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pathogenic role of p-selectin in experimental cerebral malaria: importance of the endothelial compartment.p-selectin is a leukocyte adhesion receptor expressed on the surface of activated platelets and endothelial cells. its role in the pathogenesis of cerebral malaria was explored in a murine model of cerebral malaria. infection of mice with plasmodium berghei anka led to p-selectin up-regulation in brain vessels of cerebral malaria-susceptible mice but not of cerebral malaria-resistant mice. treatment of susceptible mice with anti-mouse p-selectin mab failed to prevent the development of the neuro ...200414982832
laboratory evaluation of the ict malaria p.f./p.v. immunochromatographic test for detecting the panmalarial antigen using a rodent malaria model.we evaluated the ict malaria p.f./p.v. immunochromatographic test for the detection of the panmalarial antigen (pma) using a rodent malaria model. mice were infected with plasmodium berghei by mosquito bite, and blood was examined by microscopy and the ict test. treatment with artemether was started when the parasite density exceeded 70,000/microl. the ict pma band appeared when the parasite density was more than 2,000/microl, but it continued to be positive after the parasitemia became negative ...200414993624
orally active antimalarials: hydrolytically stable derivatives of 10-trifluoromethyl anhydrodihydroartemisinin.new fluoroartemisinin derivatives containing polar or water-soluble functionalities at c-16 (11a-j, 12a-g) were synthesized using the key intermediate 16-bromo-10-trifluoromethyl anhydrodihydroartemisinin 10. the substitution reaction from 10 was more selective than that from the nonfluorinated parent bromide; the allylic bromide 10 underwent no allylic rearrangement and provided only nucleophilic substitution products in high yields with n-, o-, and c-nucleophiles. among them, amines 11a-c appe ...200414998331
ptramp; a conserved plasmodium thrombospondin-related apical merozoite protein.a gene encoding a 352 amino acid protein with a putative signal sequence, transmembrane domain and thrombospondin structural homology repeat was identified in the genome of the human malaria parasite, plasmodium falciparum and the rodent malaria parasite, plasmodium berghei. the protein localises in the apical organelles of p. falciparum and p. berghei merozoites within intraerythrocytic schizonts and has, therefore, been termed the plasmodium thrombospondin-related apical merozoite protein (ptr ...200415003842
brain gene expression, metabolism, and bioenergetics: interrelationships in murine models of cerebral and noncerebral malaria.malaria infection can cause cerebral symptoms without parasite invasion of brain tissue. we examined the relationships between brain biochemistry, bioenergetics, and gene expression in murine models of cerebral (plasmodium berghei anka) and noncerebral (p. berghei k173) malaria using multinuclear nmr spectroscopy, neuropharmacological approaches, and real-time rt-pcr. in cerebral malaria caused by p. berghei anka infection, we found biochemical changes consistent with increased glutamatergic act ...200415003995
complement-like protein tep1 is a determinant of vectorial capacity in the malaria vector anopheles gambiae.anopheles mosquitoes are major vectors of human malaria in africa. large variation exists in the ability of mosquitoes to serve as vectors and to transmit malaria parasites, but the molecular mechanisms that determine vectorial capacity remain poorly understood. we report that the hemocyte-specific complement-like protein tep1 from the mosquito anopheles gambiae binds to and mediates killing of midgut stages of the rodent malaria parasite plasmodium berghei. the dsrna knockdown of tep1 in adults ...200415006349
plasmodium berghei parasite transformed with green fluorescent protein for screening blood schizontocidal agents.high priority has been given to new assays that facilitate and accelerate the development of novel antimalarial compounds. unlike evaluation of drugs in vitro, in which new approaches have been used to expedite identification of parasites, the conventional in vivo murine assay requires determination of parasitemia by light microscopy, an incompatible technique to test large numbers of drugs. we have investigated the possibility of using an autonomously fluorescent plasmodium berghei strain, stab ...200415013738
isonicotinic acid hydrazide: an anti-tuberculosis drug inhibits malarial transmission in the mosquito gut.we studied the transmission-blocking effect of isonicotinic acid hydrazide (inh), a widely used anti-tuberculosis drug, against plasmodium gallinaceum and plasmodium berghei. inh-treatment of infected animals did not inhibit parasite development in the blood of the vertebrate host, but did inhibit exflagellation, ookinete formation, and oocyst development in the mosquito. oocyst development was inhibited in a dose-dependent manner. the ed(50) in the p. gallinaceum/chicken/aedes aegypti model and ...200415013786
transcriptional profiling reveals suppressed erythropoiesis, up-regulated glycolysis, and interferon-associated responses in murine malaria.the primary pathophysiological events contributing to fatal malaria are the cerebral syndrome, anemia, and lactic acidosis. the molecular basis of each event has been unclear. in the present study, microarray analysis of murine transcriptional responses during the development of severe disease revealed temporal, organ-specific, and pathway-specific patterns. more than 400 genes in the brain and 600 genes in the spleen displayed transcriptional changes. dominant patterns revealed strongly suppres ...200415031794
parasitology. new ways to control malaria. 200415044794
effects of mosquito genes on plasmodium development.malaria parasites must complete a complex developmental cycle in an anopheles mosquito vector before transmission to a vertebrate host. sexual development of the parasite in the midgut is initiated in the lumen immediately after the mosquito ingests infected blood, and the resulting ookinetes must traverse the surrounding epithelial layer before transforming into oocysts. the innate immune system of the mosquito is activated during midgut invasion, but to date, no evidence has been published ide ...200415044804
efficacy and pharmacokinetics of intravenous nanocapsule formulations of halofantrine in plasmodium berghei-infected mice.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 intrave ...200415047523
ctla-4-dependent mechanisms prevent t cell induced-liver pathology during the erythrocyte stage of plasmodium berghei malaria.during the course of malaria several organs develop pathology. frequently also signs of hepatocyte damage are found. in the present work we studied the mechanisms leading to liver pathology during the erythrocyte stage of plasmodium berghei malaria. during infection, mice developed an inflammation of the liver, associated with infiltration of t cells, although only little tissue damage could be observed. histological analysis revealed the presence of ctl-associated antigen-4 (ctla-4)-positive t ...200415048707
