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visualizing non infectious and infectious anopheles gambiae blood feedings in naive and saliva-immunized mice.anopheles gambiae is a major vector of malaria and lymphatic filariasis. the arthropod-host interactions occurring at the skin interface are complex and dynamic. we used a global approach to describe the interaction between the mosquito (infected or uninfected) and the skin of mammals during blood feeding.201223272060
csp--a model for in vivo presentation of plasmodium berghei sporozoite antigens by hepatocytes.one target of protective immunity against the plasmodium liver stage in balb/c mice is represented by the circumsporozoite protein (csp), and mainly involves its recognition by ifn-γ producing specific cd8+t-cells. in a previous in vitro study we showed that primary hepatocytes from balb/c mice process plasmodium berghei (pb) csp (pbcsp) and present csp-derived peptides to specific h-2k(d) restricted cd8+t-cells with subsequent killing of the presenting cells. we now extend these observations to ...201223272182
full-length plasmodium falciparum circumsporozoite protein administered with long-chain poly(i·c) or the toll-like receptor 4 agonist glucopyranosyl lipid adjuvant-stable emulsion elicits potent antibody and cd4+ t cell immunity and protection in mice.the plasmodium falciparum circumsporozoite (cs) protein (csp) is a major vaccine target for preventing malaria infection. thus, developing strong and durable antibody and t cell responses against csp with novel immunogens and potent adjuvants may improve upon the success of current approaches. here, we compare four distinct full-length p. falciparum cs proteins expressed in escherichia coli or pichia pastoris for their ability to induce immunity and protection in mice when administered with long ...201223275094
protective role of brain water channel aqp4 in murine cerebral malaria.tragically common among children in sub-saharan africa, cerebral malaria is characterized by rapid progression to coma and death. in this study, we used a model of cerebral malaria appearing in c57bl/6 wt mice after infection with the rodent malaria parasite plasmodium berghei anka. expression and cellular localization of the brain water channel aquaporin-4 (aqp4) was investigated during the neurological syndrome. semiquantitative real-time pcr comparing uninfected and infected mice showed a red ...201223277579
a chronic scheme of cranial window preparation to study pial vascular reactivity in murine cerebral malaria.the acute implantation of a cranial window for studying cerebroarteriolar reactivity in living animals involves a highly surgically invasive craniotomy procedure at the time of experimentation, which limits its application in severely ill animals such as in the experimental murine model of cerebral malaria (ecm). to overcome this problem, a chronic window implantation scheme was designed and implemented.201323279271
aberrant sporogonic development of dmc1 (a meiotic recombinase) deficient plasmodium berghei parasites.in plasmodium, meiosis occurs in diploid zygotes as they develop into haploid motile ookinetes inside the mosquito. further sporogonic development involves transformation of ookinetes into oocysts and formation of infective sporozoites.201223285059
new markers in anopheles gambiae salivary glands after plasmodium berghei infection.in malaria, mosquito saliva and salivary glands play central roles in the multi-faceted interactions that occur among the parasite, its vector, and its host. analyzing the processes involved in the survival and maintenance of the plasmodium parasite in mosquito organs, and in its transmission into vertebrate hosts, may lead to the identification of new molecular targets for parasite control. we used comparative two-dimensional gel polyacrylamide electrophoresis (2d-page), surface-enhanced laser ...201323289400
in vitro efficiency of 9-(n-cinnamoylbutyl)aminoacridines against blood- and liver-stage malaria parasites.novel 9-aminoacridine derivatives were synthesized by linking the heteroaromatic core to different cinnamic acids through an aminobutyl chain. the test compounds demonstrated mid-nanomolar in vitro activity against erythrocytic stages of the chloroquine-resistant w2 strain of the human malaria parasite plasmodium falciparum. two of the most active derivatives also showed in vitro activity against liver-stage plasmodium berghei, with activity greater than that of the reference liver-stage antimal ...201323290049
