Publications

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antiplasmodial activity of sesquiterpene lactone from carpesium rosulatum in mice.in the previous work, methanol extracts of carpesium rosulatum (compositae) were found to have high antiplasmodial activity against plasmodium falciparum in vitro, this activity being largely attributable to a ineupatorolides a (i-a). in the present study, encouragingly, i-a was also found to have potential antimalarial activity in vivo when tested against plasmodium berghei in mice. i-a (2, 5, 10 mg kg(-1) day(-1)) exhibited a significant blood schizontocidal activity in 4-day early infection, ...200818437422
functional characterization of a redundant plasmodium trap family invasin, trap-like protein, by aldolase binding and a genetic complementation test.efficient and specific host cell entry is of exquisite importance for intracellular pathogens. parasites of the phylum apicomplexa are highly motile and actively enter host cells. these functions are mediated by type i transmembrane invasins of the trap family that link an extracellular recognition event to the parasite actin-myosin motor machinery. we systematically tested potential parasite invasins for binding to the actin bridging molecule aldolase and complementation of the vital cytoplasmi ...200818441124
processing of the circumsporozoite protein in infected hepatocytes is not dependent on aspartic proteases.cd8(+) t cells play a major role in the protective immune response against the liver stage of malaria. it was previously shown that the circumsporozoite protein (csp) is processed and presented to specific t cells by both traversed and infected hepatocytes, but their respective antigen processing requirements were not completely defined. in the present study, we show that in vitro processing of the plasmodium berghei csp by infected mouse primary hepatocytes is exclusively dependent on proteasom ...200818444957
liposomal polyethyleneglycol and polyethyleneglycol-peptide combinations for active targeting to liver in vivo.this report describes the development and evaluation of a range of polyethyleneglycol and polyethyleneglycol-peptide liposome formulations that effectively target liver in vivo. a 19-amino-acid sequence from the n-terminal region of the circumsporozoite protein of plasmodium berghei was attached to the distal end of di22:1-aminopropane-polyethyleneglycol(3400), and incorporated into liposomes containing di22:1-phosphatidylcholine and di22:1-phosphatidylethanolamine-polyethyleneglycol(5000). by s ...200818446566
blood-stage plasmodium infection induces cd8+ t lymphocytes to parasite-expressed antigens, largely regulated by cd8alpha+ dendritic cells.although cd8(+) t cells do not contribute to protection against the blood stage of plasmodium infection, there is mounting evidence that they are principal mediators of murine experimental cerebral malaria (ecm). at present, there is no direct evidence that the cd8(+) t cells mediating ecm are parasite-specific or, for that matter, whether parasite-specific cd8(+) t cells are generated in response to blood-stage infection. to resolve this and to define the cellular requirements for such priming, ...200818799734
the analgesic and antiplasmodial activities and toxicology of vernonia amygdalina.vernonia amygdalina possesses several bioactive compounds and is used in traditional medicines of southwestern uganda, along with other regions. its analgesic potential has not been investigated thus far. the present study examines the antinociceptive potential of the aqueous leaf extract (50-200 mg/kg) using three models of nociception (acetic acid-induced writhing, formalin test, and tail-flick test), antiplasmodial activity, and toxicology of the extract. the results show the extract signific ...200818800909
complete protection against p. berghei malaria upon heterologous prime/boost immunization against circumsporozoite protein employing salmonella type iii secretion system and bordetella adenylate cyclase toxoid.sterile immunity against malaria can be achieved by the induction of ifngamma-producing cd8(+) t cells that target infected hepatocytes presenting epitopes of the circumsporozoite protein (csp). in the present study we evaluate the protective efficacy of a heterologous prime/boost immunization protocol based on the delivery of the cd8(+) epitope of plasmodium berghei csp into the mhc class i presentation pathway, by either a type iii secretion system of live recombinant salmonella and/or by dire ...200818804138
carbonic anhydrase inhibitors: inhibition of plasmodium falciparum carbonic anhydrase with aromatic/heterocyclic sulfonamides-in vitro and in vivo studies.a library of aromatic/heterocyclic sulfonamides possessing a large diversity of scaffolds has been assayed for inhibition of the carbonic anhydrase (ca, ec 4.2.1.1) from the malaria parasite plasmodium falciparum (pfca). low micromolar and submicromolar in vitro inhibitors were detected, whereas several compounds showed ex vivo anti-p. falciparum activity, in cell cultures. one derivative, that is, 4-(3,4-dichlorophenylureido)thioureido-benzenesulfonamide was an effective in vitro pfca inhibitor ...200818805693
transgenic rodent plasmodium berghei parasites as tools for assessment of functional immunogenicity and optimization of human malaria vaccines. 200818806208
localisation of laminin within plasmodium berghei oocysts and the midgut epithelial cells of anopheles stephensi.abstract:200818808667
rapid identification of plasmodium-carrying mosquitoes using loop-mediated isothermal amplification.with an aim to develop a quick and simple method to survey pathogen-transmitting vectors, lamp (loop-mediated isothermal amplification) was applied to the identification of plasmodium-carrying mosquitoes, specifically a plasmodium-transmitting experimental model using rodent malaria parasite (plasmodium berghei) and anopheline mosquitoes (anopheles stephensi). the detection sensitivity limit of the lamp reaction amplifying the spect2 gene was determined to be 1 x 10(2) purified plasmodium parasi ...200818809384
pbsr is synthesized in macrogametocytes and involved in formation of the malaria crystalloids.crystalloids are transient organelles that form in developing malaria ookinetes and disappear after ookinete-to-oocyst transition. their origins and functions remain poorly understood. the plasmodium berghei scavenger receptor-like protein pbsr is essential for mosquito-to-host transmission of the parasite: pbsr knockout parasites produce normal numbers of oocysts that fail to form sporozoites, pointing to a role for pbsr in the oocyst during sporogony. here, using fluorescent protein tagging an ...200818452513
coinfection with nonlethal murine malaria parasites suppresses pathogenesis caused by plasmodium berghei nk65.mixed infection with different plasmodium species is often observed in endemic areas, and the infection with benign malaria parasites such as plasmodium vivax or p. malariae has been considered to reduce the risk of developing severe pathogenesis caused by p. falciparum. however, it is still unknown how disease severity is reduced in hosts during coinfection. in the present study, we investigated the influence of coinfection with nonlethal parasites, p. berghei xat (pb xat) or p. yoelii 17x (py ...200818453608
