| analysis of mutant plasmodium berghei parasites lacking expression of multiple pbccp genes. | plasmodium encodes a family of six secreted multi-domain adhesive proteins, termed pccps, which are released from gametocytes during emergence within the mosquito midgut. the expression and cellular localization of pccp proteins predict a role either in gametocyte development or within the mosquito midgut during the transition from gametes into the ookinete stage. however, mutant parasites lacking expression of any single pccp protein show a phenotype at the oocyst stage with a failure of oocyst ... | 2009 | 18848846 |
| screening of medicinal plants from reunion island for antimalarial and cytotoxic activity. | nine plants from reunion island, selected using ethnopharmacology and chemotaxonomy, were investigated for their potential antimalarial value. | 2008 | 18848979 |
| [not available]. | | 1948 | 18874862 |
| 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 ... | 2008 | 18922036 |
| 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, ... | 2008 | 18958160 |
| 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 ... | 2008 | 18973419 |
| 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 ... | 2008 | 18974882 |
| the n-terminal domain of plasmodium falciparum circumsporozoite protein represents a target of protective immunity. | the n-terminal domain of the circumsporozoite protein (csp) has been largely neglected in the search for a malaria vaccine in spite of being a target of inhibitory antibodies and protective t cell responses in mice. thus, in order to develop this region as a vaccine candidate to be eventually associated with other candidates and, in particular, with the very advanced c-terminal counterpart, synthetic constructs representing n- and c-terminal regions of plasmodium falciparum and plasmodium berghe ... | 2009 | 18984024 |
| anopheles gambiae apl1 is a family of variable lrr proteins required for rel1-mediated protection from the malaria parasite, plasmodium berghei. | we previously identified by genetic mapping an anopheles gambiae chromosome region with strong influence over the outcome of malaria parasite infection in nature. candidate gene studies in the genetic interval, including functional tests using the rodent malaria parasite plasmodium berghei, identified a novel leucine-rich repeat gene, apl1, with functional activity against p. berghei. | 2008 | 18989366 |
| kinome-wide rnai screen implicates at least 5 host hepatocyte kinases in plasmodium sporozoite infection. | plasmodium sporozoites, the causative agent of malaria, are injected into their vertebrate host through the bite of an infected anopheles mosquito, homing to the liver where they invade hepatocytes to proliferate and develop into merozoites that, upon reaching the bloodstream, give rise to the clinical phase of infection. to investigate how host cell signal transduction pathways affect hepatocyte infection, we used rnai to systematically test the entire kinome and associated genes in human huh7 ... | 2008 | 18989463 |
| antiplasmodial activity of root extract and fractions of croton zambesicus. | antiplasmodial activity of root extract and fractions of croton zambesicus were evaluated to ascertain the folkloric claim of its antimalarial activity and elucidate its antiplasmodial mechanism of action. | 2009 | 18996464 |
| 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 ... | 2008 | 19000816 |
| trep, a novel protein necessary for gliding motility of the malaria sporozoite. | the invasive stages of parasites of the protozoan phylum apicomplexa have the capacity to traverse host tissues and invade host cells using a unique type of locomotion called gliding motility. gliding motility is powered by a sub-membranous actin-myosin motor, and the force generated by the motor is transduced to the parasite surface by transmembrane proteins of the apicomplexan-specific thrombospondin-related anonymous protein (trap) family. these proteins possess short cytoplasmic tails that i ... | 2009 | 19000911 |
| secreted antibody is required for immunity to plasmodium berghei. | infection with plasmodium berghei is lethal to mice, causing high levels of parasitemia, severe anemia, and death. however, when mice are treated with antimalarial drugs during acute infection, they have enhanced immunity to subsequent infections. with this infection and cure model of immunity, we systematically examined the basis of adaptive immunity to infection using immunodeficient mice. in order to induce adaptive immunity, mice were infected with blood-stage parasites. when the mice develo ... | 2009 | 19001073 |
| compounds structurally related to ellagic acid show improved antiplasmodial activity. | the cancer chemopreventive agent ellagic acid (ea) is a known inhibitor of glutathione s-transferases (gsts) and possesses antiplasmodial activities in the upper-nanomolar range. in the recent drug development approach, the properties of the active site of plasmodium falciparum gst were exploited for inhibitor design by introducing one or two additional hydroxyl groups into ea, yielding flavellagic acid (fea) and coruleoellagic acid (cea), respectively. indeed, the inhibition of p. falciparum gs ... | 2009 | 19015351 |
| role for the plasmodium sporozoite-specific transmembrane protein s6 in parasite motility and efficient malaria transmission. | malaria transmission occurs by intradermal deposition of plasmodium sporozoites during the infectious bite of a female anopheles mosquito. after formation in midgut-associated oocysts sporozoites actively enter mosquito salivary glands and subsequently invade host hepatocytes where they transform into clinically silent liver stages. to date, two sporozoite-specific transmembrane proteins have been identified that perform vital functions in natural malaria transmission. the sporozoite invasin tra ... | 2009 | 19016774 |
| 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 ... | 2008 | 19017933 |
| synthesis and evaluation of 1,1'-hydrocarbylenebis(indazol-3-ols) as potential antimalarial drugs. | bis(indazol-3-ol) derivatives (5, 30-38) were prepared by alkylation of 3-alkoxyindazoles with alpha,omega-dibromides, followed by removal of the o-protecting groups. these compounds were subsequently evaluated as inhibitors of biocrystallization of ferriprotoporphyrin ix (heme) to hemozoin, a plasmodium detoxification specific process. most bis(5-nitroindazol-3-ols) were good inhibitors, however, a denitro analogue (38), the intermediate bis(3-alkoxyindazoles) (15-29) as well as bis(indazolin-3 ... | 2009 | 19025734 |
