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

During the Central African (Sahelian) drought, attacks of falciparum malaria were common in patients and their relatives shortly after their arrival in a hospital in Eastern Niger. A prospective study of 72 adult patients not admitted for malaria and 109 accompanying relatives was undertaken to investigate this observation. 23 attacks occurred in patients and 51 in relatives, with a peak frequency five days after arrival. On arrival, parasitaemia was low but reached a maximum by five days. Serum-iron and percentage saturation of transferrin were moderately increased initially, rose dramatically within forty-eight hours with near maximum saturation, and were falling by the fifth day. It is suggested that the early hyperferraemia, apparently related to refeeding, led to rapid multiplication of existing parasites and attacks of malaria. The results of experimental malarial infection of Wistar rats, half of which had been given intramuscular iron, supported this hypothesis.
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PMID:Refeeding-malaria and hyperferraemia. 4 80

Untreated malaria for more than 4 days in eleven patients decreased significantly prealbumin, transferrin levels and increased SGOT activity when compared with a control group and a group of 10 malaria patients who were admitted to the hospital at an earlier stage of the infection. Total protein was significantly lower in the group of patients admitted after five to ten days to hospital compared with the control group. In all malaria patients independent of the duration of the acute infection the 1st post albumin peak in polyacrylamide gel electrophoresis (consisting mainly of Gc-globulin, alpha-1-antichymotrypsin and alpha-1 B-glycoprotein) and creatinine were found to be significantly higher compared with the control group.
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PMID:Alterations of human serum proteins and other biochemical parameters after five to ten days of untreated acute falciparum malaria. 33 73

An haematological, biological, parasitological and immunological study about anaemia of pregnancy was carried out in two rural village of Mali Republic, where P. flaciparum malaria is hyper-endemic. The 25 pregnant women found in the villages were compared with 23 controls. One could observe that anaemia more often normochromic and regenerative usually appears during the second trimestre of pregnancy. Only a few cases with haemaglobin levels below 8 g. % are hypochromic. Serum transferrin levels were slightly higher among pregnant. None among 31 bone marrows examined showed megaloblastic changes. Haptoglobin levels below 10 mg. % were observed in 3/4 of the pregnant women versus 1/4 in controls. Like some others, this study confirms the primary responsability of malaria haemolysis in the aetiology of anaemia of pregnancy and the interest of systematic chemoprophylaxis, at least from the third month of pregnancy. Vitamin and iron therapy is to consider therafter in hyper-endemic areas of P. falciparum malaria when nutritional problems are not predominant.
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PMID:Malaria and anemia of pregnancy in an African savanna zone. Epidemiological, hematological, biological and immunological study of 2 villages of the Bamako region, Republic of Mali. 58 Sep 10

We present here the physicochemical and biochemical properties of NBD-DFO, the 7-nitrobenz-2-oxa-1,3-diazole (NBD) derivative of the siderophore, desferrioxamine B (DFO) (Lytton et al., Mol. Pharmacol. 40, 584, 1991). Modification of DFO at its terminal amine renders it more lipophilic, imparts to it fluorescent properties, and is conservative of the high-affinity iron(III) binding capacity. NBD-DFO partitions readily from aqueous solution into n-octanol (Pcoeff = 5) and displays solvent-induced shifts in absorption and fluorescence spectra. The relative quantum yield of the probe's fluorescence increases over a 10-fold range with decreasing dielectric constant of the solvent. Fluorescence is quenched upon binding of iron(III) to the probe. We demonstrate here the application of NBD-DFO for the specific detection and monitoring of iron (III) in solutions and iron(III) mobilization from cells. Interactions between fluorescent siderophore and the ferriproteins ferritin and transferrin were monitored under physiological conditions. Iron removal from ferritin was evident by the demonstrable quenching of NBD-DFO fluorescence by scavenged iron(III). Quantitation of iron sequestered from cells by NBD-DFO or from other siderophore-iron(III) complexes was accomplished by dissociation of NBD-DFO-Fe complex by acidification and addition of excess ethylenediamin-etetraacetic acid. The sensitivity of the method and the iron specificity indicate its potential for monitoring chelatable iron under conditions of iron-mediated cell damage, iron overload, and diseases of iron imbalance such as malaria.
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PMID:Monitoring of iron(III) removal from biological sources using a fluorescent siderophore. 133 42

