Publications

TitleAbstractYear
Filter
PMID
Filter
antiplasmodial and antitrypanosomal activity of bicyclic amides and esters of dialkylamino acids.several bicyclic amides and esters of dialkylamino acids were prepared. their activities against a multiresistant strain of plasmodium falciparum and against trypanosoma brucei rhodesiense (stib 900) were examined. structure-activity relationships were discussed. particularly the ester compounds showed good antiplasmodial and antitrypanosomal activity and a single compound was tested in vivo against plasmodium berghei.200919395265
disruption of nod-like receptors alters inflammatory response to infection but does not confer protection in experimental cerebral malaria.research relating to host inflammatory processes during malaria infection has focused on toll-like receptors, membrane-bound receptors implicated in innate sensing, and phagocytosis of parasitized erythrocytes by host cells. this is the first study to examine the role of nod proteins, members of the nod-like receptor (nlr) family of cytoplasmic proteins involved in pathogen recognition, in a murine model of cerebral malaria (plasmodium berghei anka, pba). here, we find that nod1nod2(-/-) mice in ...200919407112
[role of histamine and histamine receptors in the pathogenesis of malaria].a hallmark of the host response to plasmodium parasite is an inflammatory reaction characterized by elevated histaminemia levels. since histamine, which acts through four different receptors and which synthesis is under the control of the histidine decarboxylase (hdc), is endowed with pro-inflammatory and immunosuppressive activities, we hypothesized that this vaso-active amine may participe to malaria pathogenesis. combining genetic and pharmacologic approaches by using h1r(-/-), h2r(-/-), h3r( ...200919409190
rate of red blood cell destruction varies in different strains of mice infected with plasmodium berghei-anka after chronic exposure.severe malaria anaemia in the semi-immune individuals in the holo-endemic area has been observed to occur at low parasite density with individual variation in the responses. thus the following has been thought to be involved: auto-immune-mediated mechanisms of uninfected red blood cell destruction, and host genetic factors to explain the differences in individual responses under the same malaria transmission. in this study, the extent of red blood cell (rbc) destruction in different strains of s ...200919416511
localisation and timing of expression of putative plasmodium berghei rhoptry proteins in merozoites and sporozoites.invasive forms of apicomplexan parasites contain secretory organelles (which may include micronemes, rhoptries or dense granules), the contents of which mediate invasion of host cells. only few rhoptry proteins have been identified in plasmodium and then only in merozoites and none in the sporozoite or ookinete. epitope-tagged proteins (with either green fluorescent protein or c-myc) were used to analyse the expression and cellular localisation of a known plasmodium rhoptry protein (rap2/3) and ...200919428669
lisp1 is important for the egress of plasmodium berghei parasites from liver cells.most apicomplexa are obligatory intracellular parasites that multiply inside a so-called parasitophorous vacuole (pv) formed upon parasite entry into the host cell. plasmodium, the agent of malaria and the apicomplexa most deadly to humans, multiplies in both hepatocytes and erythrocytes in the mammalian host. although much has been learned on how apicomplexa parasites invade host cells inside a pv, little is known of how they rupture the pv membrane and egress host cells. here, we characterize ...200919438514
egress of plasmodium berghei gametes from their host erythrocyte is mediated by the mdv-1/peg3 protein.malaria parasites invade erythrocytes of their host both for asexual multiplication and for differentiation to male and female gametocytes - the precursor cells of plasmodium gametes. for further development the parasite is dependent on efficient release of the asexual daughter cells and of the gametes from the host erythrocyte. how malarial parasites exit their host cells remains largely unknown. we here report the characterization of a plasmodium berghei protein that is involved in egress of b ...200919438517
azathioprine favourably influences the course of malaria.azathioprine triggers suicidal erythrocyte death or eryptosis, characterized by cell shrinkage and exposure of phosphatidylserine at the erythrocyte surface. eryptosis may accelerate the clearance of plasmodium-infected erythrocytes. the present study thus explored whether azathioprine influences eryptosis of plasmodium-infected erythrocytes, development of parasitaemia and thus the course of malaria.200919442289
the high throughput sequence annotation service (ht-sas) - the shortcut from sequence to true medline words.advances in high-throughput technologies available to modern biology have created an increasing flood of experimentally determined facts. ordering, managing and describing these raw results is the first step which allows facts to become knowledge. currently there are limited ways to automatically annotate such data, especially utilizing information deposited in published literature.200919445703
hundreds of microsatellites for genotyping plasmodium yoelii parasites.genetic crosses have been employed to study various traits of rodent malaria parasites and to locate loci that contribute to drug resistance, immune protection, and disease virulence. compared with human malaria parasites, genetic crossing of rodent malaria parasites is more easily performed; however, genotyping methods using microsatellites (mss) or large-scale single nucleotide polymorphisms (snps) that have been widely used in typing plasmodium falciparum are not available for rodent malaria ...200919450732
automated classification of plasmodium sporozoite movement patterns reveals a shift towards productive motility during salivary gland infection.the invasive stages of malaria and other apicomplexan parasites use a unique motility machinery based on actin, myosin and a number of parasite-specific proteins to invade host cells and tissues. the crucial importance of this motility machinery at several stages of the life cycle of these parasites makes the individual components potential drug targets. the different stages of the malaria parasite exhibit strikingly diverse movement patterns, likely reflecting the varied needs to achieve succes ...200919455538
recrudescent plasmodium berghei from pregnant mice displays enhanced binding to the placenta and induces protection in multigravida.pregnancy-associated malaria (pam) is associated with placenta pathology and poor pregnancy outcome but the mechanisms that control the malaria parasite expansion in pregnancy are still poorly understood and not amenable for study in human subjects. here, we used a set of new tools to re-visit an experimental mouse model of pregnancy-induced malaria recrudescence, balb/c with chronic plasmodium berghei infection. during pregnancy 60% of the pre-exposed primiparous females showed pregnancy-induce ...200919461965