influence of no synthase inhibitor l-name on parasitemia and survival of plasmodium berghei infected mice.accelerated suicidal death or eryptosis of infected erythrocytes may delay development of parasitemia in malaria. eryptosis is inhibited by nitric oxide (no). the present study has been performed to explore, whether inhibition of no synthase by l-name modifies the course of malaria. we show here that l-name (>or=10 microm) increased phosphatidylserine exposure of plasmodium falciparum infected human erythrocytes, an effect significantly more marked than in noninfected human erythrocytes. we furt ...200818453756
heme oxygenase-1 is an anti-inflammatory host factor that promotes murine plasmodium liver infection.the clinically silent plasmodium liver stage is an obligatory step in the establishment of malaria infection and disease. we report here that expression of heme oxygenase-1 (ho-1, encoded by hmox1) is upregulated in the liver following infection by plasmodium berghei and plasmodium yoelii sporozoites. ho-1 overexpression in the liver leads to a proportional increase in parasite liver load, and treatment of mice with carbon monoxide and with biliverdin, each an enzymatic product of ho-1, also inc ...200818474360
common strategies to prevent and modulate experimental cerebral malaria in mouse strains with different susceptibilities.cerebral malaria (cm) is a severe complication of plasmodium falciparum infection, predominantly experienced by children and nonimmune adults, which results in significant mortality and long-term sequelae. previous studies have reported distinct susceptibility gene loci in cba/cah (cba) and c57bl/6 (b6) mice with experimental cm (ecm) caused by infection with plasmodium berghei anka. here we present an analysis of genome-wide expression profiles in brain tissue taken from b6 and cba mice with ec ...200818474652
parasite burden and cd36-mediated sequestration are determinants of acute lung injury in an experimental malaria model.although acute lung injury (ali) is a common complication of severe malaria, little is known about the underlying molecular basis of lung dysfunction. animal models have provided powerful insights into the pathogenesis of severe malaria syndromes such as cerebral malaria (cm); however, no model of malaria-induced lung injury has been definitively established. this study used bronchoalveolar lavage (bal), histopathology and gene expression analysis to examine the development of ali in mice infect ...200818483551
conserved mosquito/parasite interactions affect development of plasmodium falciparum in africa.in much of sub-saharan africa, the mosquito anopheles gambiae is the main vector of the major human malaria parasite, plasmodium falciparum. convenient laboratory studies have identified mosquito genes that affect positively or negatively the developmental cycle of the model rodent parasite, p. berghei. here, we use transcription profiling and reverse genetics to explore whether five disparate mosquito gene regulators of p. berghei development are also pertinent to a. gambiae/p. falciparum inter ...200818483558
design, synthesis and in vitro antiprotozoal activity of benzimidazole-pentamidine hybrids.a series of ten novel hybrids from benzimidazole and pentamidine were prepared using a short synthetic route. each compound was tested in vitro against the protozoa trichomonas vaginalis, giardia lamblia, entamoeba histolytica, leishmania mexicana, and plasmodium berghei, in comparison with pentamidine and metronidazole. some analogues showed high bioactivity in the low micromolar range (ic(50)<1 microm) against the first four protozoa, which make them significantly more potent than either stand ...200818486471
malaria and obesity: obese mice are resistant to cerebral malaria.the relationship between malaria and obesity are largely unknown. this is partly due to the fact that malaria occurs mainly in tropical areas where, until recently, obesity was not prevalent. it now appears, however, that obesity is emerging as a problem in developing countries. to investigate the possible role of obesity on the host-parasite response to malarial infection, this study applied a murine model, which uses the existence of genetically well characterized obese mice.200818489748
the microneme proteins ctrp and soap are not essential for plasmodium berghei ookinete to oocyst transformation in vitro in a cell free system.two plasmodium berghei ookinete micronemal proteins, circumsporozoite and trap related protein (ctrp) and secreted ookinete adhesive protein (soap) both interact with the basal lamina component laminin. following gene disruption studies it has been proposed that, apart from their role in motility, these proteins may be required for interactions leading to ookinete-to-oocyst transformation.200818489758
transmission blocking immunity in the malaria non-vector mosquito anopheles quadriannulatus species a.despite being phylogenetically very close to anopheles gambiae, the major mosquito vector of human malaria in africa, anopheles quadriannulatus is thought to be a non-vector. understanding the difference between vector and non-vector mosquitoes can facilitate development of novel malaria control strategies. we demonstrate that an. quadriannulatus is largely resistant to infections by the human parasite plasmodium falciparum, as well as by the rodent parasite plasmodium berghei. by using genetics ...200818497855
antimalarial activity of novel pyrrolizidinyl derivatives of 4-aminoquinoline.two pyrrolizidinylalkyl derivatives of 4-amino-7-chloroquinoline (mg2 and mg3) were prepared and tested in vitro against cq-sensitive and cq-resistant strains of plasmodium falciparum and in vivo in a plasmodium berghei mouse model of infection. both compounds exhibited excellent activity in all tests and low toxicity against mammalian cells. preliminary studies of the acute toxicity and of the metabolism of the most active compound mg3 indicate a promising profile as a new antimalarial drug can ...200818538567
imidazolidin-4-one peptidomimetic derivatives of primaquine: synthesis and antimalarial activity.the synthesis of imidazolidin-4-one derivatives of primaquine containing the five-membered ring at the c-terminus of a dipeptide backbone coupled to the parent drug is described. these peptidomimetic derivatives were active against a chloroquine-resistant plasmodium falciparum strain and inhibited the development of the sporogonic cycle of plasmodium berghei, affecting the appearance of oocysts in the midguts of the mosquitoes. the novel imidazolidin-4-ones are extremely stable, both in human pl ...200818539459
a plasmodium falciparum host-targeting motif functions in export during blood stage infection of the rodent malarial parasite plasmodium berghei.plasmodium falciparum (p. falciparum) secretes hundreds of proteins--including major virulence proteins--into the host erythrocyte. in order to reach the host cytoplasm, most p. falciparum proteins contain an n terminal host-targeting (ht) motif composed of 11 amino acids. in silico analyses have suggested that the ht motif is conserved throughout the plasmodium species but experimental evidence only exists for p. falciparum. here, we show that in the rodent malaria parasite plasmodium berghei ( ...200818545649