| alteration of the parasite plasma membrane and the parasitophorous vacuole membrane during exo-erythrocytic development of malaria parasites. | the rodent malaria parasite plasmodium berghei develops in hepatocytes within 48-52h from a single sporozoite into up to 20,000 daughter parasites, so-called merozoites. the cellular and molecular details of this extensive proliferation are still largely unknown. here we have used a transgenic, rfp-expressing p. berghei parasite line and molecular imaging techniques including intravital microscopy to decipher various aspects of parasite development within the hepatocyte. in late schizont stages, ... | 2009 | 19026596 |
| hiv protease inhibitors inhibit the development of preerythrocytic-stage plasmodium parasites. | recent studies have demonstrated that human immunodeficiency virus (hiv) protease inhibitors (pis) exert inhibitory effects on erythrocytic stages of the human-malaria parasite plasmodium falciparum in vitro and on erythrocytic stages of the rodent-malaria parasite plasmodium chabaudi in vivo. although it remains unclear how hiv pis inhibit the parasite, the effect seen on parasite development in the erythrocytic stages is potent. the effect on preerythrocytic stages has not yet been investigate ... | 2009 | 19032102 |
| letter to the editor on effect of cyclosporine on parasitemia and survival of plasmodium berghei-infected mice. | | 2009 | 19032941 |
| synthesis of chlorovinyl sulfones as structural analogs of chalcones and their antiplasmodial activities. | the synthesis of novel chlorovinyl sulfone-like chalcone derivatives and their antimalarial activity against cultured plasmodium falciparum parasites, hemozoin formation, hemoglobin hydrolysis and murine malaria model are described. compounds were prepared via claisen-schmidt condensation from available chloromethylphenyl sulfones with substituted aldehydes. antiplasmodial ic(50) activity of these compounds ranged between 0.025 and 10 microm, those that blocked p. falciparum development at low m ... | 2009 | 19036479 |
| filarial infection induces protection against p. berghei liver stages in mice. | chronic helminth infections such as filariasis in human hosts can be life long, since parasites are equipped with a repertoire of immune evasion strategies. in many areas where helminths are prevalent, other infections such as malaria are co-endemic. it is still an ongoing debate, how one parasite alters immune responses against another. to dissect the relationships between two different parasites residing in the same host, we established a murine model of co-infection with the filarial nematode ... | 2009 | 19049828 |
| 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 ... | 2008 | 19052285 |
| 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 ... | 2008 | 19052286 |
| 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 ... | 2008 | 19057817 |
| screening of antiplasmodial properties among some traditionally used iranian plants. | an investigation of plants was undertaken through interviews and literature surveys on plants used to treat malaria or cancer or microbial diseases in iran. | 2009 | 19059470 |
| 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 ... | 2008 | 19062681 |
| 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 ... | 2008 | 19064257 |
| egf domain ii of protein pb28 from plasmodium berghei interacts with monoclonal transmission blocking antibody 13.1. | development of a vaccine against malaria is a major global health concern. the p28 proteins expressed on the surface of ookinetes of plasmodium are the targets of transmission blocking antibodies. injection of p28 proteins in vertebrate hosts induces antibodies that inhibit oocyst formation, blocking transmission of the parasite from mosquitos to human hosts. p28 proteins are crucial for parasite protection inside the mosquito midgut. despite their importance, structural details of p28 family me ... | 2009 | 19066995 |
| wave expansion of cd34+ progenitor cells in the spleen in rodent malaria. | defense against malaria depends upon amplification of the spleen structure and function for the clearance of parasitized red blood cells (prbc). we studied the distribution and amount of cd34(+) cells in the spleens of mice infected with rodent malaria. we sought to identify these cells in the spleen and determine their relationship to infection. c57bl/6j mice were infected with self-resolving, plasmodium chabaudi cr, or one of the lethal rodent malaria strains, p. chabaudi aj and p. berghei ank ... | 2009 | 19068215 |
| passive transfer of plasmodium falciparum msp-2 pseudopeptide-induced antibodies efficiently controlled parasitemia in plasmodium berghei-infected mice. | we have developed monoclonal antibodies directed against the pseudopeptide psi-130, derived from the highly conserved malarial antigen plasmodium falciparum merozoite surface protein 2 (msp-2), for obtaining novel molecular tools with potential applications in the control of malaria. following isotype switching, these antibodies were tested for their ability to suppress blood-stage parasitemia through passive immunization in malaria-infected mice. some proved totally effective in suppressing a l ... | 2009 | 19071172 |
| 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 ... | 2008 | 19088422 |
| anopheles mosquitoes: not just flying malaria vectors... especially in the field. | the polymorphism of genes involved in the immunity of malaria vectors has been the subject of several recent studies with mosquitoes from natural populations. most of the genes examined are known for their role against plasmodium berghei and not necessarily for their role against plasmodium falciparum. it seems, therefore, to be highly important not only to be cautious when linking natural selection with malaria epidemiology but also to consider the importance of other parasites and the environm ... | 2009 | 19095498 |
| indolizidine, antiinfective and antiparasitic compounds from prosopis glandulosa var. glandulosa. | a new potent antiinfective and antiparasitic 2,3-dihydro-1h-indolizinium chloride (1) was isolated from prosopis glandulosa var. glandulosa. three additional new (2-4) and one known (5) indolizidines were also isolated, and the dihydrochloride salts of 1-3 (compounds 6, 7, and 8) were prepared. structures were determined by 1d and 2d nmr and mass spectra. compound 1 showed potent in vitro antifungal activity against cryptococcus neoformans and aspergillus fumigatus (ic(50) values = 0.4 and 3.0 m ... | 2009 | 19105653 |
