Subject: toxoplasmosis/iron
Immunology 1998 Aug;94(4):488-95
Interferon-gamma-activated primary enterocytes inhibit Toxoplasma gondii
replication: a role for intracellular iron.
Dimier IH, Bout DT
CJF INSERM 93-09 'Immunologie des Maladies Infectieuses', Equipe
associee INRA 'Immunologie Parasitaire', UFR des Sciences
Pharmaceutiques, Tours, France.
Toxoplasma gondii is an obligate intracellular parasite that infects a
wide variety of nucleated cells in its numerous intermediate hosts
including man. The oral route is the natural portal of entry of T.
gondii. Ingested organisms are released from cysts or oocysts within
the gastrointestinal tract and initially invade the intestinal
epithelium. We show that T. gondii invades and proliferates in
cultured primary rat enterocytes, obtained with an original procedure.
Activation of the enterocytes with rat recombinant interferon-gamma
(IFN-gamma) inhibits T. gondii replication, the inhibition being dose
dependent. Neither nitrogen and oxygen derivatives nor tryptophan
starvation appear to be involved in the inhibition of parasite
replication by IFN-gamma. Experiments using Fe2+ salt, carrier and
chelator indicate that intracellular T. gondii replication is iron
dependent, suggesting that IFN-gamma-treated enterocytes inhibit T.
gondii replication by limiting the availability of intracellular iron
to the parasite. Our data show that enterocytes probably play a major
role on mucosal surfaces as a first line of defence against this
coccidia, and possibly other pathogens, through an immune mechanism.
The results suggest that limiting the availability of iron could
represent a broad antimicrobial mechanism through which the activated
enterocytes exert control over intracellular pathogens.
PMID: 9767436, UI: 98440381
_________________________________________________________________
Save the above report in [Macintosh] [Text] format
Order documents on this page through Loansome Doc
_________________________________________________________________
Subject: malaria/transferrin
Blood 1995 Jun 1;85(11):3297-301
Transferrin saturation and recovery from coma in cerebral malaria.
Gordeuk VR, Thuma PE, McLaren CE, Biemba G, Zulu S, Poltera AA, Askin JE,
Brittenham GM
Department of Medicine, George Washington University Medical Center,
Washington, DC 20037, USA.
To determine if the elevated transferrin saturations found in some
patients with severe malaria are associated with an adverse outcome in
cerebral malaria, we retrospectively measured baseline saturations in
stored serum samples from 81 Zambian children with strictly defined
cerebral malaria. The children had been treated with quinine,
sulfadox-ine-pyrimethamine, and intravenous infusions of either
placebo (n = 39) or the iron chelator, desferrioxamine B (n = 42), in
a previously reported trial (Gordeuk et al, N Engl J Med 327:1473,
1992). More than one-third of children in both the placebo- and iron
chelator-treated groups had transferrin saturations exceeding 43%,
which is 3 standard deviations above the expected mean for age. Among
children receiving quinine and placebo, those with elevated
transferrin saturations had a delayed estimated median time to recover
full consciousness (68.2 hours) compared with those with saturations <
or = 43% (25.4 hours; P = .006). The addition of iron chelation to
quinine therapy in children with high saturations appeared to hasten
recovery (P = .046). We conclude that increased transferrin
saturations may be associated with delayed recovery from coma during
standard therapy for cerebral malaria and that serum iron and total
iron binding capacity should be measured in future studies.
Publication Types:
* Clinical trial
* Randomized controlled trial
PMID: 7756663, UI: 95276267
_________________________________________________________________
Save the above report in [Macintosh] [Text] format
Order documents on this page through Loansome Doc
_________________________________________________________________
Subject: ferritin/infection/cows
J Vet Med Sci 1998 Aug;60(8):943-7
Changes in iron and ferritin in anemic calves infected with Theileria sergenti.
