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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The co-endemicity of malnutrition, erythrocytopathies, transmissible diseases and iron-deficiency contribute to the prevalence of chronic anaemia in many populations of the developing world. Although iron dietary supplementation is applied or recommended in at risk populations, its use is controversial due to undesirable outcomes, particularly regarding the response to infections, including highly prevalent malaria. We hypothesized that a boosted oxidative stress due to iron supplementation have a similar impact on malaria to that of hereditary anaemias, enhancing innate response and conditioning tissues to prevent damage during infection. Thus, we have analysed antioxidant and innate responses against lethal Plasmodium yoelii during the first five days of infection in an iron-supplemented mouse. This murine model showed high iron concentration in plasma with upregulated expression of hemoxygenase-1. The sustained homeostasis after this extrinsic iron conditioning, delayed parasitemia growth that, once installed, developed without anaemia. This protection was not conferred by the intrinsic iron overload of hereditary hemochromatosis. Upon iron-supplementation, a large increase of the macrophages/dendritic cells ratio and the antigen presenting cells was observed in the mouse spleen, independently of malaria infection. Complementary, malaria promoted the splenic B and T CD4 cells activation. Our results show that the iron supplementation in mice prepares host tissues for oxidative-stress and induces unspecific cellular immune responses, which could be seen as an advantage to promote early defences against malaria infection.
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PMID:Iron supplementation in mouse expands cellular innate defences in spleen and defers lethal malaria infection. 2896 85

Upon infection, pathogen and host compete for the same iron pool, because this trace metal is a crucial micronutrient for all living cells. Iron dysregulation in the host is strongly associated with poor outcomes in several infectious diseases, including tuberculosis, AIDS, and malaria, and inefficient iron scavenging by pathogens severely affects their virulence. Hepcidin is the master regulator of iron homeostasis in vertebrates, responsible for diminishing iron export from macrophages during iron overload or infection. Hepcidin regulation in hepatocytes is well characterized and mostly dependent on interleukin-6 signaling during inflammation, although in myeloid cells, hepcidin induction and the mechanisms leading to intracellular iron regulation remain elusive. Here we show that activation of different Toll-like receptors (TLRs) by their respective ligands leads to increased iron sequestration in macrophages. By measuring the transcriptional levels of iron-related proteins (eg, hepcidin, ferroportin, and ferritin), we observed that TLR signaling can induce intracellular iron sequestration in macrophages through 2 independent but redundant mechanisms. Interestingly, TLR2 ligands or infection with Listeria monocytogenes lead to direct ferroportin transcriptional downregulation, whereas TLR4 ligands, such as lipopolysaccharide, induce hepcidin expression. Infection with Mycobacterium bovis Bacillus Calmette-Guerin promotes intracellular iron sequestration through both hepcidin upregulation and ferroportin downregulation. This is the first study in which TLR1-9-mediated iron homeostasis in human macrophages was evaluated, and the outcome of this study elucidates the mechanism of iron dysregulation in macrophages during infection.
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PMID:Role of the hepcidin-ferroportin axis in pathogen-mediated intracellular iron sequestration in human phagocytic cells. 2976 42

Iron is a key element for every single living process. On a fundamental level, targeting iron is a valuable approach for the treatment of disorders caused by iron overload. Utilizing iron chelators as therapeutic agents has received expanding consideration in chelation therapy. Approved low molecular weight (MW) iron chelators to treat iron overload may experience short half-lives and toxicities prompting moderately high adverse effects. In recent years, polymeric/macromolecular iron chelators have received attention as therapeutic agents. Polymeric iron chelators show unique pharmaceutical properties that are different to their conventional small molecule counterparts. These polymeric iron chelators possess longer plasma half-lives and reduced toxicities, thus exhibiting a significant supplement to currently using low MW iron chelator therapy. In this review, we have briefly discussed polymeric iron chelators and factors to be considered when designing clinically valuable iron chelators. We have also discussed applications of polymeric iron chelators in the diseases caused by iron overload associated with transfusional hemosiderosis, neurodegenerative disorders, malaria and cancer. With this, research findings for new polymeric iron chelators are also covered.
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PMID:Therapeutic Macromolecular Iron Chelators. 3018 50

Iron deficiency and iron-deficiency anemia (IDA) affects approximately two billion people worldwide, and most of them reside in low- and middle-income countries. In these nations, additional causes of anemia include parasitic infections like malaria, other nutritional deficiencies, chronic diseases, hemoglobinopathies, and lead poisoning. Maternal anemia in resource-poor nations is associated with low birth weight, increased perinatal mortality, and decreased work productivity. Maintaining a normal iron balance in these settings is challenging, as iron-rich foods with good bioavailability are of animal origin and either expensive and/or available in short supply. Apart from infrequent consumption of meat, inadequate vitamin C intake, and diets rich in inhibitors of iron absorption are additional important risk factors for IDA in low-income countries. In-home iron fortification of complementary foods with micronutrient powders has been shown to effectively reduce the risk of iron deficiency and IDA in infants and young children in developing countries but is associated with unfavorable changes in gut flora and induction of intestinal inflammation that may lead to diarrhea and hospitalization. In developed countries, iron deficiency is the only frequent micronutrient deficiency. In the industrialized world, IDA is more common in infants beyond the sixth month of life, in adolescent females with heavy menstrual bleeding, in women of childbearing age and older people. Other special at-risk populations for IDA in developed countries are regular blood donors, endurance athletes, and vegetarians. Several medicinal ferrous or ferric oral iron products exist, and their use is not associated with harmful effects on the overall incidence of infectious illnesses in sideropenic and/or anemic subjects. However, further research is needed to clarify the risks and benefits of supplemental iron for children exposed to parasitic infections in low-income countries, and for children genetically predisposed to iron overload.
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PMID:Iron Deficiency Anemia in Children Residing in High and Low-Income Countries: Risk Factors, Prevention, Diagnosis and Therapy. 3267 May 19


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