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

Previous investigations on the mechanism by which the host mounts an immune response against the human malaria parasite Plasmodium falciparum have not resolved whether cell-mediated responses, in the absence of circulating anti-Plasmodial antibodies, can effect the destruction of the intraerythrocytic parasite. We report that the intraerythrocytic parasite P. falciparum is lethally susceptible to the imposition of oxygen-dependent and oxygen-independent factor(s) released by interferon-gamma-activated, monocyte-derived human macrophages. In addition, trophozoite-schizont stage intraerythrocytic parasites were killed on exposure to small amounts of H2O2 generated in cell-free enzyme assays. Although parasiticidal activity was markedly enhanced by the addition of lactoperoxidase and KI, killing was abrogated by the addition of catalase. The ability of freshly isolated human monocytes, monocyte-derived macrophages (MDM), and lymphokine-activated MDM to kill or inhibit the growth and multiplication of the malaria parasites was assessed. Parasites were killed when exposed to monocytes or lymphokine-activated MDM, but not when exposed to nonactivated macrophages. The capacity to activate MDM for microbicidal activity was abrogated on neutralization of crude lymphokines or recombinant interferon-gamma with a monoclonal antibody prepared against interferon-gamma. The intraerythrocytic parasites surviving the cytotoxicity assay were inhibited in their development and appeared to be degenerating, a characteristic of "crisis" forms. Killing of P. falciparum correlated positively with the magnitude of the oxidative response, as evidenced by the reduction of nitroblue tetrazolium to formazan in the mononuclear phagocytes, and by the detection of secreted H2O2. Of particular interest was the observation that only the later developing stage of the intracellular parasite triggered the respiratory burst in the absence of antibody. A role for oxygen-independent parasiticidal factors was suggested by the finding that lymphokine-activated macrophages from a patient with chronic granulomatous disease were able to partially inhibit the growth of P. falciparum, although oxidative metabolism in these cells was impaired.
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PMID:Induction of crisis forms in the human malaria parasite Plasmodium falciparum by gamma-interferon-activated, monocyte-derived macrophages. 643 Oct 3

The murine malaria parasite Plasmodium yoelii was killed in vitro when incubated with glucose and glucose oxidase, a system generating hydrogen peroxide, or with xanthine and xanthine oxidase, a system which produces the superoxide anion and subsequently other products of the oxidative burst. Catalase blocked the killing in both cases; superoxide dismutase and scavengers of hydroxyl radicals or singlet oxygen were ineffective in the xanthine oxidase system. Thus, hydrogen peroxide appears to be the main reactive oxygen species killing P. yoelii.
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PMID:Killing of Plasmodium yoelii by enzyme-induced products of the oxidative burst. 654 75

The carriage of oxygen by the blood and the in vivo response of the brain were investigated in mice infected with a lethal strain of Plasmodium yoelii. All mice with parasitaemia exceeding 70% were severely anaemic (Hb 3.5 +/- 1.8 g/dl; mean +/- 1 SD), acidotic (blood pH 7.04 +/- 0.06) and hypoglycaemic (blood glucose 0.6 +/- 0.76 mumol/ml). The oxyhaemoglobin dissociation curve (ODC) of blood from heavily infected mice was shifted right as compared to controls, but the increase in p50 was less than expected from the accompanying acidosis. The reduced shift right was due to a decrease in the 2,3-DPG/Hb ratio in infected animals (0.72 +/- 0.12, n = 17 vs 1.10 +/- 0.09, n = 12 in controls). Despite the severity of terminal infection, the cerebral pH and the relative steady-state concentrations of PCr, ATP and Pi measured in vivo by nuclear magnetic resonance (31P NMR) were normal. Alterations in brain energy status and pH cannot account for cerebral signs or death in this proposed mouse model of cerebral malaria.
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PMID:Plasmodium yoelii: blood oxygen and brain function in the infected mouse. 664 96

A rapid reduction in parasitemia associated with damage to intraerythrocytic parasites was observed in Plasmodium vinckei-infected mice after they had received a single intravenous injection of alloxan. This was not prevented by prior injection of glucose, but was prevented by desferrioxamine or diethyldithiocarbamate. Prior injection of propanol partially blocked the phenomenon. A transient hemolysis was observed in malaria-infected mice, but not in controls, after injection of alloxan. This was also blocked by desferrioxamine, but not by glucose. Both the fall in parasitemia and hemolysis occurred, but less dramatically, when phenylhydrazine or hydrogen peroxide was injected into parasitized mice. Again, the hemolysis was blocked by desferrioxamine. These observations are consistent with the parasite death and hemolysis being mediated by reactive oxygen species, possibly hydroxyl radicals, and have implications for our understanding of hemolysis, endothelial damage, and parasite suppression in acute malaria. Our evidence that malaria parasites are susceptible to free oxygen radicals supports the view that high intraerythrocytic oxidative stress may contribute to the high frequencies in malarial areas of genes for certain erythrocyte-related traits and suggests that some antimalarial drugs may suppress parasites partly through oxidative damage.
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PMID:Evidence for reactive oxygen intermediates causing hemolysis and parasite death in malaria. 682 9