an essential role for the plasmodium nek-2 nima-related protein kinase in the sexual development of malaria parasites.the molecular control of cell division and development in malaria parasites is far from understood. we previously showed that a plasmodium gametocyte-specific nima-related protein kinase, nek-4, is required for completion of meiosis in the ookinete, the motile form that develops from the zygote in the mosquito vector. here, we show that another nima-related kinase, pfnek-2, is also predominantly expressed in gametocytes, and that pfnek-2 is an active enzyme displaying an in vitro substrate prefe ...200919491095
going live: a comparative analysis of the suitability of the rfp derivatives redstar, mcherry and tdtomato for intravital and in vitro live imaging of plasmodium parasites.fluorescent proteins have proven to be important tools for in vitro live imaging of parasites and for imaging of parasites within the living host by intravital microscopy. we observed that a red fluorescent transgenic malaria parasite of rodents, plasmodium berghei-redstar, is suitable for in vitro live imaging experiments but bleaches rapidly upon illumination in intravital imaging experiments using mice. we have therefore generated two additional transgenic parasite lines expressing the novel ...200919492329
plasmodium berghei-infection induces volume-regulated anion channel-like activity in human hepatoma cells.parasite infection can lead to alterations in the permeability of host plasma membranes. presented here is the first demonstration that this phenomenon occurs in plasmodium-infected liver cells. using the whole-cell patch-clamp technique, volume-regulated anion channel (vrac) activity was characterized in huh-7 cells (a human hepatoma cell line) before and after infection with plasmodium berghei. consistent with the presence of vracs, hypotonic bath solution induced large ion currents in huh-7 c ...200919496788
genome-wide transcriptomic profiling of anopheles gambiae hemocytes reveals pathogen-specific signatures upon bacterial challenge and plasmodium berghei infection.the mosquito anopheles gambiae is a major vector of human malaria. increasing evidence indicates that blood cells (hemocytes) comprise an essential arm of the mosquito innate immune response against both bacteria and malaria parasites. to further characterize the role of hemocytes in mosquito immunity, we undertook the first genome-wide transcriptomic analyses of adult female an. gambiae hemocytes following infection by two species of bacteria and a malaria parasite.200919500340
malaria downmodulates mrna expression and catalytic activities of cyp1a2, 2e1 and 3a11 in mouse liver.it has been reported that malaria reduces cytochrome-p450 (cyp) content and monooxygenase activities in the mammalian host liver. the mechanism by which malaria modulates cyp activities, however, remains unclear. in this study we found that activities of ethoxy- and benzyloxy-resorufin-o-dealkylases, p-nitrophenol-hydroxylase and erythromycin-n-demethylase (mediated by cyp1a, 2b, 2e1 and 3a, respectively) were depressed, while uridine-glucuronosyl-transferase (a phase 2 enzyme) was unaltered in ...200919501084
novel antimicrobial peptides isolated from skin secretions of the mexican frog hyla eximia.in this work, we describe the original characterization of peptides and proteins present in the skin secretions of the mexican amphibian hyla eximia. to this purpose, a novel water/dark extraction method, as well as the classic electrical stimulation procedure, was applied in order to extract the skin secretion. two novel antimicrobial peptides he-1 and he-2 were sequenced. in addition, a molecular mass fingerprint revealed more than one hundred different molecules. eight peptides in homogeneous ...200919508207
synthesis and antimalarial activities of optically active labdane-type diterpenes.an efficient method for the synthesis of optically active labdane-type diterpenes from (+)-manool 8 is described. we prepared the natural labdane-type diterpene 5 via key intermediate peroxide 9, and synthetic hydroxybutenolides 6 and 7 via a furan photosensitised oxygenation reaction of labdafuran (14). compounds 5, 6, 7 and 9 were evaluated as inhibitors of the beta-haematin formation and globin proteolysis, and then were assayed in a malarial murine model. compound 9 was the most promising co ...200919521902
methotrexate and aminopterin lack in vivo antimalarial activity against murine malaria species.the antifolate anticancer drug methotrexate (mtx) has potent activity against plasmodium falciparum in vitro. experience of its use in the treatment of rheumatoid arthritis indicates that it could be safe and efficacious for treating malaria. we sought to establish a murine malaria model to study the mechanism of action and resistance of mtx and its analogue aminopterin (amp). we used plasmodium berghei, plasmodium yoelii yoelii, plasmodium chabaudi and plasmodium vinckei. none of these species ...200919527714
host cell transcriptional profiling during malaria liver stage infection reveals a coordinated and sequential set of biological events.plasmodium sporozoites migrate to the liver where they traverse several hepatocytes before invading the one inside which they will develop and multiply into thousands of merozoites. although this constitutes an essential step of malaria infection, the requirements of plasmodium parasites in liver cells and how they use the host cell for their own survival and development are poorly understood.200919534804
in-depth validation of acridine orange staining for flow cytometric parasite and reticulocyte enumeration in an experimental model using plasmodium berghei.flow cytometry is potentially an effective method for counting malaria parasites, but inconsistent results have hampered its routine use in rodent models. a published two-channel method using acridine orange offers clear discrimination between the infected and uninfected erythrocytes. however, preliminary studies showed concerns when dealing with plasmodium berghei-infected blood samples with high numbers of reticulocytes. in hyperparasitemic or chronic p. berghei infection, enhanced erythropoie ...200919545567
histamine h(3) receptor-mediated signaling protects mice from cerebral malaria.histamine is a biogenic amine that has been shown to contribute to several pathological conditions, such as allergic conditions, experimental encephalomyelitis, and malaria. in humans, as well as in murine models of malaria, increased plasma levels of histamine are associated with severity of infection. we reported recently that histamine plays a critical role in the pathogenesis of experimental cerebral malaria (cm) in mice infected with plasmodium berghei anka. histamine exerts its biological ...200919547708
gamma-glutamylcysteine synthetase from plasmodium berghei.gamma-glutamylcysteine synthetase (l-glutamate-l-cysteine ligase, gamma-gcs, ec 6.3.2.2.), the rate limiting enzyme in glutathione biosynthetic pathway has been analysed in the asexual erythrocytic stages of rodent malaria parasite, plasmodium berghei and its host erythrocytes. cell-free parasite isolated by saponin lysis contained about 2 and 8 times higher activity of gamma-gcs compared to p. berghei-infected and normal mice erythrocytes respectively. subcellular fractionation revealed that th ...200919567234
