Publications
| Title | Abstract | Year Filter | PMID(sorted ascending) Filter |
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| a single fluorescence-based lamp reaction for identifying multiple parasites in mosquitoes. | vector-borne diseases, such as malaria and lymphatic filariasis, are co-endemic in large parts of the world. to develop a multiplex amplification method for the simultaneous detection of multiple insect-borne infectious diseases, we used lamp with fluorescently labeled primers to identify the spect2 gene of plasmodium berghei and the cytochrome oxidase subunit i gene of dirofilaria immitis in mosquitoes. this technique could detect as few as 100 p. berghei-infected red blood cell-equivalents or ... | 2010 | 20064511 |
| synergistic and additive effects of epigallocatechin gallate and digitonin on plasmodium sporozoite survival and motility. | most medicinal plants contain a mixture of bioactive compounds, including chemicals that interact with intracellular targets and others that can act as adjuvants to facilitate absorption of polar agents across cellular membranes. however, little is known about synergistic effects between such potential drug candidates and adjuvants. to probe for such effects, we tested the green tea compound epigallocatechin gallate (egcg) and the membrane permeabilising digitonin on plasmodium sporozoite motili ... | 2010 | 20072627 |
| integrated cytokine and metabolic analysis of pathological responses to parasite exposure in rodents. | parasitic infections cause a myriad of responses in their mammalian hosts, on immune as well as on metabolic level. a multiplex panel of cytokines and metabolites derived from four parasite-rodent models, namely, plasmodium berghei-mouse, trypanosoma brucei brucei-mouse, schistosoma mansoni-mouse, and fasciola hepatica-rat were statistically coanalyzed. (1)h nmr spectroscopy and multivariate statistical analysis were used to characterize the urine and plasma metabolite profiles in infected and n ... | 2010 | 20092362 |
| cerebral malaria: a vasculopathy. | 2010 | 20093501 | |
| immunopathology and dexamethasone therapy in a new model for malaria-associated acute respiratory distress syndrome. | malaria infection is often complicated by malaria-associated acute respiratory distress syndrome (ma-ards), characterized by pulmonary edema and hemorrhages. no efficient treatments are available for ma-ards and its pathogenesis remains poorly understood. | 2010 | 20093644 |
| characterization of two linear cationic antimalarial peptides in the scorpion mesobuthus eupeus. | plasmodium falciparum is a pathogen of human malaria which causes millions of deaths per year due to the ever-increasing drug resistance by the parasite, and thus novel antimalarial agents are urgently needed. in this work, we report two cdna clones from the scorpion mesobuthus eupeus venom gland, which encode peptides inhibiting the development of plasmodium berghei, killing intraerythrocytic p. falciparum, and toxic to the drosophila s2 cell at micromolar concentrations. one peptide of 24 amin ... | 2010 | 20097251 |
| differential effector pathways regulate memory cd8 t cell immunity against plasmodium berghei versus p. yoelii sporozoites. | malaria results in >1,000,000 deaths per year worldwide. although no licensed vaccine exists, much effort is currently focused on subunit vaccines that elicit cd8 t cell responses directed against plasmodium parasite liver stage ags. multiple immune-effector molecules play a role in antimicrobial immunity mediated by memory cd8 t cells, including ifn-gamma, perforin, trail, fas ligand, and tnf-alpha. however, it is not known which pathways are required for memory cd8 t cell-mediated immunity aga ... | 2010 | 20097864 |
| murine cerebral malaria is associated with a vasospasm-like microcirculatory dysfunction, and survival upon rescue treatment is markedly increased by nimodipine. | brain hemodynamics in cerebral malaria (cm) is poorly understood, with apparently conflicting data showing microcirculatory hypoperfusion and normal or even increased blood flow in large arteries. using intravital microscopy to assess the pial microvasculature through a closed cranial window in the murine model of cm by plasmodium berghei anka, we show that murine cm is associated with marked decreases (mean: 60%) of pial arteriolar blood flow attributable to vasoconstriction and decreased blood ... | 2010 | 20110412 |
| a semi-automated method for counting fluorescent malaria oocysts increases the throughput of transmission blocking studies. | malaria transmission is now recognized as a key target for intervention. evaluation of the plasmodium oocyst burden in the midguts of anopheles spp. is important for many of assays investigating transmission. however, current assays are very time-consuming, manually demanding and patently subject to observer-observer variation. | 2010 | 20113492 |
| parasite-derived plasma microparticles contribute significantly to malaria infection-induced inflammation through potent macrophage stimulation. | there is considerable debate as to the nature of the primary parasite-derived moieties that activate innate pro-inflammatory responses during malaria infection. microparticles (mps), which are produced by numerous cell types following vesiculation of the cellular membrane as a consequence of cell death or immune-activation, exert strong pro-inflammatory activity in other disease states. here we demonstrate that mps, derived from the plasma of malaria infected mice, but not naive mice, induce pot ... | 2010 | 20126448 |
| life cycle studies of the hexose transporter of plasmodium species and genetic validation of their essentiality. | a plasmodium falciparum hexose transporter (pfht) has previously been shown to be a facilitative glucose and fructose transporter. its expression in xenopus laevis oocytes and the use of a glucose analogue inhibitor permitted chemical validation of pfht as a novel drug target. following recent re-annotations of the p. falciparum genome, other putative sugar transporters have been identified. to investigate further if pfht is the key supplier of hexose to p. falciparum and to extend studies to di ... | 2010 | 20132450 |
| antimalarial and antitubercular nostocarboline and eudistomin derivatives: synthesis, in vitro and in vivo biological evaluation. | the synthesis of nine nostocarboline derivatives with substitutions of the 2-methyl group by alkyl, aryl and functionalized residues, 10 symmetrical bis cationic dimers linking 6-cl-norharmane through the 2-position and fifteen derivatives of the marine alkaloids eudistomin n and o is reported. these compounds were evaluated in vitro against four parasites (trypanosoma brucei rhodesiense stib 900, trypanosoma cruzi tulahuen c2c4, leishmania donovani mhom-et-67/l82 axenic amastigotes, and plasmod ... | 2010 | 20133138 |
