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plasmodium berghei nk65: studies on the effect of treatment duration and inoculum size on recrudescence.recrudescence of plasmodium berghei nk65 infection was studied to examine factors affecting recrudescence. treatment with a high dose of chloroquine did not prevent recrudescence, but an extended duration of treatment suppressed the frequency of recrudescence. infection with a larger number of parasites also resulted in more frequent recrudescences. recrudescent parasites were as sensitive to chloroquine as those before treatment. splenectomized mice were administered carbon particles, infected, ...200515961077
dispiro-1,2,4-trioxane analogues of a prototype dispiro-1,2,4-trioxolane: mechanistic comparators for artemisinin in the context of reaction pathways with iron(ii).single electron reduction of the 1,2,4-trioxane heterocycle of artemisinin (1) forms primary and secondary carbon-centered radicals. the complex structure of 1 does not lend itself to a satisfactory dissection of the electronic and steric effects that influence the formation and subsequent reaction of these carbon-centered free radicals. to help demarcate these effects, we characterized the reactions of achiral dispiro-1,2,4-trioxolane 4 and dispiro-1,2,4-trioxanes 5-7 with ferrous bromide and 4 ...200515960511
antimalarial activities and toxicities of three plants used as traditional remedies for malaria in the democratic republic of congo: croton mubango , nauclea pobeguinii and pyrenacantha staudtii.the antimalarial activities of crude extracts and 17 fractions from the partition of 80%-methanolic extracts of three plants (the stem bark of croton mubango, the stem bark of nauclea pobeguinii and the leaves of pyrenacantha staudtii) used as antimalarial remedies in the democratic republic of congo were studied both in vitro (against plasmodium falciparum) and in mice infected with pl. berghei berghei. the toxic effects of dried aqueous extracts of the plants were also investigated, in uninfec ...200515949182
plasmodium berghei ookinetes bind to anopheles gambiae and drosophila melanogaster annexins.using a proteomic approach we identified polypeptides from anopheles gambiae and drosophila melanogaster protein extracts that selectively bind purified plasmodium berghei ookinetes in vitro; these were two and three distinct polypeptides, respectively, with an apparent molecular weight of about 36 kda. combining two-dimensional electrophoresis and maldi-tof (matrix-associated laser desorption ionization time of flight) mass spectrometry we determined that the polypeptides correspond to isomorph ...200515948958
supplementation of cxcl12 (cxcl12) induces homing of cd11c+ dendritic cells to the spleen and enhances control of plasmodium berghei malaria in balb/c mice.in malaria, parasitaemia is controlled in the spleen, a multicomponent organ that undergoes changes in its cellular constituents to control the parasite. during this process, dendritic cells (dcs) orchestrate the positioning of effector cells in a timely manner for optimal parasite clearance. we have recently demonstrated that cxcl12 [stromal cell-derived factor-1 (cxcl12)] supplementation partially restores the ability to control parasitaemia in plasmodium berghei-infected mice. in the present ...200515946257
proteome analysis of separated male and female gametocytes reveals novel sex-specific plasmodium biology.gametocytes, the precursor cells of malaria-parasite gametes, circulate in the blood and are responsible for transmission from host to mosquito vector. the individual proteomes of male and female gametocytes were analyzed using mass spectrometry, following separation by flow sorting of transgenic parasites expressing green fluorescent protein, in a sex-specific manner. promoter tagging in transgenic parasites confirmed the designation of stage and sex specificity of the proteins. the male proteo ...200515935755
revealing the molecular determinants of gender in malaria parasites.malaria parasites have a complex life cycle with asexual multiplication in a vertebrate host and obligate sexual reproduction in the mosquito; however, commitment to sexual development begins in the vertebrate with differentiation of female and male gametocytes. in this issue of cell, khan et al. (2005) used elegant approaches to purify male and female gametocytes and elucidated their respective proteome, providing the basis for understanding sexual development in this pathogen.200515935749
synthesis and evaluation of beta-carbolinium cations as new antimalarial agents based on pi-delocalized lipophilic cation (dlc) hypothesis.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 b ...200515930777
driving midgut-specific expression and secretion of a foreign protein in transgenic mosquitoes with agaper1 regulatory elements.the anopheles gambiae adult peritrophic matrix protein 1 (agaper1) regulatory elements were used to drive the expression of phospholipase a2 (pla2), a protein known to disrupt malaria parasite development in mosquitoes. these agaper1 regulatory elements were sufficient to promote the accumulation of pla2 in midgut epithelial cells before a blood meal and its release into the lumen upon blood ingestion. plasmodium berghei oocyst formation was reduced by approximately 80% (74-91% range) in transge ...200515926896
genetically modified plasmodium highlights the potential of whole parasite vaccine strategies.a genetically modified malaria sporozoite might breathe new life into the traditional approach to vaccine development, that of using whole organisms. mueller and colleagues recently knocked out a gene, uis3, from the rodent parasite, plasmodium berghei, and demonstrated that the sporozoite forms could not develop beyond the stage of the life cycle in the liver (thus not giving rise to clinical disease, which is associated with blood infection) but could induce protection against subsequent chall ...200515922944
cassane- and norcassane-type diterpenes from caesalpinia crista of indonesia and their antimalarial activity against the growth of plasmodium falciparum.the ch2cl2 extract of the seed kernels of caesalpinia crista, which exhibited promising antimalarial activity against plasmodium berghei-infected mice in vivo, was examined and resulted in the isolation of seven new furanocassane-type diterpenes [caesalpinins c-g (1-5) and norcaesalpinins d and e (6, 7)] together with norcaesalpinins a-c (8-10) and 11 known compounds (norcaesalpinins a-c, 2-acetoxy-3-deacetoxycaesaldekarin e, caesalmin b, caesaldekarin e, caesalpin f, 14(17)-dehydrocaesalpin f, ...200515921414