molecular adjuvants for malaria dna vaccines based on the modulation of host-cell apoptosis.malaria represents a major global health problem but despite extensive efforts, no effective vaccine is available. various vaccine candidates have been developed that provide protection in animal models, such as a gene gun-delivered dna vaccine encoding the circumsporozoite protein (csp) of plasmodium berghei. a common shortcoming of most malaria vaccines is the requirement for multiple immunizations leaving room for improvement even for established vaccine candidates such as the csp-dna vaccine ...200919576940
antiplasmodial activity of punica granatum l. fruit rind.sun-dried rind of the immature fruit of punica granatum l. (punicaceae) (pg) is presently used as a herbal formulation (omaria) in orissa, india, for the therapy and prophylaxis of malaria. the aims of this study were (i) to assess in vitro the antiplasmodial activity of the methanolic extract, of a tannin enriched fraction and of compounds/metabolites of the antimalarial plant, (ii) to estimate the curative efficacy of the pg extracts and (iii) to explore the mechanism of action of the antiplas ...200919577622
ethanolic extract of clerodendrum violaceum gürke leaves enhances kidney function in mouse model of malaria.evaluation of the effects of daily oral administration of ethanolic extract of c. violaceum leaves (13 mg/kg body weight) for 5 days on some kidney function indices of uninfected and plasmodium berghei-infected mice was done on days 3, 8 and 14 post-infection. the indices studied include serum urea and creatinine concentrations with the specific activities of alkaline phosphatase, aspartate aminotransferase and alanine aminotransferase in the kidney. treatment of p. berghei-infected mice with et ...200919579800
anti-malarial activity of 6-(8'z-pentadecenyl)-salicylic acid from viola websteri in mice.petroleum ether extracts of viola websteri hemsl (violaceae) were reported to have anti-plasmodial activity against plasmodium falciparum in vitro, with this activity being largely attributable to 6-(8'z-pentadecenyl)-salicylic acid (6-sa).200919583856
the interaction between dc and plasmodium berghei/chabaudi-infected erythrocytes in mice involves direct cell-to-cell contact, internalization and tlr.early interactions between blood-stage plasmodium parasites and cells of the innate immune system are very important in shaping the adaptive immune response to malaria, and a number of studies have suggested that dc are responsible for this phenomenon. therefore, we examined the capacity of murine bm-derived dc to internalize parasites, be activated and produce cytokines upon in vitro interaction with murine erythrocytes infected with two different strains of rodent malaria parasites (plasmodium ...200919585512
plasmodium berghei hap2 induces strong malaria transmission-blocking immunity in vivo and in vitro.fertilization in plasmodium is a complex process that occurs in the gut of the female anopheles mosquito upon uptake of a bloodmeal. it requires the emergence of the gametocyte from the rbc and release of eight flagellate male gametes from each male cell, and subsequent fertilization of a similarly emerged immotile extracellular female macrogamete. previous studies have demonstrated that antibodies against male gamete surface proteins ingested from the blood of an infected and immunized host inh ...200919596419
malaria ookinetes exhibit multiple markers for apoptosis-like programmed cell death in vitro.abstract:200919604379
addlp, a bacterial defensin-like peptide, exhibits anti-plasmodium activity.antimicrobial defensins with the cysteine-stabilized alpha-helical and beta-sheet (csalphabeta) motif are widely distributed in three eukaryotic kingdoms. however, recent work suggests that bacteria could possess defensin-like peptides (dlps). here, we report recombinant expression, in vitro folding, structural and functional characterization of a dlp from the myxobacterium anaeromyxobacter dehalogenans (addlp). circular dichroism analysis indicates that recombinant addlp adopts a typical struct ...200919615342
evaluation of in vivo antimalarial activities of ethanolic leaf and seed extracts of telfairia occidentalis.the leaves and seeds of telfairia occidentalis are used as vegetables in making soups in southern nigeria. in this study, we investigated the antimalarial activity of leaf and seed extracts in vivo in mice infected with plasmodium berghei berghei during early and established infections. t. occidentalis leaf extract (250-750 mg/kg/day) exhibited antiplasmodial activity both in the 4-day early infection test and in established infection with a marked increase of the mean survival time, which, howe ...200919627216
mosquito immune responses and compatibility between plasmodium parasites and anopheline mosquitoes.functional screens based on dsrna-mediated gene silencing identified several anopheles gambiae genes that limit plasmodium berghei infection. however, some of the genes identified in these screens have no effect on the human malaria parasite plasmodium falciparum; raising the question of whether different mosquito effector genes mediate anti-parasitic responses to different plasmodium species.200919643026
malarial hemozoin is a nalp3 inflammasome activating danger signal.background: characteristic symptoms of malaria include recurrent fever attacks and neurodegeneration, signs that are also found in patients with a hyperactive nalp3 inflammasome. plasmodium species produce a crystal called hemozoin that is generated by detoxification of heme after hemoglobin degradation in infected red blood cells. thus, we hypothesized that hemozoin could activate the nalp3 inflammasome, due to its particulate nature reminiscent of other inflammasome-activating agents. methodol ...200919652710
initiation of plasmodium sporozoite motility by albumin is associated with induction of intracellular signalling.malaria infection is initiated when a mosquito injects plasmodium sporozoites into a mammalian host. sporozoites exhibit gliding motility both in vitro and in vivo. this motility is associated with the secretion of at least two proteins, circumsporozoite protein (csp) and thrombospondin-related anonymous protein (trap). both derive from micronemes, which are organelles that empty out of the apical end of the sporozoite. sporozoite motility can be initiated in vitro by albumin added to the medium ...201019654011
paternal effect of the nuclear formin-like protein misfit on plasmodium development in the mosquito vector.malaria parasites must undergo sexual and sporogonic development in mosquitoes before they can infect their vertebrate hosts. we report the discovery and characterization of misfit, the first protein with paternal effect on the development of the rodent malaria parasite plasmodium berghei in anopheles mosquitoes. misfit is expressed in male gametocytes and localizes to the nuclei of male gametocytes, zygotes and ookinetes. gene disruption results in mutant ookinetes with reduced genome content, ...200919662167