This long term project is aimed to study the following points: 1. Evolutionary adaptation to high altitude. 2. Population genetics of high altitude populations and 3. Mechanisms of resistance to malaria in some of these. The study suggests that the Sherpa of Nepal and the Quechua of Peru, living at altitude about 4000m, may have adapted to low oxygen pressure. The results of biochemical marker studies show that the Himalayan populations may remain genetically separated even when sharing the same village. Studies relating to resistance to falciparum malaria indicate that the immunity, conferred on the Tharu against malaria, may not involve erythrocytes exclusively.
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PMID:Researches on the biology of Himalayan populations. 695 79

The mechanism whereby heterozygous carriers of the sickle cell gene are protected against fatal malarial infections due to Plasmodium falciparum has been examined in a short term in vitro cultivation system. The results have shown that both parasite invasion of red cells and parasite growth within red cells containing sickle haemoglobin (Hb-S) is restricted, but only under conditions of low (5%) oxygen tensions. To bring this about, the cells containing Hb-S need not sickle. Furthermore the growth retardation observed in the presence of Hb-S was also found to apply to the mature forms of the parasite. These findings offer a plausible mechanism for the protection of sickle heterozygotes against falciparum malaria.
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PMID:The interaction between sickle haemoglobin and the malarial parasite Plasmodium falciparum. 701 Jun 93

This study was undertaken in recognition of the need to develop quantitative systems to evaluate the toxicity associated with hyperbaric oxygen (HBO) exposure. Malaria-infected (P. berghei berghei) mice were briefly exposed to 100% oxygen at 3 ATA on day 10 of infection. At 25, 48, and 72 h thereafter, the levels of circulating erythrcytes and percent parasitized RBC were monitored and compared to those of infected non-exposed controls. The total erythrocyte counts of the infected HBO-exposed and non-exposed mice did not differ significantly. In contrast, percent parasitized cells in the oxygen-exposed mice were lowered to 55-60% control values at 24, 48, and 72 h. The mechanism of this difference needs further study, but we believe that P. berghei-infected erythrocytes are preferentially hemolyzed as a consequence of HBO exposure. this mode system is useful in the study of HBO-induced toxicity because of its high degree of selectivity and sensitivity and its amenability to strict quantification over a period of at least several days.
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PMID:Quantification of hyperbaric oxygen-induced toxicity utilizing a malarial system. 701

In northern California, western fence lizards, Sceloporus occidentalis, are frequently parasitized by Plasmodium mexicanum, which causes malaria. Animals with this naturally occurring malarial infection are anemic: immature erythrocytes in peripheral blood become abundant (1 to 30 percent), and blood hemoglobin concentration decreases 25 percent. Maximal oxygen consumption decreases 15 percent and aerobic scope drops 29 percent in infected lizards; both correlate with blood hemoglobin concentration. Running stamina, but not burst running speed, is reduced in malarious lizards. There is a hierarchical relation between infection with malaria and effects on hematology, physiological function, and behavioral capacity. The results suggest that malarial infection may have significant effects on the ecology of lizard hosts.
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PMID:Lizards infected with malaria: physiological and behavioral consequences. 711 13

In this paper, the relation between the level of the reactive oxygen species (ROS) and relevant free radicals in the blood plasma of the BALB/c mice infected with Plasmodium berghei ANKA strain and their erythrocytic deformability (ED), and the relation between the ED and the Hb indices of these mice were studied by chemiluminescence (CL), induced CL (ICL) and laser diffraction method. The results indicated that the ED decreased with the increase of the level of ROS and free radicals in blood plasma when the anemia is developing. The use of antioxidants may restrain the course and raise the Hb index. The authors deem that the excess TNF produced in the later stage of malaria may induce the release of excess ROS and free radicals from phagocytes, which may cause damage on the deformability of erythrocytes and a drop in ED, resulting in the anemia of malaria.
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PMID:[Relationship between tumour necrosis factor and anemia of malaria]. 755 64

The aim of this review is to focus and discuss several parallel biological functions of hemoglobin besides its basic function of oxygen transport. In light of the information present in the literature the following possible physiological roles of hemoglobin are discussed: (1) hemoglobin as molecular heat transducer through its oxygenation-deoxygenation cycle, (2) hemoglobin as modulator of erythrocyte metabolism, (3) hemoglobin oxidation as an onset of erythrocyte senescence, (4) hemoglobin and its implication in genetic resistance to malaria, (5) enzymatic activities of hemoglobin and interactions with drugs, and (6) hemoglobin as source of physiological active catabolites.
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PMID:The multiple functions of hemoglobin. 755 18


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