reduced cerebral blood flow and n-acetyl aspartate in a murine model of cerebral malaria.cerebral malaria is an important cause of morbidity and mortality in many parts of the world. it has been suggested that cerebral malaria is associated with reduced perfusion due to the blockage of blood vessels by parasitized erythrocytes; although, no quantitative validation of this has been done. we infected c57bl/6 mice with the anka strain of plasmodium berghei and on day 6 of infection we investigated alterations in brain function using arterial spin labeling mri and proton mrs. mr images ...200515918069
protein farnesyltransferase inhibitors exhibit potent antimalarial activity.new therapeutics to combat malaria are desperately needed. here we show that the enzyme protein farnesyltransferase (pft) from the malaria parasite plasmodium falciparum (p. falciparum) is an ideal drug target. pft inhibitors (pftis) are well tolerated in man, but are highly cytotoxic to p. falciparum. because of their anticancer properties, pftis comprise a highly developed class of compounds. pftis are ideal for the rapid development of antimalarials, allowing "piggy-backing" on previously gar ...200515916422
transcriptome analysis of anopheles stephensi-plasmodium berghei interactions.simultaneous microarray-based transcription analysis of 4987 anopheles stephensi midgut and plasmodium berghei infection stage specific cdnas was done at seven successive time points: 6, 20 and 40h, and 4, 8, 14 and 20 days after ingestion of malaria infected blood. the study reveals the molecular components of several anopheles processes relating to blood digestion, midgut expansion and response to plasmodium-infected blood such as digestive enzymes, transporters, cytoskeletal and structural co ...200515907562
intravital observation of plasmodium berghei sporozoite infection of the liver.plasmodium sporozoite invasion of liver cells has been an extremely elusive event to study. in the prevailing model, sporozoites enter the liver by passing through kupffer cells, but this model was based solely on incidental observations in fixed specimens and on biochemical and physiological data. to obtain direct information on the dynamics of sporozoite infection of the liver, we infected live mice with red or green fluorescent plasmodium berghei sporozoites and monitored their behavior using ...200515901208
fas has a role in cerebral malaria, but not in proliferation or exclusion of the murine parasite in mice.we examined the susceptibility of murine fas-deficient mutants to malaria infection in order to investigate the role of fas in an experimental murine model of cerebral malaria (cm). we infected mice of b6 and cba wild-type and mutant backgrounds with plasmodium berghei anka. the incidence of cm in the mutant mice (b6-lpr, cba-lprcg) was decreased by about 50% compared with wild-type control strains at 2 weeks after infection. we did not observe significant differences of parasitemia during a mur ...200515900502
ookinete-induced midgut peroxidases detonate the time bomb in anopheline mosquitoes.previous analysis of the temporal-spatial relationship between ookinete migration and the cellular localization of genes mediating midgut immune defense responses suggested that, in order to survive, parasites must complete invasion before toxic chemicals ("a bomb") are generated by the invaded cell. recent studies indicate that ookinete invasion induces tyrosine nitration as a two-step reaction, in which nos induction is followed by a localized increase in peroxidase activity. peroxidases utili ...200515894189
synthesis and evaluation of new antimalarial phenylurenyl chalcone derivatives.phenylurenyl chalcone derivatives have been synthesized and tested as inhibitors of in vitro development of a chloroquine-resistant strain of plasmodium falciparum, activity of the cysteine protease falcipain-2, in vitro globin hydrolysis, beta-hematin formation, and murine plasmodium berghei malaria. the most active antimalarial compound was 1-[3'-n-(n'-phenylurenyl)phenyl]-3(3,4,5-trimethoxyphenyl)-2-propen-1-one 49, with an ic(50) of 1.76 microm for inhibition of p. falciparum development. re ...200515887974
brain macrophage activation in murine cerebral malaria precedes accumulation of leukocytes and cd8+ t cell proliferation.although the activation of brain macrophages is associated with both human and mouse cerebral malaria (cm) the relative contributions of the heterogeneous populations of brain macrophages to the disease are unknown. in this work, we dissociate for the first time inflammatory monocytes from resident brain macrophages in mice developing cm when infected with plasmodium berghei. based on the differential expression of cd45 in brain macrophage cell populations and by using bone-marrow (bm) chimeras ...200515885309
synthesis and antimalarial activity of e-2-quinolinylbenzocycloalcanones.a series of e-2-quinolinylbenzocycloalcanones 5-21 were prepared and evaluated for their activity to inhibit beta-hematin formation and the hydrolysis of hemoglobin in vitro. positive compounds for both assays were also tested for their efficacy in rodent plasmodium berghei. compounds 6, 16, 19, and 20, were the most promising. inhibition of beta-hematin formation was minimal when a hydrogen or methoxy groups were present on the position 8 of the quinoline and position 4' of the indanone ring as ...200515878218
direct processing and presentation of antigen from malaria sporozoites by professional antigen-presenting cells in the induction of cd8 t-cell responses.irradiated malaria sporozoites induce better protection than viable untreated sporozoites. we observed early differences between irradiated and viable untreated sporozoites in priming responses in vivo to a protective cd8 t-cell epitope, pb9, of the circumsporozoite protein of plasmodium berghei. sporozoites were processed for mhc class i presentation by dendritic cells (dc) to prime pb9-specific ifn-gamma-producing cd8 t cells. dc pulsed with untreated and irradiated sporozoites were similarly ...200515877610
a mitogen-activated protein kinase regulates male gametogenesis and transmission of the malaria parasite plasmodium berghei.differentiation of malaria parasites into sexual forms (gametocytes) in the vertebrate host and their subsequent development into gametes in the mosquito vector are crucial steps in the completion of the parasite's life cycle and transmission of the disease. the molecular mechanisms that regulate the sexual cycle are poorly understood. although several signal transduction pathways have been implicated, a clear understanding of the pathways involved has yet to emerge. here, we show that a plasmod ...200515864297
[automatic analysis of micronuclei by flow cytometry using anti-cd71-fitc and pi staining].to explore flow cytometry (fcm) based method for automatic analysis of micronuclei (mn) in cells staining with anti-cd71-fitc and pi.200515862014
