Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chloroquine phosphate (CP) has been formulated in a suppository base consisting of polyethylene glycol, PEG 1000 and PEG 6000 (7:3) with 0.5% polysorbate 80 included as an absorption promoter. Peak chloroquine blood levels in children (mean body weight 10 kg, age 21 months) were 0.67 +/- 0.08 micrograms/ml (after 200 mg CP) and 1.06 +/- 0.23 micrograms/ml (after 300 mg CP) following rectal administration of the suppositories. Prior to drug administration, the base level chloroquine was 0.30 +/- 0.02 micrograms/ml. Elimination half lives calculated from the rapid phase of log concentration-time curves were 3.3 h (after 200 mg CP) and 2.7 h (after 300 mg CP), respectively. Based on literature evidence the blood levels obtained with the 300 mg CP suppositories would be therapeutic in the management of malaria and rheumatoid disease.
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PMID:Chloroquine absorption in children from polyethylene glycol base suppositories. 320 29

Plasmodium berghei-infected mouse red cells have enhanced fusion capacity as triggered by addition of poly(ethylene glycol) in the presence of Ca2+. The uptake of Ca2+ in P. berghei-infected cells is greater than in normal cells, and the difference in Ca2+ uptake was found to be enhanced in the presence of poly(ethylene glycol). Fusion of normal and P. berghei-infected red cells by poly(ethylene glycol) was significantly inhibited by N-tosyl-L-lysylchloromethyl ketone and phenylmethylsulphonyl fluoride. In addition, ethyleneglycolbis(aminoethylether)tetra-acetate, N-ethylmaleimide, iodoacetamide, cystamine and tetrathionate also prevented fusion in both systems. In contrast, N-tosyl-L-phenylalanylchloromethyl ketone and N-tosyl-L-arginine methyl ester did not inhibit cell fusion. The latter enhanced fusion of infected cells but was without effect on normal cells. These results indicate that a Ca2+-activated thiol proteinase may be involved in membrane fusion in malaria-infected as well as in normal red cells. However, differences in the effect of proteinase inhibitors and substrate on fusion and Ca2+ entry show that the processes leading to fusion may not be identical.
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PMID:Mechanism of enhanced fusion capacity of mouse red cells infected with Plasmodium berghei. 641 72

Immunoglobulin-lipoprotein complexes have been investigated in the course of P. chabaudi acute infection of Swiss mice. Serum ultracentrifugation in a sucrose density gradient was used to demonstrate the presence of immunoglobulins in the enriched lipoprotein fraction of density lower than 1100. The levels of lipoprotein-bound immunoglobulins (Ig-Lp) were measured using the rate-nephelometric Immuno-Chemistry-System. IgM-Lp and IgG-Lp were significantly increased at day 9 and reached a peak at day 13 post-infection. From day 13 to day 16 they dramatically decreased. This kinetic effect was similar to that of non-specific circulating immune complexes detected by the [125I]Clq binding assay. A radioimmuno-precipitation-PEG-assay (RIPEGAssay) with [125I]Lp revealed the highest Lp precipitation with day 13 post-infection mouse sera compared to controls. Similar results were recorded when control sera were 8 times as concentrated in order to obtain Ig levels identical in both control and experimental sera. Part of the lipoprotein-bound immunoglobulins were demonstrated to be anti-Lp antibodies by the way of the RIPEGAssay using F(ab')2 fragments from infected mouse sera. Moreover, the [125I]Clq bound to the Ig-Lp complexes isolated from day 13 mouse sera. The present data suggest that the alteration of lipid metabolism which characterizes malaria infection could lead to the complexation of lipoproteins to immunoglobulins.
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PMID:[Immunoglobulin-lipoprotein complexes during P. chabaudi infection]. 675 74

The capacity of normal and malaria-infected mouse red cells to undergo fusion was investigated by phase contrast microscopy. The fusion of mouse red cells induced by 50% w/w poly(ethylene glycol)-6000 in the presence of Ca+2 is enhanced by P. berghei infection. Cells carrying parasites in the ring form stage and early trophozoite stage show slightly higher fusion induced by dimethyl sulphoxide and Ca+2 than those carrying parasites in trophozoite and schizont stages.
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PMID:Enhanced fusion capacity of malaria (Plasmodium berghei)-infected mouse red cells. 699 73

Immobilized metal-ion affinity partitioning (IMAP) is shown to be useful as a preliminary screening test and for the separation of different cell populations based upon recognition of the differences in the proteins on cell surfaces. The feasibility of using IMAP to segregate a spectrum of normal human cells (red blood cells, lymphocytes and fibroblasts) from their counterpart pathological cells has been demonstrated. A clear segregation between normal and sickle-cell anemia red blood cells (RBC), or malaria (Plasmodium vivax) infected RBCs was obtained. Further, the partition differences were found to depend on the nature and the concentrations of metal used. Cells from breast cancer and those from the lung adenocarcinoma showed differences in their partition pattern as compared to normal fibroblasts when PEG-IDA-M(II) was added to the phase system. Maximum differences between the three cell populations were observed in the presence of 10% PEG-IDA-Ni(II). Normal lymphocytes and Burkitt's lymphoma cells (Raji and Namalwa cell lines) were shown to partition differently in the presence of PEG-IDA-M(II) in the phase system. Normal lymphocytes could be distinguished from the Burkitt's lymphoma cell lines in all three phases (top, interface and bottom), in the presence of 10% PEG-IDA-Ni(II) in the system. These differences in the partition behavior could mainly be attributed to the density, surface exposure and micro-environment of histidine residues of cell membrane-associated proteins. These data, along with those obtained for normal and pathological human cells show that IMAP could be a simple and versatile tool for the segregation and study of cells.
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PMID:Segregation of normal and pathological human red blood cells, lymphocytes and fibroblasts by immobilized metal-ion affinity partitioning. 759 55