Watanabe K, Ozawa M, Ochiai H, Kamohara H, Iijima N, Negita H, Orino K,
Yamamoto S
Laboratory of Biochemistry, School of Veterinary Medicine and Animal
Sciences, Aomori, Japan.
Changes in iron and ferritin in calves infected with Theileria
sergenti were investigated to elucidate iron metabolism in animals
with extravascular hemolytic anemia. During severe anemia, serum iron
was remarkably elevated while the total iron-binding capacity remained
relatively unchanged or decreased slightly in the infected calves,
resulting in elevated transferrin saturation. The serum ferritin
concentration gradually increased with the progress of anemia. The
erythrocyte ferritin content drastically increased when mean
corpuscular volume was elevated. The concentration of non-heme iron
and ferritin in the liver, spleen, and bone marrow of the infected
calves was markedly higher than that in the respective tissues of the
control animals. In particular, the liver of the anemic calves was
found to contain 23 and 35 times as much non-heme iron and ferritin,
respectively, as that of the non-anemic healthy cattle. The liver type
(L) to heart type (H) subunit ratio of liver ferritin was
significantly higher in the protozoa-infected than in the non-infected
cattle. On the other hand, the L/H ratio of marrow ferritin was
significantly reduced by the anemia. These results indicate that the
anemic calves infected with T. sergenti apparently present symptoms of
iron overload.
PMID: 9764408, UI: 98436899
_________________________________________________________________
Save the above report in [Macintosh] [Text] format
Order documents on this page through Loansome Doc
_________________________________________________________________
Subject: iron/water/cholera
Indian J Med Res 2000 Apr;111:115-7
Effect of iron on the survival of Vibrio cholerae in water.
Joseph S, Bhat KG
Department of Microbiology, Kasturba Medical College, Mangalore.
Effect of iron in the form of ferric oxide (Fe2O3) on the survival of
V. cholerae O1 was studied. V. cholerae O1 survived for 8 days in
plain water whereas in presence of Fe2O3 it survived up to 15 days.
Presence of organic material in the water further promoted the
bacterial survival by at least 4 days. There was no difference between
the behaviour of El Tor and classical biotype. These results indicate
that the presence of iron in water could promote the survival of V.
cholerae O1 in water and may play a significant role in the
epidemiology of cholera.
PMID: 10935316, UI: 20391001
_________________________________________________________________
_________________________________________________________________
Subject: athletes foot/lactoferrin
Mycoses 2000;43(5):197-202
Oral administration of bovine lactoferrin for treatment of tinea pedis. A
placebo-controlled, double-blind study.
Yamauchi K, Hiruma M, Yamazaki N, Wakabayashi H, Kuwata H, Teraguchi S,
Hayasawa H, Suegara N, Yamaguchi H
Nutritional Science Laboratory, Morinaga Milk Industry Co., Ltd,
Kanagawa, Japan.
[Medline record in process]
A clinical study was conducted to evaluate the effectiveness of
lactoferrin, which is a protein component of cow's milk, in the
treatment of tinea pedis. Doses of either 600 mg or 2000 mg of
lactoferrin, or a placebo was orally administered daily for 8 weeks to
37 adults who were judged to have mild or moderate tinea pedis.
Dermatological improvement and antifungal efficacy were assessed. In
the analysis of all subjects, dermatological symptoms scores i(HOME) n all
groups decreased but the differences were not statistically
significant comparing the three groups. However, in the analysis
limited to subjects with moderate vesicular or interdigital tinea
pedis, dermatological symptoms scores in the lactoferrin-treated
groups decreased significantly in comparison with the placebo group (P
< 0.05). The organisms isolated were Trichophyton rubrum and
Trichophyton mentagrophytes. A mycological cure was not seen in any of
the subjects. In the 37 subjects there were no adverse events and no
subject withdrew from the study because of an adverse event. These
results suggest that orally administered lactoferrin can improve the
dermatological symptoms in some subjects. The potential usefulness of
lactoferrin as a functional food material for treating tinea pedis was
seen for the first time in this study.
