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

Excessive sequestration of Plasmodium falciparum-infected (pRBC) and uninfected erythrocytes (RBC) in the microvasculature, cytoadherence, and rosetting, have been suggested to be correlated with the development of cerebral malaria. P. falciparum erythrocyte membrane protein-1 (PfEMP1) is the parasite-derived adhesin which mediates rosetting. Herein we show that serum proteins are crucial for the rosette formation of four strains of parasites (FCR3S1, TM284, TM180, and R29), whereas the rosettes of a fifth strain (DD2) are serum independent. Some parasites, e.g., FCR3S1, can be depleted of all rosettes by washes in heparin and Na citrate and none of the rosettes remain when the parasite is grown in foetal calf serum or ALBUMAX. Rosettes of other parasites are less sensitive; e.g., 20% of TM180 and R29 and 70% of TM284 rosettes still prevail after cultivation. A serum fraction generated by ion-exchange chromatography and poly-ethylene-glycol precipitation restored 50% of FCR3S1 and approx 40 to 100% of TM180 rosettes. In FCR3S1, antibodies to fibrinogen reverted the effect of the serum fraction and stained fibrinogen bound to the pRBC surface in transmission electron microscopy. Normal, nonimmune IgM and/or IgG was also found attached to the pRBC of the four serum-dependent strains as seen by surface immunofluorescens. Our results suggest that serum proteins, known to participate in rouleaux formation of normal erythrocytes, produce stable rosettes in conjunction with the recently identified parasite-derived rosetting ligand PfEMP1.
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PMID:Rouleaux-forming serum proteins are involved in the rosetting of Plasmodium falciparum-infected erythrocytes. 1060 Apr 47

Cyanuric chloride activated polyethylene glycol (PEG)-5000 was covalently coupled to murine and human red blood cells (pegylated RBC). Our purpose was to camouflage RBC receptors, which is necessary for parasite invasion, a process essential to sustain parasitemia. Cell electrophoretic mobility analysis (CEM) of pegylated RBC distinguished a new population of cells bearing characteristic CEM. Pegylation of RBC also modified their rheological properties, which were documented by evaluation of cell deformability (based on cell transit time through calibrated micropores) and cell aggregation (as measured by ultrasonic interferometry). Homologous transfusion of pegylated RBC into murine malaria-infected mice had no significant effect on the cerebral malaria death rate in Plasmodium berghei-infected mice, but it reduced the peripheral blood parasitemia by a factor 2 while in Plasmodium yoelii infected mice, the parasitemia was dramatically reduced by a factor of 4. These experiments demonstrate that transfusion of pegylated RBC may inhibit peripheral parasitemia. Cell electrophoresis appears to be a useful tool to allow in vivo detection and to investigate the fate of transfused pegylated RBC.
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PMID:Covalent binding of polyethylene glycol to the surface of red blood cells as detected and followed up by cell electrophoresis and rheological methods. 1067 5

This study was designed to assess the binding of glycophorin A-specific antibodies to polyethylene glycol (PEG)-modified red blood cells (RBCs) and evaluate their resistance to invasion by Plasmodium falciparum malaria parasites. RBCs were conjugated with a range of concentrations (0.05 to 7.5 mM) of activated PEG derivatives of either 3.35 or 18.5 kd molecular mass. The binding of glycophorin A-specific antibodies was assessed by hemagglutination and flow cytometry. PEG-modified RBCs were assessed for their ability to form rosettes around Chinese hamster ovary (CHO) cells transiently expressing the glycophorin A binding domain of EBA-175, a P falciparum ligand crucial to RBC invasion. PEG-RBCs were also tested for their ability to be invaded by the malaria parasite. RBCs coated with 3.35 and 18.5 kd PEG demonstrated a dose-dependent inhibition of glycophorin A-specific antibody binding, CHO cell rosetting, and P falciparum invasion. These results indicate that glycophorin A epitopes responsible for antibody and parasite binding are concealed by PEG coating, rendering these cells resistant to P falciparum invasion. These studies confirm the effectiveness of PEG modification for masking RBC-surface glycoproteins. This may provide a means to prevent alloimmunization in the setting of RBC transfusion and suggests a novel method to enhance the effectiveness of exchange transfusion for the treatment of cerebral malaria.
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PMID:Polyethylene glycol-coated red blood cells fail to bind glycophorin A-specific antibodies and are impervious to invasion by the Plasmodium falciparum malaria parasite. 1115 36