a sporozoite asparagine-rich protein controls initiation of plasmodium liver stage development.plasmodium sporozoites invade host hepatocytes and develop as liver stages (ls) before the onset of erythrocytic infection and malaria symptoms. ls are clinically silent, and constitute ideal targets for causal prophylactic drugs and vaccines. the molecular and cellular mechanisms underlying ls development remain poorly characterized. here we describe a conserved plasmodium asparagine-rich protein that is specifically expressed in sporozoites and liver stages. gene disruption in plasmodium bergh ...200818551171
plasmodium lipid rafts contain proteins implicated in vesicular trafficking and signalling as well as members of the pir superfamily, potentially implicated in host immune system interactions.plasmodium parasites, the causal agents of malaria, dramatically modify the infected erythrocyte by exporting parasite proteins into one or multiple erythrocyte compartments, the cytoplasm and the plasma membrane or beyond. despite advances in defining signals and specific cellular compartments implicated in protein trafficking in plasmodium-infected erythrocytes, the contribution of lipid-mediated sorting to this cellular process has been poorly investigated. in this study, we examined the prot ...200818563749
depletion of plasmodium berghei plasmoredoxin reveals a non-essential role for life cycle progression of the malaria parasite.proliferation of the pathogenic plasmodium asexual blood stages in host erythrocytes requires an exquisite capacity to protect the malaria parasite against oxidative stress. this function is achieved by a complex antioxidant defence system composed of redox-active proteins and low mw antioxidants. here, we disrupted the p. berghei plasmoredoxin gene that encodes a parasite-specific 22 kda member of the thioredoxin superfamily. the successful generation of plasmoredoxin knockout mutants in the ro ...200818575607
rodent plasmodium: population dynamics of early sporogony within anopheles stephensi mosquitoes.early sporogony of plasmodium parasites involves 2 major developmental transitions within the insect vector, i.e., gametocyte-to-ookinete and ookinete-to-oocyst. this study compared the population dynamics of early sporogony among murine rodent plasmodium (plasmodium berghei, plasmodium chabaudi, plasmodium vinckei, and plasmodium yoelii) developing within anopheles stephensi mosquitoes. estimates of absolute densities were determined for gametocytes, ookinetes, and oocysts for 108 experimental ...200818576764
antimalarial activity in mice of resveratrol derivative from pleuropterus ciliinervis. 200818577334
simple and sensitive antimalarial drug screening in vitro and in vivo using transgenic luciferase expressing plasmodium berghei parasites.we report two improved assays for in vitro and in vivo screening of chemicals with potential anti-malarial activity against the blood stages of the rodent malaria parasite plasmodiumberghei. these assays are based on the determination of luciferase activity (luminescence) in small blood samples containing transgenic blood stage parasites that express luciferase under the control of a promoter that is either schizont-specific (ama-1) or constitutive (eef1alphaa). assay 1, the in vitro drug lumine ...200818590736
chloroquine mediated modulation of anopheles gambiae gene expression.plasmodium development in the mosquito is crucial for malaria transmission and depends on the parasite's interaction with a variety of cell types and specific mosquito factors that have both positive and negative effects on infection. whereas the defensive response of the mosquito contributes to a decrease in parasite numbers during these stages, some components of the blood meal are known to favor infection, potentiating the risk of increased transmission. the presence of the antimalarial drug ...200818596975
ampelozyziphus amazonicus ducke (rhamnaceae), a medicinal plant used to prevent malaria in the amazon region, hampers the development of plasmodium berghei sporozoites.most medicinal plants used against malaria in endemic areas aim to treat the acute symptoms of the disease such as high temperature fevers with periodicity and chills. in some endemic areas of the brazilian amazon region one medicinal plant seems to be an exception: ampelozyziphus amazonicus, locally named "indian beer" or "saracura-mira", used to prevent the disease when taken daily as a cold suspension of powdered dried roots. in previous work we found no activity of the plant extracts against ...200818599059
malaria-specific and nonspecific activation of cd8+ t cells during blood stage of plasmodium berghei infection.cerebral malaria is one of the severe complications of plasmodium falciparum infection. studies using a rodent model of plasmodium berghei anka infection established that cd8(+) t cells are involved in the pathogenesis of cerebral malaria. however, it is unclear whether and how plasmodium-specific cd8(+) t cells can be activated during the erythrocyte stage of malaria infection. we generated recombinant plasmodium berghei anka expressing ova (ova-pba) to investigate the parasite-specific t cell ...200818606696
solid microemulsion preconcentrate (nanosorb) of artemether for effective treatment of malaria.a microemulsion preconcentrate was formulated on the basis of solubility of artemether (arm) in the various oily phases and surfactants and phase diagrams. various solid adsorbents were evaluated for their ability yield solid microemulsion preconcentrates (nanosorb-arm). nanosorb-arm on dilution yielded microemulsion with average globule size of 183 nm and polydispersity index of 0.498 when determined using photon correlation spectroscopy. the antimalarial activity of nanosorb-arm, arm solution ...200818611435
both functional ltbeta receptor and tnf receptor 2 are required for the development of experimental cerebral malaria.tnf-related lymphotoxin alpha (ltalpha) is essential for the development of plasmodium berghei anka (pba)-induced experimental cerebral malaria (ecm). the pathway involved has been attributed to tnfr2. here we show a second arm of ltalpha-signaling essential for ecm development through ltbeta-r, receptor of ltalpha1beta2 heterotrimer.200818612394
antimalarial activity of a new stilbene glycoside from parthenocissus tricuspidata in mice.a novel stilbene glycoside [piceid-(1-->6)-beta-d-glucopyranoside; pbg] from parthenocissus tricuspidata was tested in vivo against plasmodium berghei. pbg exhibited significant blood schizontocidal activity in a 4-day early infection, a repository evaluation, and an established infection, with a significant mean survival time comparable to that obtained with the standard drug, chloroquine (5 mg x kg(-1) x day(-1)).200818625780
genistein-supplemented diet decreases malaria liver infection in mice and constitutes a potential prophylactic strategy.in tropical regions millions of people still live at risk of malaria infection. indeed the emergence of resistance to chloroquine and other drugs in use in these areas reinforces the need to implement alternative prophylactic strategies. genistein is a naturally occurring compound that is widely used as a food supplement and is thought to be effective in countering several pathologies. results presented here show that genistein inhibits liver infection by the plasmodium parasite, the causative a ...200818628947