| intranasal administration of the synthetic polypeptide from the c-terminus of the circumsporozoite protein of plasmodium berghei with the modified heat-labile toxin of escherichia coli (ltk63) induces a complete protection against malaria challenge. | needle-free procedures are very attractive ways to deliver vaccines because they diminish the risk of contamination and may reduce local reactions, pain or pain fear especially in young children with a consequence of increasing the vaccination coverage for the whole population. for this purpose, the possible development of a mucosal malaria vaccine was investigated. intranasal immunization was performed in balb/c mice using a well-studied plasmodium berghei model antigen derived from the circums ... | 2009 | 19111883 |
| identification and bioinformatic characterization of a multidrug resistance associated protein (abcc) gene in plasmodium berghei. | the atp-binding cassette (abc) superfamily is one of the largest evolutionarily conserved families of proteins. abc proteins play key roles in cellular detoxification of endobiotics and xenobiotics. overexpression of certain abc proteins, among them the multidrug resistance associated protein (mrp), contributes to drug resistance in organisms ranging from human neoplastic cells to parasitic protozoa. in the present study, the plasmodium berghei mrp gene (pbmrp) was partially characterized and th ... | 2009 | 19118502 |
| salivary gland transcriptome analysis during plasmodium infection in malaria vector anopheles stephensi. | understanding the tissue-specific molecular cross-talk mechanism during the mosquito-parasite interaction is of prime importance in the design of new strategies for malaria control. because mosquito salivary glands are the final destination for the parasite maturation and transmission of vector-borne diseases, identification and characterization of salivary genes and their products are equally important in order to access their effect on the infectivity of the parasite. during the last five year ... | 2009 | 19128996 |
| plasmodium male development gene-1 (mdv-1) is important for female sexual development and identifies a polarised plasma membrane during zygote development. | successful development of plasmodium sexual stages is essential for parasite survival, but the genes involved are poorly understood. we 'knocked out' the male development gene-1 (mdv-1) locus in plasmodium berghei and found it to be important in female gametocyte activation. indirect immunofluorescence assays show mdv-1 has a punctate cytoplasmic distribution in gametocytes. after activation of both females and males, mdv-1 is more peripherally located but in males exclusively it becomes concent ... | 2009 | 19136003 |
| gfp-targeting allows visualization of the apicoplast throughout the life cycle of live malaria parasites. | the plasmodium parasite, during its life cycle, undergoes three phases of asexual reproduction, these being repeated rounds of erythrocytic schizogony, sporogony within oocysts on the mosquito midgut wall and exo-erythrocytic schizogony within the hepatocyte. during each phase of asexual reproduction, the parasite must ensure that every new daughter cell contains an apicoplast, as this organelle cannot be formed de novo and is essential for parasite survival. to date, studies visualizing the api ... | 2009 | 19143588 |
| distinct roles of plasmodium rhomboid 1 in parasite development and malaria pathogenesis. | invasion of host cells by the malaria parasite involves recognition and interaction with cell-surface receptors. a wide variety of parasite surface proteins participate in this process, most of which are specific to the parasite's particular invasive form. upon entry, the parasite has to dissociate itself from the host-cell receptors. one mechanism by which it does so is by shedding its surface ligands using specific enzymes. rhomboid belongs to a family of serine proteases that cleave cell-surf ... | 2009 | 19148267 |
| [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. | 2008 | 19157293 |
| rab11a-controlled assembly of the inner membrane complex is required for completion of apicomplexan cytokinesis. | the final step during cell division is the separation of daughter cells, a process that requires the coordinated delivery and assembly of new membrane to the cleavage furrow. while most eukaryotic cells replicate by binary fission, replication of apicomplexan parasites involves the assembly of daughters (merozoites/tachyzoites) within the mother cell, using the so-called inner membrane complex (imc) as a scaffold. after de novo synthesis of the imc and biogenesis or segregation of new organelles ... | 2009 | 19165333 |
| synthesis and antimalarial activities of cyclen 4-aminoquinoline analogs. | in an attempt to augment the efficacy of 7-chloro 4-aminoquinoline analogs and also to overcome resistance to antimalarial agents, we synthesized three cyclen (1,4,7,10-tetraazacyclododecane) analogs of chloroquine [a bisquinoline derivative, 7-chloro-4-(1,4,7,10-tetraaza-cyclododec-1-yl)-quinoline hbr, and a 7-chloro-4-(1,4,7,10-tetraaza-cyclododec-1-yl)-quinoline-zn(2+) complex]. the bisquinoline displays the most potent in vitro and in vivo antimalarial activities. it displays 50% inhibitory ... | 2009 | 19171802 |
| in vivo anti-malarial effect of the beta-amino alcohol 1t on plasmodium berghei. | glycerol derivatives are a class of compounds, which are easy and inexpensive to produce with potent anti-malarial activities against blood stages of plasmodium falciparum in vitro. in the present study, one of these compounds, termed 1t, which had the lowest ic(50) values, was assessed in a murine malarial model. nuclear magnetic resonance imaging and balb/c mice infected with plasmodium berghei anka strain were treated in a 4-day suppressive test. mice received a once-daily intraperitoneal adm ... | 2009 | 19172294 |
| pharmacodynamics and pharmacokinetics studies of phenoxazinium derivatives for antimalarial agent. | in vivo antimalarial drug candidates screening test was carried out on a series of water-soluble 3,7-bis(dialkylamino)phenoxazin-5-ium derivatives. among them, 3-(diethylamino)-7-(piperidin-1-yl)phenoxazin-5-ium chloride (ssj-206) showing highest efficacy was chosen for further pharmcodynamics and pharmacokinetics study. it was supported from these data that the phenoxazinium salts, ssj-206, would be one of hopeful candidates as an oral antimalarial drug. | 2009 | 19181530 |