the in vitro and in vivo antimalarial activity of cardiospermum halicacabum l. and momordica foetida schumch. et thonn.two plants cardiospermum halicacabum l. and momordica foetida schumch. et thonn traditionally used to treat symptoms of malaria in parts of east and central africa were screened for in vitro and in vivo antimalarial activity. using the nitro tetrazolium blue-based parasite lactate dehydrogenase assay as used by [makler, m.t., ries, j.m., williams, j.a., bancroft, j.e., piper, r.c., gibbins, b.l., hinrichs, d.j., 1993. parasite lactate dehydrogenase as an assay for plasmodium falciparum drug sens ...200515848033
motility and infectivity of plasmodium berghei sporozoites expressing avian plasmodium gallinaceum circumsporozoite protein.avian and rodent malaria sporozoites selectively invade different vertebrate cell types, namely macrophages and hepatocytes, and develop in distantly related vector species. to investigate the role of the circumsporozoite (cs) protein in determining parasite survival in different vector species and vertebrate host cell types, we replaced the endogenous cs protein gene of the rodent malaria parasite plasmodium berghei with that of the avian parasite p. gallinaceum and control rodent parasite p. y ...200515839899
apoptotic plasmodium-infected hepatocytes provide antigens to liver dendritic cells.malaria starts with infection of the host liver by plasmodium sporozoites. inoculation with radiation-attenuated plasmodium sporozoites induces complete protection against malaria. protection is mediated by dendritic cells (dcs) and cd8(+) t cells, but the source of parasite antigens mediating this response remains unclear. here, we show that hepatocytes infected with irradiated plasmodium sporozoites undergo apoptosis shortly after infection. infection with irradiated sporozoites induces the re ...200515838783
arrest in the liver--a genetically defined malaria vaccine? 200515829544
thalidomide influences the function of macrophages and increases the survival of plasmodium berghei-infected cba mice.malaria remains a major cause of morbidity and mortality in vast areas of the world, mainly due to the severe forms of plasmodium falciparum infection. the exacerbated immune response, with increased production of tnf and reactive nitrogen and oxygen intermediates, plays a role in the complex pathogenesis of the disease. it is recognised that thalidomide decreases tnf production and may modulate several functions of the immune system. this work evaluated the influence of thalidomide on macrophag ...200515817259
convenient access both to highly antimalaria-active 10-arylaminoartemisinins, and to 10-alkyl ethers including artemether, arteether, and artelinate.an economical phase-transfer method is used to prepare 10-arylaminoartemisinins from dha and arylamines, and artemether, arteether, and artelinate from the corresponding alcohols. in vivo sc screens against plasmodium berghei and p. yoelii in mice reveal that the p-fluorophenylamino derivative 5 g is some 13 and 70 times, respectively, more active than artesunate; this reflects the very high sc activity of 10-alkylaminoartemisinins. however, through the po route, the compounds are less active th ...200515812783
synthesis of some cryptolepine analogues, assessment of their antimalarial and cytotoxic activities, and consideration of their antimalarial mode of action.a series of analogues of cryptolepine (1) have been synthesized and evaluated for their in vitro antiplasmodial and cytotoxic properties. the ic(50) values of several compounds (11a, 11k-m, 11o, 13) against plasmodium falciparum (strain k1) were <0.1 mum, 5-10-fold lower than that of 1 but their cytotoxicities were only 2-4 times greater than that of 1. compounds with a halogen in the quinoline ring and a halogen or a nitro group in the indole ring have enhanced antiplasmodial activity. in mice ...200515801861
the natural killer complex regulates severe malarial pathogenesis and influences acquired immune responses to plasmodium berghei anka.the natural killer complex (nkc) is a genetic region of highly linked genes encoding several receptors involved in the control of nk cell function. the nkc is highly polymorphic, and allelic variability of various nkc loci has been demonstrated in inbred mice. making use of balb.b6-cmv1r congenic mice, in which the nkc from disease-susceptible c57bl/6 mice has been introduced into the disease-resistant balb/c background, we show here that during murine malaria infection, the nkc regulates a rang ...200515784573
a strong cd8+ t cell response is elicited using the synthetic polypeptide from the c-terminus of the circumsporozoite protein of plasmodium berghei together with the adjuvant qs-21: quantitative and phenotypic comparison with the vaccine model of irradiated sporozoites.stable protective immunity can be achieved against malaria by the injection of radiation-attenuated sporozoites (gamma-spz) and is mediated by ifn-gamma producing cd8+ t cells targeting the pre-erythrocytic stages. an efficient malaria vaccine should mimic this immunity. we compared the immune response specific for the circumsporozoite protein (csp) of plasmodium berghei (p. berghei), an important target of this protective response, elicited in mice immunized with the long synthetic polypeptide ...200515780728
chemosensitizing action of cepharanthine against drug-resistant human malaria, plasmodium falciparum.we have established a system of in vitro and in vivo assays to prioritize plant extracts that can serve as a source of drug candidates for the treatment of malaria, an infectious disease that affects nearly 40% of the world's population. in the present study, we have investigated the biological potential of one such plant-derived drug lead, cepharanthine. in vitro growth inhibition studies indicated this compound possessed good antiplasmodial activity without mediating a cytotoxic response. base ...200515763374
hgf/met signalling protects plasmodium-infected host cells from apoptosis.plasmodium, the causative agent of malaria, migrates through several hepatocytes before initiating a malaria infection. we have previously shown that this process induces the secretion of hepatocyte growth factor (hgf) by traversed cells, which renders neighbour hepatocytes susceptible to infection. the signalling initiated by hgf through its receptor met has multifunctional effects on various cell types. our results reveal a major role for apoptosis protection of host cells by hgf/met signallin ...200515760460
genome update: base skews in 200+ bacterial chromosomes. 200515758208
midgut epithelial responses of different mosquito-plasmodium combinations: the actin cone zipper repair mechanism in aedes aegypti.in vivo responses of midgut epithelial cells to ookinete invasion of three different vector-parasite combinations, aedes aegypti-plasmodium gallinaceum, anopheles stephensi-plasmodium berghei, and a. stephensi-p. gallinaceum, were directly compared by using enzymatic markers and immunofluorescence stainings. our studies indicate that, in a. aegypti and a. stephensi ookinetes traverse the midgut via an intracellular route and inflict irreversible damage to the invaded cells. these two mosquito sp ...200515753303