Blood samples collected from individuals belonging to malaria endemic areas were assayed for antigen-specific circulating immune complexes in polyethylene glycol precipitates of serum by enzyme immunoassay. Sera were tested from patients with acute P. vivax and P. falciparum infections, from clinically immune individuals and also from healthy normals. Circulating immune complexes (CICs) containing immunoglobulin G and M isotypes were found to be abundant in individuals with ongoing and past infections and also in clinically immune donors. In patients with acute infection but without any past history of malaria, CICs of IgM type were found to be significantly higher. Demonstration of antigen/antibody specific CICs could be a useful indicator of active, ongoing and recent/past infection, also of the status of immune responses of individuals belonging to various endemic areas.
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PMID:Naturally occurring plasmodia-specific circulating immune complexes in individuals of malaria endemic areas in India. 1130 15

The aim of the work was to develop a new submicronic delivery system that can be used with poorly water soluble drugs for which sustained circulating concentrations are necessary. This system consists of oily core surrounded by a shell made of a copolymer of poly (D,L-lactid) and poly (ethylene glycol). Covalent coupling between the hydrophylic poly (ethylene glycol) and poly (D,L lactid) and high molecular weight of the poly (ethylene glycol) chains yield long circulating particles after intra-venous administration in mice. Halofantrine, a very effective drug administrated for the treatment of severe malaria caused by Plasmodium, for which no injectable preparation exists. Results showed that percentage of loading, yield of encapsulation and physical stability were more favourable with surface modified nanocapsules. Release of halofantrine was clearly related to partition between oil and external medium. Serum proteins in the medium, increased halofantrine release from nanocapsules and poly (ethylene glycol) grafted nanocapsules reduced this phenomenum. The pharmacokinetics of the free drug was modified to maintain it in blood circulation. It is important to note that high plasma concentrations of halofantrine were correlated with higher activity against parasites in mice infected with Plasmodium berghei.
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PMID:[Long circulating nanocapsules: interest in the treatment of severe malaria with halofantrine]. 1271 32

The Plasmodium vivax sexual stage 25 kDa protein Pvs25 is expressed on the surface of the ookinete form of the parasite. Monoclonal antibodies directed against Pvs25 block the development of P. vivax oocysts in the mosquito host. Thus, Pvs25 is a potential vaccine candidate for eliciting transmission-blocking immunity in individuals living in malaria-epidemic regions. Pvs25 which was expressed and purified for clinical trials was crystallized using polyethylene glycol as the precipitating agent and diffracts X-rays to 2.3 A. The orthorhombic Pvs25 crystal form belongs to space group P2(1)2(1)2(1), with unit-cell parameters a = 42.6, b = 59.8, c = 66.8 A and one molecule in the asymmetric unit. Reductively methylated Pvs25 crystallized in two forms: an orthorhombic P2(1)2(1)2(1) form with unit-cell parameters a = 43.4, b = 62.9, c = 66.9 A and one molecule in the asymmetric unit and a monoclinic P2(1) form with unit-cell parameters a = 53.5, b = 43.3, c = 65.3 A, beta = 104.0 degrees which was predicted to have one or two molecules in the asymmetric unit. Several native and heavy-atom data sets have been collected from Pvs25 and methylated Pvs25 crystals for use in MAD or MIR techniques.
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PMID:Crystallization and preliminary X-ray analysis of the Plasmodium vivax sexual stage 25 kDa protein Pvs25, a transmission-blocking vaccine candidate for malaria. 1503 60

The efficacy and pharmacokinetics of a new parenteral formulation of halofantrine were studied in mice infected with Plasmodium berghei. The formulation consisted of nanocapsules with an oily core, prepared from either poly(D,L-lactide) (PLA) homopolymer or PLA that was surface modified with grafted polyethylene glycol chains. They were compared with a previously described intravenous halofantrine preparation. No toxic effects were observed with halofantrine in form of nanocapsules after intravenous administration for doses of up to 100 mg/kg, whereas the solubilized form in polyethylene glycol-dimethylacetamide was toxic at this dose. The halofantrine-loaded nanocapsules showed activity that was similar to or better than that of the solution in the 4-day test and as a single dose in severely infected mice, with only minimal differences between the two nanocapsule formulations. Halofantrine pharmacokinetics were determined in parallel with parasite development in severely infected mice. Nanocapsules increased the area under the curve for halofantrine in plasma more than sixfold compared with the solution throughout the experimental period of 70 h. Furthermore, nanocapsules induced a significantly faster control of parasite development than the solution in the first 48 h posttreatment. While the parasitemia fell more rapidly with PLA nanocapsules, the effect was more sustained with the surface-modified ones. This is consistent with surface-modified nanocapsules remaining longer in the circulation. These results suggest that nanocapsule formulations could provide a more favorable halofantrine profile in the plasma and reduce the intravenous dose necessary and therefore the toxicity, thus suggesting the use of halofantrine by a parenteral route in severe malaria.
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PMID:Efficacy and pharmacokinetics of intravenous nanocapsule formulations of halofantrine in Plasmodium berghei-infected mice. 1504 23