| inflammatory changes in the central nervous system are associated with behavioral impairment in plasmodium berghei (strain anka)-infected mice. | experimental cerebral malaria is a neuroinflammatory condition that results from the host immune response to the parasite. using intravital microscopy, we investigated leukocyte recruitment in the brain microcirculation and the temporal relationship of this process to the behavioral changes observed in plasmodium berghei (strain anka)-infected c57bl/6 mice. we found that leukocyte recruitment was increased from day 5 post-infection (p.i.) onwards. histopathological changes and increased levels o ... | 2010 | 20138873 |
| concomitant infection decreases the malaria burden but escalates relapsing fever borreliosis. | about 500 million cases of malaria occur annually. however, a substantial number of patients who actually have relapsing fever (rf) borrelia infection can be misdiagnosed with malaria due to similar manifestations and geographic distributions of the two diseases. more alarmingly, a high prevalence of concomitant infections with malaria and rf borrelia has been reported. therefore, we used a mouse model to study the effects of such mixed infection. we observed a 21-fold increase in spirochete tit ... | 2010 | 20145098 |
| in vivo screening of antimalarial activity of acacia mellifera (benth) (leguminosae) on plasmodium berghei in mice. | the activities of total extracts and lupane triterpenes, isolated from the stem bark of acacia mellifera, were evaluated against plasmodium berghei strain anka in a female swiss mouse model. five isolated compounds and the crude extracts were evaluated for antimalarial activity and quinine hydrochloride was used as a positive control. only betulin and the methanolic extract produced considerable antimalarial activity in mice infected with p. berghei parasites. this study demonstrated the presenc ... | 2007 | 20162054 |
| assessment of in vivo antimalarial activity of rifampicin, isoniazide, and ethambutol combination therapy. | the existing armament of drugs for the treatment and prevention of malaria is inadequate due to development of resistance. in addition to this due to lack of economic enticement the rate of new drug development and new drug discovery in the segment of parasitic diseases is very low as compared to the other segments. this has necessitated the better deployment and usage of existing antimalarial drugs as well as discovery of antimalarial activity of drugs which are well characterized for other dis ... | 2010 | 20165870 |
| universal features of post-transcriptional gene regulation are critical for plasmodium zygote development. | a universal feature of metazoan sexual development is the generation of oocyte p granules that withhold certain mrna species from translation to provide coding potential for proteins during early post-fertilization development. stabilisation of translationally quiescent mrna pools in female plasmodium gametocytes depends on the rna helicase dozi, but the molecular machinery involved in the silencing of transcripts in these protozoans is unknown. using affinity purification coupled with mass-spec ... | 2010 | 20169188 |
| kynurenine is an endothelium-derived relaxing factor produced during inflammation. | control of blood vessel tone is central to vascular homeostasis. here we show that metabolism of tryptophan to kynurenine by indoleamine 2,3-dioxygenase (ido) expressed in endothelial cells contributes to arterial vessel relaxation and the control of blood pressure. infection of mice with malarial parasites (plasmodium berghei) or induction of endotoxemia in mice led to endothelial expression of ido, decreased plasma tryptophan concentration, increased kynurenine concentration and hypotension. p ... | 2010 | 20190767 |
| minimal role for the circumsporozoite protein in the induction of sterile immunity by vaccination with live rodent malaria sporozoites. | immunization with live plasmodium sporozoites under chloroquine prophylaxis (spz plus cq) induces sterile immunity against sporozoite challenge in rodents and, more importantly, in humans. full protection is obtained with substantially fewer parasites than with the classic immunization with radiation-attenuated sporozoites. the sterile protection observed comprised a massive reduction in the hepatic parasite load and an additional effect at the blood stage level. differences in the immune respon ... | 2010 | 20194600 |
| transmission blocking activity of a standardized neem (azadirachta indica) seed extract on the rodent malaria parasite plasmodium berghei in its vector anopheles stephensi. | the wide use of gametocytocidal artemisinin-based combination therapy (act) lead to a reduction of plasmodium falciparum transmission in several african endemic settings. an increased impact on malaria burden may be achieved through the development of improved transmission-blocking formulations, including molecules complementing the gametocytocidal effects of artemisinin derivatives and/or acting on plasmodium stages developing in the vector. azadirachtin, a limonoid (tetranortriterpenoid) abund ... | 2010 | 20196858 |
| dysregulation of angiopoietins is associated with placental malaria and low birth weight. | placental malaria (pm) is associated with adverse pregnancy outcomes including low birth weight (lbw). however, the precise mechanisms by which pm induces lbw are poorly defined. based on the essential role of angiopoietin (ang)-1 and -2 in normal placental vascular development, we hypothesized that pm may result in the dysregulation of angiopoietins and thereby contribute to lbw outcomes. | 2010 | 20208992 |
| screening of traditionally used plants for in vivo antimalarial activity in mice. | aqueous ethanol (80%) extracts of six plants used traditionally for treatment of malaria, vepris glomerata (f.hoffm.) engl (rutaceae), maranthus floribunda (bak.) f.white (chrysobalanaceae), strophanthus eminii asch. & pax ex pax (apocynaceae), cassia abbreviata oliv. (leguminosae) and caesalpinia bonducella l. fleming (fabaceae) were screened for antimalarial activity to establish validity of their claims. the extracts exhibited antimalarial activity in the 4-day peter's suppressive antimalaria ... | 2009 | 20209008 |
| suppressive effect of azithromycin on plasmodium berghei mosquito stage development and apicoplast replication. | azithromycin (azm) is a macrolide antibiotic that displays an excellent safety profile even in children and pregnant women and has been shown to have anti-malarial activity against blood stage plasmodium falciparum. this study evaluated the transmission-blocking effect of azm using a rodent malaria model. | 2010 | 20219090 |
| natural regulatory t cells mediate the development of cerebral malaria by modifying the pro-inflammatory response. | cerebral malaria (cm) is a severe neurologic complication that arises predominantly in children and non-immune adults infected with plasmodium falciparum. in the current study, the dynamics of cd4(+)cd25(+)foxp3(+) regulatory t cells (tregs) and pro- and anti-inflammatory cytokines were analyzed in p. berghei anka (p.banka)-infected c57bl/6, balb/c, and dba/2 mice. we showed that c57bl/6 mice were susceptible to cm, while balb/c and dba/2 mice were resistant to cm and succumbed to hyperparasitem ... | 2010 | 20219695 |