fitness of anopheline mosquitoes expressing transgenes that inhibit plasmodium development.one potential strategy for the control of malaria and other vector-borne diseases is the introduction into wild vector populations of genetic constructs that reduce vectorial capacity. an important caveat of this approach is that the genetic construct should have minimal fitness cost to the transformed vector. previously, we produced transgenic anopheles stephensi expressing either of two effector genes, a tetramer of the sm1 dodecapeptide or the phospholipase a2 gene (pla2) from honeybee venom. ...200415082552
contribution of cd1d-unrestricted hepatic dx5+ nkt cells to liver injury in plasmodium berghei-parasitized erythrocyte-injected mice.inoculation with erythrocytes infected with plasmodium berghei, a protozoan causing mouse lethal malaria, induces liver injury in mice, although the parasite cannot invade host hepatocytes at this infectious stage. as previously reported, hepatic infiltrates participate in this liver injury by exerting their perforin-dependent killing action. here, we have investigated the cellular mechanisms underlying p. berghei-induced incidental liver injury. hepatic lymphocytes from p. berghei-infected mice ...200415096477
comparative study of brain cd8+ t cells induced by sporozoites and those induced by blood-stage plasmodium berghei anka involved in the development of cerebral malaria.to obtain insight into the mechanisms that contribute to the pathogenesis of plasmodium infections, we developed an improved rodent model that mimics human malaria closely by inducing cerebral malaria (cm) through sporozoite infection. we used this model to carry out a detailed study on isolated t cells recruited from the brains of mice during the development of cm. we compared several aspects of the immune response related to the experimental model of plasmodium berghei anka infection induced b ...200415102792
fluoroartemisinin: trifluoromethyl analogues of artemether and artesunate.the synthesis of a series of c-10 trifluoromethyl ethers of artemisinin has been achieved from key bromide 8, itself carried out in two steps from artemisinin. the substitution of 8 with methanol, ethanol, or succinic acid allowed the access of c-10 cf(3) analogues of beta-artemether, beta-arteether, or artesunate, respectively, in good yields (up to 89%). the presence of the cf(3) group at c-10 of artemisinin clearly increased the chemical stability under simulated stomach acid conditions. for ...200415115411
identification and activity of a series of azole-based compounds with lactate dehydrogenase-directed anti-malarial activity.plasmodium falciparum, the causative agent of malaria, relies extensively on glycolysis coupled with homolactic fermentation during its blood-borne stages for energy production. selective inhibitors of the parasite lactate dehydrogenase (ldh), central to nad(+) regeneration, therefore potentially provide a route to new antimalarial drugs directed against a novel molecular target. a series of heterocyclic, azole-based compounds are described that preferentially inhibit p. falciparum ldh at sub-mi ...200415117937
calcium and a calcium-dependent protein kinase regulate gamete formation and mosquito transmission in a malaria parasite.transmission of malaria parasites to mosquitoes is initiated by the obligatory sexual reproduction of the parasite within the mosquito bloodmeal. differentiation of specialized transmission stages, the gametocytes, into male and female gametes is induced by a small mosquito molecule, xanthurenic acid (xa). using a plasmodium berghei strain expressing a bioluminescent calcium sensor, we show that xa triggers a rapid rise in cytosolic calcium specifically in gametocytes that is essential for their ...200415137943
orotate phosphoribosyltransferase and orotidine 5'-monophosphate decarboxylase exist as multienzyme complex in human malaria parasite plasmodium falciparum.plasmodium falciparum, the causative agent of the most lethal form of human malaria, totally depends on de novo pyrimidine biosynthetic pathway. orotate phosphoribosyltransferase (oprt) and orotidine 5'-monophosphate decarboxylase (ompdc), the fifth and sixth enzymes in the pathway catalyzing formation of uridine 5'-monophosphate (ump), remain largely uncharacterized in the protozoan parasite. in this study, we achieved purification of oprt and ompdc to near homogeneity from p. falciparum cultiv ...200415147974
malaria: the calcium connection. 200415152234
bioimmunotherapy of rodent malaria: co-treatment with recombinant mouse granulocyte-macrophage colony-stimulating factor and an enkephalin fragment peptide tyr-gly-gly.we have earlier shown that recombinant mouse granulocyte-macrophage colony-stimulating factor (rmgm-csf) and methionine-enkephalin co-treatment can protect mice from malaria. we now report the bioimmunotherapeutic effect of rmgm-csf and a synthetic enkephalin fragment peptide tyr-gly-gly (tgg) co-treatment on blood-induced plasmodium berghei infection in swiss mice. mice were completely aparasitimic following co-treatment with rmgm-csf (10.0 microg/kg) and tgg (2.0 mg/kg x 3 per day, intraperito ...200415158686
t cell receptor-ligand interactions: a conformational preequilibrium or an induced fit.kinetic parameters of t cell receptor (tcr) interactions with its ligand have been proposed to control t cell activation. analysis of kinetic data obtained has so far produced conflicting insights; here, we offer a consideration of this problem. as a model system, association and dissociation of a soluble tcr (st1) and its specific ligand, an azidobenzoic acid derivative of the peptide syipsaek-(aba)i (residues 252-260 from plasmodium berghei circumsporozoite protein), bound to class i mhc h-2k( ...200415178754
new evidences of antimalarial activity of bidens pilosa roots extract correlated with polyacetylene and flavonoids.bidens pilosa is among the several plants used in brazil to treat malaria. it was demonstrated that crude extracts from roots prepared with 80% ethanol by percolation are active in vitro against plasmodium falciparum and the activity is correlated with the presence of polyacetylene and flavonoids. this extract was submitted to column chromatography with ether and ether methanol (1:1) and two fractions, enriched in polyacetylene and flavonoids, respectively, were obtained. the extract and the fra ...200415182902
ectopic expression of a cecropin transgene in the human malaria vector mosquito anopheles gambiae (diptera: culicidae): effects on susceptibility to plasmodium.genetically altering the disease vector status of insects using recombinant dna technologies is being considered as an alternative to eradication efforts. manipulating the endogenous immune response of mosquitoes such as the temporal and special expression of antimicrobial peptides like cecropin may result in a refractory phenotype. using transgenic technology a unique pattern of expression of cecropin a (ceca) in anopheles gambiae was created such that ceca was expressed beginning 24 h after a ...200415185949