thymic alterations in plasmodium berghei-infected mice.the primary function of the thymus is to develop immature t-cells into cells that further in the periphery will be able to carry out immune functions. the literature has shown that thymus can be a target for many pathogens and severe structural alterations take place in this organ during infectious diseases. here, we investigated if thymus is also a target organ during experimental malaria infection by analyzing the presence of parasites inside the organ and histological alterations in thymuses ...200818635160
[maturation of dendritic cells and activation of b-lymphocytes in spleens of icr mice infected with chloroquine-resistant plasmodium berghei].to investigate the relation between activation of b-cells and maturation of dendritic cells (dc) in the spleens of icr mice infected with chloroquine-resistant (rc) or chloroquine-sensitive (n) strain of plasmodium berghei.200818637575
host biomarkers and biological pathways that are associated with the expression of experimental cerebral malaria in mice.cerebral malaria (cm) is a primary cause of malaria-associated deaths among young african children. yet no diagnostic tools are available that could be used to predict which of the children infected with plasmodium falciparum malaria will progress to cm. we used the plasmodium berghei anka murine model of experimental cerebral malaria (ecm) and high-density oligonucleotide microarray analyses to identify host molecules that are strongly associated with the clinical symptoms of ecm. comparative e ...200818644885
antimalarial activity of phenylthiazolyl-bearing hydroxamate-based histone deacetylase inhibitors.the antimalarial activity and pharmacology of a series of phenylthiazolyl-bearing hydroxamate-based histone deacetylase inhibitors (hdacis) was evaluated. in in vitro growth inhibition assays approximately 50 analogs were evaluated against four drug resistant strains of plasmodium falciparum. the range of 50% inhibitory concentrations (ic(50)s) was 0.0005 to >1 microm. five analogs exhibited ic(50)s of <3 nm, and three of these exhibited selectivity indices of >600. the most potent compound, wr3 ...200818644969
global metabolic responses of nmri mice to an experimental plasmodium berghei infection.we present a metabolism-driven top-down systems biology approach to characterize metabolic changes in the mouse resulting from an infection with plasmodium berghei, using high-resolution (1)h nmr spectroscopy and multivariate data analysis techniques. twelve female nmri mice were infected intravenously with approximately 20 million p. berghei-parasitized erythrocytes. urine and plasma samples were collected 4-6 h before infection, and at days 1, 2, 3, and 4 postinfection. multivariate analysis o ...200818646786
imc1b is a putative membrane skeleton protein involved in cell shape, mechanical strength, motility, and infectivity of malaria ookinetes.membrane skeletons are cytoskeletal elements that have important roles in cell development, shape, and structural integrity. malaria parasites encode a conserved family of putative membrane skeleton proteins related to articulins. one member, imc1a, is expressed in sporozoites and localizes to the pellicle, a unique membrane complex believed to form a scaffold onto which the ligands and glideosome are arranged to mediate parasite motility and invasion. imc1b is a closely related structural paral ...200818650444
development of smedds using natural lipophile: application to beta-artemether delivery.the objective of the present investigation was to formulate self-microemulsifying drug delivery systems (smedds) using a novel, indigenous natural lipophile (n-lct) as an oily phase. smedds based on n-lct and commercially available modified oil (capryol 90) were formulated and their application in improving the delivery of a lipophilic anti-malarial drug, beta-artemether (bam) was also evaluated. bam-loaded smedds were characterized with respect to mean globule size and in vitro drug release pro ...200818652886
concurrent gastro-intestinal nematode infection does not alter the development of experimental cerebral malaria.concurrent helminth infections have been suggested to be associated with protection against cerebral malaria in humans, a condition characterised by systemic inflammation. here we show that a concurrent chronic gastro-intestinal nematode infection does not alter the course of murine cerebral malaria. mice infected with heligmosomoides polygyrus, and co-infected with plasmodium berghei anka 14 days later, developed malaria parasitemia, weight loss and anemia, at the same rate as mice without nema ...200818656411
gene expression, antiparasitic activity, and functional evolution of the drosomycin family.drosophila employs various antimicrobial peptides as effective weapons to defend against diverse pathogens. drosomycin is an inducible antifungal peptide initially isolated from the drosophila melanogaster haemolymph. here we report the expression pattern of seven drosomycin genes in four different developmental stages (egg, larva, pupa and adult). results show that drosomycin and drosomycin-2 are expressed in larva, pupa and adult, whereas drosomycin-1 and drosomycin-6 were not detected in all ...200818657321
electrospray ionization-ion trap mass spectrometry study of pqaapro and pqproaa mimetic derivatives of the antimalarial primaquine.electrospray ionization-ion trap mass spectrometry (esi-ms) of imidazolidin-4-one peptidomimetic derivatives of the antimalarial drug primaquine (pq) is reported. these compounds contain the imidazolidin-4-one moiety either at the n- or the c-terminal of a dipeptide backbone, thus respectively mimicking pq-amino acid-proline (pqaapro) and pqproaa derivatives of pq. both the peptidomimetics and precursors previously developed by us are promising drug candidates, as they were found to be active ag ...200818657994
control of pathogenic cd8+ t cell migration to the brain by ifn-gamma during experimental cerebral malaria.previous studies have shown that ifn-gamma is essential for the pathogenesis of cerebral malaria (cm) induced by plasmodium berghei anka (pba) in mice. however, the exact role of ifn-gamma in the pathway (s) leading to cm has not yet been described. here, we used 129p2sv/ev mice which develop cm between 7 and 14 days post-infection with pba. in this strain, both cd4(+) and cd8(+) t cells were involved in the effector phase of cm. when 129p2sv/ev mice deficient in the ifn-gamma receptor alpha cha ...200818665903
chemically attenuated plasmodium sporozoites induce specific immune responses, sterile immunity and cross-protection against heterologous challenge.vaccination with plasmodium sporozoites attenuated by irradiation or genetic manipulation induces a protective immune response in rodent malaria models. recently, vaccination with chemically attenuated p. berghei sporozoites (cas) has also been shown to elicit sterile immunity in mice. here we show that vaccination with cas of p. yoelii also protects against homologous infection and that a p. berghei cas vaccine cross protects against heterologous challenge with p. yoelii sporozoites. vaccinatio ...200818672017
synthesis, antimalarial activity, and intracellular targets of mefas, a new hybrid compound derived from mefloquine and artesunate.a new synthetic antimalarial drug, a salt derived from two antimalarial molecules, mefloquine (mq) and artesunate (as), here named mefas, has been tested for its pharmacological activity. combinations of as plus mq hydrochloride are currently being used in areas with drug-resistant plasmodium falciparum parasites; although as clears parasitemia in shorter time periods than any other antimalarial drug, it does not cure infected patients; in addition, mq causes side effects and is rather expensive ...200818710907
