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

The soluble amphiphilic glycoprotein, Ag1 (gp60), purified from supernatants of in vitro cultures of Plasmodium falciparum has a molecular mass of 60 kDa and did not exhibit size variation in the different P. falciparum isolates tested by immunoblotting. Ag1 was shown to interact with the lectin Erythrina christagalli agglutinin, which is specific for carbohydrates bearing beta-D-galactose(1-4)-D-N-acetylglucosamine. Indirect immunofluorescence studies showed that Ag1 is located on the surface of trophozoites and schizonts but not on the surface of merozoites. Ag1 is recognized by human immune sera from six different malaria-endemic regions. Ag1 induces in vitro proliferation of lymphocytes from malaria-immune individuals in an antigen-specific manner.
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PMID:Biochemical characterization, localization and immunostimulating properties of a soluble glycoprotein, Ag1, isolated from in vitro cultures of Plasmodium falciparum. 225 Dec 41

We have studied intestinal function and liver blood flow in Thai adults with complicated and uncomplicated falciparum malaria. The absorption of 3 orally administered test sugars, D-xylose, 3-O-methyl-D-glucose, and L-rhamnose, was greatly reduced in complicated malaria, while the lactulose/rhamnose absorption ratio was significantly increased. Hepatic blood flow was concomitantly reduced in severe malaria. These deviations reverted to normal in convalescence. Neither sugar absorption nor liver blood flow was reduced in uncomplicated falciparum malaria.
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PMID:Reduced hepatic blood flow and intestinal malabsorption in severe falciparum malaria. 272 5

We have studied the effect of infection with the blood-stage of Plasmodium yoelii 17X, a nonlethal parasite, on plasma membrane antigens, receptors, and secretory properties of macrophages (M phi) in murine liver, spleen, and blood. mAb F4/80 (M phi specific), F7/4 (a marker for immature and immunologically activated M phi, as well as neutrophils), and Mac-1, which binds to the type 3 complement receptor, were used to measure the distribution and total content of antigens in situ and to assay surface expression of antigens on M phi isolated by collagenase perfusion-digestion and adherence. We also examined respiratory burst activity after stimulation with PMA, FcR activity, Ia antigen expression, and binding of 125I-mannose-BSA and unopsonized sheep erythrocytes by isolated M phi. In the normal animal, spleen M phi expressed Mac-1 and F7/4 antigens and relatively high levels of respiratory burst activity, in contrast to Kupffer cells in liver, where all three features were virtually absent. The introduction of parasitized erythrocytes into the circulation resulted in a large influx of F4/80+ M phi into the blood, liver, and spleen, where local M phi proliferation could also contribute. Liver M phi during malaria infection showed increased Mac-1 and 7/4 antigen and an increased respiratory burst potential compared with uninfected controls. Increases in total, but not specific activity of FcR, Ia antigen, and binding of unopsonized sheep erythrocytes were found in spleen and liver M phi populations after infection. In both populations, there was an early but persistent marked reduction in specific binding and uptake of 125I-mannose-BSA. These results confirm and extend observations that normal Kupffer cells are relatively homogeneous in morphology, surface markers, and anatomical location, in contrast to M phi in normal spleen, and that both of these populations differ from resident M phi elsewhere, including the peritoneal cavity. In the course of infection by P. yoelii, M phi with high levels of opsonic receptors (CR3, FcR) and respiratory burst potential are mobilized in large numbers at specific sites such as liver and spleen, in accordance with an important role for M phi in the clearance of parasitized erythrocytes from blood.
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PMID:Macrophage plasma membrane and secretory properties in murine malaria. Effects of Plasmodium yoelii blood-stage infection on macrophages in liver, spleen, and blood. 300 Dec 15