comparative study on schizontocidal activity of recrystallized or crude daphnetin against malaria parasites.to compare the schizontocidal activity of recrystallized or crude daphnetin against malaria parasites in vivo.200415745243
do malaria ookinete surface proteins p25 and p28 mediate parasite entry into mosquito midgut epithelial cells?p25 and p28 are related ookinete surface proteins highly conserved throughout the plasmodium genus that are under consideration as candidates for inclusion in transmission-blocking vaccines. previous research using transgenic rodent malaria parasites lacking p25 and p28 has demonstrated that these proteins have multiple partially redundant functions during parasite infection of the mosquito vector, including an undefined role in ookinete traversal of the mosquito midgut epithelium, and it has be ...200515733320
antimalarial activities and therapeutic properties of febrifugine analogs.febrifugine is the active principal isolated 50 years ago from the chinese herb chang shan (dichroa febrifuga lour), which has been used as an antimalarial in chinese traditional medicine for more than 2,000 years. however, intensive study of the properties of febrifugine has been hindered for decades due to its side effects. we report new findings on the effects of febrifugine analogs compared with those of febrifugine extracted from the dry roots of d. febrifuga. the properties of the extracte ...200515728920
functional and biochemical modifications in skeletal muscles from malarial mice.although it is well established that patients suffering from malaria experience skeletal muscle problems (contracture, aches, fatigue, weakness), detailed studies have not been performed to investigate changes in the contractile function and biochemical properties of intact and skinned skeletal muscles of mammals infected with malaria. to this end, we investigated such features in the extensor digitorium longus (edl, fast-twitch, glyocolytic) and in the soleus (sol, slow-twitch, oxidative) muscl ...200515728139
design, synthesis and antimalarial activity of trifluoromethylartemisinin-mefloquine dual molecules. 200515723441
c3d binding to the circumsporozoite protein carboxy-terminus deviates immunity against malaria.the immunogenicity of recombinant protein or anti-viral dna vaccines can be significantly improved by the addition of tandem copies of the complement fragment c3d. we sought to determine if the efficacy of a circumsporozoite protein (csp)-based dna vaccine delivered to mouse skin by gene gun was improved by using this strategy. instead, we found that c3d suppressed the protective immunity against plasmodium berghei malaria infection and deviated immunity, most notably by suppressing the inductio ...200515710912
differences in the neurochemical characteristics of the cortex and striatum of mice with cerebral malaria.fatal murine cerebral malaria is an encephalitis and not simply a local manifestation in the brain of a systemic process. histopathologically, murine cerebral malaria has been characterized by monocyte adherence to the endothelium of the microvasculature, activation of microglial cells, swelling of endothelial cell nuclei, microvasculature damage, and breakdown of the blood-brain barrier with cerebral oedema. brain parenchymal cells have been proposed to be actively involved in the pathogenesis ...200515700754
plasmodium liver stage developmental arrest by depletion of a protein at the parasite-host interface.plasmodium parasites of mammals, including the species that cause malaria in humans, infect the liver first and develop there into clinically silent liver stages. liver stages grow and ultimately produce thousands of first-generation merozoites, which initiate the erythrocytic cycles causing malaria pathology. here, we present a plasmodium protein with a critical function for complete liver stage development. uis4 (up-regulated in infective sporozoites gene 4) is expressed exclusively in infecti ...200515699336
the anopheles gambiae gamma1 laminin directly binds the plasmodium berghei circumsporozoite- and trap-related protein (ctrp). 200515694493
imidazolidin-4-one derivatives of primaquine as novel transmission-blocking antimalarials.imidazolidin-4-one derivatives of primaquine were synthesized as potential double prodrugs of the parent drug. the title compounds inhibit the development of the sporogonic cycle of plasmodium berghei, affecting the appearance of oocysts in the midguts of the mosquitoes. the imidazolidin-4-ones are very stable, both in human plasma and in ph 7.4 buffer, indicating that they are active per se. thus, imidazolidin-4-ones derived from 8-aminoquinolines represent a new entry in antimalarial structure ...200515689174
parasitology. malaria vaccines: back to the future? 200515681372
in vivo antimalarial activity of essential oils from cymbopogon citratus and ocimum gratissimum on mice infected with plasmodium berghei.the essential oils obtained by hydrodistillation from fresh leaves of cymbopogon citratus and ocimum gratissimum growing in cameroon were analyzed by gc and gc/ms. the main constituents of the oil of ocimum gratissimum were gamma-terpinene (21.9 %), beta-phellandrene (21.1 %), limonene (11.4 %) and thymol (11.2 %), while the oil of cymbopogon citratus contained geranial (32.8 %), neral (29.0 %), myrcene (16.2 %) and beta-pinene (10.5 %). the effects of these oils on the growth of plasmodium berg ...200515678368
the chemotherapy of rodent malaria. lxii. drug combinations to impede the selection of drug resistance, part 5: rates of development of resistance to some inhibitors of folate metabolism and to artesunate.in recent years infection with chloroquine-resistant plasmodium falciparum has been combatted with two long-acting antimalarials, pyrimethamine and sulfadoxine, in the combination known as fansidar that exerts a strong, synergistic action on the asexual stages of the parasite. this second-line regimen, however, is failing increasingly because of the selection of resistant clones in endemic areas, and effective, safe, alternative drugs or drug combinations that are also affordable are urgently ne ...200415667710
invariant valpha14 chain nkt cells promote plasmodium berghei circumsporozoite protein-specific gamma interferon- and tumor necrosis factor alpha-producing cd8+ t cells in the liver after poxvirus vaccination of mice.understanding the protective mechanism in the liver induced by recombinant vaccines against the pre-erythrocytic stages of malaria is important for vaccine development. most studies in mice have focused on splenic and peripheral blood t cells and identified gamma interferon (ifn-gamma)-producing cd8+ t cells as correlates of protection, which can be induced by prime-boost vaccination with recombinant poxviruses. invariant natural killer t (valpha14inkt) cells can also protect against liver stage ...200515664925