| disruption of plasmodium sporozoite transmission by depletion of sporozoite invasion-associated protein 1. | accumulation of infectious plasmodium sporozoites in anopheles spp. salivary glands marks the final step of the complex development of the malaria parasite in the insect vector. sporozoites are formed inside midgut-associated oocysts and actively egress into the mosquito hemocoel. traversal of the salivary gland acinar cells correlates with the sporozoite's capacity to perform continuous gliding motility. here, we characterized the cellular role of the plasmodium berghei sporozoite invasion-asso ... | 2009 | 19181869 |
| anopheles fibrinogen-related proteins provide expanded pattern recognition capacity against bacteria and malaria parasites. | the fibrinogen-related protein family (frep, also known as fbn) is an evolutionarily conserved immune gene family found in mammals and invertebrates. it is the largest pattern recognition receptor gene family in anopheles gambiae, with as many as 59 putative members, while the drosophila melanogaster genome has only 14 known frep members. our sequence and phylogenetic analysis suggest that this remarkable gene expansion in the mosquito is the result of tandem duplication of the fibrinogen domain ... | 2009 | 19193639 |
| effect of dequalinium on the oxidative stress in plasmodium berghei-infected erythrocytes. | the bisquinoline drug dequalinium (dq) has demonstrated remarkable activity against some infection diseases, including malaria. oxidative stress represents a biochemical target for potential antimalarials. in this work, we have tested the ability of this compound to modify the oxidative status in plasmodium berghei-infected erythrocytes. after hemolysis, activities of superoxide dismutase (sod), catalase (cat), glutathione cycle, and dehydrogenase enzymes were investigated. the activity of gluco ... | 2009 | 19205739 |
| challenges in the determination of early predictors of cerebral malaria: lessons from the human disease and the experimental murine models. | cerebral malaria (cm) is a life-threatening complication of malaria caused by plasmodium falciparum, and it claims around two million lives a year, mainly those of children in sub-saharan africa. a number of works, particularly in murine models of cm, showed that several mediators are involved in the development of the disease, including monocytes, t lymphocytes, cytokines, chemokines, platelets, nitric oxide scavengers and heme, among others, but a comprehensive understanding of the pathogenesi ... | 2009 | 19212133 |
| the immunomodulatory effect of sambucol on leishmanial and malarial infections. | a nontoxic dose of sambucol, an immunomodulator commercially sold as an immune stimulator, was examined in murine models of leishmaniasis and malaria. sambucol causes a shift in the immune response, as demonstrated in human monocyte cultures, to th1 (inflammation-associated) responses. treatment of leishmania-infected mice with sambucol delayed the development of the disease. as there was no direct in vitro anti-leishmanial effect, the observed partial protection in vivo is most likely related t ... | 2009 | 19214946 |
| anti-malarial activities of andrographis paniculata and hedyotis corymbosa extracts and their combination with curcumin. | herbal extracts of andrographis paniculata (ap) and hedyotis corymbosa (hc) are known as hepato-protective and fever-reducing drugs since ancient time and they have been used regularly by the people in the south asian sub-continent. methanolic extracts of these two plants were tested in vitro on choloroquine sensitive (mrc-pf-20) and resistant (mrc-pf-303) strains of plasmodium falciparum for their anti-malarial activity. | 2009 | 19216765 |
| host-parasite interactions revealed by plasmodium falciparum metabolomics. | intracellular pathogens have devised mechanisms to exploit their host cells to ensure their survival and replication. the malaria parasite plasmodium falciparum relies on an exchange of metabolites with the host for proliferation. here we describe a mass spectrometry-based metabolomic analysis of the parasite throughout its 48 hr intraerythrocytic developmental cycle. our results reveal a general modulation of metabolite levels by the parasite, with numerous metabolites varying in phase with the ... | 2009 | 19218089 |
| identification of a transcription factor in the mosquito-invasive stage of malaria parasites. | gene expression in plasmodium parasites undergoes significant changes in each developmental stage, but the transcription factors (tfs) regulating these changes have not been identified. we report here a plasmodium tf (ap2-o) that activates gene expression in ookinetes, the mosquito-invasive form, and has a dna-binding domain structurally related to that of a plant tf, apetala2 (ap2). ap2-o mrna is pre-synthesized by intraerythrocytic female gametocytes and translated later during ookinete develo ... | 2009 | 19220746 |
| candidate selection and preclinical evaluation of n-tert-butyl isoquine (gsk369796), an affordable and effective 4-aminoquinoline antimalarial for the 21st century. | n-tert-butyl isoquine (4) (gsk369796) is a 4-aminoquinoline drug candidate selected and developed as part of a public-private partnership between academics at liverpool, mmv, and gsk pharmaceuticals. this molecule was rationally designed based on chemical, toxicological, pharmacokinetic, and pharmacodynamic considerations and was selected based on excellent activity against plasmodium falciparum in vitro and rodent malaria parasites in vivo. the optimized chemistry delivered this novel synthetic ... | 2009 | 19222165 |
| a baculovirus dual expression system-based malaria vaccine induces strong protection against plasmodium berghei sporozoite challenge in mice. | we have previously shown that a recombinant baculovirus that displays plasmodium berghei circumsporozoite protein (pbcsp), a homolog of the leading human malaria vaccine candidate, on the viral envelope protected 60% of mice against p. berghei infection. here, we describe a second-generation baculovirus vaccine based on the "baculovirus dual expression system," which drives pbcsp expression by a dual promoter that consists of tandemly arranged baculovirus-derived polyhedrin and mammal-derived cy ... | 2009 | 19223476 |