Hypoglycemia may develop in patients with severe untreated malaria and can complicate the course of treatment with parenteral quinine as a result of quinine-induced hyperinsulinemia. Intravenous quinine is used increasingly as the therapy of choice in patients with severe malaria, most of whom are children. To assess the importance of both pretreatment and quinine-related hypoglycemia in children in an area in which the disease is endemic, we prospectively studied 95 Malawian children with falciparum malaria and altered consciousness who were treated with intravenous quinine. Nineteen patients had hypoglycemia before treatment. Seven (37 percent) died, and five of the survivors (26 percent) had neurologic sequelae. The corresponding values for patients who were initially normoglycemic were 4 percent and 4 percent, respectively (P less than 0.0001). Hypoglycemia was associated with low plasma insulin concentrations and with elevated plasma concentrations of lactate, alanine, and 5'-nucleotidase--a finding that suggests that impaired hepatic gluconeogenesis but not hyperinsulinemia contributes to the pathogenesis of pretreatment hypoglycemia. All patients were given quinine dihydrochloride in a 5 percent dextrose infusion, and those with hypoglycemia received 50 percent dextrose. Hypoglycemia recurred in seven of the patients with pretreatment hypoglycemia, but these episodes were also not associated with hyperinsulinemia. Of the 76 children who were initially normoglycemic, none became hypoglycemic during the course of treatment with intravenous quinine. We conclude that hypoglycemia is a frequent complication of falciparum malaria in children and that it reflects severe disease and is associated with a poor prognosis. We did not find it to be a complication of quinine treatment.
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PMID:Blood glucose levels in Malawian children before and during the administration of intravenous quinine for severe falciparum malaria. 305 May 16

A series of polyhydroxyphenol glycosides including bioflavonoid-glycosides structurally-related to phlorizin (phloretin-2-beta-glucoside) have been tested for their capacity to inhibit permeation pathways induced in red cell membranes by intraerythrocytic Plasmodium falciparum parasites. The permeation through these pathways has been assessed on trophozoites by sorbitol-mediated hemolysis based on a novel technique of high sensitivity and time resolution which has been adapted for handling relatively large number of samples in microtitration plates. Changes in the number of phenolic groups and to a lesser extent changes in the relative position of these groups had a substantial effect on the inhibitory efficacy of the phlorizin derivatives. Diglycoside derivatives were completely ineffective while various monoglycoside derivatives had comparable effects. Structure-activity relationship (SAR) studies of 3-monosubstituted phlorizin derivatives indicate that the inhibitory potency varied considerably with the chemical nature of the group substituted in the 3 position. Inhibition correlated best (r = 0.90) with Hammett's constant, underscoring the role of the electron withdrawing capacity of the chemical groups substituted on the hydroxydihydrochalcone moiety. On the other hand, substitution with lipophilic groups had either minimal effects or reduced the inhibitory power of the derivatives. Inhibition of transport correlated with the inhibition of intraerythrocytic parasite growth and provides a basis for new therapeutic approaches of malaria. Based on the SAR studies, a 3-isothiocyano analog of phlorizin was synthesized and shown to block irreversibly the above permeation pathways (20 microM, 10 min reaction at ambient temperature) as well as the intraerythrocytic growth of the parasite. The present study provides proof for the involvement of amino groups in red cell membrane components as controlling elements of the permeation pathways induced by the intraerythrocytic parasite. The putative groups could serve as targets for affinity labeling of the membrane components associated with the permeation function.
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PMID:Bioflavonoid effects on in vitro cultures of Plasmodium falciparum. Inhibition of permeation pathways induced in the host cell membrane by the intraerythrocytic parasite. 305 28

Phlorizin (phloretin-2-beta-glucoside) is a drug which effectively inhibits intraerythrocytic malaria growth in in vitro cultures of Plasmodium falciparum IC50 = 16 +/- 7 microM). Work with synchronously grown cultures indicates that susceptibility to phlorizin is apparent at the trophozoite stage and onward, and that 2-8 hours exposure to the drug causes an irreversible arrest of parasite growth. The drug has also been found to inhibit pores which are induced by the parasite in the host cell membrane (IC50 = 17 +/- 2 microM) and which are apparently essential for intraerythrocytic growth. The effect on the pores is apparent soon after exposure of the cells to the drug and can be reversed, although extensive washing and incubation in culture conditions are required to achieve it. The results of this study indicate that the putative site of action of phlorizin on the pores is on the cytoplasmic surface of the host cell membrane. The drug which normally cannot permeate uninfected red cells, gains access to the cytoplasm via the pores, appearing in the host cell membrane. Those become eventually the target of phlorizin itself. The proposed mechanism of action of phlorizin on malarial growth invokes blockade of the pores, although additional effects of the drug on intraerythrocytic parasites cannot be ruled out.
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PMID:On the mode of action of phlorizin as an antimalarial agent in in vitro cultures of Plasmodium falciparum. 309 99