| artemisinin directly targets malarial mitochondria through its specific mitochondrial activation. | the biological mode of action of artemisinin, a potent antimalarial, has long been controversial. previously we established a yeast model addressing its mechanism of action and found mitochondria the key in executing artemisinin's action. here we present data showing that artemisinin directly acts on mitochondria and it inhibits malaria in a similar way as yeast. specifically, artemisinin and its homologues exhibit correlated activities against malaria and yeast, with the peroxide bridge playing ... | 2010 | 20221395 |
| a peroxidase/dual oxidase system modulates midgut epithelial immunity in anopheles gambiae. | extracellular matrices in diverse biological systems are cross-linked by dityrosine covalent bonds catalyzed by the peroxidase/oxidase system. we show that a peroxidase, secreted by the anopheles gambiae midgut, and dual oxidase form a dityrosine network that decreases gut permeability to immune elicitors. this network protects the microbiota by preventing activation of epithelial immunity. it also provides a suitable environment for malaria parasites to develop within the midgut lumen without i ... | 2010 | 20223948 |
| a putative kinase-related protein (pkrp) from plasmodium berghei mediates infection in the midgut and salivary glands of the mosquito. | the completion of the plasmodium (malaria) life cycle in the mosquito requires the parasite to traverse first the midgut and later the salivary gland epithelium. we have identified a putative kinase-related protein (pkrp) that is predicted to be an atypical protein kinase, which is conserved across many species of plasmodium. the pkrp gene encodes a rna of about 5300 nucleotides that is expressed as a 90kda protein in sporozoites. targeted disruption of the pkrp gene in plasmodium berghei, a rod ... | 2010 | 20227415 |
| functional identification of the plasmodium centromere and generation of a plasmodium artificial chromosome. | the artificial chromosome represents a useful tool for gene transfer, both as cloning vectors and in chromosome biology research. to generate a plasmodium artificial chromosome (pac), we had to first functionally identify and characterize the parasite's centromere. a putative centromere (pbcen5) was cloned from chromosome 5 of the rodent parasite p. berghei based on a plasmodium gene-synteny map. plasmids containing pbcen5 were stably maintained in parasites during a blood-stage infection with h ... | 2010 | 20227667 |
| pretreatment with cry1ac protoxin modulates the immune response, and increases the survival of plasmodium-infected cba/ca mice. | malaria is a major global health problem that kills 1-2 million people each year. despite exhaustive research, naturally acquired immunity is poorly understood. cry1a proteins are potent immunogens with adjuvant properties and are able to induce strong cellular and humoral responses. in fact, it has been shown that administration of cry1ac protoxin alone or with amoebic lysates induces protection against the lethal infection caused by the protozoa naegleria fowleri. in this work, we studied whet ... | 2010 | 20300584 |
| tomatine adjuvantation of protective immunity to a major pre-erythrocytic vaccine candidate of malaria is mediated via cd8+ t cell release of ifn-gamma. | the glycoalkaloid tomatine, derived from the wild tomato, can act as a powerful adjuvant to elicit an antigen-specific cell-mediated immune response to the circumsporozoite (cs) protein, a major pre-erythrocytic stage malaria vaccine candidate antigen. using a defined mhc-class-i-restricted cs epitope in a plasmodium berghei rodent model, antigen-specific cytotoxic t lymphocyte activity and ifn-gamma secretion ex vivo were both significantly enhanced compared to responses detected from similarly ... | 2010 | 20300588 |
| up- and down-modulation of liver cytochrome p450 activities and associated events in two murine malaria models. | the mechanisms by which malaria up and down-regulates cyp activities are not understood yet. it is also unclear whether cyp activities are modulated during non-lethal malaria infections. this study was undertaken to evaluate the time course of cyp alterations in lethal (plasmodium berghei anka) and non-lethal (plasmodium chabaudi chabaudi) murine malaria. additionally, hypotheses on the association of cyp depression with enhanced nitric oxide (no) production, and of cyp2a5 induction with endopla ... | 2010 | 20307316 |
| algorithms to predict cerebral malaria in murine models using the shirpa protocol. | plasmodium berghei anka infection in c57bl/6 mice induces cerebral malaria (cm), which reproduces, to a large extent, the pathological features of human cm. however, experimental cm incidence is variable (50-100%) and the period of incidence may present a range as wide as 6-12 days post-infection. the poor predictability of which and when infected mice will develop cm can make it difficult to determine the causal relationship of early pathological changes and outcome. with the purpose of contrib ... | 2010 | 20334682 |
| murine cerebral malaria: how far from human cerebral malaria? | 2010 | 20335068 | |
| membrane fusion triggers rapid degradation of two gamete-specific, fusion-essential proteins in a membrane block to polygamy in chlamydomonas. | the plasma membranes of gametes are specialized for fusion, yet, once fusion occurs, in many organisms the new zygote becomes incapable of further membrane fusion reactions. the molecular mechanisms that underlie this loss of fusion capacity (block to polygamy) remain unknown. during fertilization in the green alga chlamydomonas, the plus gamete-specific membrane protein fus1 is required for adhesion between the apically localized sites on the plasma membranes of plus and minus gametes that are ... | 2010 | 20335357 |
| ancient chinese methods are remarkably effective for the preparation of artemisinin-rich extracts of qing hao with potent antimalarial activity. | ancient chinese herbal texts as far back as the 4th century zhou hou bei ji fang describe methods for the use of qing hao (artemisia annua) for the treatment of intermittent fevers. today, the a. annua constituent artemisinin is an important antimalarial drug and the herb itself is being grown and used locally for malaria treatment although this practice is controversial. here we show that the ancient chinese methods that involved either soaking, (followed by wringing) or pounding, (followed by ... | 2010 | 20335947 |
| anti-infective discorhabdins from a deep-water alaskan sponge of the genus latrunculia. | bioassay- and lc-ms-guided fractionation of a methanol extract from a new deep-water alaskan sponge species of the genus latrunculia resulted in the isolation of two new brominated pyrroloiminoquinones, dihydrodiscorhabdin b and discorhabdin y (2), along with six known pyrroloiminoquinone alkaloids, discorhabdins a (3), c (4), e (5), and l (6), dihydrodiscorhabdin c (7), and the benzene derivative 8. compounds 3, 4, and 7 exhibited anti-hcv activity, antimalarial activity, and selective antimicr ... | 2010 | 20337497 |
