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

The risks of morbidity and mortality associated with transfusion are so great that no transfusion should be given until it is decided that it is absolutely necessary and then only with the utmost care. The unfavorable effects of transfusion reviewed are: hemolytic reaction; bacterial contamination; febrile reaction due to leukoagglutinins; urticaria; anaphylaxis; problems associated with the transfusion of excess potassium, ammonia, and acid; transmission of hepatitis, cytomegalic inclusion disease, toxoplasmosis, and malaria; pulmonary insufficiency; air embolism; and circulatory overload.
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PMID:Adverse effects of transfusions. 126 10

Because hypoglycaemia is common in severe malaria, intravenous glucose is often given empirically to patients on admission to hospital. To investigate the metabolic response to rapid glucose injection in acute malaria, 50 ml of 50% w/v (25 g) dextrose was given over 5 min to 10 adult patients (7 males, 3 females; mean age 30 years) with acute falciparum malaria. Five patients with severe infections were studied between doses of intravenous quinine; 5 cases were uncomplicated and previously untreated. The patients with severe malaria had lower pre-injection plasma glucose concentrations than patients with uncomplicated infections (mean +/- standard deviation, 4.2 +/- 0.9 vs 5.8 +/- 1.1 mmol/litre, 2P less than 0.015). However, peak glucose concentrations (18.6 +/- 4.8 vs 17.0 +/- 2.4 mmol/litre) and integrated responses (AUC0-245 min) were similar in the groups (2P greater than 0.1 in each case), and pre- and post-injection plasma insulin concentrations and AUC0-245 min values were also not significantly different (2P greater than 0.05 in each case). No 'rebound' hypoglycaemia was observed. The patients with severe malaria had higher peak plasma lactate concentrations than the uncomplicated patients (2.5 +/- 0.7 vs 1.5 +/- 0.9 mmol/litre, 2P less than 0.05), but the highest plasma lactate achieved and the greatest maximum post-injection rise were only 3.8 and 0.8 mmol/litre respectively. The average maximum reduction in plasma potassium after injection was 0.2 mmol/litre at 35 min. These data suggest that injections of hypertonic dextrose given empirically in conventional doses to non-acidotic patients with acute, severe malaria are not harmful, but the metabolic response in patients with an established acidosis remains unknown.
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PMID:The metabolic response to rapid intravenous glucose injection in acute falciparum malaria. 188 67

Plasma membrane electron transport was studied in a protozoan cell, Tetrahymena pyriformis, by assaying transmembrane ferricyanide reduction and the reduction of iron compounds. The rates of ferricyanide reduction varied between 0.5 and 2.5 mumol/g dry wt. per min, with a pH optimum at 7.0-7.5. Other active non-permeable electron acceptors, with redox potentials from +360 to -125 mV, were cytochrome c, hexaammine ruthenium chloride, ferric-EDTA, ammonium ferric citrate, and indigo di-, tri- and tetrasulfonates. It was found that Tetrahymena cells can reduce external electron acceptors with redox potentials at pH 7.0 down to -125 mV. Ferricyanide stimulates ciliary action. Transmembrane ferricyanide reduction by Tetrahymena was not inhibited by such mitochondrial inhibitors as antimycin A, 2-n-heptyl-4-hydroxyquinoline N-oxide, or potassium cyanide, but it responded to inhibitors of glycolysis. Transmembrane ferricyanide reduction by Tetrahymena appears to involve a plasma membrane electron transport chain similar to those of other animal cells. As in other cells, the transmembrane electron transport is associated with proton release which may be involved in internal pH control. The transmembrane redox system differs from that of mammalian cells in a 20-fold greater sensitivity to chloroquine and quinacrine. The Tetrahymena ferricyanide reduction is also inhibited by chlorpromazine and suramin. Sensitivity to these drugs indicates that the transplasma membrane electron transport and associated proton pumping may be a target for drugs used against malaria, Trypanosomes and other protozoa.
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PMID:Chloroquine-sensitive transplasmalemma electron transport in Tetrahymena pyriformis: a hypothesis for control of parasite protozoa through transmembrane redox. 190 70