Parasitic protozoa and helminths and parasitic/vector insects each have distinct requirements for cryopreservation. Most parasitic protozoa respond to cryopreservation stresses similarly to other single cell suspensions, but few species are currently routinely cryopreserved by protocols specifically designed for vitrification. With slow equilibrium cooling, some protozoa osmotically dehydrated by solutes concentrated in the residual unfrozen fraction will survive by vitrifying. Several species of helminths, together with insect embryos cannot be cryopreserved by slow cooling protocols and have an absolute requirement for vitrification. Studies incorporating slow cooling and stepped cooling of both protozoa and helminths, particularly the intraerythrocytic stages of malaria and the schistosomula larvae of Schistosoma mansoni have aided in the design of vitrification protocols for parasites. For helminths, the most widely used cryopreservation protocol, originally successful for cryopreserving S. mansoni schistosomula, consists of the addition of ethanediol in two steps, followed by rapid cooling (approximately 5100 degrees C min(-1)) to -196 degrees C. This technique exploits the temperature-dependent differential in permeability of the cryoprotectant additive (CPA) to first permeate into the organism at 37 degrees C followed by a dehydration-mediated internal CPA increase in concentration resulting from incubation in a second higher CPA concentration at 0 degree C. Samples are rapidly warmed/diluted (approximately 14,000 degrees C min(-1)) to recover the organisms from liquid nitrogen storage. Variations on this technique have also been successful in cryopreserving the larvae and adult worms of filariae, muscle stage larvae of Trichinella spp., the infective stages of gastro-intestinal nematode parasites and insect embryos. Other protocols where the dehydration step precedes CPA addition have been used to cryopreserve entomogenous nematode larvae by vitrification. Techniques that utilize high concentrations of CPA cocktails and slower cooling, developed for the vitrification of mammalian embryos, have been applied to the cryopreservation of parasitic protozoa, but with limited success to date. Where cryopreservation by classical slow cooling methods is possible, vitrification has enhanced the levels of survival obtained. And vitrification has enabled the successful cryopreservation of those parasitic species not able to be cryopreserved by traditional methods. Since a limited number of parasitic organisms has been cryopreserved using vitrification protocols, there is considerable scope for further improvement in the cryopreservation techniques used for many parasitic species.
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PMID:Parasite cryopreservation by vitrification. 1561 6

Serum concentrations of circulating immune complexes (CIC), complement factors (Factor B, C4, C8) and complement activities (CH50 and AH50) were determined in Nigerian school children having urinary schistosomiasis with or without symptomatic malaria by polyethylene glycol precipitation method, single radial immunodiffusion and total haemolytic activities respectively. One hundred and forty-seven children were recruited from St. John's Primary School, Mokola, Ibadan, Nigeria.RP ovale only, mixed infection of P. ovale with P. falciparum or mixed infection of P. malariae with P. falciparum were found in subjects with asymptomatic malaria without urinary schistosomiasis (M-USS) but P. malariae or P. falciparum was found in subjects with co-infection of urinary schistosomiasis and asymptomatic malaria (M + USS). Mean value of C4 concentration was significantly reduced in M - USS subjects or subjects having both USS and asymptomatic malaria (M + USS) compared with non-infected controls. Serum concentration of Factor B(FB) was significantly reduced while AH50 was significantly increased in urinary schisosomiasis subjects without malaria (USS-M) compared with M-USS subjects or the controls. These observations implied that complement system in USS-M subjects is activated predominantly via alternative pathway (APW) while complement system is activated via classical pathway (CPW) in M-USS or M+USS subjects. The switch of complement activation pathway from alternative type in USS-M subjects to classical type in M-USS subjects may explain the lower malaria parasite densities often found in children harbouring Schistosoma haematobium parasites.
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PMID:Complement factors and circulating immune complexes in children with urinary schistosomiasis and asymptomatic malaria. 1597 48

The Anopheles gambiae mosquito is the main vector of malaria transmission in sub-Saharan Africa. We present here a 1.5A crystal structure of AgamOBP1, an odorant binding protein (OBP) from the A. gambiae mosquito. The protein crystallized as a dimer with a unique binding pocket consisting of a continuous tunnel running through both subunits of the dimer and occupied by a PEG molecule. We demonstrate that AgamOBP1 undergoes a pH dependent conformational change that is associated with reduced ligand binding. A predominance of acid-labile hydrogen bonds involving the C-terminal loop suggests a mechanism in which a drop in pH causes C-terminal loop to open, leaving the binding tunnel solvent exposed, thereby lowering binding affinity for ligand. Because proteins from two distantly related insects also undergo a pH dependent conformational change involving the C-terminus that is associated with reduced ligand affinity, our results suggest a common mechanism for OBP activity.
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PMID:The crystal structure of an odorant binding protein from Anopheles gambiae: evidence for a common ligand release mechanism. 1630 Jul 42


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