PMID: 10948819, UI: 20404620
_________________________________________________________________
Save the above report in [Macintosh] [Text] format
Order documents on this page through Loansome Doc
_________________________________________________________________
Subject: iron/bacteria/copper/ferment
Bacterial Reduction of Copper-Contaminated Ferric Oxide: Copper Toxicity and
the Interaction Between Fermentative and Iron-Reducing Bacteria
J. T. Markwiese, P. J. S. Colberg
_________________________________________________________________
Abstract
Fe(III) oxide is an important heavy-metal sink, and bacteria are
responsible for much of the Fe(III) reduced in nonsulfidogenic aquatic
environments, yet factors governing the bacterial reduction of heavy
metal-contaminated iron oxide are largely unknown. In this study with
a stabilized bacterial consortium enriched from metal-contaminated
sediments, we demonstrate that Cu toxicity impedes anaerobic carbon
oxidation and bacterial reduction of hydrous ferric oxide (HFO). In
the enrichment culture, a Clostridium sp. fermented lactate to
propionate and acetate and Fe(III) reducers coupled acetate oxidation
to HFO reduction. Increasing the amount of Cu in the culture medium
significantly extended the time before Fe(III) reduction occurred and
decreased the reduction rate, but did not affect the extent of HFO
reduction. The Clostridium had a higher Cu-complexation capacity than
the Fe(III) reducer Shewanella alga. Iron reduction was inhibited
until almost all of the dissolved Cu was removed from solution and
occurred two to seven times faster if the sediment enrichment culture
was fed lactate instead of acetate. Our findings suggest that
fermentative bacteria play a role in ameliorating heavy metal toxicity
to iron-reducing bacteria. Fermenters may therefore enhance metal
release in sediments by facilitating the bacterial reductive
dissolution of heavy metal-contaminated HFO.
_________________________________________________________________
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
_________________________________________________________________
____ the above report in [Macintosh] [Text] format
_____ documents on this page through Loansome Doc
_________________________________________________________________
Subject: meningitis/iron
J Child Neurol 1995 Mar;10(2):93-99
A persistent biochemical marker for partially treated meningitis/ventriculitis.
Katnik R
Michigan State University, Department of Pediatrics/Human Development,
Kalamazoo 49008, USA.
Regulation of circulating iron is important in bacterial, yeast, and
fungal infections. In the present study, cerebrospinal fluid levels of
ferritin, an iron-binding protein, were determined in controls and in
patients with central nervous system pyogenic and viral infections.
Among 441 controls, cerebrospinal fluid ferritin level was higher than
18 ng/mL in two relapsed patients with central nervous system
leukemia, 12 with bacteremia or pneumonia, and one with hemorrhagic
herpes simplex encephalitis. Cerebrospinal fluid ferritin levels were
more than 18 ng/mL in 13 of 63 patients diagnosed with nonhemorrhagic
aseptic meningitis/ventriculitis, when defined solely by negative
cerebrospinal fluid culture. Conversely, cerebrospinal fluid ferritin
exceeded 18 ng/mL in culture-proven meningitis (46 of 47 cases) and
ventriculitis (five of five cases). Cases of indolent cryptococcus and
tuberculous meningitis showed modest increases despite traditional
cerebrospinal fluid markers, at times, being normal. Cerebrospinal
fluid ferritin levels did not correlate with cerebrospinal fluid
neutrophil count, cerebrospinal fluid protein concentration, serum
ferritin level, or patient age. In 16 of 19 cases monitored
sequentially during ongoing antibiotic treatment, levels remained over
18 ng/mL (average, 15.0 days; range, 1 to 54 days). This observation
suggests that obtaining cerebrospinal fluid ferritin levels is helpful
whenever traditional laboratory benchmarks normalize, as during acute
or chronic antibiotic therapy, or create confusion with positive
cultures stemming from sample contamination.