[cerebral malaria, a key role for endothelial cells?].five to six hundred millions of people, throughout the world, suffer from malaria and more than one million die each year as a consequence, in about 20% of the cases, of cerebral malaria, an important complication of plasmodium falciparum infection (holding & snow, 2001). despite many studies, the physiopathology of these cerebral occurrences is not understood, especially concerning the intricacy and respective roles of the various mechanisms identified: sequestration of parasitized red cells in ...200415662934
a plasmodium sporozoite protein with a membrane attack complex domain is required for breaching the liver sinusoidal cell layer prior to hepatocyte infection.plasmodium sporozoites are injected into the mammalian host during mosquito blood feeding and carried by the blood stream to the liver, where they infect hepatocytes and develop into erythrocyte-invasive forms. to reach the hepatocytes, sporozoites must cross the liver sinusoidal cell layer, which separates the hepatocytes from the circulatory system. little is known about the molecular mechanisms by which sporozoites breach this cellular barrier. here we report that a protein with a membrane at ...200515659064
overexpression and altered nucleocytoplasmic distribution of anopheles ovalbumin-like srpn10 serpins in plasmodium-infected midgut cells.the design of effective, vector-based malaria transmission blocking strategies relies on a thorough understanding of the molecular and cellular interactions that occur during the parasite sporogonic cycle in the mosquito. during plasmodium berghei invasion, transcription from the srpn10 locus, encoding four serine protease inhibitors of the ovalbumin family, is strongly induced in the mosquito midgut. herein we demonstrate that intense induction as well as redistribution of srpn10 occurs specifi ...200515659062
medicine: knockout malaria vaccine? 200515650722
a comprehensive survey of the plasmodium life cycle by genomic, transcriptomic, and proteomic analyses.plasmodium berghei and plasmodium chabaudi are widely used model malaria species. comparison of their genomes, integrated with proteomic and microarray data, with the genomes of plasmodium falciparum and plasmodium yoelii revealed a conserved core of 4500 plasmodium genes in the central regions of the 14 chromosomes and highlighted genes evolving rapidly because of stage-specific selective pressures. four strategies for gene expression are apparent during the parasites' life cycle: (i) housekeep ...200515637271
abca1 gene deletion protects against cerebral malaria: potential pathogenic role of microparticles in neuropathology.the atp-binding cassette transporter a1 (abca1) modulates the transbilayer distribution of phosphatidylserine at the outer leaflet of the plasma membrane. this external exposure of phosphatidylserine is a hallmark of microparticle production and is impaired in abca1(-/-) mice. in this study, we report about the complete resistance to cerebral malaria of these mice. on analysis of histological and systemic parameters we evidenced an impairment of cellular responses to plasmodium berghei anka infe ...200515632021
gene expression in plasmodium berghei ookinetes and early oocysts in a co-culture system with mosquito cells.using an in vitro development system for plasmodium berghei sporogonic stages and microarray technology we examined parasite gene expression during ookinete invasion of aedes cells and the ensuing oocyst development. a number of genes were found to be differentially expressed. the most prominent class of up-regulated elements corresponded to products involved in protein synthesis and metabolism. furthermore, several previously studied genes with a known in vivo developmental profile matched publ ...200515610814
[additive therapeutic effect of a combination of artemether and daphnetin against plasmodium berghei in mice].to investigate the therapeutic effect of a combination of artemether and daphnetin against plasmodium berghei anka strain in mice.200415597713
[construction of the subtracted cdna libraries related to artemisinin-resistance of plasmodium berghei].to construct the subtracted cdna libraries related to artemisinin-resistance of plasmodium berghei using suppression subtractive hybridization pcr (ssh pcr).200415597707
a surface phospholipase is involved in the migration of plasmodium sporozoites through cells.plasmodium sporozoites, injected by mosquitoes into the skin of the host, traverse cells during their migration to hepatocytes where they continue their life cycle. the mechanisms used by the parasite to rupture the plasma membrane of the host cells are not known. here we report the presence of a phospholipase on the surface of plasmodium berghei sporozoites (p. berghei phospholipase; pb pl) and demonstrate that it is involved in the establishment of a malaria infection in vivo. pb pl is highly ...200415590623
curcumin for malaria therapy.malaria remains a major global health concern. new, inexpensive, and effective antimalarial agents are urgently needed. here we show that curcumin, a polyphenolic organic molecule derived from turmeric, inhibits chloroquine-resistant plasmodium falciparum growth in culture in a dose dependent manner with an ic(50) of approximately 5 microm. additionally, oral administration of curcumin to mice infected with malaria parasite (plasmodium berghei) reduces blood parasitemia by 80-90% and enhances th ...200515582601
the role of programmed cell death in plasmodium-mosquito interactions.many host-parasite interactions are regulated in part by the programmed cell death of host cells or the parasite. here we review evidence suggesting that programmed cell death occurs during the early stages of the development of the malaria parasite in its vector. zygotes and ookinetes of plasmodium berghei have been shown to die by programmed cell death (apoptosis) in the midgut lumen of the vector anopheles stephensi, or whilst developing in vitro. several morphological markers, indicative of ...200415582523
a proteomic analysis of malaria biology: integration of old literature and new technologies.the genomic revolution has brought a new vitality into research on plasmodium, its insect and vertebrate hosts. at the cellular level nowhere is the impact greater than in the analysis of protein expression and the 'assembly' of the supramolecular machines that together comprise the functional cell. the repetitive phases of invasion and replication that typify the malaria life cycle, together with the unique phase of sexual differentiation provide a powerful platform on which to investigate the ...200415582521