| novel inhibitor of plasmodium histone deacetylase that cures p. berghei-infected mice. | histone deacetylases (hdac) are potential targets for the development of new antimalarial drugs. the growth of plasmodium falciparum and other apicomplexans can be suppressed in the presence of potent hdac inhibitors in vitro and in vivo; however, in vivo parasite suppression is generally incomplete or reversible after the discontinuation of drug treatment. furthermore, most established hdac inhibitors concurrently show broad toxicities against parasites and human cells and high drug concentrati ... | 2009 | 19223622 |
| major surface glycoproteins of insect forms of trypanosoma brucei are not essential for cyclical transmission by tsetse. | procyclic forms of trypanosoma brucei reside in the midgut of tsetse flies where they are covered by several million copies of glycosylphosphatidylinositol-anchored proteins known as procyclins. it has been proposed that procyclins protect parasites against proteases and/or participate in tropism, directing them from the midgut to the salivary glands. there are four different procyclin genes, each subject to elaborate levels of regulation. to determine if procyclins are essential for survival an ... | 2009 | 19223969 |
| the glutathione biosynthetic pathway of plasmodium is essential for mosquito transmission. | infection of red blood cells (rbc) subjects the malaria parasite to oxidative stress. therefore, efficient antioxidant and redox systems are required to prevent damage by reactive oxygen species. plasmodium spp. have thioredoxin and glutathione (gsh) systems that are thought to play a major role as antioxidants during blood stage infection. in this report, we analyzed a critical component of the gsh biosynthesis pathway using reverse genetics. plasmodium berghei parasites lacking expression of g ... | 2009 | 19229315 |
| molecular biology and biochemistry of malarial parasite pyrimidine biosynthetic pathway. | metabolic pathways in the malarial parasite are markedly different from the host, eg, hemoglobin, fatty acids, folate and nucleic acids. understanding of metabolic function will illuminate new chemotherapeutic targets for drug development, including the identification of target(s) for drugs in current use. the parasite-contained pyrimidine biosynthetic pathway is essential for growth and development in the human host. plasmodium falciparum carbonic anhydrase, producing hco3- as a pyrimidine prec ... | 2003 | 19230569 |
| the role of nitric oxide and its up/downstream molecules in malaria: cytotoxic or preventive? | the current study investigated the involvement of nitric oxide (no) and related molecules in malaria target organs of outbred mf1 mice during lethal plasmodium berghei and non-lethal p. c. chabaudi infections, in order to evaluate whether changes in no production are beneficial or detrimental to the host. a number of methods have been applied to test this hypothesis, including griess microassay, electrochemical assay, rt-pcr and western blot. the results show that reactive nitrogen intermediate ... | 2003 | 19230570 |
| primaquine dipeptide derivatives bearing an imidazolidin-4-one moiety at the n-terminus as potential antimalarial prodrugs. | primaquine dipeptide derivatives bearing an imidazolidin-4-one moiety at the n-terminus were synthesized and evaluated as potential transmission-blocking antimalarial prodrugs. all compounds were hydrolyzed to the parent dipeptide derivative of primaquine in neutral and basic solutions, with half lives ranging from 0.7 to 31 h at 37 degrees c, depending on the nature of the substituents present in the imidazolidin-4-one moiety and in the c-terminal amino acid directly coupled to primaquine. the ... | 2009 | 19232784 |
| variant-specific immunity to plasmodium berghei in pregnant mice. | we have investigated the immunological basis of pregnancy-related plasmodium berghei recrudescence in immune mice with substantial preexisting immunity. specifically, we examined the relevance of this experimental model to the study of pregnancy-associated malaria (pam) caused by p. falciparum in women with substantial preexisting protective immunity. we used mice with immunity induced prior to pregnancy and employed flow cytometry to assess their levels of immunoglobulin g (igg) recognizing ant ... | 2009 | 19237516 |
| polymeric linear peptide chimeric vaccine-induced antimalaria immunity is associated with enhanced in vitro antigen loading. | immunization of mice with plasmodium berghei or plasmodium yoelii synthetic linear peptide chimeras (lpcs) based on the circumsporozoite protein protects against experimental challenge with viable sporozoites. the immunogenicity of lpcs is significantly enhanced by spontaneous polymerization. to better understand the antigenic properties of polymeric antimalarial peptides, we studied the immune responses elicited in mice immunized with a polymer or a monomer of a linear peptide construct specifi ... | 2009 | 19237530 |
| glatiramer acetate reduces the risk for experimental cerebral malaria: a pilot study. | cerebral malaria (cm) is associated with high mortality and morbidity caused by a high rate of transient or persistent neurological sequelae. studies on immunomodulatory and neuroprotective drugs as ancillary treatment in murine cm indicate promising potential. the current study was conducted to evaluate the efficacy of glatiramer acetate (ga), an immunomodulatory drug approved for the treatment of relapsing remitting multiple sclerosis, in preventing the death of c57bl/6j mice infected with pla ... | 2009 | 19250545 |
| influence of paclitaxel on parasitemia and survival of plasmodium berghei infected mice. | paclitaxel triggers suicidal erythrocyte death or eryptosis, characterized by exposure of phosphatidylserine at the erythrocyte surface and cell shrinkage. eryptosis of infected erythrocytes may delay development of parasitemia and thus favourably influence the course of malaria. the present study explored whether paclitaxel influences in vitro parasite growth and eryptosis of plasmodium falciparum infected human erythrocytes and in vivo parasitemia and survival of plasmodium berghei infected mi ... | 2009 | 19255513 |
| [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 ... | 2008 | 19256421 |
| isolation and identification of a potent antimalarial and antibacterial polyacetylene from bidens pilosa. | diseases caused by malaria parasites and pathogenic bacteria were thought to be on the brink of eradication in the 1950-1960s, but they have once again become a serious threat to mankind as a result of the appearance of multidrug resistant strains. the spread of these multidrug resistant organisms has prompted a worldwide search for new classes of effective antimalarial and antibacterial drugs. natural products have been recognized as highly important candidates for this purpose. our attention h ... | 2009 | 19263339 |