recombinant scorpine: a multifunctional antimicrobial peptide with activity against different pathogens.scorpine is an antimicrobial peptide whose structure resembles a hybrid between a defensin and a cecropin. it exhibits antibacterial activity and inhibits the sporogonic development of parasites responsible for murine malaria. in this communication we report the production of scorpine in a heterelogous system, using a specific vector containing its cloned gene. the recombinantly expressed scorpine (rscp) in (anopheles gambie) cells showed antibacterial activity against (bacillus subtilis) and (k ...200818726072
a role of ige and cd23/no immune pathway in age-related resistance of lewis rats to plasmodium berghei anka?in contrast to young rats, adult rats given i.p. plasmodium berghei anka (pba) control the parasitaemia and repair their anaemia. here, we investigated whether ige and cd23/no immune pathway could be implicated in this age-related resistance of adult rats to pba. eight-week-old rats displayed significantly higher levels of plasma total ige (p=0.01) and soluble cd23 (p=0.003) during the peak of parasitaemia, compared to 4-week-old rats. ige fc-binding antibody or aminoguanidine administration to ...200818761417
reverse genetics screen identifies six proteins important for malaria development in the mosquito.transmission from the vertebrate host to the mosquito vector represents a major population bottleneck in the malaria life cycle that can successfully be targeted by intervention strategies. however, to date only about 25 parasite proteins expressed during this critical phase have been functionally analysed by gene disruption. we describe the first systematic, larger scale generation and phenotypic analysis of plasmodium berghei knockout (ko) lines, characterizing 20 genes encoding putatively sec ...200818761621
design and in vivo pharmacodynamic evaluation of nanostructured lipid carriers for parenteral delivery of artemether: nanoject.the objective of the present investigation was to explore the potential of nanostructured lipid carriers (nlc) for the intravenous delivery of artemether (arm), a poorly water-soluble antimalarial agent. the nlc of arm (nanoject) were formulated by employing a microemulsion template technique. the nlc were evaluated for particle size, encapsulation efficiency, in vitro drug release and in vitro hemolysis. the antimalarial activity of the nanoject and conventional arm injectable formulation was e ...200818765274
influence of chlorpromazine on eryptosis, parasitemia and survival of plasmodium berghe infected mice.chlorpromazine has previously been shown to trigger suicidal erythrocyte death or eryptosis, which is characterized by exposure of phosphatidylserine at the erythrocyte surface and cell shrinkage. premature suicidal death of infected erythrocytes is in turn considered to delay development of parasitemia and thus favourably influence the clinical course of malaria. the present experiments have been performed to explore whether chlorpromazine influences in vitro parasite growth and eryptosis of pl ...200818769053
hyperbaric oxygen prevents early death caused by experimental cerebral malaria.cerebral malaria (cm) is a syndrome characterized by neurological signs, seizures and coma. despite the fact that cm presents similarities with cerebral stroke, few studies have focused on new supportive therapies for the disease. hyperbaric oxygen (hbo) therapy has been successfully used in patients with numerous brain disorders such as stroke, migraine and atherosclerosis.200818769544
computational analysis of constraints on noncoding regions, coding regions and gene expression in relation to plasmodium phenotypic diversity.malaria-causing plasmodium species exhibit marked differences including host choice and preference for invading particular cell types. the genetic bases of phenotypic differences between parasites can be understood, in part, by investigating constraints on gene expression and genic sequences, both coding and regulatory.200818769675
immunological profile of a plasmodium vivax ama-1 n-terminus peptide-carbon nanotube conjugate in an infected plasmodium berghei mouse model.we have covalently conjugated an n-terminus plasmodium vivax apical membrane antigen-1 (ama-1) peptide to functionalized carbon nanotubes (f-cnt). immunological characterization of this molecular conjugate revealed that the immunogen-ama-1 peptide was appropriately presented after being conjugated to cnts as well as being recognized by balb/c polyclonal antibodies. subsequent experiments lead us to assess the ama-1 peptide alone, as well as the cnt-peptide conjugate regarding rodent malarial inf ...200818771700
intracellular calcium levels in the plasmodium berghei ookinete.ookinetes are the motile and invasive stages of plasmodium parasites in the mosquito host. here we explore the role of intracellular ca2+ in ookinete survival and motility as well as in the formation of oocysts in vitro in the rodent malaria parasite plasmodium berghei. treatment with the ca2+ ionophore a23187 induced death of the parasite, an effect that could be prevented if the ookinetes were co-incubated with insect cells before incubation with the ionophore. treatment with the intracellular ...200818775093
memory cd8 t cell responses exceeding a large but definable threshold provide long-term immunity to malaria.infection of mice with sporozoites of plasmodium berghei or plasmodium yoelii has been used extensively to evaluate liver-stage protection by candidate preerythrocytic malaria vaccines. unfortunately, repeated success of such vaccines in mice has not translated readily to effective malaria vaccines in humans. thus, mice may be used better as models to dissect basic parameters required for immunity to plasmodium-infection than as preclinical vaccine models. in turn, this basic information may aid ...200818780790
oxidative folding of synthetic polypeptides s-protected as tert-butylthio derivatives.a new method for oxidative folding of synthetic polypeptides assembled by stepwise solid phase synthesis is introduced. folding is obtained in excellent yields by reacting s-tert-butylthiolated polypeptides with a 100-fold molar excess of cysteine at 37 degrees c in a slightly alkaline buffer containing chaotropic salts, and in the presence of air-oxygen. this novel protocol has been applied to the folding of s-tert-butylthiolated human thymus and activation-regulated chemokine (hu-tarc) derivat ...200818781562
effect of cyclosporine on parasitemia and survival of plasmodium berghei infected mice.cyclosporine triggers suicidal erythrocyte death or eryptosis, which is characterized by cell shrinkage and exposure of phosphatidylserine at the erythrocyte surface. the present study explored whether cyclosporine influences eryptosis of plasmodium infected erythrocytes, development of parasitemia and thus the course of the disease. annexin v binding was utilized to depict phosphatidylserine exposure and forward scatter in facs analysis to estimate erythrocyte volume. in vitro infection of huma ...200818789889