| mosquito cell line glycoproteins: an unsuitable model system for the plasmodium ookinete-mosquito midgut interaction? | abstract: | 2010 | 20338056 |
| neuropathogenesis of human and murine malaria. | 2010 | 20338809 | |
| preclinical evaluation of the antifolate qn254, 5-chloro- n'6'-(2,5-dimethoxy-benzyl)-quinazoline-2,4,6-triamine, as an antimalarial drug candidate. | drug resistance against dihydrofolate reductase (dhfr) inhibitors-such as pyrimethamine (pm)-has now spread to almost all regions where malaria is endemic, rendering antifolate-based malaria treatments highly ineffective. we have previously shown that the di-amino quinazoline qn254 [5-chloro-n'6'-(2,5-dimethoxy-benzyl)-quinazoline-2,4,6-triamine] is active against the highly pm-resistant plasmodium falciparum v1s strain, suggesting that qn254 could be used to treat malaria in regions with a high ... | 2010 | 20350951 |
| small variant surface antigens and plasmodium evasion of immunity. | antigenic variation at the plasmodium-infected erythrocyte surface plays a critical role in malaria disease severity and host immune evasion. our current understanding of the role of plasmodium variant surface antigens in antigenic variation and immune evasion is largely limited to the extensive work carried out on the plasmodium falciparum var gene family. although homologues of var genes are not present in other malaria species, small variant gene families comprising the rif and stevor genes i ... | 2010 | 20353305 |
| exoerythrocytic plasmodium parasites secrete a cysteine protease inhibitor involved in sporozoite invasion and capable of blocking cell death of host hepatocytes. | plasmodium parasites must control cysteine protease activity that is critical for hepatocyte invasion by sporozoites, liver stage development, host cell survival and merozoite liberation. here we show that exoerythrocytic p. berghei parasites express a potent cysteine protease inhibitor (pbicp, p. berghei inhibitor of cysteine proteases). we provide evidence that it has an important function in sporozoite invasion and is capable of blocking hepatocyte cell death. pre-incubation with specific ant ... | 2010 | 20361051 |
| cerebral malaria: in praise of epistemes. | 2010 | 20363672 | |
| cerebral malaria: human versus mouse studies. | 2010 | 20382077 | |
| murine cerebral malaria: the whole story. | 2010 | 20382078 | |
| rapid quantification of the effects of blotting for correlation of light and cryo-light microscopy images. | recent technical developments allowed the accurate correlation of fluorescently labelled organelles in living cells to cryo-electron micrographs. we aimed at expanding this approach to plasmodium berghei sporozoites, the motile forms of a rodent malaria parasite, which can be imaged by cryo-electron tomography in toto without the need for sectioning. sporozoites are crescent shaped eukaryotic cells that move on flat supports including em grids in a circular, unidirectional manner. while sporozoi ... | 2010 | 20384834 |
| three members of the 6-cys protein family of plasmodium play a role in gamete fertility. | the process of fertilization is critically dependent on the mutual recognition of gametes and in plasmodium, the male gamete surface protein p48/45 is vital to this process. this protein belongs to a family of 10 structurally related proteins, the so called 6-cys family. to identify the role of additional members of this family in plasmodium fertilisation, we performed genetic and functional analysis on the five members of the 6-cys family that are transcribed during the gametocyte stage of p. b ... | 2010 | 20386715 |
| a role for cd4+ and cd8+ cells and not for cd25+ cells in the control of plasmodium berghei anka blood stage parasites in rats. | in previous studies of the infection of rats by p. berghei anka, we have shown that primary blood stage infection induced the expansion of cd4+ t cells and cd8+ t cells in adult resistant rats while the number of cd4+cd25+ cells was found to be higher in young susceptible rats. in this work, the respective contribution of each cell population was determined in young and adult rats treated with monoclonal antibodies. down-regulation of surface cd25 molecules, including those expressed by cd4+ cel ... | 2010 | 20387739 |
| blood-stage plasmodium berghei infection leads to short-lived parasite-associated antigen presentation by dendritic cells. | despite extensive evidence that plasmodium species are capable of stimulating the immune system, the association of malaria with a higher incidence of other infectious diseases and reduced responses to vaccination against unrelated pathogens suggests the existence of immune suppression. recently, we provided evidence that blood-stage plasmodium berghei infection leads to suppression of mhc class i-restricted immunity to third party (non-malarial) antigens as a consequence of systemic dc activati ... | 2010 | 20391433 |
| synthesis, in vitro and in vivo antimalarial assessment of sulfide, sulfone and vinyl amide-substituted 1,2,4-trioxanes prepared via thiol-olefin co-oxygenation (toco) of allylic alcohols. | thiol-olefin co-oxygenation (toco) methodology has been applied to the synthesis of a small library of weak base and polar 1,2,4-trioxanes. the 1,2,4-trioxane units synthesised exhibit remarkable stability as they survive base catalysed hydrolysis and mixed anhydride/amine coupling reactions. this unique stability feature has enabled a range of novel substitution patterns to be incorporated within the spiro 1,2,4-trioxane unit. selected analogues express potent in vitro nm antimalarial activity, ... | 2010 | 20401383 |
| alpha-tocopherol transfer protein disruption confers resistance to malarial infection in mice. | various factors impact the severity of malaria, including the nutritional status of the host. vitamin e, an intra and extracellular anti-oxidant, is one such nutrient whose absence was shown previously to negatively affect plasmodium development. however, mechanisms of this plasmodium inhibition, in addition to means by which to exploit this finding as a therapeutic strategy, remain unclear. | 2010 | 20403155 |
| evaluation of the in vivo antimalarial activity of ethanolic leaf and stembark extracts of anthocleista djalonensis. | to evaluate the in vivo antimalarial activities of ethanolic leaf and stembark extracts of anthocleista djalonensis used traditionally as malarial remedy in southern nigeria in mice infected with plasmodium berghei berghei. | 2009 | 20407556 |
| alterations in urine, serum and brain metabolomic profiles exhibit sexual dimorphism during malaria disease progression. | metabolic changes in the host in response to plasmodium infection play a crucial role in the pathogenesis of malaria. alterations in metabolism of male and female mice infected with plasmodium berghei anka are reported here. | 2010 | 20412601 |