anopheles gambiae pgrplc-mediated defense against bacteria modulates infections with malaria parasites.recognition of peptidoglycan (pgn) is paramount for insect antibacterial defenses. in the fruit fly drosophila melanogaster, the transmembrane pgn recognition protein lc (pgrp-lc) is a receptor of the imd signaling pathway that is activated after infection with bacteria, mainly gram-negative (gram-). here we demonstrate that bacterial infections of the malaria mosquito anopheles gambiae are sensed by the orthologous pgrplc protein which then activates a signaling pathway that involves the rel/nf ...200919662170
ca/c1 peptidases of the malaria parasites plasmodium falciparum and p. berghei and their mammalian hosts--a bioinformatical analysis.in genome-wide screens we studied ca/c1 peptidases of malaria-causing plasmodia and their hosts (man and mouse). for plasmodium falciparum and p. berghei, several new ca/c1 peptidase genes encoding proteases of the l- and b-family with specific promoter modules were identified. in addition, two new human ca/c1 peptidase loci and one new mouse gene locus were found; otherwise, the sets of ca/c1 peptidase genes in man and mouse seem to be complete now. in each species studied there is a multitude ...200919663681
fertilization is a novel attacking site for the transmission blocking of malaria parasites.malaria parasites perform sexual reproduction in mosquitoes where a pair of gametes fertilizes and differentiates into zygotes, and a single zygote produces several thousands of progeny infectious to next vertebrates. although the parasite fertilization step has been considered as achilles' heel of parasite life cycle and thus a critical target for blocking malaria transmission in the mosquito, its molecular mechanisms are largely unknown. previously, we identified that generative cell specific ...201019665985
characterization of plasmodium falciparum calcium-dependent protein kinase 4.in plasmodium berghei, the orthologous gene of p. falciparum calcium-dependent protein kinase 4 (pfcdpk4) was reported to be essential for the exflagellation of male gametocytes. to elucidate the role of pfcdpk4 in p. falciparum gametogenesis, we characterized the biological function of pfcdpk4 in vitro. pfcdpk4 was purified as a fusion protein that was labeled with [gamma-(32)p]atp; this labeling was then eliminated by phosphatase. phosphorylation activity of pfcdpk4 was eliminated when its put ...200919666141
vital role for the plasmodium actin capping protein (cp) beta-subunit in motility of malaria sporozoites.summary successful malaria transmission from the mosquito vector to the mammalian host depends crucially on active sporozoite motility. sporozoite locomotion and host cell invasion are driven by the parasite's own actin/myosin motor. a unique feature of this motor machinery is the presence of very short subpellicular actin filaments. therefore, f-actin stabilizing proteins likely play a central role in parasite locomotion. here, we investigated the role of the plasmodium berghei actin capping pr ...200919682250
bioassay-guided fractionation and in vivo antiplasmodial effect of fractions of chloroform extract of artemisia maciverae linn.in the search for new plant-derived anti-malarial compounds, chromatographic fractions of chloroform extract of whole plants of artemisia maciverae were tested in vivo using chloroquine resistant and chloroquine sensitive plasmodium berghei nk 65 infected swiss albino mice. one fraction and a sub-fraction of this were most active at 10/mg and cleared parasitemia in mice within 3 days. the different fractions and sub-fractions were tested with different reagents to determine the broad classes of ...200919695214
pathogenic roles of cd14, galectin-3, and ox40 during experimental cerebral malaria in mice.an in-depth knowledge of the host molecules and biological pathways that contribute towards the pathogenesis of cerebral malaria would help guide the development of novel prognostics and therapeutics. genome-wide transcriptional profiling of the brain tissue during experimental cerebral malaria (ecm ) caused by plasmodium berghei anka parasites in mice, a well established surrogate of human cerebral malaria, has been useful in predicting the functional classes of genes involved and pathways alte ...200919710907
quantitative assessment of dna replication to monitor microgametogenesis in plasmodium berghei.targeting the crucial step of plasmodium transition from vertebrate host to mosquito vector is a promising approach to eliminate malaria. uptake by the mosquito activates gametocytes within seconds, and in the case of male (micro) gametocytes leads to rapid dna replication and the release of eight flagellated gametes. we developed a sensitive assay to monitor p. berghei microgametocyte activation based on [(3)h]hypoxanthine incorporation into dna. optimal ph range and xanthurenic acid concentrat ...200919712704
cd8 t cell immunity to plasmodium permits generation of protective antibodies after repeated sporozoite challenge.individuals living in malaria endemic areas are subject to repeated infections yet fail to develop sterilizing immunity, however, immunization of mice with attenuated sporozoites or subunit vaccines has shown the ability to protect mice against a sporozoite challenge. we recently reported that mice primed with dendritic cells coated with the dominant circumsporozoite cd8 t cell epitope from plasmodium berghei followed by a boost with recombinant listeria monocytogenes expressing the same epitope ...200919712771
construction of transgenic plasmodium berghei as a model for evaluation of blood-stage vaccine candidate of plasmodium falciparum chimeric protein 2.9.the function of the 19 kda c-terminal region of the merozoite surface protein 1 (msp1-19) expressed by plasmodium has been demonstrated to be conserved across distantly related plasmodium species. the green fluorescent protein (gfp) is a reporter protein that has been widely used because it can be easily detected in living organisms by fluorescence microscopy and flow cytometry.200919727400
il-10 plays a crucial role for the protection of experimental cerebral malaria by co-infection with non-lethal malaria parasites.cerebral malaria is an infrequent but serious complication of plasmodium falciparum infection in humans. co-infection with different plasmodium species is common in endemic areas and the existence of benign malaria parasites, such as plasmodium vivax, during p. falciparum infection has been considered to reduce the risk of developing pathogenesis. however, it is still unknown how disease severity is reduced in the host during co-infection. in the present study, we investigated the influence of c ...201019735663
highly efficient subcloning of rodent malaria parasites by injection of single merosomes or detached cells.this protocol describes a method for obtaining rodent plasmodium parasite clones with high efficiency, which takes advantage of the normal course of plasmodium in vitro exoerythrocytic development. at the completion of development, detached cells/merosomes form, which contain hundreds to thousands of merozoites. as all parasites within a single detached cell/merosome derive from the same sporozoite, we predicted them to be genetically identical. to prove this, hepatoma cells were infected simult ...200919745825