real-time, in vivo analysis of malaria ookinete locomotion and mosquito midgut invasion.invasion of the anopheles mosquito midgut by the plasmodium ookinete is a critical step in the malaria transmission cycle. we have generated a fluorescent p. berghei transgenic line that expresses gfp in the ookinete and oocyst stages, and used it to perform the first real-time analysis of midgut invasion in the living mosquito as well as in explanted intact midguts whose basolateral plasma membranes were vitally stained. these studies permitted detailed analysis of parasite motile behaviour in ...200415186403
imaging movement of malaria parasites during transmission by anopheles mosquitoes.malaria is contracted when plasmodium sporozoites are inoculated into the vertebrate host during the blood meal of a mosquito. in infected mosquitoes, sporozoites are present in large numbers in the secretory cavities of the salivary glands at the most distal site of the salivary system. however, how sporozoites move through the salivary system of the mosquito, both in resting and feeding mosquitoes, is unknown. here, we observed fluorescent plasmodium berghei sporozoites within live anopheles s ...200415186404
comparative and functional genomics of the innate immune system in the malaria vector anopheles gambiae.in much of africa, the mosquito anopheles gambiae is the major vector of human malaria, a devastating infectious disease caused by plasmodium parasites. vector and parasite interact at multiple stages and locations, and the nature and effectiveness of this reciprocal interaction determines the success of transmission. many of the interactions engage the mosquito's innate immunity, a primitive but very effective defense system. in some cases, the mosquito kills the parasite, thus blocking the tra ...200415199960
neuropeptide-containing cells in the cortex and striatum of mice with cerebral malaria.central nervous system tissue of mice infected with plasmodium berghei anka (pba) exhibits similar histopathological features to those in post-mortem human cerebral malaria (cm) tissue. in this study, the neurochemical characteristics of pba-infected and control mice were compared. substance p-containing neurones were almost completely lost from the cortex and striatum of pba-infected mice seven days after inoculation, whereas the intensity of calbindin immunolabelling was increased compared wit ...200315206748
recent developments in marine indole alkaloid synthesis.the manzamine alkaloids such as manzamine a, b, and c belongs to a unique family of cyctotoxic beta-carbline linked azacycles, which have been isolated from several marine sponges. manzamine a has recently been shown to exhibit in vivo antimalarial activity against parasite plasmodium berghei. further progress was added recently by the isolation of the new and closely related members such as nakadomarin a, as well as an ingenious proposal for their biosynthetic pathway. martefragin a, isolated f ...200315206780
[studies on the antigens of invasive stages of plasmodium yoelii and plasmodium berghei].to detect the rhoptry and surface proteins of invasive stages of plasmodium yoelii and p. berghei with monoclonal antibodies.200315108514
combination effects of chloroquine with the febrifugine and isofebrifugine mixture against a blood-induced infection with chloroquine-resistant plasmodium berghei nk65 in icr mice.the combination effects of chloroquine with a mixture of febrifugine and isofebrifugine were evaluated against a blood-induced infection with chloroquine-resistant p. berghei nk65 in icr mice. mice in the untreated control showed a progressively increasing parasitemia leading to mouse death. a two-day dosage of 20 mg base/kg of chloroquine alone showed little effect against p. berghei nk65 infection, and all mice died from day 13 to 14 with an increasing parasitemia. a four-day dosage of 1 mg/kg ...200314669265
activation of transforming growth factor beta by malaria parasite-derived metalloproteinases and a thrombospondin-like molecule.much of the pathology of malaria is mediated by inflammatory cytokines (such as interleukin 12, interferon gamma, and tumor necrosis factor alpha), which are part of the immune response that kills the parasite. the antiinflammatory cytokine transforming growth factor (tgf)-beta plays a crucial role in preventing the severe pathology of malaria in mice and tgf-beta production is associated with reduced risk of clinical malaria in humans. here we show that serum-free preparations of plasmodium fal ...200314676296
malaria parasites lacking eef1a have a normal s/m phase yet grow more slowly due to a longer g1 phase.eukaryotic elongation factor 1a (eef1a) plays a central role in protein synthesis, cell growth and morphology. malaria parasites possess two identical genes encoding eef1a (eef1aa and eef1ab). using pbeef1a-plasmodium berghei mutants that lack an eef1a gene, we demonstrate that the level of eef1a production affects the proliferation of blood stages and parasite fitness. pbeef1a- parasites can complete the vertebrate and mosquito phases of the life cycle, but the growth phase of the asexual blood ...200314651637
isolation of plasmodium berghei ookinetes in culture using nycodenz density gradient columns and magnetic isolation.background: large scale in vitro production of the mosquito stages of malaria parasites remains elusive, with only limited success for complete sporogonic development and only one report of development through to infective sporozoites. the initial step in this process is the production, in vitro, of ookinetes from gametocytaemic blood. methods for isolation of these ookinetes from blood cells have been described; however, in addition to yield often being low, processing time and potential for co ...200314613512
in-vivo antimalarial activity of some oxygenated xanthones.a series of oxygenated xanthones was prepared so that the antimalarial activity of each compound could be evaluated in vivo, using 4-day suppressive assays against plasmodium berghei anka in balb/c mice. when given in a dose of 20 mg/kg.day for 4 days, most of the compounds produced significant chemosuppression of parasitaemia. the most active compound was 1,3,6,8-tetrahydroxyxanthone, which reduced the percentage of erythrocytes infected by 70.5%, followed by norlichexanthone (44.3%) and its is ...200314613627
the role of reactive oxygen species on plasmodium melanotic encapsulation in anopheles gambiae.malaria transmission depends on the competence of some anopheles mosquitoes to sustain plasmodium development (susceptibility). a genetically selected refractory strain of anopheles gambiae blocks plasmodium development, melanizing, and encapsulating the parasite in a reaction that begins with tyrosine oxidation, and involves three quantitative trait loci. morphological and microarray mrna expression analysis suggest that the refractory and susceptible strains have broad physiological difference ...200314623973
inhibition of platelet adherence to brain microvasculature protects against severe plasmodium berghei malaria.some patients with plasmodium falciparum infections develop cerebral malaria, acute respiratory distress, and shock and ultimately die even though drug therapy has eliminated the parasite from the blood, suggesting that a systemic inflammatory response contributes to malarial pathogenesis. plasmodium berghei-infected mice are a well-recognized model of severe malaria (experimental severe malaria [esm]), and infected mice exhibit a systemic inflammatory response. because platelets are proposed to ...200314573677