plasmodium berghei: lack of antimalarial activity of an analogue of folate precursor, 2,4-diamino-6-hydroxymethylpteridine in a mouse model.it was earlier hypothesized that the malarial parasite may convert precursors of folate analogues to synthesize de novo inhibitors toxic to itself, but not to the mammalian cell. it was suggested that one such analogue, 2,4-diamino-6-hydroxymethylpteridine (dap) may be converted to aminopterin (amp), a known dihydrofolate reductase inhibitor. in the present study, we evaluated the ability of dap to inhibit proliferation of plasmodium berghei nk65 in mice, with(out) folinic acid rescue. cumulativ ...200818789931
use of a drosophila model to identify genes regulating plasmodium growth in the mosquito.we performed a forward genetic screen, using drosophila as a surrogate mosquito, to identify host factors required for the growth of the avian malaria parasite, plasmodium gallinaceum. we identified 18 presumed loss-of-function mutants that reduced the growth of the parasite in flies. presumptive mutation sites were identified in 14 of the mutants on the basis of the insertion site of a transposable element. none of the identified genes have been previously implicated in innate immune responses ...200818791251
class ii-restricted protective immunity induced by malaria sporozoites.the irradiated-sporozoite vaccine elicits sterile immunity against plasmodium parasites in experimental rodent hosts and human volunteers. based on rodent malaria models, it has been proposed that cd8+ t cells are the key protective effector mechanism required in sporozoite-induced immunity. to investigate the role of class ii-restricted immunity in protective immunity, we immunized beta2-microglobulin knockout (beta2m-/-) mice with irradiated plasmodium yoelii or p. berghei sporozoites. sterile ...200818160479
can transgenic mosquitoes afford the fitness cost?in a recent study, sm1-transgenic anopheles stephensi, which are resistant partially to plasmodium berghei, had higher fitness than non-transgenic mosquitoes when they were maintained on plasmodium-infected blood. this result should be interpreted cautiously with respect to malaria control using transgenic mosquitoes because, despite the evolutionary advantage conferred by the transgene, a concomitant cost prevents it from invading the entire population. indeed, for the spread of a resistance tr ...200818164248
protective cd8 t cells against plasmodium liver stages: immunobiology of an 'unnatural' immune response.summary: immunization with high doses of irradiated sporozoites delivered by the bites of infected mosquitoes has been shown to induce protective responses against malaria, mediated in part by cd8(+) t cells. in contrast, natural transmission involving low exposure to live sporozoite antigen fails to elicit strong immunity. in this review, we examine how irradiated sporozoite immunization breaks the natural host-parasite interaction and induces protective cd8(+) t cells. upon biting, the malaria ...200818837788
complement factors c1q, c3 and c5 in brain and serum of mice with cerebral malaria.the patho-mechanisms leading to brain damage due to cerebral malaria (cm) are yet not fully understood. immune-mediated and ischaemic mechanisms have been implicated. the role of complement factors c1q, c3 and c5 for the pathogenesis of cm were investigated in this study.200818847493
semisynthesis and antiplasmodial activity of the quinoline alkaloid aurachin e.a one-step synthesis of the rare aurachin e (1) from the easily accessible aurachin c (2) and cyanogen bromide is described. 3-bromocarbamoylquinoline (5) is formed in a side reaction with concomitant loss of the 3-farnesyl residue. in an alternative approach, aurachin d (3) was reacted with phosgene and sodium azide to form the imidazolone ring of 1 via n-acylation. unexpectedly, the initial reaction occurred at the carbonyl group of 3 to give 1h-pyrrolo[3,2-c]quinoline 4. the reaction sequence ...200818922036
gene disruption of plasmodium falciparum p52 results in attenuation of malaria liver stage development in cultured primary human hepatocytes.difficulties with inducing sterile and long lasting protective immunity against malaria with subunit vaccines has renewed interest in vaccinations with attenuated plasmodium parasites. immunizations with sporozoites that are attenuated by radiation (ras) can induce strong protective immunity both in humans and rodent models of malaria. recently, in rodent parasites it has been shown that through the deletion of a single gene, sporozoites can also become attenuated in liver stage development and, ...200818958160
mdr1a (abcb1)-deficient cf-1 mutant mice are susceptible to cerebral malaria induced by plasmodium berghei anka.under experimental conditions, plasmodium berghei infection causes cerebral malaria (cm) in susceptible strains of mice such as c57bl/6 and cba/ca, whereas balb/c or dba/2j strains serve as a model for cm-resistant mice. the aim of the present study was to investigate the susceptibility of the cf1 mouse strain, carrying a spontaneous mutation of the mdr1a gene, to infection with plasmodium berghei anka (pba). the mdr1a gene codes for p-glycoprotein (p-gp/abcb1), an efflux pump that is one of the ...200818973419
proteomic profiling of plasmodium sporozoite maturation identifies new proteins essential for parasite development and infectivity.plasmodium falciparum sporozoites that develop and mature inside an anopheles mosquito initiate a malaria infection in humans. here we report the first proteomic comparison of different parasite stages from the mosquito -- early and late oocysts containing midgut sporozoites, and the mature, infectious salivary gland sporozoites. despite the morphological similarity between midgut and salivary gland sporozoites, their proteomes are markedly different, in agreement with their increase in hepatocy ...200818974882
structural basis for parasite-specific functions of the divergent profilin of plasmodium falciparum.profilins are key regulators of actin dynamics. they sequester actin monomers, forming a pool for rapid polymer formation stimulated by proteins such as formins. apicomplexan parasites utilize a highly specialized microfilament system for motility and host cell invasion. their genomes encode only a small number of divergent actin regulators. we present the first crystal structure of an apicomplexan profilin, that of the malaria parasite plasmodium falciparum, alone and in complex with a polyprol ...200819000816
cutting edge: selective blockade of light-lymphotoxin beta receptor signaling protects mice from experimental cerebral malaria caused by plasmodium berghei anka.studies in experimental cerebral malaria (ecm) in mice have identified t cells and tnf family members as critical mediators of pathology. in this study we report a role for light-lymphotoxin beta receptor (ltbetar) signaling in the development of ecm and control of parasite growth. specific blockade of light-ltbetar, but not light-herpesvirus entry mediator interactions, abrogated the accumulation of parasites and the recruitment of pathogenic cd8(+) t cells and monocytes to the brain during inf ...200819017933
concurrent infection with heligmosomoides polygyrus modulates murine host response against plasmodium berghei anka infection.we investigated whether concurrent infection with heligmosomoides polygyrus, an intestinal nematode, modulated anti-malaria parasite immunity and development of experimental cerebral malaria (ecm) in mice. the c57bl/6 mice infected with plasmodium berghei anka showed typical symptoms of ecm. interestingly, preceding h. polygyrus infection did not alter ecm development, despite accelerated p. berghei growth in vivo. our observation provides a new insight that ecm can be induced in a fashion indep ...200819052285
