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

Following residual spraying of houses in Pemba Island with dieldrin as part of a malaria eradication programme, Anopheles gambiae were found breeding in salt-water pools in many parts of the island. Studies were made on the bionomics of this salt-water form of the mosquito, dealing in particular with its behaviour, feeding preferences, role as a malaria vector, larval reaction to brackish water and adult susceptibility to dieldrin.The first-stage larvae of the freshwater and salt-water forms were found to exhibit a distinct difference in their reaction to 75% sea water, the former dying within 1(1/2) hours and the latter surviving 6 hours or more. It is suggested that this reaction may provide the best way of distinguishing with certainty between the two forms in East Africa.The results of precipitin tests and indoor and outdoor catches showed that, after spraying, the salt-water form was mainly exophilic with a preference for feeding on cattle. Exposure of adult to 0.4% dieldrin by the WHO test method indicated that they were still susceptible to that insecticide after two spraying cycles.
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PMID:The bionomics of salt-water Anopheles gambiae in East Africa. 1395 21

Anti-malarial drugs have been used in various ways to prevent malaria in the resident populations of endemic areas for nearly 100 years. The primary aim of most early studies was to interrupt transmission. This was rarely achieved, but administration of anti-malarial drugs either through medication of salt or by mass administration frequently led to a marked reduction in the prevalence of malaria infection and in the incidence of clinical attacks. Chemoprophylaxis is highly effective in reducing mortality and morbidity from malaria in young children and pregnant women living in endemic areas, but is difficult to sustain and, in some studies, has impaired the development of naturally acquired immunity. Intermittent preventive treatment, in which full therapeutic doses of a drug are given at defined intervals, has the potential to provide some of the benefits of sustained chemoprophylaxis in pregnant women and young children without some of its drawbacks and is a promising new approach to malaria control.
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PMID:The use of anti-malarial drugs to prevent malaria in the population of malaria-endemic areas. 1497 90

The Pakistani Punjab experienced several devastating malaria epidemics during the twentieth century. Since the 1980s, however, malaria has been at a low ebb, while in other areas of Pakistan and neighbouring India malaria is on the increase. This raises the question of whether transmission in the Pakistani Punjab may have been influenced by a change in vector species abundance or composition, possibly induced by environmental changes. To investigate this question, routinely-collected government entomological data for the period 1970 to 1999 for the district of Bahawalnagar, in the Indus Basin irrigation system in the southern Punjab, was analysed. Our findings suggest that Anopheles stephensi has increased in prevalence and became more common than A. culicifacies during the 1980s. This shift in species dominance may be due to the large-scale ecological changes that have taken place in the Punjab, where irrigation-induced waterlogging of soil with related salinization has created an environment favourable for the more salt-tolerant A. stephensi. Some biotypes of A. stephensi are suspected of being less efficient vectors and, therefore, the shift in species dominance might have played a role in the reduced transmission in the Punjab, although further research is needed to investigate the effect of other transmission-influencing factors.
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PMID:Malaria vectors in the changing environment of the southern Punjab, Pakistan. 1513 83

Development of new drugs is one of the strategies for malaria control. The biosynthesis of several isoprenoids in Plasmodium falciparum was recently described. Interestingly, some intermediates and final products biosynthesized by this pathway in mammals differ from those biosynthesized in P. falciparum. These facts prompted us to evaluate various terpenes, molecules with a similar chemical structure to the intermediates of the isoprenoids pathway, as potential antimalarial drugs. Different terpenes and S-farnesylthiosalicylic acid were tested on cultures of the intraerythrocytic stages of P. falciparum, and the 50% inhibitory concentrations for each one were found: farnesol, 64 microM; nerolidol, 760 nM; limonene, 1.22 mM; linalool, 0.28 mM; and S-farnesylthiosalicylic acid, 14 microM. All the terpenes tested inhibited dolichol biosynthesis in the trophozoite and schizont stages when [1-(n)-(3)H]farnesyl pyrophosphate triammonium salt ([(3)H]FPP) was used as precursor. Farnesol, nerolidol, and linalool showed stronger inhibitory activity on the biosynthesis of the isoprenic side chain of the benzoquinone ring of ubiquinones in the schizont stage. Treatment of schizont stages with S-farnesylthiosalicylic acid led to a decrease in intensity of the band corresponding a p21(ras) protein. The inhibitory effect of terpenes and S-farnesylthiosalicylic acid on the biosynthesis of both dolichol and the isoprenic side chain of ubiquinones and the isoprenylation of proteins in the intraerythrocytic stages of P. falciparum appears to be specific, because overall protein biosynthesis was not affected. Combinations of some terpenes or S-farnesylthiosalicylic acid tested in this work with other antimalarial drugs, like fosmidomycin, could be a new strategy for the treatment of malaria.
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PMID:Terpenes arrest parasite development and inhibit biosynthesis of isoprenoids in Plasmodium falciparum. 1521 1