Acute-phase serum (APS) collected from Plasmodium berghei-infected rats inhibited phagocytosis of trypsinized rat erythrocytes and of erythrocytes from P. berghei-infected rats. Macrophages (M phi) incubated with APS or heat-aggregated acute-phase serum (HAAPS) for 6 h, followed by 18 h incubation in serum-free medium, exhibited significantly higher levels of phagocytosis than M phi similarly cultured but with normal rat serum. When APS was present at the time of assay, it inhibited erythrophagocytosis by M phi which had been in culture for 0 or 24 h. M phi activation by HAAPS was inhibited by 2-deoxy-D-glucose, which suggests that activation by HAAPS is Fc-receptor mediated. Adsorption of APS with staphylococcal protein A abrogated the ability of APS to inhibit phagocytosis and that of HAAPS to effect M phi activation, suggesting that immune complexes are involved in both processes. Surface-bound immunoglobulins eluted from erythrocytes of P. berghei-infected rats promoted phagocytosis of trypsinized erythrocytes by HAAPS-activated M phi but not by resting M phi. These results indicate that the immunoglobulins which bind to infected or damaged erythrocytes during malarial infections promote erythrophagocytosis by activated M phi and that the immune complexes in serum from rats with acute malaria may inhibit erythrophagocytosis early in the infection but may, over time, induce changes in the M phi which later facilitate erythrophagocytosis.
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PMID:Plasmodium berghei malaria: effects of acute-phase serum and erythrocyte-bound immunoglobulins on erythrophagocytosis by rat peritoneal macrophages. 351 Jan 64

The capacity of Plasmodia to synthesize sialic acids was investigated by adding radioactive acetate to short-term in vitro cultures of the intraerythrocytic asexual forms of three malaria parasites (the human malaria Plasmodium falciparum in Aotus trivirgatus erythrocytes; the simian malaria P. knowlesi in rhesus monkey erythrocytes; the rodent malaria P. berghei in mouse erythrocytes) and to cultures of extracellular zygotes of the avian malaria P. gallinaceum. Radioactive acetate was added to normal rhesus monkey erythrocytes and to cells of the murine myeloma NS-1 for comparison. Although [1-14C]-acetate labeled many proteins with each malaria parasite and the NS-1 cells, analysis of purified sialic acids revealed that only with the NS-1 cells was radioactivity incorporated into sialic acids. Furthermore, N-acetyl[6-3H]mannosamine was not incorporated into sialic acids or malarial glycoproteins when added to P. knowlesi cultures. All of the malaria parasites underwent growth or differentiation during these experiments as measured by [35S]methionine uptake into protein and by light microscopy. Extracellular parasites largely free of erythrocyte membranes were prepared to determine whether Plasmodia contain sialic acids that are not labeled by exogenous precursors. Purified merozoites of P. knowlesi and zygotes of P. gallinaceum did not contain detectable amounts of sialic acids on chemical analysis. Thus, although we could show that Plasmodia can incorporate radioactive sugars such as glucosamine, galactose and mannose into proteins, presumably glycoproteins, they do not synthesize sialic acids or sialo-glycoproteins, nor do they contain sialo-glycoconjugates of host origin.
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PMID:Malaria parasites do not contain or synthesize sialic acids. 637 Aug 20

An increased frequency of high titers of antibodies against A, B, ORh+ trypsinized, and ORh+ neuraminidase-treated human red blood cells was observed in the sera of Africans living in a malaria endemic area, and Europeans with primary malaria attacks. In the latter group, titers of agglutinins against neuraminidase treated RBC were increased in 84% of individuals and were of the IgM class. Inhibition experiments with beta-D-galactose and lactose showed that this agglutinin was directed to the T antigen of human RBC. Its possible implication in malaria related anemia is discussed.
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PMID:[Demonstration of an abnormal increase of anti-T hemagglutinin titers in malaria infected patients]. 640 66

Cryptococcal meningitis is an uncommon infection globally, including Nigeria. This systemic fungal infection often is associated with immunodeficiency. The most common causes of meningitis in Nigeria in the 2-3 year age group are the malaria parasites and bacteria. The concomitant infections of Cryptococcal neoformans and Plasmodium falciparum are uncommon. We present here the report of a case of fatal cryptococcal meningitis with malaria infection in a 2 year old child from Nigeria (one of the malaria endemic regions of the world). This case emphasizes the importance of doing a combination of fungal and bacterial cultures as well as looking for malarial parasites in the determination of etiological agents of meningitis in any hospital in Africa. We suggest that cerebrospinal fluid from meningitis cases must be cultured using Sabouraud dextrose agar and any growth on the agar must be examined using Indian ink.
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PMID:Cryptococcal meningitis with malaria. A case report. 793 35


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