PMID: 7782615, UI: 95301873
_________________________________________________________________
____ the above report in [Macintosh] [Text] format
_____ documents on this page through Loansome Doc
_________________________________________________________________
Subject: bacteria/iron
J Infect Dis 1994 Nov;170(5):1248-1255
Hypertriglyceridemic serum, very low density lipoprotein, and iron enhance
Mycobacterium avium replication in human macrophages.
Douvas GS, May MH, Pearson JR, Lam E, Miller L, Tsuchida N
Department of Basic Sciences and Oral Research, School of Dentistry,
University of Colorado Health, Sciences Center, Denver 80262.
The growth of Mycobacterium avium 7497, serovar 4, in cultured human
macrophages is enhanced by Fe3+ and serum lipids over 7 days. Iron
(1-80 micrograms/mL) added to macrophages cultured in normal serum
resulted in 10-fold increases in growth. If iron-supplemented
macrophages were cultured in serum from hypertriglyceridemic donors
after infection, M. avium growth increased 10(3)- to 10(4)-fold.
Without macrophages, differences in bacterial growth between sera were
not seen. Removal of very low density lipoprotein (VLDL) eliminated
the differences between sera. Isolated VLDL from hyperlipidemic serum
resulted in 10(5)-fold increases in growth over that seen with VLDL
from normal sera. Accelerated M. avium growth in macrophages cultured
with hyperlipidemic serum was partly inhibited by the addition of
superoxide dismutase (1000 IU/mL). Results suggest that iron
stimulates O2-induced oxidation of VLDL and its subsequent
accumulation in macrophages. The resultant iron- and lipid-laden cells
become excellent hosts for mycobacterial growth.
PMID: 7963720, UI: 95052845
_________________________________________________________________
____ the above report in [Macintosh] [Text] format
_____ documents on this page through Loansome Doc
_________________________________________________________________
Subject: iron/supplementation/bacteria
Haematologia (Budap) 1993;25(2):69-84
Adequate iron stores and the 'Nil nocere' principle.
Hollan S, Johansen KS
National Institute of Haematology, Blood Transfusion and Immunology,
Budapest.
There is a need to change the policy of unselective iron
supplementation during periods of life with physiologically increased
cell proliferation. Levels of iron stores to be regarded as adequate
during infancy and pregnancy are still not well established. Recent
data support the view that it is not justified to interfere with
physiological adaptations developed through millions of years by
sophisticated and precisely coordinated regulation of iron absorption,
utilization and storage. Recent data suggest that the chelatable
intracellular iron pool regulates the expression of proteins with
central importance in cellular iron metabolism (TfR, ferritin, and
erythroid 5-aminolevulinic synthetase) in a coordinately controlled
way through an iron dependent cytosolic mRNA binding protein, the iron
regulating factor (IRF). This factor is simultaneously a sensor and a
regulator of iron levels. The reduction of ferritin levels during
highly increased cell proliferation is a mirror of the increased
density of TfRs. An abundance of data support the vigorous competition
for growth-essential iron between microbial pathogens and their
vertebrate hosts. The highly coordinated regulation of iron metabolism
is probably crucial in achieving a balance between the blockade of
readily accessible iron to invading organisms and yet providing
sufficient iron for the immune system of the host. The most evident
adverse clinical effects of excess iron have been observed in
immunodeficient patients in tropical countries and in AIDS patients.