plasmodium berghei ookinetes glide and release pbs25 and circumsporozoite thrombospondin-related protein on solid surface substrata.plasmodium spp. development within mosquito vectors includes invasive ookinete and sporozoites stages, which display gliding movements during invasion of the midgut and salivary glands, respectively. sporozoite gliding has been well documented, and several proteins released during sporozoite's locomotion have been described. however, proteins on the ookinete gliding trails are poorly described. in the present study, we documented that 2 proteins, pbs25 and circumsporozoite thrombospondin-related ...201019747017
altered nucleotide receptor expression in a murine model of cerebral malaria.in cerebral malaria, the most severe complication of malaria, both neurotransmission mechanisms and energy metabolism are affected. to understand how metabolic changes modify neurotransmission, we examined p2 receptor expression in a murine model of cerebral malaria. quantitative polymerase chain reaction experiments revealed that parasite deposition was greatest in the cerebellum, compared with other areas of the brain, suggesting a correlation between brain parasitemia and loss of control of m ...200919758097
the ig domain protein cd9p-1 down-regulates cd81 ability to support plasmodium yoelii infection.invasion of hepatocytes by plasmodium sporozoites is a prerequisite for establishment of a malaria natural infection. the molecular mechanisms underlying sporozoite invasion are largely unknown. we have previously reported that cd81 is required on hepatocytes for infection by plasmodium falciparum and plasmodium yoelii sporozoites. cd81 belongs to the tetraspanin superfamily of transmembrane proteins. by interacting with each other and with other transmembrane proteins, tetraspanins may play a r ...200919762465
a cyclic gmp signalling module that regulates gliding motility in a malaria parasite.the ookinete is a motile stage in the malaria life cycle which forms in the mosquito blood meal from the zygote. ookinetes use an acto-myosin motor to glide towards and penetrate the midgut wall to establish infection in the vector. the regulation of gliding motility is poorly understood. through genetic interaction studies we here describe a signalling module that identifies guanosine 3', 5'-cyclic monophosphate (cgmp) as an important second messenger regulating ookinete differentiation and mot ...200919779564
structure-activity relationship of antiparasitic and cytotoxic indoloquinoline alkaloids, and their tricyclic and bicyclic analogues.based on the indoloquinoline alkaloids cryptolepine (1), neocryptolepine (2), isocryptolepine (3) and isoneocryptolepine (4), used as lead compounds for new antimalarial agents, a series of tricyclic and bicyclic analogues, including carbolines, azaindoles, pyrroloquinolines and pyrroloisoquinolines was synthesized and biologically evaluated. none of the bicyclic compounds was significantly active against the chloroquine-resistant strain plasmodium falciparum k1, in contrast to the tricyclic der ...200919781948
'stalled' malaria parasite becomes vaccine fodder. 200519795586
dissecting the genetic basis of resistance to malaria parasites in anopheles gambiae.the ability of anopheles gambiae mosquitoes to transmit plasmodium parasites is highly variable between individuals. however, the genetic basis of this variability has remained unknown. we combined genome-wide mapping and reciprocal allele-specific rna interference (rasrnai) to identify the genomic locus that confers resistance to malaria parasites and demonstrated that polymorphisms in a single gene encoding the antiparasitic thioester-containing protein 1 (tep1) explain a substantial part of t ...200919797663
statins fail to improve outcome in experimental cerebral malaria and potentiate toll-like receptor-mediated cytokine production by murine macrophages.cerebral malaria is responsible for a large proportion of the estimated one million deaths caused by plasmodium falciparum malaria annually. this disease is associated with excessive pro-inflammatory cytokine production resulting from dysregulated host responses to infection. on the basis of reports indicating potent activity against host-mediated inflammatory disorders such as sepsis, we examined the activity of statins (3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors) on malaria-ass ...200919815878
anopheles mortality is both age- and plasmodium-density dependent: implications for malaria transmission.daily mortality is an important determinant of a vector's ability to transmit pathogens. original simplifying assumptions in malaria transmission models presume vector mortality is independent of age, infection status and parasite load. previous studies illustrate conflicting evidence as to the importance of plasmodium-induced vector mortality, but very few studies to date have considered the effect of infection density on mosquito survival.200919822012
changes in cell migration-related molecules expressed by thymic microenvironment during experimental plasmodium berghei infection: consequences on thymocyte development.we previously showed alterations in the thymus during experimental infection with plasmodium berghei. such alterations comprised histological changes, with loss of cortical-medullary limits, and the intrathymic presence of parasites. as the combination of chemokines, adhesion molecules and extracellular matrix (ecm) is critical to appropriate thymocyte development, we analysed the thymic expression of ecm ligands and receptors, as well as chemokines and their respective receptors during the expe ...201019824923
the crystal structures of macrophage migration inhibitory factor from plasmodium falciparum and plasmodium berghei.malaria, caused by plasmodium falciparum and related parasites, is responsible for millions of deaths each year, mainly from complications arising from the blood stages of its life cycle. macrophage migration inhibitory factor (mif), a protein expressed by the parasite during these stages, has been characterized in mammals as a cytokine involved in a broad spectrum of immune responses. it also possesses two catalytic activities, a tautomerase and an oxidoreductase, though the physiological signi ...200919827093
preliminary studies on the effects of orally-administered transforming growth factor-beta on protozoan diseases in mice.transforming growth factor beta-1 (tgf-beta1) is a pleiotropic cytokine with both pro- and antiinflammatory properties, depending on its environment and concentration. the present study evaluated the effects of orally-delivered tgf-beta1 on mice parenterally-infected with various protozoan parasites. we report that while orally-administered tgf-beta1 seems to confer partial protection against murine chronic babesiosis and acute trypanosomosis, no beneficial clinical effects were observed against ...200919827745
structure-activity relationship studies of manzamine a: amidation of positions 6 and 8 of the beta-carboline moiety.twenty manzamine amides were synthesized and evaluated for in vitro antimalarial and antimicrobial activities. the amides of manzamine a (1) showed significantly reduced cytotoxicity against vero cells, although were less active than 1. the structure-activity analysis showed that linear, short alkyl groups adjacent to the amide carbonyl at position 8 are favored for antimalarial activity, while bulky and cyclic groups at position 6 provided the most active amides. most of the amides showed poten ...200919833520