design, synthesis and evaluation of 5-substituted amino-2,4-diamino-8-chloropyrimido-[4,5-b]quinolines as novel antimalarials.novel 5-substituted amino-2,4-diamino-8-chloropyrimido-[4,5-b]quinolines were designed based on a pharmacophore developed for potent antimalarial activity using chem-x and moe softwares. the designed molecules were synthesized by following a novel route and were evaluated by rane's test for blood schizonticidal activity in mice infected by plasmodium berghei. based on the mean survival time (mst) data, of the nine compounds evaluated, three had curative potential when compared with chloroquine.200515582413
genetically modified plasmodium parasites as a protective experimental malaria vaccine.malaria is a mosquito-borne disease that is transmitted by inoculation of the plasmodium parasite sporozoite stage. sporozoites invade hepatocytes, transform into liver stages, and subsequent liver-stage development ultimately results in release of pathogenic merozoites. liver stages of the parasite are a prime target for malaria vaccines because they can be completely eliminated by sterilizing immune responses, thereby preventing malarial infection. using expression profiling, we previously ide ...200415580261
functional characterization of an lccl-lectin domain containing protein family in plasmodium berghei.using bioinformatic, proteomic, immunofluorescence, and genetic cross methods, we have functionally characterized a family of putative parasite ligands as potential mediators of cell-cell interactions. we name these proteins the limulus clotting factor c, coch-5b2, and lgl1 (lccl)-lectin adhesive-like protein (lap) family. we demonstrate that this family is conserved amongst plasmodium spp. it possesses a unique arrangement of adhesive protein domains normally associated with extracellular prote ...200415562607
in vitro and in vivo antimalarial activity of peptidomimetic protein farnesyltransferase inhibitors with improved membrane permeability.a series of protein farnesyltransferase inhibitor ester prodrugs of fti-2148 (17) were synthesized in order to evaluate the effects of ester structure modification on antimalarial activity and for further development of a farnesyltransferase inhibitor with in vivo activity. evaluation against p. falciparum in red blood cells showed that all the investigated esters exhibited significant antimalarial activity, with the benzyl ester 16 showing the best inhibition (ed50=150 nm). additionally, compou ...200415556768
identification and characterisation of rama homologues in rodent, simian and human malaria species. 200415555735
activity of benzothiazoles and chemical derivatives on plasmodium falciparum.malaria is a major health concern particularly in africa which has about 90% of the worldwide annual clinical cases. the increasing number of drug-resistant plasmodium falciparum justifies the search for new drugs in this field. antimalarial activity of 2-substituted 6-nitro- and 6-amino-benzothiazoles and their anthranilic acids has been tested. an in vitro study has been performed on w2 and 3d7 strains of p. falciparum and on clinical isolates from malaria-infected patients. toxicity has been ...200415552398
increased expression of indoleamine 2,3-dioxygenase in murine malaria infection is predominantly localised to the vascular endothelium.products of the kynurenine pathway of tryptophan metabolism have been implicated in the pathogenesis of murine and human cerebral malaria. indoleamine 2,3-dioxygenase is the first and rate-limiting enzyme in this pathway and we have developed an immunohistochemical method for its detection in tissues from normal and malaria-infected mice. mice were infected with plasmodium berghei anka, a murine model of cerebral malaria, or p. berghei k173, a non-cerebral malaria model. vascular endothelial cel ...200415542091
detection of a new cerebral malaria susceptibility locus, using cba mice.human cerebral malaria (cm) during acute plasmodium falciparum infection is a serious neurological complication that leads to coma and death. p. berghei anka infection of cba mice is a useful experimental model of cm. to identify host susceptibility loci, we performed chromosomal mapping in crossbred populations of both cm-susceptible cba and cm-resistant dba/2 mice. one significant region for a cm-susceptible locus in cba mice was mapped to h2 region on chromosome 17, tentatively designated cms ...200415536567
a malaria membrane skeletal protein is essential for normal morphogenesis, motility, and infectivity of sporozoites.membrane skeletons are structural elements that provide mechanical support to the plasma membrane and define cell shape. here, we identify and characterize a putative protein component of the membrane skeleton of the malaria parasite. the protein, named pbimc1a, is the structural orthologue of the toxoplasma gondii inner membrane complex protein 1 (tgimc1), a component of the membrane skeleton in tachyzoites. using targeted gene disruption in the rodent malaria species plasmodium berghei, we sho ...200415533999
essential role of membrane-attack protein in malarial transmission to mosquito host.after ingestion of infected blood by a mosquito, malarial parasites are fertilized in the mosquito midgut and develop into motile ookinetes. these ookinetes invade epithelial cells by rupturing the cell membrane and migrate through the cytoplasm toward the basal lamina, on which they develop to oocysts. here we report that a microneme protein with a membrane-attack complex and perforin (macpf)-related domain, which we name membrane-attack ookinete protein (maop), is produced in the ookinete stag ...200415520375
rifampicin antagonizes the effect of choloroquine on chloroquine-resistant plasmodium berghei in mice.chloroquine (cq)-resistant plasmodium falciparum appears to decrease cq accumulation in its food vacuole by enhancing its efflux via an active membrane pump, which has been reported to be a p-glycoprotein-like transporter. rifampicin (rif) is a p-glycoprotein inhibitor and also has some antimalarial activity. it is hoped that a combination of choloroquine-rifampicin (cq + rif) would be advantageous in the treatment of cq-resistant malaria. swiss albino mice were inoculated with cq-resistant p. b ...200415507775
anti-malarial activity of some xanthones isolated from the roots of andrographis paniculata.four xanthones were isolated from the roots of andrographis paniculata using a combination of column and thin-layer chromatographic methods. they were characterized as (i) 1,8-di-hydroxy-3,7-dimethoxy-xanthone, (ii) 4,8-dihydroxy-2,7-dimethoxy-xanthone, (iii) 1,2-dihydroxy-6,8-dimethoxy-xanthone and (iv) 3,7,8-trimethoxy-1-hydroxy xanthone by ir, ms and nmr spectroscopic methods. in vitro study revealed that compound 1,2-dihydroxy-6,8-dimethoxy-xanthone possessed substantial anti-plasmodial acti ...200415507344