baculovirus virions displaying plasmodium berghei circumsporozoite protein protect mice against malaria sporozoite infection.the display of foreign proteins on the surface of baculovirus virions has provided a tool for the analysis of protein-protein interactions and for cell-specific targeting in gene transfer applications. to evaluate the baculovirus display system as a vaccine vehicle, we have generated a recombinant baculovirus (acnpv-cspsurf) that displays rodent malaria plasmodium berghei circumsporozoite protein (pbcsp) on the virion surface as a fusion protein with the major baculovirus envelope glycoprotein g ...200314599800
8-quinolinamines and their pro prodrug conjugates as potent blood-schizontocidal antimalarial agents.synthesis and antimalarial activities of n8-(4-amino-1-methylbutyl)-5-alkoxy-4-ethyl-6-methoxy-8-quinolinamines (5) and their pro prodrug analogues (6-7) prepared by covalently linking 5 to the redox-sensitive (8) and esterase-sensitive (9) linkers through the amide linkage are reported. the most effective 8-quinolinamines [5c (r=c5h11) and 5f (r=c8h17)] have exhibited in vitro and in vivo biological efficacy superior to that of the standard drug chloroquine against both drug-sensitive and drug- ...200314527552
rheumatoid factor-like igm in plasmodium berghei (apicomplexa: haemosporida) infections of balb/c mice.groups of female balb/c mice infected by intravenous injection with 50 erythrocytes containing plasmodium berghei vincke et lips, 1948 were sacrificed on days 3 through 12 after infection. rheumatoid factor-like igm (rf-igm) and parasite-specific igg levels were determined by enzyme-linked immunosorbent assay in serum specimens and in culture medium removed from spleen cell cultures established at sacrifice. all four mouse igg subisotypes were recognized by rf-igm molecules induced by plasmodium ...200314535342
plasmepsin 4, the food vacuole aspartic proteinase found in all plasmodium spp. infecting man.plasmepsins are aspartic proteinases of the malaria parasite, and seven groups of plasmepsins have been identified by comparing genomic sequence data available for the genes encoding these enzymes from plasmodium falciparum, plasmodium vivax, plasmodium knowlesi, plasmodium berghei, and plasmodium yoelii. the food vacuole plasmepsins typified by plasmepsin 4 from p. falciparum (pfpm4) constitute one of these groups. genes encoding the ortholog of pfpm4 have been cloned from plasmodium ovale, pla ...200314550891
heterologous promoter activity in stable and transient plasmodium knowlesi transgenes. 200314550898
[genetic analysis of host resistance to rodent malaria in mice]. 200314562624
why is the plasmodium falciparum hexose transporter a promising new drug target?chemotherapy of malaria parasites is limited by established drug resistance and lack of novel treatment options. intraerythrocytic stages of plasmodium falciparum, the causative agent of severe malaria, are wholly dependent upon host glucose for energy. a facilitative hexose transporter (pfht), encoded by a single-copy gene, mediates glucose uptake and is therefore an attractive potential target. the authors first established heterologous expression in xenopus laevis to allow functional characte ...200314498822
erythrocyte g protein-coupled receptor signaling in malarial infection.erythrocytic mechanisms involved in malarial infection are poorly understood. we have found that signaling via the erythrocyte beta2-adrenergic receptor and heterotrimeric guanine nucleotide-binding protein (galphas) regulated the entry of the human malaria parasite plasmodium falciparum. agonists that stimulate cyclic adenosine 3',5'-monophosphate production led to an increase in malarial infection that could be blocked by specific receptor antagonists. moreover, peptides designed to inhibit ga ...200314500986
quinine distribution in mice with plasmodium berghei malaria.the disposition of a single 80 mg/kg injection of quinine base was compared in control and plasmodium berghei-infected mice. pharmacokinetic parameters were determined on repeated whole blood samples from caudal vein (experiment 1) and quinine distribution was evaluated in tissues and blood fractions from mice sacrificed two hours post dosing (experiment 2). quinine concentrations were assessed by high performance liquid chromatography with fluorometric detection. whole blood concentrations and ...200314503660
the age-related resistance of rats to plasmodium berghei infection is associated with differential cellular and humoral immune responses.in this study, we investigated how the age of rats would affect the course of infection of and the immune response to plasmodium berghei. both young (4-week-old) and adult rats (8-week-old) can be infected with p. berghei anka strain, with significantly higher levels of infected red blood cells in young rats. while 100% of young rats succumbed to infection, adult rats were able to clear blood parasites and no mortality was observed. analysis of cellular distribution and circulating cytokines dem ...200313129529
artemisinin derivatives bearing mannich base group: synthesis and antimalarial activity.novel artemisinin derivatives bearing mannich base group were prepared and tested for their antimalarial activity. these water-soluble artemisinin derivatives were more stable than sodium artesunate and few compounds were found to be more active against plasmodium berghei in mice than artesunic acid by oral administration. two most potent derivatives 17b and 17d were examined for their antimalarial activity against plasmodium knowlesi in rhesus monkeys.200313129573
metabolites of febrifugine and its synthetic analogue by mouse liver s9 and their antimalarial activity against plasmodium malaria parasite.quinazolinone type alkaloids, febrifugine (1) and isofebrifugine (2), isolated from dichroa febrifuga roots, show powerful antimalarial activity against plasmodium falciparum. unfortunately, their emetic effect and other undesirable side effects have precluded their clinical use for malaria. because of their antimalarial potency, analogues were searched for, with the goal of preserving the strong antimalarial activity, while dramatically reducing side effects. we expected that compounds useful i ...200313678413
soluble major histocompatibility complex-peptide octamers with impaired cd8 binding selectively induce fas-dependent apoptosis.fluorescence-labeled soluble major histocompatibility complex class i-peptide "tetramers" constitute a powerful tool to detect and isolate antigen-specific cd8(+) t cells by flow cytometry. conventional "tetramers" are prepared by refolding of heavy and light chains with a specific peptide, enzymatic biotinylation at an added c-terminal biotinylation sequence, and "tetramerization" by reaction with phycoerythrin- or allophycocyanin-labeled avidin derivatives. we show here that such preparations ...200312407102
