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

A lipid analysis was performed on the avian malaria parasite Plasmodium lophurae, freed from duckling erythrocytes by immune hemolysis, and on the erythrocytes and plasmas of normal and P. lophurae-infected ducklings. Major lipids of normal erythrocytes were: phosphatidylcholine (40% of total lipids), phosphatidylethanolamine (20%), cholesterol (20%), sphingomyelin (11%), and glycosphingolipids (5%). Major fatty acids of erythrocyte total phospholipids (74% of total lipids) were 16:0 (22%), 18:2 (n-6) (21%), 18.1 (n-7, n-9) (18%), 18:0 (9%), 20:4 (n-6) (9%), 22:6 (n-3) (5%). Erythrocyte phosphatidylcholine was greater than 90% the diacyl form, while phosphatidylethanolamine was approximately 44% alkoxy forms and phosphatidylinositol approximately 11% alkoxy forms. Major fatty aldehydes of phosphatidylethanolamine were 16:0 (47%), 18:1 (23%), 18:0 (14%), and 14:0 (12%). The lipid composition of P. lophurae (plus the parasitophorous vacuole membrane) was qualitatively and quantitatively different from that of the duckling erythrocyte in a number of respects. Major lipids were phosphatidylcholine (40%), phosphatidylethanolamine (36%), cholesterol (8%), phosphatidylinostol (4%), 1,2-diacylglycerols (3%), sphingomyelin (2%), and glycosphingolipids (2%). Diphosphatidylglycerol (approximately 1%) was also detected. The major fatty acids of parasite total phospholipids (86% of total lipids) were more saturated than those of the erythrocyte, and octadecenoic acids were notably elevated: 18:1 (33%), 16:0 (26%), 18:0 (16%), 18:2 (12%), 20:4 (3%), and 22:6 (3%). Parasite phosphatidylcholine and phosphatidylethanolamine were greater than 93% the diacyl form and phosphatidylinositol was approximately 25% alkoxy forms. Major fatty aldehydes of the phosphatidylethanolamine were 14:0 (62%), unidentified long chain forms (24%), 16:0 (7%), 18:0 (4%), 18:1 (3%). The lipid composition of the infected erythrocyte reflected the separate contributions of the erythrocyte and parasite. The major lipids of normal duckling plasma were phosphatidylcholine (33%), triacylglycerols (22%), cholesterol esters (20%), cholesterol (12%), phosphatidylethanolamine (5%), and sphingomyelin (2%). The fatty acids of plasma total lipids were 18:1 (26%), 16:0 (26%), 18:2 (12%), 20:4 (12%), 18:0 (9%), 22:6 (3%). Plasma phosphoglycerides were remarkably lower in C18 unsaturated fatty acids and higher in 20:4 than the erythrocyte phosphoglycerides. Infection of ducklings with P. lophurae caused increases in plasma unesterified fatty acids, triacylglycerols and cholesterol esters, and a notable rise in the 18:1 content of all fatty acid-containing plasma neutral lipids. These findings are compared with those reported for other species of Plasmodium infecting other avian and mammalian hosts.
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PMID:Lipids of Plasmodium lophurae, and of erythrocytes and plasma of normal and P. lophurae-infected Pekin ducklings. 84 41

A simple, rapid, and accurate high-performance liquid chromatographic method using fluorescence detection is described for the measurement of ciprofloxacin in plasma, whole blood, and erythrocytes. Ciprofloxacin and the internal standard difloxacin were separated on a mu-Bondapak C18 column (30 cm x 3.9 mm inside diameter, 10 microns particle size), using a mobile phase of 0.1 M phosphate buffer (pH 2.5):acetonitrile (75:25, vol/vol). The retention times were 5.1 min for ciprofloxacin and 7.9 min for difloxacin. The compounds were extracted from the three biological fluids using protein precipitation followed by a single-step liquid-liquid extraction. The assay is precise, with interassay coefficients of variation of less than or equal to 9.1% and an accuracy of less than or equal to 7.4% at 0.5 and 5.0 micrograms/ml (n = 5). The mean extraction recoveries of ciprofloxacin in plasma, whole blood, and erythrocytes were 84.4, 63.9, and 48.0%. The limit of detection for ciprofloxacin is 25 ng/ml. Ciprofloxacin concentrations in the three biological fluids were measured in patients with uncomplicated falciparum malaria to demonstrate the application of the method.
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PMID:Measurement of ciprofloxacin in human plasma, whole blood, and erythrocytes by high-performance liquid chromatography. 192 83