Non-heme iron is essential for the asexual growth of the human malaria parasite Plasmodium falciparum in mature erythrocytes. Utilization of iron bound to serum transferrin by the parasitized cells has been postulated, but direct evidence for its specific delivery has not been reported. Here we demonstrate that normal levels of transferrin in human serum are not required for intraerythrocytic P. falciparum growth: culture medium immunodepleted 500-1000 fold in human transferrin was capable of supporting parasitemias and rates of invasion comparable to those observed in non-depleted medium. 55Fe bound to transferrin was not taken up by infected cells. A transferrin-independent non-heme iron uptake activity was, however, detected in both infected and uninfected erythrocytes when iron was presented to the cells as 55Fe-NTA or 55Fe-citrate. Although the uptake activity was not parasite specific, the radiolabel was found in association with parasites mechanically released from the infected erythrocytes, indicating that it is delivered to the intracellular organism. Evidence is presented that the transferrin-independent iron uptake activity is time-, temperature- and concentration-dependent, but apparently not energy-dependent.
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PMID:A transferrin-independent iron uptake activity in Plasmodium falciparum-infected and uninfected erythrocytes. 143 78

Parasite infection causes marked perturbations in the host immune system, as shown by hypergammaglobulinemia, autoimmunity and immune depression, but there is little information on the number, specificities and performance of B cell clones activated in the course of infection. We have addressed these questions in a model of murine malaria induced by Plasmodium chabaudi, where primary infection results in very marked B cell responses that shift in Ig isotype pattern in immunoprotected animals, and where immunity can be transferred to naive recipients by injection of serum from late, but not early, infection. We have quantitated B cells responding to infection in two distinct functional compartments, namely blast cells and Ig-secreting cells, and compared normal with immune animals. We have also determined the frequencies of clonal specificities towards several autoantigens (DNA, myosin, transferrin and red cells), non-self protein or polysaccharide antigens (KLH, levan and dextran), and parasite antigens in both compartments, by measuring blast cell reactivities in limiting dilution analyses and Ig secretion in ELISASPOT assays. This experimental design allowed us to assess the specificity of the B cell responses, to compare the clonal composition of these two B cell compartments, and to evaluate putative specific response regulation at the step of terminal differentiation. Our results show that, in this particular experimental system: (i) B cell responses in primary infection are truly non-specific while immune animals show a greater ability to control the massive non-specific response; (ii) parasite specific B cells, particularly those committed to IgG production, are selectively stimulated in immune individuals; (iii) autoreactive B cells are not selectively stimulated, but increased autoantibody production may result from perturbation in the control of terminal differentiation in the respective clones; (iv) clones with specificity to some non-self antigens (e.g. KLH and dextran) are selectively engaged and regulated, which might have implications for the immunosuppression following infection.
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PMID:Clonal analysis of B lymphocyte responses to Plasmodium chabaudi infection of normal and immunoprotected mice. 177 17

Free radicals, intermediates in the tissue damage caused by radiation, are formed, inter alia, in interactions catalyzed by iron, which synergizes with radiation and some cytostatics (anthracyclins) in causing cell damage. Conversely, iron chelators can counteract cell damage. Similarly, antioxidants can slow atherogenesis, caused in part by oxidative stress and free radicals. Cell damage is also prevented by physiological defense systems like superoxide dismutase, against endogenous free radicals formed by granulocytes, monocytes, etc. Iron can thus induce free radicals which cause DNA double strand breaks and oncogene activation. This is suggested by four epidemiological studies suggesting a higher cancer risk in patients with larger iron stores than in those with small iron stores. In addition to its effect on carcinogenesis, iron can also maintain the growth of malignant cells as well as growth of pathogens. Breast cancer cells, for instance, display 5-15 times more transferrin receptors than normal breast tissue. Iron-carrying transferrin is in fact a growth factor. Hyposideremia in patients with cancer or infection is not a paraphenomenon but a functioning defense mechanism ('nutritional immunity'). If this immunity is broken by iron administration, relapses of diseases like tuberculosis, brucellosis, and malaria have been described. While iron-deficiency anemia should of course be diagnosed, treated and if possible prevented, there are good reasons to avoid over-utilization of medicamental iron.
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PMID:Iron, free radicals and cancer. 182 Apr 88