plasmodium falciparum carbonic anhydrase is a possible target for malaria chemotherapy.plasmodiumfalciparum is responsible for the majority of life-threatening cases of human malaria. the global emergence of drug-resistant malarial parasites necessitates identification and characterization of novel drug targets. carbonic anhydrase (ca) is present at high levels in human red cells and in p. falciparum. existence of at least three isozymes of the alpha < class was demonstrated in p. falciparum and a rodent malarial parasite plasmodium berghei. the major isozyme ca1 was purified and ...200415499996
platelet depletion by anti-cd41 (alphaiib) mab injection early but not late in the course of disease protects against plasmodium berghei pathogenesis by altering the levels of pathogenic cytokines.accumulating evidence indicates that platelets play a critical role in the pathogenesis of experimental severe malaria (esm) elicited by infection with plasmodium berghei. mice injected on day 1 of p berghei infection (early) with either anti-cd41 or anti-cd61 monoclonal antibodies (mabs) exhibited significantly (p<.001) increased survival from esm compared with infection controls, indicating that platelets function early in the disease. in contrast, groups of mice treated on days 4, 5, and 6 (l ...200515494426
a protective merozoite protein of plasmodium falciparum shares an epitope with surface antigens of paramecium.a plasmodium falciparum cdna expression clone, lambdapf9, had been identified earlier as a protective epitope, using anti-lambdapf9 antibodies and combinatorial phagotopes. a segment of the pf9 gene showed homology with paramecium immobilization surface antigens such as 51b, 51a and 156g. a synthetic pf9-peptide was designed from this region, and specific antibodies were raised. each of these anti-pf9 antibodies and combinatorial reagents, as well as anti-paramecium 51b antibodies, recognized th ...200415491471
plasmodium berghei: efficacy and safety of combinations of chloroquine and promethazine in chloroquine resistant infections in gravid mice.efficacy and safety of combinations ofchloroquine (cq) and doses of promethazine (pr) against cq resistant plasmodium berghei infections in gravid mice was evaluated. parasites were cleared faster in mice treated with cq combined with doses of pr ranging from 20mg/kg to 50mg/kg (3.4 +/- 0.5 to 2.7 +/- 0.7) compared with cq alone (4.7 +/- 0.8) (p<0.5). parturition resulting in live pups in animals treated with cq and 20mg/ kg and 30mg/kg of pr (81%) was significantly higher than in animals treate ...200415490800
in vitro and in vivo antimalarial studies of striga hermonthica and tapinanthus sessilifolius extracts.the antimalarial activities of the methanol extracts of striga hermonthica (whole plant) and tapinanthus sessilifolius (leaves), commonly used in northern nigeria for the treatment of malaria, were evaluated. in the in vitro antiplasmodial analysis, the extracts of t. sessilifolius and s. hermonthica utilized in the study, displayed mild to weak activities with ic50 values of 200.5 and 274.8 microg/ml respectively. this was investigated, using the multidrug resistant plasmodium falciparum, k1 st ...200415490799
plasmodium berghei: dehydroepiandrosterone sulfate reverses chloroquino-resistance in experimental malaria infection; correlation with glucose 6-phosphate dehydrogenase and glutathione synthesis pathway.in plasmodium falciparum-infected cells or in p. berghei infected mice, increase of reduced glutathione (gsh) levels confers resistance to chloroquine (cq). gsh is synthesized within the cells through a complex biochemical pathway composed of several well known enzymes, in which glucose-6-phosphate dehydrogenase (g6pd) plays an important role. the physiological hormone dehydroepiandrosterone sulfate (dheas) is a potent inhibitor of g6pd activity, and g6pd deficiency is known to exert antimalaria ...200415476661
antimalarial activity of bidens pilosa l. (asteraceae) ethanol extracts from wild plants collected in various localities or plants cultivated in humus soil.bidens pilosa (asteraceae), a medicinal plant used worldwide, has antimalarial activity as shown in previous work. this study tested ethanol extracts from wild plants collected in three different regions of brazil and from plants cultivated in various soil conditions. the extracts were active in mice infected with p. berghei: doses of < or =500 mg/kg administered by oral route reduced malaria parasitaemia and mouse mortality; higher doses were found to be less effective. tested in vitro against ...200415476304
proteome analysis of rhoptry-enriched fractions isolated from plasmodium merozoites.the rhoptries of plasmodium species participate in merozoite invasion and modification of the host erythrocyte. however, only a few rhoptry proteins have been identified using conventional gene identification protocols. to investigate the protein organization of this organelle and to identify new rhoptry proteins, merozoite rhoptries from three different plasmodium rodent species were enriched by sucrose density gradient fractionation, and subjected to proteome analysis using multidimensional pr ...200415473688
conditional mutagenesis using site-specific recombination in plasmodium berghei.reverse genetics in plasmodium, the genus of parasites that cause malaria, still faces major limitations. only red blood cell stages of this haploid parasite can be transfected. consequently, the function of many essential genes in these and subsequent stages, including those encoding vaccine candidates, cannot be addressed genetically. here, we establish conditional mutagenesis in plasmodium by using site-specific recombination and the flp/frt system of yeast. site-specific recombination is ind ...200415465918
inducible peroxidases mediate nitration of anopheles midgut cells undergoing apoptosis in response to plasmodium invasion.plasmodium berghei invasion of anopheles stephensi midgut cells causes severe damage, induces expression of nitric-oxide synthase, and leads to apoptosis. the present study indicates that invasion results in tyrosine nitration, catalyzed as a two-step reaction in which nitric-oxide synthase induction is followed by increased peroxidase activity. ookinete invasion induced localized expression of peroxidase enzymes, which catalyzed protein nitration in vitro in the presence of nitrite and h(2)o(2) ...200415456781
[effect of splenectomy on the evolution and relapse of plasmodium berghei vincke and lips infection in the white rat]. 195015435003
[tissular phase of plasmodium berghei]. 195015413859
response of plasmodium berghei to antimalarial drugs. 194915398092