cloning and characterization of four anopheles gambiae serpin isoforms, differentially induced in the midgut by plasmodium berghei invasion.the genomic locus srpn10 of the malaria vector anopheles gambiae codes for four alternatively spliced serine protease inhibitors of the serpin superfamily. the four 40- to 42-kda isoforms differ only at their c terminus, which bears the reactive site loop, and exhibit protein sequence similarity with other insect serpins and mammalian serpins of the ovalbumin family. inhibition experiments with recombinant purified srpn10 serpins reveal distinct and specific inhibitory activity of three isoforms ...200312456678
oral artesunate prevents plasmodium berghei anka infection in mice.artesunate, a semi-synthetic derivative of a naturally occurring anti-malarial artemisinin was compared with chloroquine in c57bl/6 mice infected with plasmodium berghei anka (pba). a 7-day oral administration of artesunate prevented parasitaemia at 10 mg/kg/day. however, recrudescence of parasitaemia and cerebral malaria occurred upon cessation of treatment followed by death within 28 days. however, a 14-day course of artesunate (100 mg/kg/day) prevented completely the development of parasitaem ...200312543147
encapsulation of peptides in biodegradable microspheres prolongs their mhc class-i presentation by dendritic cells and macrophages in vitro.biodegradable microspheres (ms) consisting of poly(d,l-lactide-co-glycolide) (plga) represent a promising alternative to conventional adjuvants. the adjustable pulsatile release of encapsulated material from such ms offers the potential to mimic the priming and boosting injections of conventional immunization regimens. in this paper, we demonstrate that ms can serve as antigen reservoirs in antigen presenting cells (apc), so that antigen is presented for extended periods of time (up to 9 days). ...200312559806
ccr5 deficiency decreases susceptibility to experimental cerebral malaria.infection of susceptible mouse strains with plasmodium berghei anka (pba) is a valuable experimental model of cerebral malaria (cm). two major pathologic features of cm are the intravascular sequestration of infected erythrocytes and leukocytes inside brain microvessels. we have recently shown that only the cd8+ t-cell subset of these brain-sequestered leukocytes is critical for progression to cm. chemokine receptor-5 (ccr5) is an important regulator of leukocyte trafficking in the brain in resp ...200312560237
synthesis and in vitro and in vivo antimalarial activity of n1-(7-chloro-4-quinolyl)-1,4-bis(3-aminopropyl)piperazine derivatives.three series of monoquinolines consisting of a 1,4-bis(3-aminopropyl)piperazine linker and a large variety of terminal groups were synthesized. our aim was to prove that in related bisquinoline, it is the second quinoline moiety that is responsible for cytotoxicity and that it is not an absolute requirement for overcoming resistance to chloroquine (cq). eleven compounds displayed a higher selectivity index (ratio cc50/ic50 activity) than cq, and one of them cured mice infected by plasmodium berg ...200312570376
new semisynthetic quassinoids with in vivo antimalarial activity.on the basis of a comparative analysis for stability in mouse serum between 15-o-acetylbruceolide and bruceolide 15-methyl carbonate, several 3,15-dialkyl carbonates of bruceolide were synthesized and their in vitro antimalarial activity was assessed. methyl, ethyl, and isopropyl carbonates with pronounced in vitro activity were further evaluated for in vivo antimalarial potency. both the methyl and ethyl carbonates significantly increased the life span of mice as compared with 3,15-di-o-accetyl ...200312570385
cam kinase ii-alpha activity, levels and ca/calmodulin dependent phosphorylation of substrate proteins in mice brain during fatal murine cerebral malaria.the activity and levels of cam kinase ii-alpha was investigated in the cytosolic and membrane fraction of mice cerebral cortex and cerebellum using an experimental model of fatal murine cerebral malaria (fmcm). in parallel, ca(2+)/calmodulin dependent phosphorylation of target substrate proteins was studied using syntide-2 as substrate. pathology of fmcm resulted in decreased cam kinase-ii activity in both cortex and cerebellum though western analysis revealed no appreciable changes in the level ...200312499055
relationship of chloroquine-induced redistribution of a neutral aminopeptidase to hemoglobin accumulation in malaria parasites.to study the relationship between neutral aminopeptidase activity and hemoglobin accumulation in malaria parasites, we treated mice infected with plasmodium berghei nyu-2 with chloroquine intraperitoneally in doses ranging from 0.3 to 3 micromol per 25 g mouse. preparations of infected erythrocytes (normalized to represent 1000 parasites per 1000 erythrocytes) hydrolyzed 1200 nmol of leucine-p-nitroanilide per minute per milliliter of packed erythrocytes, which was 10x more than that of uninfect ...200312573290
perforin-dependent brain-infiltrating cytotoxic cd8+ t lymphocytes mediate experimental cerebral malaria pathogenesis.experimental cerebral malaria (ecm) resulting from plasmodium berghei anka infection involves t lymphocytes. however, the mechanisms of t cell-mediated pathogenesis remain unknown. we found that, in contrast to ecm-susceptible c57bl6 mice, perforin-deficient (pfp-ko) mice were resistant to ecm in the absence of brain lesions, whereas cytoadherence of parasitized erythrocytes and massive accumulation of activated/effector cd8 lymphocytes were observed in both groups of mice. ecm is induced in pfp ...200312574396
p-selectin contributes to severe experimental malaria but is not required for leukocyte adhesion to brain microvasculature.plasmodium berghei-infected mice, a well-recognized model of experimental cerebral malaria (ecm), exhibit many of the hallmarks of a systemic inflammatory response, with organ damage in brain, lung, and kidneys. identification of the molecules mediating pathogenesis of the inflammatory response, such as leukocyte adhesion, may lead to new therapies. indeed, mice lacking the cell adhesion molecule p-selectin were significantly (p = 0.005) protected from death due to p. berghei malaria compared wi ...200312654808
cytokine and chemokine responses in a cerebral malaria-susceptible or -resistant strain of mice to plasmodium berghei anka infection: early chemokine expression in the brain.a comparative study was carried out on cytokine and chemokine responses in a cerebral malaria (cm)-susceptible or -resistant strain of mice (c57bl/6 or balb/c respectively) in plasmodium berghei anka infection. c57bl/6 mice died by 10 days after infection when parasitemia was approximately 15-20% with cerebral symptoms, while balb/c mice survived until week 3 after infection. although both strains showed t(h)1-skewed responses on day 4 after infection, significantly higher levels of ifn-gamma, t ...200312697663
chloroquine-induced masking of a lipid that promotes ferriprotoporphyrin ix dimerization in malaria.mice infected with the nyu-2 strain of plasmodium berghei were used to study the effect of chloroquine on masking of a lipid that promotes ferriprotoporphyrin ix dimerization. more than 40% of this lipid was masked and unable to promote dimerization in membrane ghosts from erythrocytes of untreated, infected mice. thus, preparations of membrane ghosts dimerized 57 +/- 6 nmol of ferriprotoporphyrin ix during a 2-h incubation, whereas the lipids extracted from these preparations dimerized 101 +/- ...200312697766