| antiplasmodial activity of ajuga bracteosa against plasmodium berghei infected balb/c mice. | the present work was undertaken to evaluate antiplasmodial activity of ethanolic leaves extract of traditional medicinal plant ajuga bracteosa in plasmodium berghei infected balb/c mice along with its phytochemical screening and acute toxicity test to support its traditional use as a remedy for malaria. | 2010 | 20418560 |
| functional evaluation of plasmodium export signals in plasmodium berghei suggests multiple modes of protein export. | the erythrocytic stage development of malaria parasites occurs within the parasitophorous vacuole inside the infected-erythrocytes, and requires transport of several parasite-encoded proteins across the parasitophorous vacuole to several locations, including the cytosol and membrane of the infected cell. these proteins are called exported proteins; and a large number of such proteins have been predicted for plasmodium falciparum based on the presence of an n-terminal motif known as the plasmodiu ... | 2010 | 20419102 |
| oral activated charcoal prevents experimental cerebral malaria in mice and in a randomized controlled clinical trial in man did not interfere with the pharmacokinetics of parenteral artesunate. | safe, cheap and effective adjunct therapies preventing the development of, or reducing the mortality from, severe malaria could have considerable and rapid public health impact. oral activated charcoal (oac) is a safe and well tolerated treatment for acute poisoning, more recently shown to have significant immunomodulatory effects in man. in preparation for possible efficacy trials in human malaria, we sought to determine whether oac would i) reduce mortality due to experimental cerebral malaria ... | 2010 | 20419161 |
| filaria-induced il-10 suppresses murine cerebral malaria. | filarial nematodes achieve long survival in their hosts due to their capacity to modulate immune responses. therefore, immunomodulation by filarial nematodes may alter responses to concomitant infections such as malaria. cerebral malaria (cm), a severe complication of plasmodium falciparum infections, is triggered as a consequence of the immune response developed against malaria parasites. the question arises whether prior infection with helminth parasites is beneficial against cm. in the presen ... | 2010 | 20420933 |
| in vitro and in vivo antimalarial and cytotoxic activity of five plants used in congolese traditional medicine. | the in vitro antiplasmodial activity and cytotoxicity of methanolic and dichloromethane extracts from five congolese plants were evaluated. the plants were selected following an ethnobotanical survey conducted in d.r. congo and focusing on plants used traditionally to treat malaria. the in vivo antimalarial activity of aqueous and methanolic extracts active in vitro was also determined in mice infected by plasmodium berghei berghei. | 2010 | 20430094 |
| prophylactic and curative activities of extracts from warburgia ugandensis sprague (canellaceae) and zanthoxylum usambarense (engl.) kokwaro (rutaceae) against plasmodium knowlesi and plasmodium berghei. | this work reports the anti-plasmodial activities of warburgia ugandensis and zanthoxylum usambarense commonly used as phytomedicines against malaria by some kenyan communities. | 2010 | 20435133 |
| differential effects of c3d on the immunogenicity of gene gun vaccines encoding plasmodium falciparum and plasmodium berghei msp1(42). | the complement fragment c3d mediates b-cell activation via simultaneous engagement of the b-cell receptor and cd21 by antigen/c3d conjugates. several studies demonstrated the potential of c3d as a molecular adjuvant for vaccination. in this work, c3d exerted differential effects on humoral immune responses after gene gun immunization of mice with plasmids encoding the malaria blood stage antigen msp1(42) depending on the nature of the protein (plasmodium falciparum vs. plasmodium berghei msp), t ... | 2010 | 20438877 |
| crystallization and preliminary structural characterization of the two actin-depolymerization factors of the malaria parasite. | the malaria parasite plasmodium depends on its actin-based motor system for motility and host-cell invasion. actin-depolymerization factors are important regulatory proteins that affect the rate of actin turnover. plasmodium has two actin-depolymerization factors which seem to have different functions and display low sequence homology to the higher eukaryotic family members. plasmodium actin-depolymerization factors 1 and 2 have been crystallized. the crystals diffracted x-rays to maximum resolu ... | 2010 | 20445265 |
| in vivo antimalarial evaluation of gomphostenins. | the present study aims to evaluate the in vivo antimalarial potential of the leaf extract of gomphostemma niveum and two new compounds; named as gomphostenin (gn-6) and acetyl gomphostenin (gn-10) isolated and purified from this plant against plasmodium berghei in mice. | 2010 | 20452412 |
| platelet factor 4 regulation of monocyte klf4 in experimental cerebral malaria. | cerebral malaria continues to be a difficult to treat complication of plasmodium falciparum infection in children. we have shown that platelets can have major deleterious immune functions in experimental cerebral malaria (ecm). one of the platelet derived mediators we have identified as particularly important is platelet factor 4/cxcl4. our prior work demonstrated that pf4(-/-) mice are protected from ecm, have reduced plasma cytokines, and have reduced t-cell trafficking to the brain. we now sh ... | 2010 | 20454664 |
| lipophilic bisphosphonates are potent inhibitors of plasmodium liver-stage growth. | nitrogen-containing bisphosphonates, drugs used to treat bone resorption diseases, also have activity against a broad range of protists, including blood-stage plasmodium spp. here, we show that new-generation "lipophilic" bisphosphonates designed as anticancer agents that block protein prenylation also have potent activity against plasmodium liver stages, with a high (>100) therapeutic index. treatment of mice with the bisphosphonate bph-715 and challenge with plasmodium berghei sporozoites reve ... | 2010 | 20457823 |
| beneficial effect of aurothiomalate on murine malaria. | premature death of plasmodium-infected erythrocytes is considered to favourably influence the clinical course of malaria. aurothiomalate has previously been shown to trigger erythrocyte death or eryptosis, which is characterized by cell membrane scrambling leading to phosphatidylserine exposure at the cell surface. phosphatidylserine-exposing cells are rapidly cleared from circulating blood. the present study thus tested whether sodium aurothiomalate influences the intraerythrocytic parasite dev ... | 2010 | 20459650 |
| in vitro and in vivo anti-malarial activity of boerhavia elegans and solanum surattense. | there is an urgent need to identify new anti-malarial drug targets for both prophylaxis and chemotherapy, due to the increasing problem of drug resistance to malaria parasites. in the present study, the aim was to discover novel, effective plant-based extracts for the activity against malaria. | 2010 | 20462416 |