merozoite surface protein 4/5 provides protection against lethal challenge with a heterologous malaria parasite strain.immunization with merozoite surface protein 4/5 (msp4/5), the murine malaria homologue of plasmodium falciparum msp4 and msp5, has been shown to protect mice against challenge by parasites expressing the homologous form of the protein. the gene encoding msp4/5 was sequenced from a number of plasmodium yoelii isolates in order to assess the level of polymorphism in the protein. the gene was found to be highly conserved among the 13 p. yoelii isolates sequenced, even though many of the same isolat ...200415385485
a profound alteration of blood tcrb repertoire allows prediction of cerebral malaria.cerebral malaria (cm) is one of the severe complications of plasmodium infection. in murine models of cm, talphabeta cells have been implicated in the neuropathogenesis. to obtain insights into the tcrb repertoire during cm, we used high throughput cdr3 spectratyping and set up new methods and software tools to analyze data. we compared pbl and spleen repertoires of mice infected with plasmodium berghei anka that developed cm (cm(+)) or not (cm(-)) to evidence modifications of the tcrb repertoir ...200415383590
effector and memory cd8+ t cells as seen in immunity to malaria.transgenic (tg) mice carrying a t-cell receptor (tcr) specific for a cd8(+) t-cell epitope expressed in pre-erythrocytic stages of plasmodium yoelii has proven to be a valuable tool to advance our understanding of this anti-parasite t-cell response, as it occurs in vivo. the visualization of cd8(+) t cells in vivo and ex vivo greatly facilitated research aimed at characterizing basic features of this t-cell response such as the kinetics of differentiation and proliferation and the in vivo antige ...200415361248
plasmodium berghei ookinetes induce nitric oxide production in anopheles pseudopunctipennis midguts cultured in vitro.the anopheles pseudopunctipennis nitric oxide synthase gene (apnos) was identified and its partial sequence showed high homology with nos from a. stephensi, a. gambiae (putative sequence), and drosophila melanogaster. apnos was mainly expressed in male and female adult mosquitoes and was induced by a blood meal. nitric oxide (no) was produced by in vitro-cultured mosquito midguts inoculated by enema with plasmodium berghei ookinetes, saccharomyces cerevisiae, gram-positive bacteria (micrococcus ...200415350609
quantitative plasmodium sporozoite neutralization assay (tsna).the circumsporozoite (cs) protein is the major surface protein of plasmodium sporozoites. antibodies to the immunodominant repeat domain of cs immobilize sporozoites and prevent infection of hepatocytes. plasmodium falciparum vaccines containing cs repeats are undergoing human trials in endemic areas, and proof of efficacy has been obtained. the correlates of protection are under investigation. levels of anti-repeat antibodies in the serum of the human volunteers have been measured mostly by enz ...200415350520
disruption of plasmodium berghei merozoite surface protein 7 gene modulates parasite growth in vivo.merozoite invasion of red blood cells is crucial to the development of the parasite that causes malaria. merozoite surface proteins (msps) mediate the first interaction between parasite and erythrocyte. in plasmodium falciparum, they include a complex of products from at least 3 genes (msp1, msp6, and msp7), one of which, msp7, is part of a gene family containing 3 and 6 adjacent members in plasmodium yoelii and plasmodium falciparum, respectively. we have identified and disrupted msp7 in the pl ...200515339842
identification of an antimalarial synthetic trioxolane drug development candidate.the discovery of artemisinin more than 30 years ago provided a completely new antimalarial structural prototype; that is, a molecule with a pharmacophoric peroxide bond in a unique 1,2,4-trioxane heterocycle. available evidence suggests that artemisinin and related peroxidic antimalarial drugs exert their parasiticidal activity subsequent to reductive activation by haem, released as a result of haemoglobin digestion by the malaria-causing parasite. this irreversible redox reaction produces carbo ...200415318224
intravital microscopy demonstrating antibody-mediated immobilisation of plasmodium berghei sporozoites injected into skin by mosquitoes.previous studies have shown that mosquitoes inject plasmodium sporozoites into avascular portions of the skin of their rodent host rather than directly into the blood circulation. then, over time, these sporozoites move into the circulation, from where they reach the liver to initiate a malaria infection. by use of intravital microscopy of the skin, we present direct morphological evidence of mosquito probing that introduces sporozoites into avascular tissue, of the migration of these sporozoite ...200415313126
[preparation and identification of monoclonal antibodies against the region ii+ motif in circumsporozoite protein of plasmodium falciparum].to develop and identify the monoclonal antibodies (mcabs) against region ii+ motif in circumsporozoite protein of plasmodium falciparum.200415281447
mulinane-type diterpenoids from azorella compacta display antiplasmodial activity.two mulinane-type diterpenoids were isolated from azorella compacta; namely 20-hydroxymulin-11,13-dienyl acetate and 13,14-dihydroxymulin-11-en-20-oic acid. the structures were elucidated by analysis of their spectroscopic data. these compounds, as well as three previously isolated diterpenes, were evaluated as potential in vivo growth inhibitors of plasmodium berghei nk 65 on infected mice at an intraperitoneal dose of 10 mg/kg/day. sixty percent and forty-two percent growth inhibition were obt ...200415280000
a plasmodium berghei reference line that constitutively expresses gfp at a high level throughout the complete life cycle.green fluorescent protein (gfp) is a well-established reporter protein for the examination of biological processes. this report describes a recombinant plasmodium berghei, pbgfpcon, that constitutively expresses gfp in a growth responsive manner in its cytoplasm from a transgene that is integrated into the genome and controlled by the strong promoter from a p. berghei elongation factor-1alpha gene. all life cycle forms of pbgfpcon except for male gametes can be easily visualized by fluorescent m ...200415279948
duffy antigen is important for the lethal effect of the lethal strain of plasmodium yoelii 17xl.we studied the potential role of the duffy antigen and glycophorin a as receptors for rodent malaria parasite invasion of erythrocytes. parasitemia increased exponentially after infection with plasmodium berghei nk65, p. chabaudi, and p. vinckei in duffy antigen knockout, glycophorin a knockout, and wild-type mice, indicating that the duffy antigen and glycophorin a are not essential for these malaria parasites. however, parasitemia of the duffy antigen knockout mice infected with p. yoelii 17xl ...200415278442
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