiting iron availability. However, chloroquine-induced
augmentation of MDM anticryptococcal activity was unaffected by iron
nitriloacetate, demonstrating that chloroquine worked by a mechanism
independent of iron deprivation. There was an inverse correlation
between growth of C. neoformans in cell-free media and pH, suggesting
that some of the effect of chloroquine on the anticryptococcal
activity of MDM could be explained by relatively poor growth at higher
pH. Chloroquine enhanced MDM anticryptococcal activity against all
tested cryptococcal strains except for one large-capsule strain which
was not phagocytosed. Positive effects of chloroquine were also seen
in monocytes from both HIV-infected and -uninfected donors. Finally,
chloroquine was therapeutic in experimental cryptococcosis in outbred
and severe combined immunodeficient mice. Thus, chloroquine enhances
the activity of mononuclear phagocytes against C. neoformans by
iron-independent, pH-dependent mechanisms and is therapeutic in murine
models of cryptococcosis. Chloroquine might have clinical utility for
the prophylaxis and treatment of human cryptococcosis.
PMID: 9294133, UI: 97439787
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Subject: malaria/Hiv
> Malaria Twice As Likely Among HIV-1-Positive People
http://www.docguide.com/dgc.nsf/news/D85CAFF138D59BFC85256962004B2E90
People who are infected with the human immunodeficiency
1 (HIV-1) virus positive may be twice as likely to develop
malaria as are HIV-1-negative people, research in Uganda
has found.
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