| the kennedy phospholipid biosynthesis pathways are refractory to genetic disruption in plasmodium berghei and therefore appear essential in blood stages. | phosphatidylcholine (pc) and phosphatidylethanolamine (pe) are the main membrane phospholipids (pls) of plasmodium parasites and can be generated by the de novo (kennedy) cdp-choline and cdp-ethanolamine pathways and by the cdp-diacylglycerol dependent pathway. the kennedy pathways initiate from exogenous choline and ethanolamine involving choline kinase (ck) and ethanolamine kinase (ek), followed by the choline-phosphate cytidylyltransferase (cct) and ethanolamine-phosphate cytidylyltransferase ... | 2010 | 20478340 |
| in vitro antiplasmodial and phytochemical study of five artemisia species from iran and in vivo activity of two species. | the extract from artemisia annua, containing artemisinin, has been proven active against multidrug resistant plasmodium falciparum in previous studies. the purpose of this paper was to study five artemisia species from iran for their in vitro and in vivo antimalarial property and detection of artemisinin in the active species by chromatographic and spectroscopic methods including nuclear magnetic resonance (nmr) spectroscopy. dried plants were extracted by 80% ethanol, and total extracts were in ... | 2010 | 20480374 |
| plasmodium infection alters anopheles gambiae detoxification gene expression. | anopheles gambiae has been shown to change its global gene expression patterns upon plasmodium infection. while many alterations are directly related to the mosquito's innate immune response, parasite invasion is also expected to generate toxic by-products such as free radicals. the current study aimed at identifying which loci coding for detoxification enzymes are differentially expressed as a function of plasmodium berghei infection in midgut and fat body tissues. | 2010 | 20482856 |
| vitamin c deficiency fails to protect mice from malaria. | nutritional deficiencies are frequent in malaria-endemic areas. it seems that micronutrient antioxidants play an important role in malaria parasite's proliferation. thus, the effect of vitamin c deficiency on malaria infection was examined in mice. when vitamin c deficient mice, l-gulono-gamma-lactone oxidase gene knockout mice which are unable to synthesize ascorbic acid, were infected with a lethal dose of plasmodium berghei nk65-infected red blood cells, the knockout mice showed similar paras ... | 2010 | 20484858 |
| plasmodium chabaudi chabaudi malaria parasites can develop stable resistance to atovaquone with a mutation in the cytochrome b gene. | plasmodium falciparum, has developed resistance to many of the drugs in use. the recommended treatment policy is now to use drug combinations. the atovaquone-proguanil (ap) drug combination, is one of the treatment and prophylaxis options. atovaquone (atq) exerts its action by inhibiting plasmodial mitochondria electron transport at the level of the cytochrome bc1 complex. plasmodium falciparum in vitro resistance to atq has been associated with specific point mutations in the region spanning co ... | 2010 | 20492669 |
| arthemeter-loaded lipid nanoparticles produced by modified thin-film hydration: pharmacokinetics, toxicological and in vivo anti-malarial activity. | artemether-loaded lipid nanoparticles (arm-lnp) composed of 5% (w/v) lipid mass were produced by a modified thin-film hydration method using glyceryl trimyristate (solid lipid) and soybean oil (as liquid lipid in a concentration ranging from 0 to 45% (w/v) with respect to the total lipid mass). the particles were loaded with 10% of the anti-malarial arm and surface-tailored with a combination of non-ionic, cationic or anionic surfactants. arm-lnp were further characterized for their mean particl ... | 2010 | 20493255 |
| inhibition of plasmodium sporozoites infection by targeting the host cell. | there is a great need of new drugs against malaria because of the increasing spread of parasite resistance against the most commonly used drugs in the field. we found that monensin, a common veterinary antibiotic, has a strong inhibitory effect in plasmodium berghei and plasmodium yoelii sporozoites hepatocyte infection in vitro. infection of host cells by another apicomplexan parasite with a similar mechanism of host cell invasion, toxoplasma tachyzoites, was also inhibited. treatment of mice w ... | 2010 | 20493847 |
| vegf promotes malaria-associated acute lung injury in mice. | the spectrum of the clinical presentation and severity of malaria infections is broad, ranging from uncomplicated febrile illness to severe forms of disease such as cerebral malaria (cm), acute lung injury (ali), acute respiratory distress syndrome (ards), pregnancy-associated malaria (pam) or severe anemia (sa). rodent models that mimic human cm, pam and sa syndromes have been established. here, we show that dba/2 mice infected with p. berghei anka constitute a new model for malaria-associated ... | 2010 | 20502682 |
| comparison of plasmodium berghei challenge models for the evaluation of pre-erythrocytic malaria vaccines and their effect on perceived vaccine efficacy. | the immunological mechanisms responsible for protection against malaria infection vary among plasmodium species, host species and the developmental stage of parasite, and are poorly understood. a challenge with live parasites is the most relevant approach to testing the efficacy of experimental malaria vaccines. nevertheless, in the mouse models of plasmodium berghei and plasmodium yoelii, parasites are usually delivered by intravenous injection. this route is highly artificial and particularly ... | 2010 | 20507620 |
| protective effect of amiodarone in malaria. | according to previous observations, amiodarone triggers suicidal erythrocyte death or eryptosis, which is characterized by cell shrinkage and exposure of phosphatidylserine at the erythrocyte surface. eryptosis may in turn accelerate the clearance of plasmodium-infected erythrocytes. the present study tested whether amiodarone augments phosphatidylserine exposure of plasmodium-infected erythrocytes, interferes with the development of parasitemia and thus influences the course of malaria. the in ... | 2010 | 20510873 |
| crystal structure of arginase from plasmodium falciparum and implications for l-arginine depletion in malarial infection . | the 2.15 a resolution crystal structure of arginase from plasmodium falciparum, the parasite that causes cerebral malaria, is reported in complex with the boronic acid inhibitor 2(s)-amino-6-boronohexanoic acid (abh) (k(d) = 11 microm). this is the first crystal structure of a parasitic arginase. various protein constructs were explored to identify an optimally active enzyme form for inhibition and structural studies and to probe the structure and function of two polypeptide insertions unique to ... | 2010 | 20527960 |
| adf2 is required for transformation of the ookinete and sporozoite in malaria parasite development. | malaria parasites undergo two rounding-up transformations in their life cycle: the ookinete-to-oocyst transformation in the mosquito midgut, and the sporozoite-to-eef (exo-erythrocytic form) differentiation in the host hepatocyte. both events are characterized by the loss of polarity, implying that cytoskeletal reorganization is involved. in other eukaryotes, regulation of the actin skeleton is fundamental to subcellular remodeling. although filamentous actin is well known to be involved in the ... | 2010 | 20529666 |