The phospholipid and fatty acid compositions of the host infected erythrocyte plasma membrane (IEPM) have been determined for erythrocytes infected with the human malaria parasite Plasmodium falciparum. IEPM were prepared by selective lysis of the host erythrocyte (but not of the parasite membranes) with 0.1% saponin, followed by differential centrifugation. The purity of the IEPM was determined by measuring the membrane-specific enzyme markers acetylcholinesterase, glutamate dehydrogenase and lactate dehydrogenase, and by immunoelectron microscopy using monoclonal antibodies specific for human erythrocyte glycophorin A (4E7) and for a 195 kDa parasite membrane glycoprotein (Pf6 3B10.1). Both approaches demonstrated that the host erythrocyte plasma membrane preparation was free from contamination by parasite membranes. During intra-erythrocytic development of the parasite, the phospholipid composition of the erythrocyte membrane was strikingly altered. IEPM contained more phosphatidylcholine (38.7% versus 31.7%) and phosphatidylinositol (2.1% versus 0.8%) and less sphingomyelin (14.6% versus 28.0%) than normal uninfected erythrocytes. Similar alterations in phospholipid composition were determined for erythrocyte membranes of parasitized cells isolated by an alternative method utilizing polycationic polyacrylamide microbeads (Affigel 731). The total fatty acid compositions of the major phospholipids in IEPM were determined by g.l.c. The percentage of polyunsaturated fatty acids in normal erythrocyte phospholipids (39.4%) was much higher than in phospholipids from purified parasites (23.3%) or IEPM (24.0%). The unsaturation index of phospholipids in IEPM was considerably lower than in uninfected erythrocytes (107.5 versus 161.0) and was very similar to that in purified parasites (107.5 versus 98.5). Large increases in palmitic acid (C16:0) (from 21.88% to 31.21%) and in oleic acid (C18:1) (from 14.64% to 24.60%), and major decreases in arachidonic acid (C20:4) (from 17.36% to 7.85%) and in docosahexaenoic acid (C22:6) (from 4.34% to 1.8%) occurred as a result of infection. The fatty acid profiles of individual phospholipid classes from IEPM resembled in many instances the fatty acid profiles of parasite phospholipids rather than those of uninfected erythrocytes. Analysis of IEPM from P. falciparum-infected erythrocytes (trophozoite stage) revealed that, during intra-erythrocytic maturation of the parasite, the host erythrocyte phospholipid composition was markedly refashioned. These alterations were not dependent on the method used to isolate the IEPM, with similar results obtained using either a saponin-lysis method or binding to Affigel beads. Since mature erythrocytes have negligible lipid synthesis and metabolism, these alterations must occur as a result of parasite-directed metabolism of erythrocyte lipids and/or trafficking of lipids between the parasite and erythrocyte membranes.
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PMID:Modification of host cell membrane lipid composition by the intra-erythrocytic human malaria parasite Plasmodium falciparum. 200 Dec 27

A rapid and highly sensitive high-performance liquid chromatographic assay for thymidylate synthase activity is described. The assay is based on the separation of the substrate, deoxyuridylate (dUMP), and its product, deoxythymidylate (dTMP), on a LiChrosorb RP-8 reversed-phase column with 44 mM triethylammonium phosphate (pH 7.0) as mobile phase and a flow-rate of 1.0 ml/min. In addition, using a mu Bondapak C18 reversed-phase column with 10 mM potassium phosphate (pH 4.0) and a gradient of 0-28% methanol, dUMP, dTMP and deoxythymidine (dTdR) are well separated within 30 min. The latter system is also applied to assay thymidine kinase activity with dTdR and dTMP as substrate and product, respectively. This method is sensitive enough to measure dTMP at concentrations as low as 25 pmol, and it was used to show that crude extracts of the human malaria parasite Plasmodium falciparum contain thymidylate synthase but not thymidine kinase activity.
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PMID:High-performance liquid chromatographic assay for thymidylate synthase from the human malaria parasite, Plasmodium falciparum. 265 57