signalling in malaria parasites. the malsig consortium.depending on their developmental stage in the life cycle, malaria parasites develop within or outside host cells, and in extremely diverse contexts such as the vertebrate liver and blood circulation, or the insect midgut and hemocoel. cellular and molecular mechanisms enabling the parasite to sense and respond to the intra- and the extra-cellular environments are therefore key elements for the proliferation and transmission of plasmodium, and therefore are, from a public health perspective, stra ...200919839262
malaria: targeting parasite and host cell kinomes.malaria still remains one of the deadliest infectious diseases, and has a tremendous morbidity and mortality impact in the developing world. the propensity of the parasites to develop drug resistance, and the relative reluctance of the pharmaceutical industry to invest massively in the developments of drugs that would offer only limited marketing prospects, are major issues in antimalarial drug discovery. protein kinases (pks) have become a major family of targets for drug discovery research in ...201019840874
determination of the expression of lymphocyte surface markers and cytokine levels in a mouse model of plasmodium berghei.this study aimed to determine the changes in lymphocyte surface markers and cytokine profiles during a malarial infection in a mouse model of malaria. mononuclear cells obtained from the spleens of the mice infected with plasmodium berghei (p. berghei) were stained with anti-mouse cd3, anti-mouse cd4, anti-mouse cd8, anti-mouse cd19, anti-mouse cd152, anti-mouse pan natural killer (nk), anti-mouse cd80 monoclonal antibodies and expression of surface markers was evaluated by flow cytometry. in th ...200919845111
identification of a novel cerebral malaria susceptibility locus (berr5) on mouse chromosome 19.cerebral malaria (cm) is an acute, generally lethal condition characterized by high fever, seizures and coma. the genetic component to cm can be investigated in mouse models that vary in degree of susceptibility to infection with plasmodium berghei anka. using survival time to measure susceptibility in an informative f2 cross (n=257), we identified linkage to chromosome 19 (berr5 (berghei resistance locus 5), lod=4.69) controlling, in part, the differential response between resistant balb/c and ...201019865103
interferon and interferon inducers in protozoal infections.several interferon inducers (newcastle disease virus, statolon, and poly ri:poly rc) as well as exogenous mouse interferon protect mice from sporozoite-induced plasmodium berghei malaria, as long as they are administered before the end of the preerythrocytic phase of development of the parasite. the protective effect of the interferon inducers was related to their interferon-inducing effect; the protective effect of the interferon preparations was related to the interferon titer of the preparati ...197019873669
modification of oxidative status in plasmodium berghei-infected erythrocytes by e-2-chloro-8-methyl-3-[(4'-methoxy-1'-indanoyl)-2'-methyliden]-quinoline compared to chloroquine.e-2-chloro-8-methyl-3-[(4'-methoxy-1'-indanoyl)-2'-methyliden]-quinoline (iq) is a new quinoline derivative which has been reported as a haemoglobin degradation and ss-haematin formation inhibitor. the haemoglobin proteolysis induced by plasmodium parasites represents a source of amino acids and haeme, leading to oxidative stress in infected cells. in this paper, we evaluated oxidative status in plasmodium berghei-infected erythrocytes in the presence of iq using chloroquine (cq) as a control. a ...200919876558
neither mosquito saliva nor immunity to saliva has a detectable effect on the infectivity of plasmodium sporozoites injected into mice.malaria infection is initiated when a female anopheles mosquito probing for blood injects saliva, together with sporozoites, into the skin of its mammalian host. prior studies had suggested that saliva may enhance sporozoite infectivity. using rodent malaria models (plasmodium berghei and p. yoelii), we were unable to show that saliva had any detectable effect on sporozoite infectivity. this is encouraging for plans to immunize humans with washed, attenuated p. falciparum sporozoites because man ...201019884338
limited role of cd4+foxp3+ regulatory t cells in the control of experimental cerebral malaria.cerebral malaria (cm) associated with plasmodium berghei anka (pba) infection is an accepted model of human cm. cm during pba infection critically depends on sequestration of t cells into the brain. several studies aimed to address the role of regulatory t cells (t(reg)) in modulating this pathogenic t cell response. however, these studies are principally hampered due to the fact that until recently no reagents were available to deplete foxp3(+) t(reg) specifically. to study the function of t(re ...200919890049
a role for immune responses against non-cs components in the cross-species protection induced by immunization with irradiated malaria sporozoites.immunization with irradiated plasmodium sporozoites induces sterile immunity in rodents, monkeys and humans. the major surface component of the sporozoite the circumsporozoite protein (cs) long considered as the antigen predominantly responsible for this immunity, thus remains the leading candidate antigen for vaccines targeting the parasite's pre-erythrocytic (pe) stages. however, this role for cs was questioned when we recently showed that immunization with irradiated sporozoites (irrspz) of a ...200919890387
analgesic and antimalarial activities of crude leaf extract and fractions of acalypha wilkensiana.antiplasmodial and analgesic activities of leaf extract and fractions of acalypha wilkensiana were evaluated to ascertain the folkloric claim of its antimalarial and analgesic activities.201019892007
accelerated clearance of plasmodium-infected erythrocytes in sickle cell trait and annexin-a7 deficiency.the course of malaria does not only depend on the virulence of the parasite plasmodium but also on properties of host erythrocytes. here, we show that infection of erythrocytes from human sickle cell trait (hba/s) carriers with ring stages of p. falciparum led to significantly enhanced pge(2) formation, ca(2+) permeability, annexin-a7 degradation, phosphatidylserine (ps) exposure at the cell surface, and clearance by macrophages. p. berghei-infected erythrocytes from annexin-a7-deficient (annexi ...200919910682
phosphothioate oligodeoxynucleotides inhibit plasmodium sporozoite gliding motility.plasmodium sporozoites, transmitted to the mammalian host through a mosquito bite, travel to the liver, where they invade hepatocytes, and develop into a form that is then able to infect red blood cells. in spite of the importance of innate immunity in controlling microbial infections, almost nothing is known about its role during the liver stage of a malaria infection. here, we tested whether synthetic cpg phosphothioate (ps) oligodeoxynucleotides (odns), which bind to toll-like receptor 9 (tlr ...201019912239