transformation of sporozoites into early exoerythrocytic malaria parasites does not require host cells.malaria parasite species that infect mammals, including humans, must first take up residence in hepatic host cells as exoerythrocytic forms (eef) before initiating infection of red blood cells that leads to malaria disease. despite the importance of hepatic stages for immunity against malaria, little is known about their biology and antigenic composition. here, we show that sporozoites, the parasites' transmission stage that resides in the mosquito vector salivary glands, can transform into earl ...200312707302
[long circulating nanocapsules: interest in the treatment of severe malaria with halofantrine].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- ...200312714932
predominant cell-mediated immunity in the oral mucosa: gene gun-based vaccination against infectious diseases.direct immunization via epithelial surfaces has been considered for many vaccine approaches, including dna vaccines. it remains to be determined, however, which body site is suitable for genetic vaccination.200312727024
the histone h4 gene of plasmodium falciparum is developmentally transcribed in asexual parasites.histones are abundant nuclear core proteins that are present in all eukararyotes and are responsible for linking chromosomes and packaging them into tight chromatin aggregates. the histone h2a, h2b, and h3 genes and a partial sequence of the histone h4 gene from plasmodium falciparum have been previously identified and share a high level of nucleotide sequence identity. in this study, we compare the histone h4 sequence of the human malaria p. falciparum with the sequences of two mouse malarias, ...200312739134
efficacy comparison of intravenous artelinate and artesunate in plasmodium berghei-infected sprague-dawley rats.this paper reports the comparative antimalarial efficacy of intravenous artelinate and artesunate in rats. prior to efficacy experiments, a plasmodium berghei-sprague-dawley rat model of malaria was developed, in which the clearance effects of intravenous drugs could be readily compared. in efficacy experiments, groups of p. berghei-infected rats were given 3 daily intravenous treatments of artelinate or artesunate at molar equivalent dose rates (total of 0-191.2 micromoles/kg). artelinate was s ...200312741507
om-174, a new adjuvant with a potential for human use, induces a protective response when administered with the synthetic c-terminal fragment 242-310 from the circumsporozoite protein of plasmodium berghei.the goal of this project was the evaluation of a novel immunomodulatory adjuvant for human use, om-174, which is a soluble adjuvant derived from escherichia coli lipid a. for this study, we used a synthetic peptide, known for its safety and reproducibility and the murine model of balb/c mice. the long peptide (pbcs 242-310) used corresponds to the c-terminal region of the circumsporozoite protein (csp) that is the major protein on the surface of plasmodium sporozoites. subcutaneous injections of ...200312744882
chemokine receptor ccr2 is not essential for the development of experimental cerebral malaria.infection with plasmodium berghei anka induces cerebral malaria in susceptible mice. brain-sequestered cd8(+) t cells are responsible for this pathology. we have evaluated the role of ccr2, a chemokine receptor expressed on cd8(+) t cells. infected ccr2-deficient mice were as susceptible to cerebral malaria as wild-type mice were, and cd8(+) t-cell migration to the brain was not abolished.200312761155
intercellular adhesion molecule 1 is important for the development of severe experimental malaria but is not required for leukocyte adhesion in the brain.plasmodium berghei-infected mice, a well-recognized model of experimental cerebral malaria (ecm), exhibit a systemic inflammatory response. most investigators hypothesize that leukocytes bind to endothelial cells via intercellular adhesion molecule 1 (icam-1), which causes endothelial damage, increased microvascular permeability, and, ultimately, death. icam-1-deficient mice on an ecm-susceptible c57bl/6 background were significantly (p = .04) protected from p. berghei mortality compared with ic ...200312769195
a short synthesis and biological evaluation of potent and nontoxic antimalarial bridged bicyclic beta-sulfonyl-endoperoxides.the syntheses and in vitro antimalarial screening of 50 bridged, bicyclic endoperoxides of types 9-13 are reported. in contrast to antimalarial trioxanes of the artemisinin family, but like yingzhaosu a and arteflene, the peroxide function of compounds 9-13 is contained in a 2,3-dioxabicyclo[3.3.1]nonane system 6. peroxides 9 and 10 (r(1) = oh) are readily available through a multicomponent, sequential, free-radical reaction involving thiol-monoterpenes co-oxygenation (a toco reaction). beta-sul ...200312773055
validation of the hexose transporter of plasmodium falciparum as a novel drug target.chemotherapy of malaria parasites is limited by established drug resistance and lack of novel targets. intraerythrocytic stages of plasmodium falciparum are wholly dependent on host glucose for energy. glucose uptake is mediated by a parasite-encoded facilitative hexose transporter (pfht). we report that o-3 hexose derivatives inhibit uptake of glucose and fructose by pfht when expressed in xenopus oocytes. selectivity of these derivatives for pfht is confirmed by lack of inhibition of hexose tr ...200312792024
the chemotherapy of rodent malaria. lxi. drug combinations to impede the selection of drug resistance, part 4: the potential role of 8-aminoquinolines.the influence of combinations containing the blood schizontocides chloroquine (cq) or mefloquine (mef), together with the 8-aminoquinolines (8aq) primaquine (pq) or the new, long-acting compound, tafenoquine (taf), on the rate of selection of resistance to the individual compounds was examined using the asexual, intra-erythrocytic stages in rodent malaria models. the two main procedures used were a 'serial technique' (st) and the '2%- relapse technique' (2%rt). the st provided evidence for the c ...200312803854
plasmodium falciparum: new vector with bi-directional promoter activity to stably express transgenes. 200312810052
different responses of three rodent plasmodia species, plasmodium yoelii 17xl, p. berghei nk65 and p. chabaudi as on treatment with febrifugine and isofebrifugine mixture from hydrangea macrophylla var. otaksa leaf in icr mice.the antimalarial activity of hydrangea macrophylla var. otaksa alkaloids was evaluated against plasmodium yoelii 17xl, p. berghei nk65 and p. chabaudi as in icr mice. for trials in p. yoelii 17xl or p. chabaudi as infections, mice were infected intraperitoneally with 10(5), 10(6) and 10(7) parasitized erythrocytes, respectively, and in p. berghei nk65 infections, mice were infected intraperitoneally with 10(3), 10(4) and 10(5) parasitized erythrocytes, respectively. three days after injection, m ...200312820234