In searching for efficient, safe and radically curative agent and causal prophylactics for malaria, seven 2-methyl-5-substituted phenoxy-6-methoxy-8-(1-methyl-4-aminobutylamino)-quinolines (II1-7) were synthesized and their antimalarial activities were compared with the corresponding 4-methyl substituted derivatives of primaquine. The starting material, 2-nitro-4-methoxy-5-bromo-acetanilide (III), was prepared from p-methoxy aniline through acetylation, bromination and nitration. III was then condensed with substituted phenols in the presence of potassium carbonate. The condensed products were subsequently hydrolyzed with dilute alcoholic hydrochloric acid to yield 2-nitro-4-methoxy-5-substituted phenoxy-aniline (V) which underwent Skraup's reaction with 2-butenal to provide the key intermediates 2-methyl-5-substituted phenoxy-6-methoxy-8-nitroquinolines (VI). These 8-nitroquinoline derivatives were reduced to 8-aminoquinoline derivatives (VII). The latter were condensed with 4-bromo-1-phthalimido-pentane and then hydrolyzed with hydrazine hydrate, the final products were obtained as oxalate or succinate. The structure of the target compounds and unknown intermediates were confirmed by elementary and spectral analysis. Primary biological evaluation showed that all compounds II1-7 were much less active than the 4-methyl substituted derivatives and slightly less active than primaquine in both causal prophylactic test against Plasmodium yoelii and suppressive antimalarial test against P. berhei.
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PMID:[Synthesis of 2-methyl-5-substituted phenoxy-primaquine and antimalarials activity]. 223 31

Schizonts of the malaria parasite Plasmodium falciparum synthesize a 195 kDa surface glycoprotein (gp195) that is processed into several smaller products including one of 83 kDa, which, in the case of the Camp strain, is sequentially processed into 73 and 67 kDa products. gp195 and its processing intermediates larger than 83 kDa were not precipitated from culture supernates, but the 83 and 73 kDa products were precipitated by three monoclonal antibodies (McAbs). The 83 and 73 kDa products were affinity purified from culture supernates by adsorbing to McAb 7B2 coupled to Affigel 10 and eluting either with 0.2 N acetic acid, pH 2.8, or with 3 M potassium isothiocyanate (KSCN). The epitope recognized by McAb 7B2 was denatured by acid elution but could be regenerated by treating with 8 M urea followed by dialysis. The implications of renaturing antigens to regenerate epitopes should be considered in studies on the purification, function and immunogenicity of malaria antigens.
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PMID:Characterization of gp195 processed products purified from Plasmodium falciparum culture supernates. 244 21

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

The asexual stages of Plasmodium living within the erythrocyte result in growth-related changes in the permeability properties of the red cell for substances such as glucose, amino acids, purine nucleosides, sodium, potassium, calcium, zinc, iron and several antimalarial drugs such as chloroquine, amodiaquine and mefloquine. In most cases such changes do not appear to be due to a modification in the affinity or specificity of red cell transporters; indeed, for most substances the membrane-associated transporters are either unaffected or are partially inactivated. In malaria-infected erythrocytes, where a striking increase in influx has been observed, it has been attributed to the insertion of parasite-encoded transporters into the red cell membrane or the formation of aqueous leaks and/or pores. Leak formation, in the vast majority of cases, does not appear to be dependent on the insertion of plasmodial proteins into the red cell membrane. However, since the data presently available are less than satisfactory for discriminating amongst the various possible transport mechanisms future studies will require painstaking efforts and carefully controlled conditions to discriminate amongst the various transport systems which are operational in the malaria-infected red cell and the parasite.
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PMID:The Wellcome Trust lecture. Mechanisms of molecular trafficking in malaria. 328 92