Chloroquine and ammonium chloride, by virtue of their basic properties, have been shown to raise endocytic and lysosomal pH and thereby interfere with normal iron metabolism in a variety of cell types, including mononuclear phagocytes. Cellular iron metabolism is of critical importance to Legionella pneumophila, an intracellular bacterial pathogen whose capacity to multiply in human mononuclear phagocytes is dependent upon the availability of intracellular iron. In view of this, we have studied the effects of chloroquine and ammonium chloride on L. pneumophila intracellular multiplication in human monocytes. Chloroquine, at a concentration of 20 microM, and ammonium chloride, at a concentration of 20 mM, inhibited L. pneumophila intracellular multiplication by 1.4 +/- 0.2 (SEM) logs and 1.5 +/- 0.2 logs, respectively. Chloroquine- and ammonium chloride-induced inhibition of L. pneumophila intracellular multiplication was completely reversed by iron nitrilotriacetate, an iron compound which is soluble in the neutral to alkaline pH range, but not by iron transferrin, which depends upon acidic intracellular conditions to release iron. Chloroquine had no major direct effect on L. pneumophila multiplication in artificial media except at extremely high concentrations (15,000-fold that which inhibited L. pneumophila multiplication in mononuclear phagocytes), and inhibition at such concentrations was not reversed by iron nitrilotriacetate. This study demonstrates that chloroquine and ammonium chloride inhibit the intracellular multiplication of L. pneumophila by limiting the availability of iron to the bacterium. It is possible that such a mechanism of action underlies chloroquine's antimicrobial effect against other intracellular pathogens, such as the agents of malaria and tuberculosis.
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PMID:Chloroquine inhibits the intracellular multiplication of Legionella pneumophila by limiting the availability of iron. A potential new mechanism for the therapeutic effect of chloroquine against intracellular pathogens. 205 29

Chloroquine is a weak base which has been shown to inhibit lysosomal acidification. Chloroquine inhibits iron uptake in reticulocytes at a concentration of 0.5 mM. It is also effective in the control of malaria and other parasitic diseases. We now report that chloroquine inhibits NADH diferric transferrin reductase as well as the proton release stimulated by diferric transferrin from liver and HeLa cells. Ammonium chloride which also inhibits endosome acidification does not significantly inhibit the NADH diferric transferrin reduction. NADH diferric transferrin reductase of isolated rat liver plasma membrane is inhibited by chloroquine at concentrations similar to those required for inhibition of diferric transferrin reduction by whole cells. Ferricyanide reduction by whole cells is also inhibited by chloroquine. These observations provide an alternative mechanism for chloroquine control of acidification of endosomes and suggests a new approach to control of protozoal parasites through inhibition of a transmembrane oxidoreductase which controls transmembrane proton movement.
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PMID:Transplasma membrane electron and proton transport is inhibited by chloroquine. 217 87

Haematological and iron parameters, measured in 907 children aged from 6 months to 5 years in rural Gambia at the start of the rainy season, differed from those in American reference populations as follows: mean haemoglobin levels were much lower at ages 1 and 2 years and mean levels of mean corpuscular volume (MCV) were lower at all ages (at age 1 year mean haemoglobin was 11.2 g/dl and mean MCV 68.2 fl); in a sample of 249 children randomly selected from the whole study population, mean serum iron levels were similar but mean transferrin saturation and mean serum ferritin levels were lower, especially at ages 1-3 years (at age 1 year mean serum iron was 11.1 mumol/l, mean transferrin saturation 16.9%, and geometric mean serum ferritin 8.8 ng/ml. A total of 213 children (23%) whose haemoglobin and mean corpuscular volume were both less than the 3rd percentile of the reference population received oral iron or placebo from their mothers during the rainy season when malaria transmission is maximal. Mean levels of haemoglobin, mean corpuscular volume, serum iron, transferrin saturation and serum ferritin rose in the iron-treated group and fell in the placebo group at all ages, except under 1 year for serum ferritin, to produce significant differences between the groups by the end of the study. Total iron-binding capacity showed no significant changes during the study. We concluded that oral iron given by the mother during the rainy season can be used to treat iron-deficiency anaemia in Gambian children who would otherwise become more anaemic.
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PMID:Iron-deficiency anaemia and its response to oral iron: report of a study in rural Gambian children treated at home by their mothers. 247 48


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