a nonadjuvanted polypeptide nanoparticle vaccine confers long-lasting protection against rodent malaria.we have designed and produced a prototypic malaria vaccine based on a highly versatile self-assembling polypeptide nanoparticle (sapn) platform that can repetitively display antigenic epitopes. we used this platform to display a tandem repeat of the b cell immunodominant repeat epitope (dppppnpn)(2)d of the malaria parasite plasmodium berghei circumsporozoite protein. administered in saline, without the need for a heterologous adjuvant, the sapn construct p4c-mal conferred a long-lived, protecti ...200919915055
alpha-tocopherol transfer protein inhibition is effective in the prevention of cerebral malaria in mice.nutritional status likely plays an important role in determining the outcome of protozoan infections. despite the evidence of plasmodium sensitivity to oxidative stress, the potential role of vitamin e, a free radical scavenger, on the outcome of cerebral malaria (cm) has yet to be elucidated.201019923370
new 1-aryl-3-substituted propanol derivatives as antimalarial agents.this paper describes the synthesis and in vitro antimalarial activity against a p. falciparum 3d7 strain of some new 1-aryl-3-substituted propanol derivatives. twelve of the tested compounds showed an ic(50) lower than 1 microm. these compounds were also tested for cytotoxicity in murine j774 macrophages. the most active compounds were evaluated for in vivo activity against p. berghei in a 4-day suppressive test. compound 12 inhibited more than 50% of parasite growth at a dose of 50 mg/kg/day. i ...200919924051
visualisation and quantitative analysis of the rodent malaria liver stage by real time imaging.the quantitative analysis of plasmodium development in the liver in laboratory animals in cultured cells is hampered by low parasite infection rates and the complicated methods required to monitor intracellular development. as a consequence, this important phase of the parasite's life cycle has been poorly studied compared to blood stages, for example in screening anti-malarial drugs. here we report the use of a transgenic p. berghei parasite, pbgfp-luc(con), expressing the bioluminescent report ...200919924309
synthesis and antimalarial evaluation of 1, 3, 5-trisubstituted pyrazolines.a series of 1,3,5-trisubstituted pyrazolines were synthesized and evaluated for in vitro antimalarial efficacy against chloroquine sensitive (mrc-02) as well as chloroquine resistant (rkl9) strains of plasmodium falciparum. the activity was at nano molar concentration. beta-hematin formation inhibition activity (bhia(50)) of the pyrazolines were determined and correlated with antimalarial activity. a reasonably good correlation (r=0.62) was observed between antimalarial activity (ic(50)) and bhi ...201019926176
the murine cerebral malaria phenomenon.p.berghei anka infection in cba or cb57bl/6 mice is used widely as a murine 'model' of human cerebral malaria (hcm), despite markedly different histopathological features. the pathology of the murine model is characterised by marked inflammation with little or no intracerebral sequestration of parasitised erythrocytes, whereas hcm is associated with intense intracerebral sequestration, often with little inflammatory response. there are now more than ten times as many studies each year of the mur ...201019932638
plasmodium berghei crystalloids contain multiple lccl proteins.malaria crystalloids are unique organelles of unknown function that are present only in the mosquito-specific ookinete and early oocyst stages of the parasite. recently, crystalloid formation in plasmodium berghei was linked to the parasite protein pbsr, a member of the plasmodium lccl protein family composed of six modular multidomain proteins involved in sporozoite development and infectivity. here, we show by fluorescent protein tagging that two other lccl protein family members are targeted ...201019932717
role of plasmodium berghei cgmp-dependent protein kinase in late liver stage development.the liver is the first organ infected by plasmodium sporozoites during malaria infection. in the infected hepatocytes, sporozoites undergo a complex developmental program to eventually generate hepatic merozoites that are released into the bloodstream in membrane-bound vesicles termed merosomes. parasites blocked at an early developmental stage inside hepatocytes elicit a protective host immune response, making them attractive targets in the effort to develop a pre-erythrocytic stage vaccine. he ...201019940133
discovery of plasmodium modulators by genome-wide analysis of circulating hemocytes in anopheles gambiae.insect hemocytes mediate important cellular immune responses including phagocytosis and encapsulation and also secrete immune factors such as opsonins, melanization factors, and antimicrobial peptides. however, the molecular composition of these important immune cells has not been elucidated in depth, because of their scarcity in the circulating hemolymph, their adhesion to multiple tissues and the lack of primary culture methods to produce sufficient material for a genome-wide analysis. in this ...200919940242
experimental cerebral malaria progresses independently of the nlrp3 inflammasome.cerebral malaria is the most severe complication of plasmodium falciparum infection in humans and the pathogenesis is still unclear. using the p. berghei anka infection model of mice, we investigated a potential involvement of nlrp3 and the inflammasome in the pathogenesis of cerebral malaria. nlrp3 mrna expression was upregulated in brain endothelial cells after exposure to p. berghei anka. although beta-hematin, a synthetic compound of the parasites heme polymer hemozoin, induced the release o ...201019950187
the comparative antimalarial properties of weak base and neutral synthetic ozonides.thirty-three n-acyl 1,2,4-dispiro trioxolanes (secondary ozonides) were synthesized. for these ozonides, weak base functional groups were not required for high antimalarial potency against plasmodium falciparum in vitro, but were necessary for high antimalarial efficacy in plasmodium berghei-infected mice. a wide range of logp/d(ph)(7.4) values were tolerated, although more lipophilic ozonides tended to be less metabolically stable.201019962893
glutathione reductase and thioredoxin reductase: novel antioxidant enzymes from plasmodium berghei.malaria parasites adapt to the oxidative stress during their erythrocytic stages with the help of vital thioredoxin redox system and glutathione redox system. glutathione reductase and thioredoxin reductase are important enzymes of these redox systems that help parasites to maintain an adequate intracellular redox environment. in the present study, activities of glutathione reductase and thioredoxin reductase were investigated in normal and plasmodium berghei-infected mice red blood cells and th ...200919967095
experimental splenectomies and malaria in mice.to evaluate the importance of spleen in malaric infection in murino model, comparing the parasitemia and the titles of immunoglobulins in the different groups.200920011827