The usefulness of sodium artesunate (3), a water-soluble derivative of artemisinin (1), is impaired by its poor stability in aqueous solution. To overcome the ease of hydrolysis of the ester group in 3, a new series of derivatives of dihydroartemisinin (2) was prepared in which the solubilizing moiety, which contains a carboxylate group, is joined to dihydroartemisinin by an ether rather than an ester linkage. The new derivatives were prepared in good yield by treatment of dihydroartemisinin with an appropriate alcohol under boron trifluoride etherate catalysis at room temperature. All major condensation products are the beta isomer. Hydrolysis of the esters with 2.5% KOH/MeOH gave the corresponding potassium salts, which were converted to free acids (8b-d) by acidification. The derivatives were tested in vitro against two clones of human malaria, Plasmodium falciparum D-6 (Sierra Leone clone) and W-2 (Indochina clone). No cross-resistance to the antimalarial agents mefloquine, chloroquine, pyrimethamine, sulfadoxine, and quinine was observed. In general, the new compounds are more effective against the W-2 than the D-6 strain. Esters (5a-d) possess activity comparable to that of the parent compounds 1 and 2; however, conversion of the esters to their corresponding carboxylates (7a-d) or acids (8b-d), with the exception of artelinic acid (8d), drastically decreases the antimalarial activities in both cell lines. Artelinic acid, which is both soluble and stable in 2.5% K2CO3 solution, possesses superior in vivo activity against Plasmodium berghei than artemisinin or artesunic acid.
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PMID:Antimalarial activity of new water-soluble dihydroartemisinin derivatives. 366 21

Previous studies have suggested that malaria induces changes in erythrocytic membrane permeability and susceptibility to osmotic lysis. The present study investigated erythrocytic transport of sodium with cells from Rhesus monkeys infected with Plasmodium knowlesi. Red blood cell sodium concentration was significantly elevated in 37 parasitized animals (21.8+/-1.2 mM; mean +/-SEM), as compared to 23 control animals (10.0+/-0.38 mM). The cellular sodium increased with the density of parasitemia and the cellular potassium decreased in proportion to the elevation of sodium. Nonparasitized as well as parasitized erythrocytes possessed this abnormality of cation metabolism. Effective chloroquine therapy reversed the changes over a period of 4 days. Active sodium outflux rate constants were depressed in animals with malaria (0.202+/-0.012), as compared to controls (0.325+/-0.027). Passive sodium influx rate constants were higher in infected monkeys (0.028+/-0.002) than in control animals (0.019+/-0.002). The cross incubation of malarial plasma with normal red blood cells induced a 22% diminution in active sodium outflux but no changes were observed in sodium influx. It is concluded that malaria alters erythrocytic sodium transport in all erythrocytes. The elevated intracellular sodium concentration is the net result of decreased sodium outflux and increased sodium influx. The plasmodium organism or the affected host may produce a circulating substance that is deleterious to erythrocytic membrane cation transport.
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PMID:Alterations of red blood cell sodium transport during malarial infection. 497 61

Experimental procedures are described that lead to the formation of sealed red cell ghosts capable of efficient invasion by malaria parasites. Both human and monkey cells have been studied with respect to invasion by Plasmodium falciparum and P. knowlesi respectively. Resealed ghosts containing about half the normal concentration of haemoglobin are prepared by osmotic lysis and resealing at a haematocrit of 70%. When examined in the scanning electron microscope, populations of these ghosts contain few echinocytes, but have an abundance of stomatocytic forms. When undiluted haemolysate is substituted for the aqueous saline diluent, in which the cells are suspended for lysis and resealing, discocytes result, with a morphology very similar to that of the original cells. Invasion is somewhat, but not dramatically higher for this material. An investigation of the effect of intracellular potassium concentration revealed that this had no major effect on invasion. A small increase in invasion resulted from addition of 50 or 100 mg/ml of albumin to the medium in which the cells were resealed, but intra-erythrocytic protein content per se is evidently not a major factor in determining the efficiency of invasion. Augmentation of the cytoplasmic ATP concentration during lysis and resealing increased the level of parasitaemia significantly, and the parasites in these ghosts developed normally and gave rise to viable merozoites. It was found that albumin at certain concentrations passed freely into the lysed cells and reached equilibrium with that in the external medium. By contrast, the high molecular weight solute Blue Dextran 2000 was completely excluded from the lysed cells.
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PMID:Properties of red cell ghost preparations susceptible to invasion by malaria parasites. 636 66


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