ELISA is widely used as a means to detect antibodies, but the potential of ELISA plates as an immunosorbent for the purification of specific antibodies does not seem to have been evaluated. In this study, ELISA plates coated with peptides representing short sequences of various antigens from Plasmodium falciparum, the etiologic agent of human malaria, have been successfully used as a means to purify small amounts of the corresponding antibodies. ELISA plates, identical to those used for antibody detection, also permitted the evaluation of various elution conditions for each pairing of peptide and serum; we tested four eluting buffers (0.2 M glycine, pH 2.5; 0.2 M lysine, pH 11.5; 3.0 M MgCl2, 0.075 M Hepes, 25% ethylene glycol, pH 7.1-7.2 and 4 M NH4SCN in 0.1 M NaH2PO4, pH 6.0) with four pairs of peptides and sera. The ELISA plates could also be used to estimate the affinity of the eluted antibodies by the technique of Pullen et al. (1986). The eluted antibodies were compared to those obtained by immunopurification on recombinant proteins adsorbed on nitrocellulose filters. In contrast to the latter, they were not contaminated by antibodies directed against the carrier moiety of the recombinant protein. When used in immunofluorescence assays with various stages of the parasite the antibodies immunopurified on peptides bound to ELISA plates were able to react with the native antigens in the parasite.
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PMID:Fast immunopurification of small amounts of specific antibodies on peptides bound to ELISA plates. 850 53

An immunogenic and tolerogenic characterisation of monomethoxypoly(ethylene glycol) conjugated proteins was carried out using, as immunogen models, an anti-malaria chimera monoclonal antibody (PfChMab) and a macrophage colony stimulating factor (M-CSF). Two conjugates of PfChMab were prepared by polymer derivatisation of 19 and 33% protein amino groups and one conjugate of M-CSF was obtained by modification of 24% amino groups. In mice M-CSF was found to elicit rapidly high IgG and IgM levels whereas the monomethoxypoly(ethylene glycol) derivatised M-CSF stimulated a significantly lower immunoresponse. Native PfChMab was found to induce a delayed immunoresponse with high IgM levels but low production of IgG. Furthermore, similar immunogenic profiles were obtained with the native and modified protein forms. The pre-administration of polymer conjugated M-CSF to mice subsequently treated with the native protein was found to suppress up to 75% of anti-native M-CSF IgG, while IgM production was not affected. On the other hand the pre-administration of monomethoxypoly(ethylene glycol) derivatised PfChMab was found to reduce significantly the generation of anti-native PfChMab IgM. Such suppression depended on the degree of modification: the conjugate with the higher number of polymer chains was more effective in suppressing the immunoresponse.
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PMID:Immunogenic and tolerogenic properties of monomethoxypoly(ethylene glycol) conjugated proteins. 1048 10

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

A rapid, sensitive and selective gas chromatographic method with flame ionization detection was developed for the determination of paraldehyde in small blood samples taken from children. Whole blood samples (300 microl) collected in a 3 ml Wheaton glass sample vial were spiked with acetone (internal standard: 15 ng) followed by addition of concentrated hydrochloric acid. The mixture was heated in the sealed airtight sample vial in a water bath (96 Celsius; 5 min) to depolymerize paraldehyde to acetaldehyde. A 2 ml aliquot of the headspace was analyzed by gas chromatography with flame ionization detector using a stainless steel column (3 m x 4 mm i.d.) packed with 10% Carbowax 20 M/ 2% KOH on 80/100 Chromosorb WAW. Calibration curves were linear from 1.0-20 microg (r2>0.99). The limit of detection was 1.5 microg/ml, while relative mean recoveries at 2 and 18 microg were 105.6 +/- 8.4 and 101.2 +/- 5.9%, respectively (n = 10 for each level). Intra- and inter-assay relative standard deviations at 2, 10 and 18 microg were <15%. There was no interference from other drugs concurrently used in children with severe malaria, such as anticonvulsants (diazepam, phenytoin, phenobarbitone), antipyretics/analgesics (paracetamol and salicylate), antibiotics (gentamicin, chloramphenicol, benzyl penicillin) and antimalarials (chloroquine, quinine, proguanil, cycloguanil, pyrimethamine and sulfadoxine). The method was successfully applied for pharmacokinetic studies of paraldehyde in children with convulsions associated with severe malaria.
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PMID:Determination of paraldehyde by gas chromatography in whole blood from children. 1513 15

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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