Following the demonstration of the antimalarial effect of the long chain saturated alcohol n-hentriacontanol ((CH2)29CH2OH), isolated from the Bolivian endemic solanaceous plant Cuatresia sp., we have tested the effect of the C18 fatty acids oleic, elaidic, linoleic, and linoleic on malaria parasites. These fatty acids inhibited the parasitemic development in mice infected with Plasmodium vinckei petteri or with Plasmodium yoelii nigeriensis in a 4-day suppressive test. To gain a deeper discernment of the antimalarial mode of action, the effects of these compounds were evaluated on Plasmodium falciparum growth in culture. Whereas n-hentriacontanol did not show any inhibition of this parasite, on the contrary, the C18 acids displayed a considerably inhibitory activity at < or = 200 micrograms/ml both in intact infected cells and in free parasites. In order to understand the mechanism of their antimalarial action, several tests were performed. No hemolysis of infected cells could be observed up to 500 microgram/ml. No effect on the lipid peroxidation, ATP levels, transport through the parasite-induced permeability pathways, or on the phagocytosis of the infected cells could be observed. The cytotoxic effect of the fatty acids was very rapid: full inhibition of nucleic acids and protein syntheses was observed in less than 30 min. This inhibition was not relieved by the addition of deferrioxamine or FeCl3, indicating that fatty acids (FA) do not act by facilitating the transport of iron. Inhibition was relieved in neither the presence of orotic acid or its methyl ester, indicating that FA do not act at the mitochondrial level of pyrimidine synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antimalarial effects of C18 fatty acids on Plasmodium falciparum in culture and on Plasmodium vinckei petteri and Plasmodium yoelii nigeriensis in vivo. 762 73

We sought to characterize factors released by sonicated human erythrocytes that stimulate peripheral blood mononuclear cells (PBMC) to release tumour necrosis factor-alpha (TNF). This response is not inhibited by polymyxin B, indicating that contaminating lipopolysaccharide (LPS) is not responsible. When erythrocyte lysates are fractionated by reverse-phase chromatography using a gradient of n-propanol on Sep-Pak C18 cartridges, the TNF-inducing activity elutes as a single peak. The erythrocyte-derived TNF-inducing activity is unaffected by digestion with proteases but is destroyed by mild base hydrolysis or digestion by lipases, indicating that compounds containing ester-linked acyl chains may be essential. These properties are similar to those of TNF stimulators that we have previously identified in erythrocytes infected with malaria parasites, except that the TNF-inducing activity per cell is about 200 times higher in parasitized erythrocytes than in uninfected erythrocytes. Lipase-digested erythrocyte lysates inhibit the TNF-inducing factors of both normal and malaria-infected erythrocytes, suggesting that lipase digestion creates partial structures which compete with active components for macrophage receptors. Such receptors may recognize a common structure that contains an inositol monophosphate (IMP)-like component, as IMP also inhibits the TNF response to erythrocyte-derived factors and to parasite lysates whereas it does not affect the response to LPS. We conclude that lysed erythrocytes release specific cytokine-inducing factors that may contribute to the fever response to non-infectious tissue injury.
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PMID:Stimulators of tumour necrosis factor production released by damaged erythrocytes. 783 44

A reversed-phase high-performance liquid chromatographic method using acetonitrile-methanol-(1M) perchloric acid-water (30:9:0.8:95, v/v/v/v) at a flow of 1.5 ml min-1 on mu-Bondapak C18 column with UV (254 nm) detection has been developed for the separation of sulphadoxine, sulphalene and sulphamethoxazole from other antimalarials. Calibration curves were linear in the range 0.5-100 micrograms ml-1. The limit of quantitation was 50 ng ml-1. Within-day and day-to-day coefficients of variation averaged 2.1 and 6.45%, respectively. The extraction recovery of sulphadoxine from plasma, red blood cells and whole blood was 90.28, 92.05 and 94.69%, respectively. The method has been used for the determination of sulphadoxine concentrations in plasma, red blood cells and whole blood of eight healthy and 50 Plasmodium falciparum malaria cases after administration of two tablets of Fansidar. Mean sulphadoxine concentration in plasma was higher than red blood cells or whole blood. Sulphadoxine concentration in plasma and whole blood of P. falciparum malaria cases was significantly higher as compared to healthy volunteers while it was the same in red blood cells. Sulphadoxine was absorbed much less in red blood cells than in plasma or whole blood.
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PMID:Sulphadoxine concentrations in plasma, red blood cells and whole blood in healthy and Plasmodium falciparum malaria cases after treatment with Fansidar using high-performance liquid chromatography. 784 Dec 29

A modification of existing HPLC assay methods is described for the measurement of dapsone and monoacetyldapsone in 50-microliter samples of plasma and whole blood. This method, in particular the use of small sample volumes dried onto filter paper strips, is applicable to multi-sample clinical and pharmacokinetic studies in children with malaria, who are often anaemic, and where sample volume must be kept to a minimum. Basified samples were extracted into 5 ml of ethyl acetate-tert.-butylmethyl ether (1:1, v/v), chromatographed on a mu BondapaK C18, 10-micron column with water-acetonitrile-glacial acetic acid (81:17.5:5, v/v) containing 2 g/l l-octanesulphonic acid as the mobile phase and detected at 274 nm.
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PMID:Measurement of physiological concentrations of dapsone and its monoacetyl metabolite: a miniaturised assay for liquid or filter paper-absorbed samples. 870 46