With acknowledged difficulties in achieving satisfactory compliance rates for the large-scale delivery of many antiporositic drugs, the use of medicated salt has often been seen as a useful way to improve the level o f treatment in target populations. Iodinated salt is said to have contributed to a decline in endemic goitre, and salt medicated with chloroquine and/or other antimalorials, or with diethylcarbomazine, has been widely used in public health programmes against malaria and filariosis respectively. In this article, however, David Payne suggests that chloroquinized salt programmes may have been a major factor in promoting chloroquine resistance in Plasmodium falciparum.
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PMID:Did medicated salt hasten the spread of chloroquine resistance in Plasmodium falciparum? 1546 62

Plasmodium falciparum is the main causative agent of tropical malaria, the most severe parasitic disease in the world. Growing resistance of Plasmodia towards available drugs is an increasing problem in countries where malaria is endemic. As Plasmodia are sensitive to oxidative stress, augmenting this in the parasite represents a promising principle for the development of novel antimalarial drugs. The NADP-dependent glutamate dehydrogenase (GDH) of P.falciparum is largely responsible for the production of NADPH in the parasite, which in turn serves as electron source for the antioxidative enzymes glutathione reductase and thioredoxin reductase. As GDH does not occur in the host erythrocyte, GDH is a particularly attractive target for drug therapy. The three-dimensional structure of P.falciparum GDH in the unligated state has been determined by X-ray crystallography to a resolution of 2.7A. Compared to the mammalian enzymes, two amino acid residues are exchanged in the putative active site of the parasite GDH. The most obvious differences between parasite and human GDH are the subunit interfaces of the hexameric proteins. In the parasite protein, several salt-bridges mediate contacts between the subunits whereas in the human enzyme these interactions are mainly of hydrophobic nature. Furthermore, P.falciparum GDH possesses a unique N-terminal extension that does not occur in any other GDH sequence so far studied. These findings might be exploited for the design of peptidomimetics capable of disrupting the oligomeric organisation of the parasite enzyme.
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PMID:The crystal structure of Plasmodium falciparum glutamate dehydrogenase, a putative target for novel antimalarial drugs. 1587 95

Several beta-carbolines including naturally occurring substances and their corresponding cationic derivatives were synthesized and evaluated for antimalarial (antiplasmodial) activity in vitro and in vivo. A tetracyclic carbolinium salt was elucidated for antileishmanial and antitrypanosomal activities in vitro as well as antiplasmodial activity. Quarternary carbolinium cations showed much higher potencies in vitro than electronically neutral beta-carbolines and a good correlation was observed between pi-delocalized lipophilic cationic (DLC) structure and antimalarial efficacy. beta-Carbolinium compounds exhibit medium suppressive activity in vivo against rodent malaria.
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PMID:Synthesis and evaluation of beta-carbolinium cations as new antimalarial agents based on pi-delocalized lipophilic cation (DLC) hypothesis. 1593 Jul 77