soap, a novel malaria ookinete protein involved in mosquito midgut invasion and oocyst development.an essential, but poorly understood part of malaria transmission by mosquitoes is the development of the ookinetes into the sporozoite-producing oocysts on the mosquito midgut wall. for successful oocyst formation newly formed ookinetes in the midgut lumen must enter, traverse, and exit the midgut epithelium to reach the midgut basal lamina, processes collectively known as midgut invasion. after invasion ookinete-to-oocyst transition must occur, a process believed to require ookinete interaction ...200312828632
antimalarial activity of cinchona-like plants used to treat fever and malaria in brazil.for centuries, malaria was treated with the bark of cinchona calisaya and cinchona succirubra plants named "quinas" in brazil, from which the quinine molecule was isolated. other plant species known also as "quinas" are used to treat fever and malaria, like deianira erubescens (roots and leaves), strychnos pseudoquina (bark), and remijia ferruginea (bark). based on this popular knowledge, we evaluated the in vivo antimalarial activity of the ethanol crude extracts of these plant species in mice ...200312860318
in vivo antimalarial activity of vernonia amygdalina.extracts from the leaves and root bark of vernonia amygdalina are assessed for antimalarial activity against drug-sensitive plasmodium berghei in mice. a standard inoculum of 1 x 10(7) infected erythrocytes is used, and leaf and root-bark extracts of 500 mg/kg, 250 mg/kg or 125 mg/kg are used in a four-day suppression test and a rane test of established infection. leaf extract produced 67% suppression of parasitaemia in the four-day test, while root-bark extract produced 53.5% suppression. these ...200312866916
transfected plasmodium knowlesi produces bioactive host gamma interferon: a new perspective for modulating immune responses to malaria parasites.transgenic pathogenic microorganisms expressing host cytokines such as gamma interferon (ifn-gamma) have been shown to manipulate host-pathogen interaction, leading to immunomodulation and enhanced protection. expression of host cytokines in malaria parasites offers the opportunity to investigate the potential of an immunomodulatory approach by generating immunopotentiated parasites. using the primate malaria parasite plasmodium knowlesi, we explored the conditions for expressing host cytokines ...200312874315
in vivo antimalarial activities of mono- and bis quaternary ammonium salts interfering with plasmodium phospholipid metabolism.we previously showed that quaternary ammonium salts have potent antimalarial activities against the blood stage of drug-resistant plasmodium falciparum. in the present study, 13 compounds of this series were comparatively assessed in murine in vivo malarial models. mice infected with plasmodium berghei were successfully treated with 11 quaternary ammonium salts in a 4-day suppressive test with a once-daily intraperitoneal administration. the dose required to decrease parasitemia by 50% (ed(50)) ...200312878525
protracted protection to plasmodium berghei malaria is linked to functionally and phenotypically heterogeneous liver memory cd8+ t cells.we previously demonstrated that protection induced by radiation-attenuated (gamma) plasmodium berghei sporozoites is linked to mhc class i-restricted cd8(+) t cells specific for exoerythrocytic-stage ags, and that activated intrahepatic memory cd8(+) t cells are associated with protracted protection. in this study, we further investigated intrahepatic memory cd8(+) t cells to elucidate mechanisms required for their maintenance. using phenotypic markers indicative of activation (cd44, cd45rb), mi ...200312902507
the dynamics of interactions between plasmodium and the mosquito: a study of the infectivity of plasmodium berghei and plasmodium gallinaceum, and their transmission by anopheles stephensi, anopheles gambiae and aedes aegypti.knowledge of parasite-mosquito interactions is essential to develop strategies that will reduce malaria transmission through the mosquito vector. in this study we investigated the development of two model malaria parasites, plasmodium berghei and plasmodium gallinaceum, in three mosquito species anopheles stephensi, anopheles gambiae and aedes aegypti. new methods to study gamete production in vivo in combination with gfp-expressing ookinetes were employed to measure the large losses incurred by ...200312906877
the lack of suppressor of cytokine signalling-1 (socs1) protects mice from the development of cerebral malaria caused by plasmodium berghei anka.cerebral malaria is a severe complication of infection with plasmodium berghei anka involving the th1 cytokines tnf-alpha and ifn-gamma. suppressor of cytokine signalling-1 (socs1) is an important component in the regulatory cascade controlling inflammatory responses and signalling through ifn-gamma. contrary to the expectation that socs1-deficient mice, in which ifn-gamma responses are uncontrolled and which are more sensitive to ifn-gamma, may show heightened susceptibility, mice lacking socs1 ...200312911518
pharmacological assessment of the role of nitric oxide in mice infected with lethal and nonlethal species of malaria.this pharmacological investigation sought to determine whether nitric oxide (no) had an antiparasitic effect and/or mediated pathology in mice infected with nonlethal p. chabaudi or lethal p. berghei. nitric oxide synthase (nos) inhibitors were evaluated for their ability to inhibit the rise in reactive nitrogen intermediates (rni) induced by bacterial lipopolysaccharide (lps) in mice. the more effective compound, aminoguanidine (ag) inhibited the rise in rni induced by p. chabaudi and increased ...200312911523
age-related susceptibility and resistance to plasmodium berghei in mice and rats. 200312932766
cd1d-restricted nkt cells contribute to malarial splenomegaly and enhance parasite-specific antibody responses.cd1d-restricted nkt cells are a novel t cell lineage with unusual features. they co-express some nk cell receptors and recognize glycolipid antigens through an invariant t cell receptor (tcr) in the context of cd1d molecules. upon activation through the tcr, nkt cells produce large amounts of ifn-gamma and il-4. it has been proposed that rapid cytokine output by activated nkt cells may induce bystander activation of other lymphoid lineages. the impact of cd1d-restricted nkt cell activation in th ...200312938235
potentiation of the antimalarial action of chloroquine in rodent malaria by drugs known to reduce cellular glutathione levels.ferriprotoporphyrin ix (fp) is released inside the food vacuole of the malaria parasite during the digestion of host cell hemoglobin. fp is detoxified by its biomineralization to hemozoin. this process is effectively inhibited by 4-aminoquinolines. as a result fp accumulates in the membrane fraction and associates with enzymes of infected cells in parallel with parasite killing. free fp is degraded by reduced glutathione (gsh). this degradation is inhibited by chloroquine (cq) and amodiaquine (a ...200312948862