failure of two distinct anti-apoptotic approaches to reduce mortality in experimental cerebral malaria.cerebral malaria is responsible for a high proportion of mortality in human plasmodium falciparum infection. previous studies have reported the presence of apoptosis in endothelial cells, astrocytes, neurons, and glial cells in experimental murine cerebral malaria caused by infection with plasmodium berghei anka. using this model, we tested two strategies, which have been shown to improve survival in murine models of sepsis: 1) treatment with z-vad, a pancaspase inhibitor; and 2) overexpression ...200819052286
reduced protective effect of plasmodium berghei immunization by concurrent schistosoma mansoni infection.studies on concomitant schistosomiasis and human and experimental malaria have shown a variation in the immunospecific response, as well as an increase in the severity of both parasitoses. in the present study, a murine co-infection model was used to determine the effects of a co-infection with schistosoma mansoni and plasmodium berghei on the protective immunity acquired by repeated malarial infections and subsequent curative treatment with chloroquine. our results have demonstrated that, compa ...200819057817
possible involvement of ifn-gamma in early mortality of plasmodium berghei nk65-infected balb/c mice after febrifugine treatment.parasitemia patterns, survival and cytokine levels of plasmodium berghei nk65-infected balb/c mice, treated orally with the alkaloidal mixture of febrifugine and isofebrifugine at a dose of 1 mg/kg twice a day for 4 consecutive days were monitored. whereas the untreated mice showed a progressive increase in parasitemia and ultimate death, the alkaloid mixture-treated group showed a transient suppression of parasitemia during the course of treatment. however, the parasitemia increased on disconti ...200819062681
the fatty acid biosynthesis enzyme fabi plays a key role in the development of liver-stage malarial parasites.the fatty acid synthesis type ii pathway has received considerable interest as a candidate therapeutic target in plasmodium falciparum asexual blood-stage infections. this apicoplast-resident pathway, distinct from the mammalian type i process, includes fabi. here, we report synthetic chemistry and transfection studies concluding that plasmodium fabi is not the target of the antimalarial activity of triclosan, an inhibitor of bacterial fabi. disruption of fabi in p. falciparum or the rodent para ...200819064257
influence of amitriptyline on eryptosis, parasitemia and survival of plasmodium berghei-infected mice.plasmodia express a sphingomyelinase, which is apparently required for their development. on the other hand, the sphingomyelinase product ceramide has previously been shown to delay parasite development. moreover, ceramide triggers suicidal erythrocyte death or eryptosis, characterized by exposure of phosphatidylserine at the erythrocyte surface and cell shrinkage. accelerated eryptosis of infected erythrocytes is considered to clear infected erythrocytes from circulating blood and, thus, to fav ...200819088422
[construction and expression of plasmodium berghei chimeric protein in pichia pastoris and its immunogenicity in mice].to produce an erythrocytic stage chimeric protein of plasmodium berghei in pichia pastoris and evaluate its immunogenicity.200819157293
[natural concentration of antimalaric components in tropical arthropods (in vitro)].alcohol, hexane and dichlorometane extracts of 751 samples of costa rican arthropods were studied for the presence of antimalaric components. with plasmodium berghei we set an in vitro model in which the effect of the extract was determined by staining of the parasites with cresil brilliant blue. active extracts at concentration of 50 mg or less, were considered positive. promissory extracts were found in the orders lepidoptera (24.1%), coleoptera (32.8%), hemiptera (38.5%) and polydesmida (81.3 ...200819256421
in vivo antimalarial activity of leaves of plectranthus amboinicus (lour) spreng on plasmodium berghei yoelii.an invivo study of aqueous extract of the leaves of plectranthus amboinicus on plasmodium berghei yoelii was conducted on laboratory infected albino mice and compared with standard drug chloroquine. reduction of parasitemia at 250 mg/kg and 500 mg/kg of aqueous extract for 24 hrs, 48 hrs, 72 hrs and 96 hrs were determined. the reduction of parasitemia after 96 hrs was 100%, 67.9% and 76.2% for standard, 250 mg/kg and 500 mg/kg of aqueous extract respectively. the isolation of active principle re ...200819301696
chemical attenuation of plasmodium berghei sporozoites induces sterile immunity in mice.radiation and genetic attenuation of plasmodium sporozoites are two approaches for whole-organism vaccines that protect against malaria. we evaluated chemical attenuation of sporozoites as an alternative vaccine strategy. sporozoites were treated with the dna sequence-specific alkylating agent centanamycin, a compound that significantly affects blood stage parasitemia and transmission of murine malaria and also inhibits plasmodium falciparum growth in vitro. here we show that treatment of plasmo ...200818174336
recombinant human erythropoietin increases survival and reduces neuronal apoptosis in a murine model of cerebral malaria.cerebral malaria (cm) is an acute encephalopathy with increased pro-inflammatory cytokines, sequestration of parasitized erythrocytes and localized ischaemia. in children cm induces cognitive impairment in about 10% of the survivors. erythropoietin (epo) has - besides of its well known haematopoietic properties - significant anti-inflammatory, antioxidant and anti-apoptotic effects in various brain disorders. the neurobiological responses to exogenously injected epo during murine cm were examine ...200818179698
protection against cerebral malaria by the low-molecular-weight thiol pantethine.we report that administration of the low-molecular-weight thiol pantethine prevented the cerebral syndrome in plasmodium berghei anka-infected mice. the protection was associated with an impairment of the host response to the infection, with in particular a decrease of circulating microparticles and preservation of the blood-brain barrier integrity. parasite development was unaffected. pantethine modulated one of the early steps of the inflammation-coagulation cascade, i.e., the transbilayer tra ...200818195363
antiplasmodial triterpenoids from ekebergia capensis.from the stem bark of ekebergia capensis, 10 new triterpenoid compounds, ekeberins a (1), b (2), c1 (3), c2 (4), c3 (5), d1 (6), d2 (7), d3 (8), d4 (9), and d5 (10), were isolated together with 17 known compounds. the structures of these new compounds were elucidated on the basis of the results of spectroscopic analysis, and the absolute configuration of compounds 6-10 were determined by partial synthesis from known compounds and using the mosher ester method. several of these compounds were scr ...200818220356