Excess iron also increases the risk of initiation and promotion of
malignant processes by iron binding to DNA and by the iron-catalysed
release of free radicals. Oxygen radicals were shown to damage
critical biomolecules leading, apart from cancer, to a variety of
human disease states, including inflammation and atherosclerosis. They
are also involved in processes of aging and thrombosis. Recent
clinical trials have suggested that the use of iron-chelators, natural
and synthetic antioxidants, and anti-TfR monoclonal antibodies can
contribute in retarding malignant cell proliferation. Hypoferraemia
during pregnancy is--like haemodilution--an adaptation to the risks
involved in the natural hypercoagulable state of pregnancy. It may
also serve to prevent the risk of infections and mutagenicity in the
highly proliferating tissues of the foetus. Blunted erythropoiesis has
been revealed during the first 30 weeks of pregnancy by the use of the
newly developed method of determining the soluble serum transferrin
receptor. The lack of increase in erythropoietin levels proves that
there is no hypoxia. Decreases in Hb and iron levels are parts of a
physiological adaptation. As a consequence they should neither be
treated nor prevented. It is stressed that whenever a widespread and
ingrained routine medical intervention has to be changed it is
essential to first monitor the potential health effects of the
recommended change in a national policy.
Publication Types:
* Review
* Review, tutorial
PMID: 8244202, UI: 94063698
______________________(HOME) ___________________________________________
Subject: antioxidants/infection
J Nutr Sci Vitaminol (Tokyo) 1993;39 Suppl:S23-S33
Antioxidants in infection.
Keusch GT
Department of Medicine, New England Medical Center, Boston, MA.
Endogenous oxidation reactions are essential for the normal
biochemistry of life and are especially critical for leukocyte
microbial killing mechanisms in host defense to infectious diseases.
However, reactive oxidative intermediates can damage normal tissues
unless kept under antioxidant control. Three selected examples of
oxidant-antioxidant systems involved in infectious diseases are
discussed, regulation of molecular iron catalyzed oxidations,
superoxide scavengers and inhibitors of nitric oxide synthase in
septic shock, and the use of glutathione replacement therapy in HIV
infection and AIDS. The data suggest that antioxidants, and therapy
based on increasing antioxidant potential, have a major impact on
clinical infectious diseases.
Publication Types:
* Review
* Review, tutorial
PMID: 8164064, UI: 94216964
_________________________________________________________________
Infect Immun 2000 Oct;68(10):5785-93
Pathogenesis of infection by clinical and environmental strains of vibrio
vulnificus in iron-dextran-treated mice.
Starks AM, Schoeb TR, Tamplin ML, Parveen S, Doyle TJ, Bomeisl PE, Escudero
GM, Gulig PA
Department of Molecular Genetics and Microbiology, College of
Medicine, University of Florida, Gainesville, Florida.
[Medline record in process]
Vibrio vulnificus is an opportunistic pathogen that contaminates
oysters harvested from the Gulf of Mexico. In humans with compromising
conditions, especially excess levels of iron in plasma and tissues,
consumption of contaminated seafood or exposure of wounds to
contaminated water can lead to systemic infection and disfiguring skin
infection with extremely high mortality. V. vulnificus-associated
diseases are noted for the rapid replication of the bacteria in host
tissues, with extensive tissue damage. In this study we examined the
virulence attributes of three virulent clinical strains and three
attenuated oyster or seawater isolates in mouse models of systemic
disease. All six V. vulnificus strains caused identical skin lesions
in subcutaneously (s.c.) inoculated iron dextran-treated mice in terms
of numbers of recovered CFU and histopathology; however, the inocula
required for identical frequency and magnitude of infection were at
least 350-fold higher for the environmental strains. At lethal doses,
all strains caused s. c. skin lesions with extensive edema, necrosis
of proximate host cells, vasodilation, and as many as 10(8) CFU/g,
especially in perivascular regions. These data suggest that the
differences between these clinical and environmental strains may be
related to growth in the host or susceptibility to host defenses. In
non-iron dextran-treated mice, strains required 10(5)-fold-higher
inocula to cause an identical disease process as with iron dextran
treatment. These results demonstrate that s.c. inoculation of iron
dextran-treated mice is a useful model for studying systemic disease
caused by V. vulnificus.
PMID: 10992486, UI: 20448940
_________________________________________________________________
Save the above report in [Macintosh] [Text] format
Order documents on this page through Loansome Doc
_________________________________________________________________
(HOME)