| leucine-rich repeat protein complex activates mosquito complement in defense against plasmodium parasites. | leucine-rich repeat-containing proteins are central to host defense in plants and animals. we show that in the mosquito anopheles gambiae, two such proteins that antagonize malaria parasite infections, lrim1 and apl1c, circulate in the hemolymph as a high-molecular-weight complex held together by disulfide bridges. the complex interacts with the complement c3-like protein, tep1, promoting its cleavage or stabilization and its subsequent localization on the surface of midgut-invading plasmodium b ... | 2009 | 19264986 |
| cd27 is a thymic determinant of the balance between interferon-gamma- and interleukin 17-producing gammadelta t cell subsets. | the production of cytokines such as interferon-gamma and interleukin 17 by alphabeta and gammadelta t cells influences the outcome of immune responses. here we show that most gammadelta t lymphocytes expressed the tumor necrosis factor receptor family member cd27 and secreted interferon-gamma, whereas interleukin 17 production was restricted to cd27(-) gammadelta t cells. in contrast to the apparent plasticity of alphabeta t cells, the cytokine profiles of these distinct gammadelta t cell subset ... | 2009 | 19270712 |
| plasmodium berghei: efficacy of 5-fluoroorotate in combination with commonly used antimalarial drugs in a mouse model. | resistance to antimalarial antifolates necessitates a search for new antimetabolites targeting other enzymes of the folate metabolic pathway. in this study, 5-fluoroorotate (foa), reported to be an inhibitor of thymidylate synthase, was assayed against plasmodium berghei nk 65 in mice, with(out) an oral uridine supplement. foa (2.5 and 5.0 mg/kg bw.) was tested alone, or in a double and triple combination with a fixed oral dose of 1.25 and 2.5 mg/kg of pyrimethamine (pyr); 1.0 and 2.0 mg/kg of d ... | 2009 | 19271282 |
| a possible mechanism for the suppression of plasmodium berghei development in the mosquito anopheles gambiae by the microsporidian vavraia culicis. | microsporidian parasites of mosquitoes offer a possible way of controlling malaria, as they impede the development of plasmodium parasites within the mosquito. the mechanism involved in this interference process is unknown. | 2009 | 19277119 |
| caspar controls resistance to plasmodium falciparum in diverse anopheline species. | immune responses mounted by the malaria vector anopheles gambiae are largely regulated by the toll and imd (immune deficiency) pathways via the nf-kappab transcription factors rel1 and rel2, which are controlled by the negative regulators cactus and caspar, respectively. rel1- and rel2-dependent transcription in a. gambiae has been shown to be particularly critical to the mosquito's ability to manage infection with the rodent malaria parasite plasmodium berghei. using rna interference to deplete ... | 2009 | 19282971 |
| synthesis, antimalarial activity, and preclinical pharmacology of a novel series of 4'-fluoro and 4'-chloro analogues of amodiaquine. identification of a suitable "back-up" compound for n-tert-butyl isoquine. | on the basis of a mechanistic understanding of the toxicity of the 4-aminoquinoline amodiaquine (1b), three series of amodiaquine analogues have been prepared where the 4-aminophenol "metabolic alert" has been modified by replacement of the 4'-hydroxy group with a hydrogen, fluorine, or chlorine atom. following antimalarial assessment and studies on mechanism of action, two candidates were selected for detailed adme studies and in vitro and in vivo toxicological assessment. 4'-fluoro-n-tert-buty ... | 2009 | 19284751 |
| host cell entry by apicomplexa parasites requires actin polymerization in the host cell. | apicomplexa are obligate intracellular parasites that actively invade host cells using their membrane-associated, actin-myosin motor. the current view is that host cell invasion by apicomplexa requires the formation of a parasite-host cell junction, which has been termed the moving junction, but does not require the active participation of host actin. using toxoplasma gondii tachyzoites and plasmodium berghei sporozoites, we show that host actin participates in parasite entry. parasites induce t ... | 2009 | 19286135 |
| plasmodium chabaudi: expression of active recombinant chabaupain-1 and localization studies in anopheles sp. | plasmodium cysteine proteases have been shown to be immunogenic and are being used as malaria potential serodiagnostic markers and vaccine targets. genes encoding two plasmodium chabaudi cysteine proteases chabaupain-1 (cp-1) and chabaupain-2 (cp-2) were identified and further expressed in escherichia coli. solubilisation of recombinant cp-1 and cp-2 was achieved by decreasing the temperature of induction. anopheles gambiae tissues infected with plasmodium were analyzed by western blotting using ... | 2009 | 19292986 |
| identification of a metabolically stable triazolopyrimidine-based dihydroorotate dehydrogenase inhibitor with antimalarial activity in mice. | plasmodium falciparum causes 1-2 million deaths annually. yet current drug therapies are compromised by resistance. we previously described potent and selective triazolopyrimidine-based inhibitors of p. falciparum dihydroorotate dehydrogenase (pfdhodh) that inhibited parasite growth in vitro; however, they showed no activity in vivo. here we show that lack of efficacy against p. berghei in mice resulted from a combination of poor plasma exposure and reduced potency against p. berghei dhodh. for ... | 2009 | 19296651 |
| antiplasmodial and antidiabetic activities of ethanolic leaf extract of heinsia crinata. | the ethanolic leaf extract of heinsia crinata, grown particularly for the leaf in niger delta region of nigeria, was evaluated for antiplasmodial activity in plasmodium berghei-infected mice as well as for hypoglycemic and antidiabetic activities in alloxan-induced diabetic rats. h. crinata (450-1,350 mg/kg/day) exhibited significant (p < .05) blood schizonticidal activity in both the 4-day early infection test and established infection with a considerable mean survival time, though not comparab ... | 2009 | 19298206 |
| 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 ... | 2008 | 19301696 |