| genome wide analysis of inbred mouse lines identifies a locus containing ppar-gamma as contributing to enhanced malaria survival. | the genetic background of a patient determines in part if a person develops a mild form of malaria and recovers, or develops a severe form and dies. we have used a mouse model to detect genes involved in the resistance or susceptibility to plasmodium berghei malaria infection. to this end we first characterized 32 different mouse strains infected with p. berghei and identified survival as the best trait to discriminate between the strains. we found a locus on chromosome 6 by linking the survival ... | 2010 | 20531941 |
| murine malaria is associated with significant hearing impairment. | plasmodium falciparum malaria has been suspected to cause hearing loss. developmental, cognitive and language disorders have been observed in children, surviving cerebral malaria. this prospective study aims to evaluate whether malaria influences hearing in mice. | 2010 | 20540722 |
| a possible key molecule for the invasion of the plasmodium berghei ookinetes into the midgut epithelium of anopheles gambiae mosquitoes. | in order to identify molecules necessary for the invasion of the mosquito midgut epithelium by plasmodia, interaction assays between both these structures were devised. | 2010 | 20554998 |
| metamorphosis of the malaria parasite in the liver is associated with organelle clearance. | malaria parasites encounter diverse conditions as they cycle between their vertebrate host and mosquito vector. within these distinct environments, the parasite undergoes drastic transformations, changing both its morphology and metabolism. plasmodium species that infect mammals must first take up residence in the liver before initiating red blood cell infection. following penetration into hepatocytes, the parasite converts from an invasion-competent, motile, elongated sporozoite to a metabolica ... | 2010 | 20567259 |
| synthesis and evaluation of alpha-halogenated analogues of 3-(acetylhydroxyamino)propylphosphonic acid (fr900098) as antimalarials. | three alpha-halogenated analogues of 3-(acetylhydroxyamino)propylphosphonic acid (fr900098) have been synthesized from diethyl but-3-enylphosphonate using a previously described method for the alpha-halogenation of alkylphosphonates. these analogues were evaluated for antimalarial potential in vitro against plasmodium falciparum and in vivo in the p. berghei mouse model. all three analogues showed higher in vitro and/or in vivo potency than the reference compounds. | 2010 | 20568776 |
| spirotetrahydro beta-carbolines (spiroindolones): a new class of potent and orally efficacious compounds for the treatment of malaria. | the antiplasmodial activity of a series of spirotetrahydro beta-carbolines is described. racemic spiroazepineindole (1) was identified from a phenotypic screen on wild type plasmodium falciparum with an in vitro ic(50) of 90 nm. structure-activity relationships for the optimization of 1 to compound 20a (ic(50) = 0.2 nm) including the identification of the active 1r,3s enantiomer and elimination of metabolic liabilities is presented. improvement of the pharmacokinetic profile of the series transl ... | 2010 | 20568778 |
| in vitro and in vivo antimalarial evaluation of semi-synthetic derivatives of gomphostenin. | a novel series of semi-synthetic gomphostenin derivatives (1-9) were prepared utilizing c-14 hydroxyl group for the first time and studied for their antimalarial properties. in vitro antiplasmodial activity was evaluated against both the chloroquine sensitive and resistant strains of plasmodium falciparum. most of the compounds exhibited superior or comparable antiplasmodial activity compared to parent compound, that is, gomphostenin (gn). based upon in vitro antiplasmodial activity, compounds w ... | 2010 | 20570512 |
| glutathione reductase-null malaria parasites have normal blood stage growth but arrest during development in the mosquito. | malaria parasites contain a complete glutathione (gsh) redox system, and several enzymes of this system are considered potential targets for antimalarial drugs. through generation of a gamma-glutamylcysteine synthetase (gamma-gcs)-null mutant of the rodent parasite plasmodium berghei, we previously showed that de novo gsh synthesis is not critical for blood stage multiplication but is essential for oocyst development. in this study, phenotype analyses of mutant parasites lacking expression of gl ... | 2010 | 20573956 |
| dimeric cyclohexane-1,3-dione oximes inhibit wheat acetyl-coa carboxylase and show anti-malarial activity. | a series of dimeric 1,3-cyclohexanedione oxime ethers were synthesized and found to have significant antiplasmodial activity with ic(50)'s in the range 3-12 microm. the most active dimer was tested in the plasmodium berghei mouse model of malaria and at a dose of 48 mg/kg gave a 45% reduction in parasitaemia. several commercial herbicides, all known to be inhibitors of maize acetyl-coa carboxylase, were also tested for antimalarial activity, but were essentially inactive with the exception of bu ... | 2010 | 20580556 |
| arp1, an actin-related protein, in plasmodium berghei. | actin-related proteins (arps) constitute a family of eukaryotic cytoskeletal proteins involved in such diverse events as cell motility, cytokinesis, vesicle transport, and chromatin remodelling. previously, in a study of plasmodium berghei gene expression in ookinetes and oocysts, we detected stage-specific increased expression of a gene encoding an arp. here we further characterize this gene and the encoded protein. we present a phylogenetic and three-dimensional modelling analysis as well as c ... | 2010 | 20580650 |
| the plasmodium eukaryotic initiation factor-2alpha kinase ik2 controls the latency of sporozoites in the mosquito salivary glands. | sporozoites, the invasive form of malaria parasites transmitted by mosquitoes, are quiescent while in the insect salivary glands. sporozoites only differentiate inside of the hepatocytes of the mammalian host. we show that sporozoite latency is an active process controlled by a eukaryotic initiation factor-2alpha (eif2alpha) kinase (ik2) and a phosphatase. ik2 activity is dominant in salivary gland sporozoites, leading to an inhibition of translation and accumulation of stalled mrnas into granul ... | 2010 | 20584882 |
| cognitive dysfunction is sustained after rescue therapy in experimental cerebral malaria, and is reduced by additive antioxidant therapy. | neurological impairments are frequently detected in children surviving cerebral malaria (cm), the most severe neurological complication of infection with plasmodium falciparum. the pathophysiology and therapy of long lasting cognitive deficits in malaria patients after treatment of the parasitic disease is a critical area of investigation. in the present study we used several models of experimental malaria with differential features to investigate persistent cognitive damage after rescue treatme ... | 2010 | 20585569 |