The production of pro-inflammatory cytokines, such as interleukins 1 and 6 and tumour necrosis factors, occurs rapidly following trauma or invasion of the body by pathogenic organisms. The cytokines mediate the wide range of symptoms associated with trauma and infection, such as fever, anorexia, tissue wasting, acute phase protein production and immunomodulation. In part, the symptoms result from a co-ordinated response, in which the immune system is activated and nutrients released, from endogenous sources, to provide substrate for the immune system. Although the cytokine mediated response is an essential part of the response to trauma and infection, excessive production of pro-inflammatory cytokines, or production of cytokines in the wrong biological context, are associated with mortality and pathology in a wide range of diseases, such as malaria, sepsis, rheumatoid arthritis, inflammatory bowel disease, cancer and AIDS. Cytokine biology can be modulated by antiinflammatory drugs, recombinant cytokine receptor antagonists and nutrients. Among the nutrients, fats have a large potential for modulating cytokine biology. A number of trials have demonstrated the anti-inflammatory effects of fish oils, which are rich in n-3 polyunsaturated fatty acids, in rheumatoid arthritis, inflammatory bowel disease, psoriasis and asthma. Animal studies, conducted by ourselves and others, indicate that a range of fats can modulate pro-inflammatory cytokine production and actions. In summary fats rich in n-6 polyunsaturated fatty acids enhance IL1 production and tissue responsiveness to cytokines, fats rich in n-3 polyunsaturated fatty acids have the opposite effect, monounsaturated fatty acids decrease tissue responsiveness to cytokines and IL6 production is enhanced by total unsaturated fatty acid intake. There are a large number of potential cellular mechanisms which may mediate the effects observed. The majority relate to the ability of fats to alter the composition of membrane phospholipids. As a consequence of alterations in phospholipid composition, membrane fluidity may change, altering binding of cytokines to receptors and G protein activity. The nature of substrate for various signalling pathways associated with cytokine production and actions may also be changed. Consequently, alterations in eicosanoid production and activation of protein kinase C may occur. We have examined a number of these potential mechanisms in peritoneal macrophages of rats fed fats with a wide range of fatty acid composition. We have found that the total C18:2 and 20:4 diacyl species of phosphatidylethanolamine in peritoneal macrophages relates in a positive curvilinear fashion with dietary linoleic acid intake; that TNF induced IL1 and IL6 production relate in a positive curvilinear fashion to linoleic acid intake; that leukotriene B4 production relates positively with dietary linoleic acid intake over a range of moderate intakes and is suppressed at high intakes, while PGE2 production is enhanced. There was no clear relationship between linoleic acid intake and membrane fluidity, however fluidity was influenced in a complex manner by the type of fat in the diet, the period over which the fat was fed and the presence of absence of TNF stimulation. None of the proposed mechanisms, acting alone, can explain the positive effect of dietary linoleic acid intake on pro-inflammatory cytokine production. However each may be involved, in part, in the modulatory effects observed.
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PMID:Modulation of pro-inflammatory cytokine biology by unsaturated fatty acids. 955 30

Induction of proinflammatory cytokine responses by glycosylphosphatidylinositols (GPIs) of intraerythrocytic Plasmodium falciparum is believed to contribute to malaria pathogenesis. In this study, we purified the GPIs of P. falciparum to homogeneity and determined their structures by biochemical degradations and mass spectrometry. The parasite GPIs differ from those of the host in that they contain palmitic (major) and myristic (minor) acids at C-2 of inositol, predominantly C18:0 and C18:1 at sn-1 and sn-2, respectively, and do not contain additional phosphoethanolamine substitution in their core glycan structures. The purified parasite GPIs can induce tumor necrosis factor alpha release from macrophages. We also report a new finding that adults who have resistance to clinical malaria contain high levels of persistent anti-GPI antibodies, whereas susceptible children lack or have low levels of short-lived antibody response. Individuals who were not exposed to the malaria parasite completely lack anti-GPI antibodies. Absence of a persistent anti-GPI antibody response correlated with malaria-specific anemia and fever, suggesting that anti-GPI antibodies provide protection against clinical malaria. The antibodies are mainly directed against the acylated phosphoinositol portion of GPIs. These results are likely to be valuable in studies aimed at the evaluation of chemically defined structures for toxicity versus immunogenicity with implications for the development of GPI-based therapies or vaccines.
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PMID:Glycosylphosphatidylinositol anchors of Plasmodium falciparum: molecular characterization and naturally elicited antibody response that may provide immunity to malaria pathogenesis. 1110 99


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