| macromolecular prodrugs. xii. primaquine conjugates: synthesis and preliminary antimalarial evaluation. | new primaquine conjugates 5-7 with glucosamine and two polymers of polyaspartamide type, poly[alpha,beta-(n-2-hydroxyethyl-dl-aspartamide)] (phea) and poly[alpha,beta-(n-3-hydroxypropyl-dl-aspartamide)] (phpa), were synthesized, characterized and screened for their antimalarial activity. the conjugates differed in the type of covalent bonding, length of the spacer between the polymeric carrier and drug, molecular mass and drug-loading. blood-schizontocidal activity of the prepared conjugates was ... | 2009 | 19304563 |
| dissection of mechanisms involved in the regulation of plasmodium falciparum calcium-dependent protein kinase 4. | recent studies have demonstrated that calcium-dependent protein kinases (cdpks) are used by calcium to regulate a variety of biological processes in the malaria parasite plasmodium. cdpk4 has emerged as an important enzyme for parasite development, because its gene disruption in rodent parasite plasmodium berghei causes major defects in sexual differentiation of the parasite ( billker, o., dechamps, s., tewari, r., wenig, g., franke-fayard, b., and brinkmann, v. (2004) cell 117, 503-514 ). despi ... | 2009 | 19307175 |
| plasmodium berghei anka: selection of resistance to piperaquine and lumefantrine in a mouse model. | we have selected piperaquine (pq) and lumefantrine (lm) resistant plasmodium berghei anka parasite lines in mice by drug pressure. effective doses that reduce parasitaemia by 90% (ed(90)) of pq and lm against the parent line were 3.52 and 3.93 mg/kg, respectively. after drug pressure (more than 27 passages), the selected parasite lines had pq and lm resistance indexes (i(90)) [ed(90) of resistant line/ed(90) of parent line] of 68.86 and 63.55, respectively. after growing them in the absence of d ... | 2009 | 19318094 |
| characterization of cerebral malaria in the outbred swiss webster mouse infected by plasmodium berghei anka. | plasmodium berghei anka (pba) infection in susceptible inbred mouse strains is the most commonly used experimental model to study pathogenesis of cerebral malaria (cm). indeed, many concepts on mechanisms related to this complication have arisen from works using this model. although inbred strains present several advantages and are indicated for most studies, the use of outbred models can show unique usefulness in a number of approaches such as fine post-quantitative trait loci mapping and disco ... | 2009 | 19335550 |
| a small molecule inhibitor of signal peptide peptidase inhibits plasmodium development in the liver and decreases malaria severity. | the liver stage of plasmodium's life cycle is the first, obligatory step in malaria infection. decreasing the hepatic burden of plasmodium infection decreases the severity of disease and constitutes a promising strategy for malaria prophylaxis. the efficacy of the gamma-secretase and signal peptide peptidase inhibitor ly411,575 in targeting plasmodium liver stages was evaluated both in human hepatoma cell lines and in mouse primary hepatocytes. ly411,575 was found to prevent plasmodium's normal ... | 2009 | 19337374 |
| antigen presentation by dendritic cells in vivo. | dendritic cells (dc) are heterogenous, comprising several subpopulations of migratory and lymphoid-organ-resident types. recent studies addressing the role of each subset in antigen presentation in vivo have revealed a complex division of labor within the dc network. in addition to cd8(+) dc, migratory lung or dermal dc can cross-present antigen in vivo. migratory dc also transport to the lymph nodes antigens that can be transferred to resident dc for presentation. in inflammatory conditions, th ... | 2009 | 19342210 |
| ip-10-mediated t cell homing promotes cerebral inflammation over splenic immunity to malaria infection. | plasmodium falciparum malaria causes 660 million clinical cases with over 2 million deaths each year. acquired host immunity limits the clinical impact of malaria infection and provides protection against parasite replication. experimental evidence indicates that cell-mediated immune responses also result in detrimental inflammation and contribute to severe disease induction. in both humans and mice, the spleen is a crucial organ involved in blood stage malaria clearance, while organ-specific di ... | 2009 | 19343215 |
| immunization with radiation-attenuated plasmodium berghei sporozoites induces liver ccd8alpha+dc that activate cd8+t cells against liver-stage malaria. | immunization with radiation (gamma)-attenuated plasmodia sporozoites (gamma-spz) confers sterile and long-lasting immunity against malaria liver-stage infection. in the p. berghei gamma-spz model, protection is linked to liver cd8+ t cells that express an effector/memory (t(em)) phenotype, (cd44(hi)cd45rb(lo)cd62l(lo)), and produce ifn-gamma. however, neither the antigen presenting cells (apc) that activate these cd8+ t(em) cells nor the site of their induction have been fully investigated. beca ... | 2009 | 19347042 |
| cd4(+) t cell response in early erythrocytic stage malaria: plasmodium berghei infection in balb/c and c57bl/6 mice. | plasmodium berghei anka causes lethal malaria in mice. it is well established that c57bl/6 mice die early with fulminant symptoms including convulsion, whereas balb/c mice survive this phase and die later of anemia and prostration. early death in c57bl/6 mice has been considered to result from the adverse effects of inflammatory cytokines. to elucidate the cd4(+) t cell responses in early death due to severe malaria, the kinetics of cd4(+) t cells were compared by analyzing cell surface markers ... | 2009 | 19352703 |
| impact of cerebral malaria on brain distribution of mefloquine. | cerebral malaria (cm) is the most severe complication of plasmodium falciparum malaria. the aim of this study was to investigate the influence of cm on the cerebral uptake of mefloquine (mq), in an experimental model of mice infected with plasmodium berghei anka (pba). drug diffusion in brain is closely related to efflux pumps such as p-glycoprotein (p-gp/abcb1/mdr1) and breast cancer resistant protein (bcrp/abcg2), two major components of the blood-brain barrier (bbb) which can be modified by i ... | 2009 | 19356112 |
| enhanced antimalarial effects of chloroquine by aqueous vernonia amygdalina leaf extract in mice infected with chloroquine resistant and sensitive plasmodium berghei strains. | the emergence and spread of plasmodium falciparum with resistance to chloroquine (cq), the safest and cheapest antimalarial drug coupled with the increasing cost of alternative drugs especially in developing countries have necessitated the need to optimize antimalarial actions of plant extracts and restore chloroquine efficacy. | 2008 | 19357729 |