A recombinant form of Plasmodium falciparum beta-ketoacyl-ACP reductase (PfFabG) was overexpressed in Escherichia coli BL-21 codon plus (DE3). The resulting insoluble inclusion bodies were separated from cellular debris by extensive washing with buffer containing 0.05% Tween 20 and solubilized by homogenization with 8 M urea. Attempts to refold PfFabG from solubilized inclusion bodies employing Rotofor (separation based on different pIs of proteins in a mixture) followed by Ni(2+) or cation exchange chromatography were not successful either by bringing down the urea concentration instantaneously, stepwise, or by dialysis. Denatured PfFabG was therefore initially purified by cation exchange chromatography and was then correctly refolded at a final concentration of 100-200 microg/ml in a 20 mM Na-acetate buffer, pH 5.3, with 300 mM NaCl, 10% glycerol, and 0.05% Tween 20. The protein was found to be properly folded only in the presence of the cofactor NADPH and salt at a concentration 300 mM by drop dilution method at 2-8 degrees C for 12 h. The purified final product was >98% pure by denaturing gel electrophoresis. The purified protein was biologically active in a standard enzymatic assay using acetoacetyl-CoA as a substrate. The enzyme was found to be stable up to fourth day of purification and glycerol was found to stabilize enzyme activity for several weeks, during storage. This effort paves the way for elucidation of the structure-function correlations for PfFabG as well as exploration of the enzyme for developing inhibitors against it for combating malaria.
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PMID:Production and purification of refolded recombinant Plasmodium falciparum beta-ketoacyl-ACP reductase from inclusion bodies. 1593 98

A complex of three phosphoproteins (P0, P1 and P2) constitutes the stalk region at the GTPase center of the eukaryotic large ribosomal subunit, amongst which the protein P0 plays the most crucial role. Earlier studies have shown the functional complementation of the conditional P0-null mutant of Saccharomyces cerevisiae (W303dGP0) with orthologous P0 genes from fungal and mammalian organisms, but not the protozoan parasite Leishmania infantum. In this paper we show that the PfP0 gene from the protozoan malaria parasite Plasmodium falciparum can functionally complement the conditional P0-null W303dGP0 mutant of S. cerevisiae. Unlike the above orthologous genes, PfP0 gene could also rescue the D67dGP0 strain, which in addition to being a conditional null for ScP0 gene, is a null-mutant for both ScP1alpha and beta genes. However, under stress conditions such as high temperature, salt and osmolarity, PfP0 gene could not rescue D67dGP0 strain. Ribosomes purified from W303dGP0 carrying PfP0 gene did not contain ScP1 protein, indicating a lack of binding of ScP1 to PfP0 protein. Yeast 2-hybrid analysis further confirmed the lack of binding of ScP1 to PfP0 protein. The polymerizing activities of ribosomes with ScP0 or PfP0 protein, in the absence of ScP1 protein, were found to be about 40-45% that of ribosomes with all the yeast P-proteins. In its sensitivity to the inhibitor sordarin, PfP0 was similar to the P0 protein from the fungus Aspergillus fumigatus. These results indicate a closer functional relationship of P. falciparum P0 gene to fungal P0 genes.
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PMID:Functional complementation of yeast ribosomal P0 protein with Plasmodium falciparum P0. 1609 8

A new approach to malarial chemotherapy based on quaternary ammonium that targets membrane biogenesis during intraerythrocytic Plasmodium falciparum development has recently been developed. To increase the bioavailability, nonionic chemically modified prodrugs were synthesized. In this paper, the pharmacological properties of a bisthiazolium salt (T3) and its bioprecursor (TE3) were studied. Their antimalarial activities were determined in vitro against the growth of P. falciparum and in vivo against the growth of P. vinckei in mice. Pharmacokinetic evaluations were performed after T3 (1.3 and 3 mg/kg of body weight administered intravenously; 6.4 mg/kg administered intraperitoneally) and TE3 (1.5 and 3 mg/kg administered intravenously; 12 mg/kg administered orally) administrations to rats. After intraperitoneal administration, very low doses offer protection in a murine model of malaria (50% efficient dose [ED50] of 0.2 to 0.25 mg/kg). After oral administration, the ED50 values were 13 and 5 mg/kg for T3 and TE3, respectively. Both compounds exerted antimalarial activity in the low nanomolar range. After TE3 administration, rapid prodrug-drug conversion occurred; the mean values of the pharmacokinetic parameters for T3 were as follows: total clearance, 1 liter/h/kg; steady-state volume of distribution, 14.8 liters/kg; and elimination half-life, 12 h. After intravenous administration, T3 plasma concentrations increased in proportion to the dose. The absolute bioavailability was 72% after intraperitoneal administration (T3); it was 15% after oral administration (TE3). T3 plasma concentrations (8 nM) 24 h following oral administration of TE3 were higher than the 50% inhibitory concentrations for the most chloroquine-resistant strains of P. falciparum (6.3 nM).
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PMID:Pharmacological properties of a new antimalarial bisthiazolium salt, T3, and a corresponding prodrug, TE3. 1612 32


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