| divergent roles of irak4-mediated innate immune responses in two experimental models of severe malaria. | severe malaria represents a clinical spectrum of disease. we propose that innate immune inflammatory responses to malaria play key roles in the pathogenesis and clinical outcomes of distinct severe malaria syndromes. to investigate this hypothesis, mice deficient in irak4, central to toll-like receptor (tlr)-mediated signaling, were studied in two experimental models of malaria: plasmodium berghei (pba) and plasmodium chabaudi (pccas). irak4(-/-)mice had decreased pro-inflammatory cytokine produ ... | 2010 | 20595480 |
| accumulation of plasmodium berghei-infected red blood cells in the brain is crucial for the development of cerebral malaria in mice. | cerebral malaria is the most severe complication of human infection with plasmodium falciparum. it was shown that plasmodium berghei anka-induced cerebral malaria was prevented in 100% of mice depleted of cd8+ t cells 1 day prior to the development of neurological signs. however, the importance of parasites in the brains of these mice was never clearly investigated. moreover, the relevance of this model to human cerebral malaria has been questioned many times, especially concerning the relative ... | 2010 | 20605973 |
| exploiting cross-priming to generate protective cd8 t-cell immunity rapidly. | the number of memory cd8 t cells generated by infection or vaccination correlates strongly with the degree of protection observed in infection and tumor models. therefore, rapid induction of protective numbers of effector and memory cd8 t cells may be crucial in the case of malignancy, pandemic infection, or bioterrorism. many studies have shown that amplifying t-cell numbers by prime-boost vaccination is most effective with a substantial time interval between immunizations. in contrast, immuniz ... | 2010 | 20616089 |
| natural immunization against malaria: causal prophylaxis with antibiotics. | malaria remains the most prevalent vector-borne infectious disease and has the highest rates of fatality. current antimalarial drug strategies cure malaria or prevent infections but lack a sustained public health impact because they fail to expedite the acquisition of protective immunity. we show that antibiotic administration during transmission of the parasite plasmodium berghei results in swift acquisition of long-lived, life cycle-specific protection against reinfection with live sporozoites ... | 2010 | 20630856 |
| targeting glutathione by dimethylfumarate protects against experimental malaria by enhancing erythrocyte cell membrane scrambling. | the balance between gsh-levels and oxidative stress is critical for cell survival. the gsh-levels of erythrocytes are dramatically decreased during infection with plasmodium spp. we therefore investigated the consequences of targeting gsh for erythrocyte and plasmodium survival in vitro and in vivo using dimethylfumarate (dmf) at therapeutically established dosage. we first show that noninfected red blood cells (rbc) exposed to dmf undergo changes typical of apoptosis or eryptosis, such as cell ... | 2010 | 20631250 |
| essential role for il-27 receptor signaling in prevention of th1-mediated immunopathology during malaria infection. | successful resolution of malaria infection requires induction of proinflammatory immune responses that facilitate parasite clearance; however, failure to regulate this inflammation leads to immune-mediated pathology. the pathways that maintain this immunological balance during malaria infection remain poorly defined. in this study, we demonstrate that il-27r-deficient (wsx-1(-/-)) mice are highly susceptible to plasmodium berghei nk65 infection, developing exacerbated th1-mediated immune respons ... | 2010 | 20631310 |
| anopheles gambiae prs1 modulates plasmodium development at both midgut and salivary gland steps. | invasion of the mosquito salivary glands by plasmodium is a critical step for malaria transmission. from a sage analysis, we previously identified several genes whose expression in salivary glands was regulated coincident with sporozoite invasion of salivary glands. to get insights into the consequences of these salivary gland responses, here we have studied one of the genes, prs1 (plasmodium responsive salivary 1), whose expression was upregulated in infected glands, using immunolocalization an ... | 2010 | 20634948 |
| activity of a trisubstituted pyrrole in inhibiting sporozoite invasion and blocking malaria infection. | malaria infection is initiated by plasmodium sporozoites infecting the liver. preventing sporozoite infection would block the obligatory first step of the infection and perhaps reduce disease severity. in addition, such an approach would decrease plasmodium vivax hypnozoite formation and therefore disease relapses. here we describe the activity of a trisubstituted pyrrole, 4-[2-(4-fluorophenyl)-5-(1-methylpiperidine-4-yl)-1h-pyrrol-3-yl] pyridine, in inhibiting motility, invasion, and consequent ... | 2010 | 20643897 |
| extreme cd8 t cell requirements for anti-malarial liver-stage immunity following immunization with radiation attenuated sporozoites. | radiation-attenuated plasmodium sporozoites (ras) are the only vaccine shown to induce sterilizing protection against malaria in both humans and rodents. importantly, these "whole-parasite" vaccines are currently under evaluation in human clinical trials. studies with inbred mice reveal that ras-induced cd8 t cells targeting liver-stage parasites are critical for protection. however, the paucity of defined t cell epitopes for these parasites has precluded precise understanding of the specific ch ... | 2010 | 20657824 |
| protein kinase c θ deficiency increases resistance of c57bl/6j mice to plasmodium berghei infection-induced cerebral malaria. | protein kinase c θ (pkcθ) functions as a core component of the immunological synapse and serves as a key protein in the integrated t-cell antigen receptor (tcr)/cd28-induced signaling cascade leading to t-cell activation. however, the involvement of pkcθ in host-mediated immune responses to pathogens has not been thoroughly investigated. we tested the consequences of pkcθ ablation on the host response to infection by plasmodium berghei anka (pba). we found that both pkcθ(+/+) and pkcθ(-/-) c57bl ... | 2010 | 20660606 |
| self-microemulsifiyng suppository formulation of β-artemether. | parasitic diseases are of immense global significance as around 30% of world's population experiences parasitic infections. among these, malaria is the most life-threatening disease. various routes of administration have been explored for delivering antimalarial actives. the present investigation aims at formulating self-microemulsifying suppositories of β-artemether with faster onset of action and prolonged effect to be administered by rectal route. these were compared with conventional polyeth ... | 2010 | 20661674 |