| the plasmodium hu homolog, which binds the plastid dna sequence-independent manner, is essential for the parasite's survival. | the nuclear genome of the human malaria parasite plasmodium falciparum encodes a homolog of the bacterial hu protein (pfhu). in this study, we characterised pfhu's physiological function. pfhu, which is targeted exclusively to the parasite's plastid, bound its natural target--the plastid dna--sequence-independently and complemented lack of hu in escherichia coli. the hu gene could not be knocked-out from the genome of plasmodium berghei, implying that hu is important for the parasite's survival. ... | 2009 | 19358847 |
| anopheles gambiae croquemort scrbq2, expression profile in the mosquito and its potential interaction with the malaria parasite plasmodium berghei. | the scavenger receptor family comprises transmembrane proteins involved in the recognition of polyanionic ligands. several studies have established that members of this family are involved both in immunity and in developmental processes. in drosophila melanogaster, one of the best characterized scavenger receptors is croquemort, which participates in the recognition of apoptotic cells in the embryo. although comparative genomic studies have revealed the presence of four orthologs of this recepto ... | 2009 | 19366631 |
| antimalarial activity of betulinic acid and derivatives in vitro against plasmodium falciparum and in vivo in p. berghei-infected mice. | malaria is one of the most important tropical diseases and mainly affects populations living in developing countries. reduced sensitivity of plasmodium sp. to formerly recommended antimalarial drugs places an increasing burden on malaria control programs as well as on national health systems in endemic countries. the present study aims to evaluate the antimalarial activity of betulinic acid and its derivative compounds, betulonic acid, betulinic acid acetate, betulinic acid methyl ester, and bet ... | 2009 | 19367418 |
| nanoencapsulation increases quinine antimalarial efficacy against plasmodium berghei in vivo. | the aims of this work were to develop quinine (qn)-loaded nanocapsules, to evaluate their efficacy in vivo and to determine their pharmacokinetics and erythrocyte partition coefficient. plasmodium berghei-infected wistar rats were used to evaluate the efficacy of qn-loaded nanocapsules using different dosing regimens. pharmacokinetics was evaluated after intravenous administration of free or nanoencapsulated qn (25 mg/kg) to infected rats. the qn partition coefficient into p. berghei-infected er ... | 2009 | 19369041 |
| clonal conditional mutagenesis in malaria parasites. | we describe here an efficient method for conditional gene inactivation in malaria parasites that uses the flp/frt site-specific recombination system of yeast. the method, developed in plasmodium berghei, consists of inserting frt sites in the chromosomal locus of interest in a parasite clone expressing the flp recombinase via a developmental stage-specific promoter. using promoters active in mosquito midgut sporozoites or salivary gland sporozoites to drive expression of flp or its thermolabile ... | 2009 | 19380117 |
| molecular genetics and comparative genomics reveal rnai is not functional in malaria parasites. | techniques for targeted genetic disruption in plasmodium, the causative agent of malaria, are currently intractable for those genes that are essential for blood stage development. the ability to use rna interference (rnai) to silence gene expression would provide a powerful means to gain valuable insight into the pathogenic blood stages but its functionality in plasmodium remains controversial. here we have used various rna-based gene silencing approaches to test the utility of rnai in malaria p ... | 2009 | 19380379 |
| two c-type lectins cooperate to defend anopheles gambiae against gram-negative bacteria. | c-type lectins (ctls) are a family of proteins that share a common structural motif, the carbohydrate recognition domain, and may act as receptors in pathogen recognition. indeed, some vertebrate ctls, particularly the collectins, are unequivocally implicated in the innate immune response to certain microbes. although studies in insects and other invertebrates have described ctl activation of effector immune responses in vitro, the contribution of these ctls to immune defenses in vivo is still p ... | 2009 | 19380589 |
| piperaquine pharmacodynamics and parasite viability in a murine malaria model. | piperaquine (pq) is an important partner drug in antimalarial combination treatments, but the long half-life of pq raises concerns about drug resistance. our aim was to investigate the extended antimalarial effect of pq in a study of drug efficacy, reinoculation outcomes, and parasite viability after the administration of a single dose of pq in the murine malaria model. initially, male swiss mice were inoculated with plasmodium berghei and at 64 h after parasite inoculation were given pq phospha ... | 2009 | 19380600 |
| kinetics of mosquito-injected plasmodium sporozoites in mice: fewer sporozoites are injected into sporozoite-immunized mice. | malaria is initiated when the mosquito introduces sporozoites into the skin of a mammalian host. to successfully continue the infection, sporozoites must invade blood vessels in the dermis and be transported to the liver. a significant number of sporozoites, however, may enter lymphatic vessels in the skin or remain in the skin long after the mosquito bite. we have used fluorescence microscopy of plasmodium berghei sporozoites expressing a fluorescent protein to evaluate the kinetics of sporozoi ... | 2009 | 19390607 |
| rosiglitazone modulates the innate immune response to plasmodium falciparum infection and improves outcome in experimental cerebral malaria. | for severe malarial syndromes such as cerebral malaria, adverse clinical outcomes are often mediated by the immune system rather than caused by the parasite directly. however, few therapeutic agents have been developed to modulate the host's immunopathological responses to infection. here, we report that the peroxisome proliferator-activated receptor gamma (ppargamma) agonist rosiglitazone modulated the host response to malaria by enhancing phagocytic clearance of malaria-parasitized erythrocyte ... | 2009 | 19392627 |