synthesis and antimalarial activity of semicarbazone and thiosemicarbazone derivatives.seventeen semicarbazone and thiosemicarbazone derivatives were prepared and tested in vitro against a chloroquine resistant strain of plasmodium falciparum (w2) to evaluate their antiplasmodial potential. three thiosemicarbazones were found to be active against the parasite and non-toxic to human peripheral blood mononuclear cells (pbmc). among these, compound 5b presented the lowest ic50 value against p. falciparum (7.2 microm) and was the least toxic in the pbmc proliferation assay (ic50=73.5 ...200818222568
synthesis and antimalarial activity of carbamate and amide derivatives of 4-anilinoquinoline.a series of 4-anilinoquinolines bearing an amino side chain linked to the aromatic ring with a carbamate or an amide bond were synthesized and evaluated for their antimalarial activity and their cytotoxicity upon mrc-5 cells. among the 17 compounds, a majority was found to be active in the low nanomolar range against both chloroquine-sensitive and -resistant strains of plasmodium falciparum in vitro with relative low cytotoxicity. two compounds were then tested on mice infected by plasmodium ber ...200818226428
inhibition of histamine-mediated signaling confers significant protection against severe malaria in mouse models of disease.from the inoculation of plasmodium sporozoites via anopheles mosquito bites to the development of blood-stage parasites, a hallmark of the host response is an inflammatory reaction characterized by elevated histamine levels in the serum and tissues. given the proinflammatory and immunosuppressive activities associated with histamine, we postulated that this vasoactive amine participates in malaria pathogenesis. combined genetic and pharmacologic approaches demonstrated that histamine binding to ...200818227221
malaria-infected mice are cured by oral administration of new artemisinin derivatives.in four or five chemical steps from the 1,2,4-trioxane artemisinin, a new series of 23 trioxane dimers has been prepared. eleven of these new trioxane dimers cure malaria-infected mice via oral dosing at 3 x 30 mg/kg. the clinically used trioxane drug sodium artesunate prolonged mouse average survival to 7.2 days with this oral dose regimen. in comparison, animals receiving no drug die typically on day 6-7 postinfection. at only 3 x 10 mg/kg oral dosing, seven dimers prolong the lifetime of mala ...200818232653
beta-hematin interaction with the hemopexin domain of gelatinase b/mmp-9 provokes autocatalytic processing of the propeptide, thereby priming activation by mmp-3.gelatinase b or matrix metalloproteinase-9 is involved in inflammation and in autoimmune and vascular diseases. in contrast to the constitutive and homeostatic matrix metalloproteinase-2, matrix metalloproteinase-9 is an inducible enzyme. furthermore, it needs tight regulation, and a major control mechanism of its enzymatic activity is the activation of the latent enzyme by proteolysis of the 87 residue propeptide. activated matrix metalloproteinase-9 is detected in many vascular or hematologica ...200818237197
the gram-negative bacteria-binding protein gene family: its role in the innate immune system of anopheles gambiae and in anti-plasmodium defence.gram-negative bacteria-binding proteins (gnbps) are pattern recognition receptors which contribute to the defensive response against plasmodium infection in anopheles. we have characterized the gnbp gene family in anopheles gambiae at the molecular level, and show that they are functionally diverse components of the a. gambiae innate immune system. gnbpb4 is a major factor in the defence against a broad range of pathogens, while the other gnbps have narrower defence specificities. gnbpb4 is asso ...200818237283
new bis(2-aminoimidazoline) and bisguanidine dna minor groove binders with potent in vivo antitrypanosomal and antiplasmodial activity.a series of 75 guanidine and 2-aminoimidazoline analogue molecules were assayed in vitro against trypanosoma brucei rhodesiense stib900 and plasmodium falciparum k1. the dicationic diphenyl compounds exhibited the best activities with ic 50 values against t. b. rhodesiense and p. falciparum in the nanomolar range. five compounds (7b, 9a, 9b, 10b, and 14b) cured 100% of treated mice upon ip administration at 20 mg/kg in the difficult to cure t. b. rhodesiense stib900 mouse model. overall, the com ...200818247550
mutation underlying resistance of plasmodium berghei to atovaquone in the quinone binding domain 2 (qo(2)) of the cytochrome b gene.the anti-malarial agent atovaquone specifically targets the cytochrome bc(1) complex and inhibits the parasite respiration. resistance to this drug, a coenzyme q analogue, is associated with mutations in the mitochondrial cytochrome b gene. we previously reported atovaquone resistant mutations in plasmodium berghei, in the first quinone binding domain (qo(1)) of the cytochrome b gene (m133i and l144s) with v284f in the sixth transmembrane domain. however, in p. falciparum the most common mutatio ...200818248769
single-dose protection against plasmodium berghei by a simian adenovirus vector using a human cytomegalovirus promoter containing intron a.human adenovirus serotype 5 (adh5) vector vaccines elicit strong immune responses to the encoded antigen and have been used in various disease models. we designed adh5 vectors expressing antigen under the control of a human cytomegalovirus (hcmv) immediate-early promoter containing its intron a sequence. the transcriptional levels of antigen and immune responses to antigen for vectors with the hcmv promoter with the intron a sequence (lp) were greater than those for adh5 vectors using the hcmv p ...200818256155
the guanylhydrazone cni-1493: an inhibitor with dual activity against malaria-inhibition of host cell pro-inflammatory cytokine release and parasitic deoxyhypusine synthase.malaria is still a major cause of death in the tropics. there is an urgent need for new anti-malarial drugs because drug-resistant plasmodia frequently occur. over recent years, we elucidated the biosynthesis of hypusine, a novel amino acid contained in eukaryotic initiation factor 5a (eif-5a) in plasmodium. hypusine biosynthesis involves catalysis of deoxyhypusine synthase (dhs) in the first step of post-translational modification. in a screen for new inhibitors of purified plasmodium dhs, cni- ...200818256853
antimalarial dual drugs based on potent inhibitors of glutathione reductase from plasmodium falciparum.plasmodium parasites are exposed to higher fluxes of reactive oxygen species and need high activities of intracellular antioxidant systems providing a steady glutathione flux. as a future generation of dual drugs, 18 naphthoquinones and phenols (or their reduced forms) containing three different linkers between the 4-aminoquinoline core and the redox active component were synthesized. their antimalarial effects have been characterized in parasite assays using chloroquine-sensitive and -resistant ...200818260613
single-dose immunogenicity and protective efficacy of simian adenoviral vectors against plasmodium berghei.simian adenoviral vectors (sad) offer an attractive alternative to standard human adenovirus serotype 5 (adh5) subunit vaccination, due to pre-existing immunity affecting vaccine performance. we have used a mouse model of liver-stage malaria to test the efficiency of three chimpanzee-origin adenoviral vectors, adc6, adc7 and adc9 containing me.trap as an insert. adc7 and adc9 elicited strong immunogenicity ( approximately 20% of cd8(+) t cells in spleen), equivalent to or outperforming adh5 and ...200818266272
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