shared, unique and redundant functions of three members of the class i myosins (myoa, myob and myof) in motility and chemotaxis in dictyostelium.most cell types express two distinct forms of myosin i, amoeboid and short, distinguished by differences in their tail domains. both types of myosin i have been implicated in the regulation of pseudopod formation in dictyostelium discoideum. we examined three members of the myosin i family, one amoeboid, myob, and two short, myoa and myob, for shared, unique and redundant functions in motility and chemotaxis. we used computer-assisted methods for reconstructing and motion analyzing cells, and ex ...200312953059
antimalarial effect of agmatine on plasmodium berghei k173 strain.to study the antimalarial effect of agmatine (agm) on chloroquine-susceptible plasmodium berghei k173 strain (s strain) and the p berghei k173 resistant strain (r strain).200312956942
new methods and software tools for high throughput cdr3 spectratyping. application to t lymphocyte repertoire modifications during experimental malaria.immune repertoires of t or b cells are very often studied by complementary determining region 3 (cdr3) spectratyping. however, data obtained with this method is usually subject to a biased eye analysis. we developed recently the iseapeaks software package to retrieve and handle peak data from automated sequencers, from which cdr3 spectratype data is obtained. we describe a general strategy for cdr3 spectratype analysis based on two new specific modules and multivariate statistics. the first modu ...200312957400
in vivo gene silencing in plasmodium berghei--a mouse malaria model.rna interference (rnai) has emerged as a specific and efficient tool to silence gene expression in a variety of organisms and cell lines. an important prospect for rnai technology is its possible application in the treatment of diseases using short interfering rnas (sirnas). however, the effect of sirnas in adult animals and their potential to treat or prevent diseases are yet to be fully investigated. the main goal of the present study is to find out whether it was possible to carry out rnai on ...200312963018
studies on the use of cassia singueana in malaria ethnopharmacy.cassia singueana (family: fabaceae) is used in northern nigeria for the treatment of acute malaria attack. we investigated the activities of the methanol extract of the root bark of this plant against rodent plasmodia infection, nociception, pyrexia and inflammation in mice and rats. the studies were carried out using acetic acid-induced writhing, hot plate algesia, rodent plasmodia (plasmodium berghei) in mice; formalin test, yeast-induced pyrexia and egg-albumin-induced inflammation in rats. t ...200312963153
a new rodent model to assess blood stage immunity to the plasmodium falciparum antigen merozoite surface protein 119 reveals a protective role for invasion inhibitory antibodies.antibodies capable of inhibiting the invasion of plasmodium merozoites into erythrocytes are present in individuals that are clinically immune to the malaria parasite. those targeting the 19-kd cooh-terminal domain of the major merozoite surface protein (msp)-119 are a major component of this inhibitory activity. however, it has been difficult to assess the overall relevance of such antibodies to antiparasite immunity. here we use an allelic replacement approach to generate a rodent malaria para ...200312963693
crystal structure of plasmodium berghei lactate dehydrogenase indicates the unique structural differences of these enzymes are shared across the plasmodium genus.as plasmodium rely extensively on homolactic fermentation for energy production, plasmodium falciparum lactate dehydrogenase (pfldh)--the key enzyme in this process--has previously been suggested as a novel target for antimalarials. this enzyme has distinctive kinetic and structural properties that distinguish it from its human homologues. in this study, we now describe the expression, kinetic characterisation and crystal structure determination of the ldh from plasmodium berghei. this enzyme is ...200312967707
a gene-family encoding small exported proteins is conserved across plasmodium genus.a gene-family, named sep, encoding small exported proteins conserved across plasmodium species has been identified. sep proteins (13-16 kda) contain a predicted signal peptide at the nh(2)-terminus, an internal hydrophobic region and a polymorphic, low-complexity region at the carboxy-terminus. one member of the plasmodium berghei family, pbsep1, encodes an integral membrane protein expressed along the entire erythrocytic cycle. immunolocalisation results indicated that pbsep1 is targeted to the ...200312615320
characterization of a unique aspartate-rich protein of the set/taf-family in the human malaria parasite, plasmodium falciparum, which inhibits protein phosphatase 2a.a search for physiological inhibitors of protein phosphatases led to the identification of a plasmodium falciparum (pf) cdna that had the potential to code for an aspartate-rich protein and hence named arp. the pfarp was virtually identical to its plasmodium berghei counterpart in gene structure and protein sequence. the pfarp coding sequence contained two introns, and the predicted protein contained 269 amino acid residues. its primary structure showed significant similarity to eukaryotic prote ...200312615323
a unique insertion in plasmodium berghei glucose-6-phosphate dehydrogenase-6-phosphogluconolactonase: evolutionary and functional studies.plasmodium berghei glucose-6-phosphate dehydrogenase-6-phosphogluconolactonase (g6pd-6pgl) is a bifunctional enzyme with significant sequence similarity in both the 6pgl and g6pd domains to the plasmodium falciparum enzyme. a recombinant form of the p. berghei enzyme was found to have both g6pd and 6pgl activities, and therefore catalyses the first two steps in the pentose phosphate pathway. genes encoding very similar proteins are also found in three other malarial parasites, plasmodium yoelii, ...200312615331
orally active, antimalarial, anticancer, artemisinin-derived trioxane dimers with high stability and efficacy.in only two steps and in 70% overall yield, naturally occurring trioxane artemisinin (1) was converted on a gram scale into c-10-carba trioxane dimer 3. this new, very stable dimer was then transformed easily in one additional step into four different dimers 4-7. alcohol and diol dimers 4 and 5 and ketone dimer 7 are 10 times more antimalarially potent in vitro than artemisinin (1), and alcohol and diol dimers 4 and 5 are strongly growth inhibitory but not cytotoxic toward several human cancer c ...200312620083
influence of cd4+cd25+ t cells on plasmodium berghei nk65 infection in balb/c mice.cd4(+) t cells co-expressing cd25 (cd4(+)cd25(+) t cells) have been identified as immunoregulatory suppressors modulating autoimmune response. beside that, autoimmune response was supposed to be associated with malaria infection. based on these data, we hypothesised that cd4(+)cd25(+) t cells may influence protective immunity to malaria parasites, while suppressing autoimmune response arising throughout the course of malarial infection. to test this possibility, we evaluated the kinetics of cd4( ...200312633655
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