synthesis and antiplasmodial activity of new indolone n-oxide derivatives.a series of 66 new indolone-n-oxide derivatives was synthesized with three different methods. compounds were evaluated for in vitro activity against cq-sensitive (3d7), cq-resistant (fcb1), and cq and pyrimethamine cross-resistant (k1) strains of plasmodium falciparum (p.f.), as well as for cytotoxic concentration (cc(50)) on mcf7 and kb human tumor cell lines. compound 26 (5-methoxy-indolone-n-oxide analogue) had the most potent antiplasmodial activity in vitro (<3 nm on fcb1 and = 1.7 nm on 3d ...201020014857
plasmepsin 4-deficient plasmodium berghei are virulence attenuated and induce protective immunity against experimental malaria.plasmodium parasites lacking plasmepsin 4 (pm4), an aspartic protease that functions in the lysosomal compartment and contributes to hemoglobin digestion, have only a modest decrease in the asexual blood-stage growth rate; however, pm4 deficiency in the rodent malaria parasite plasmodium berghei results in significantly less virulence than that for the parental parasite. p. berghei deltapm4 parasites failed to induce experimental cerebral malaria (ecm) in ecm-susceptible mice, and ecm-resistant ...201020019192
transcription factor ap2-sp and its target genes in malarial sporozoites.the malarial sporozoite is the stage that infects the liver, and genes expressed in this stage are potential targets for vaccine development. here, we demonstrate that specific gene expression in this stage is regulated by an ap2-related transcription factor, designated ap2-sp (apetala2 in sporozoites), that is expressed from the late oocyst to the salivary gland sporozoite. disruption of the ap2-sp gene did not affect parasite replication in the erythrocyte but resulted in loss of sporozoite fo ...201020025671
mosquito immune defenses against plasmodium infection.the causative agent of malaria, plasmodium, has to undergo complex developmental transitions and survive attacks from the mosquito's innate immune system to achieve transmission from one host to another through the vector. here we discuss recent findings on the role of the mosquito's innate immune signaling pathways in preventing infection by the plasmodium parasite, the identification and mechanistic description of novel anti-parasite molecules, the role that natural bacteria harbored in the mo ...201020026176
antimalarial activity of ultra-short peptides.ultra-short peptides 1-9 were designed and synthesized with phenylalanine, ornithine and proline amino acid residues and their effect on antimalarial activity was analyzed. on the basis of the ic(50) data for these compounds, the effects of nature, polarity, and amino acid sequence on plasmodium berghei schizont cultures were analyzed too. tetrapeptides phe-orn-phe-orn (4) and lys-phe-phe-orn (5) showed a very important activity with ic(50) values of 3.31 and 2.57 microm, respectively. these two ...200920032878
synthesis and evaluation of phenylequine for antimalarial activity in vitro and in vivo.synthesis of the potent antiplasmodial 4-aminoquinoline, phenylequine (pq), is reported for the first time. pq and the two analogues show increased efficacy in moving from the chloroquine sensitive d10 to the chloroquine resistant k1 strain in vitro. the in vivo efficacy of pq, and salts thereof, have been determined in plasmodium berghei anka and plasmodium yoelii. phenylequine hydrochloride has shown an ed(50) of 0.81 in p. yoelii (cf chloroquine ed(50)=1.31).201020034790
the plasmodium serine-type sera proteases display distinct expression patterns and non-essential in vivo roles during life cycle progression of the malaria parasite.parasite proteases play key roles in several fundamental steps of the plasmodium life cycle, including haemoglobin degradation, host cell invasion and parasite egress. plasmodium exit from infected host cells appears to be mediated by a class of papain-like cysteine proteases called 'serine repeat antigens' (seras). a sera subfamily, represented by plasmodium falciparum sera5, contains an atypical active site serine residue instead of a catalytic cysteine. members of this seraser subfamily are a ...201020039882
in vivo antimalarial activity of ethanolic leaf extract of stachytarpheta cayennensis.to evaluate the in vivo antiplasmodial activity of the ethanol leaf extract of stachytarpheta cayennensis in the treatment of various ailment in niger delta region of nigeria, in plasmodium berghei infected mice.200820040937
a dispensable plasmodium locus for stable transgene expression.the ribosomal small subunit locus has been used for transgene expression in the rodent malaria parasites, plasmodium berghei and plasmodium yoelii, but this strategy utilizes single crossover integration and is thus prone to reversion by plasmid excision. targeting of the ribosomal subunit locus may also have a negative effect on oocyst development in the mosquito. in p. berghei, the p230 paralog locus has been used for transgene expression. here, we show that the p. yoelii s1 locus (sporozoite ...201020045029
meutxkbeta1, a scorpion venom-derived two-domain potassium channel toxin-like peptide with cytolytic activity.recent studies have demonstrated that scorpion venom contains unique two-domain peptides with the peculiarity of possessing different functions, i.e. neurotoxic and cytolytic activities. here we report systematic characterization of a new two-domain peptide (named meutxkbeta1) belonging to the tstxkbeta molecular subfamily from the scorpion mesobuthus eupeus by molecular cloning, biochemical purification, recombinant expression, functional assays, cd and nmr studies. its full-length bioactive fo ...201020045493
schistosoma mansoni infection reduces the incidence of murine cerebral malaria.plasmodium and schistosoma are two of the most common parasites in tropical areas. deregulation of the immune response to plasmodium falciparum, characterized by a th1 response, leads to cerebral malaria (cm), while a th2 response accompanies chronic schistosomiasis.201020051114
a single fluorescence-based lamp reaction for identifying multiple parasites in mosquitoes.vector-borne diseases, such as malaria and lymphatic filariasis, are co-endemic in large parts of the world. to develop a multiplex amplification method for the simultaneous detection of multiple insect-borne infectious diseases, we used lamp with fluorescently labeled primers to identify the spect2 gene of plasmodium berghei and the cytochrome oxidase subunit i gene of dirofilaria immitis in mosquitoes. this technique could detect as few as 100 p. berghei-infected red blood cell-equivalents or ...201020064511
synergistic and additive effects of epigallocatechin gallate and digitonin on plasmodium sporozoite survival and motility.most medicinal plants contain a mixture of bioactive compounds, including chemicals that interact with intracellular targets and others that can act as adjuvants to facilitate absorption of polar agents across cellular membranes. however, little is known about synergistic effects between such potential drug candidates and adjuvants. to probe for such effects, we tested the green tea compound epigallocatechin gallate (egcg) and the membrane permeabilising digitonin on plasmodium sporozoite motili ...201020072627
Displaying items 4101 - 4200 of 5568