statins decrease neuroinflammation and prevent cognitive impairment after cerebral malaria.cerebral malaria (cm) is the most severe manifestation of plasmodium falciparum infection in children and non-immune adults. previous work has documented a persistent cognitive impairment in children who survive an episode of cm that is mimicked in animal models of the disease. potential therapeutic interventions for this complication have not been investigated, and are urgently needed. hmg-coa reductase inhibitors (statins) are widely prescribed for cardiovascular diseases. in addition to their ...201223300448
calculation of the three-dimensional structures of two antigenic sequences, pro-pro-pro-pro-asn-pro-asn-asp-pro and pro-pro-pro-pro-asn-pro-asn-asp-pro-pro-pro, of the circumsporozoite protein from a malaria-causing plasmodium.using the chain build-up procedure based on the program ecepp, we have computed the lowest energy structures for two terminally blocked subsequences from the antigenic circumsporozoite protein of plasmodium berghei, that is known to cause malaria in animals. the full antigenic sequence is an octapeptide proline-rich tandem repeat, (pro-pro-pro-pro-asn-pro-asn-asp)(2). we computed the structures for the first octapeptide plus one pro from the second octapeptide, terminally blocked ch(3)co-pro-pro ...201323307231
novel diaryl ureas with efficacy in a mouse model of malaria.exploration of triclosan analogs has led to novel diaryl ureas with significant potency against in vitro cultures of drug-resistant and drug-sensitive strains of the human malaria parasite plasmodium falciparum. compound 18 demonstrated ec(50) values of 37 and 55 nm versus in vitro cultured parasite strains and promising in vivo efficacy in a plasmodium berghei antimalarial mouse model, with >50% survival at day 31 post-treatment when administered subcutaneously at 256 mg/kg. this series of comp ...201323313245
plasmodium berghei anka infection in icr mice as a model of cerebral malaria.animal models with various combination of host-parasite have long been employed to study malaria pathogenesis. here, we describe the combination of plasmodium berghei anka infection in inbred icr mice as a model of cerebral malaria (cm).201223323093
early and late acute lung injury and their association with distal organ damage in murine malaria.severe malaria is characterised by cerebral oedema, acute lung injury (ali) and multiple organ dysfunctions, however, the mechanisms of lung and distal organ damage need to be better clarified. ninety-six c57bl/6 mice were injected intraperitoneally with 5×10(6)plasmodium berghei anka-infected erythrocytes or saline. at day 1, plasmodium berghei infected mice presented greater number of areas with alveolar collapse, neutrophil infiltration and interstitial oedema associated with lung mechanics i ...201323328346
hemozoin induces lung inflammation and correlates with malaria-associated acute respiratory distress syndrome.malaria-associated acute respiratory distress syndrome (ma-ards) is a deadly complication of malaria, and its pathophysiology is insufficiently understood. both in humans and in murine models, ma-ards is characterized by marked pulmonary inflammation. we investigated the role of hemozoin in ma-ards in c57bl/6 mice infected with plasmodium berghei nk65, p. berghei anka, and p. chabaudi as. by quantifying hemozoin in the lungs and measuring the disease parameters of ma-ards, we demonstrated a high ...201323328641
isolation and analysis of brain-sequestered leukocytes from plasmodium berghei anka-infected mice.we describe a method for isolation and characterization of adherent inflammatory cells from brain blood vessels of p. berghei anka-infected mice. infection of susceptible mouse-strains with this parasite strain results in the induction of experimental cerebral malaria, a neurologic syndrome that recapitulates certain important aspects of plasmodium falciparum-mediated severe malaria in humans. mature forms of blood-stage malaria express parasitic proteins on the surface of the infected erythrocy ...201323329000
cryo-electron tomography reveals four-membrane architecture of the plasmodium apicoplast.the apicoplast is a plastid organelle derived from a secondary endosymbiosis, containing biosynthetic pathways essential for the survival of apicomplexan parasites. the toxoplasma apicoplast clearly possesses four membranes but in related plasmodium spp. the apicoplast has variably been reported to have either three or four membranes.201323331966
novel type ii fatty acid biosynthesis (fas ii) inhibitors as multistage antimalarial agents.malaria is a potentially fatal disease caused by plasmodium parasites and poses a major medical risk in large parts of the world. the development of new, affordable antimalarial drugs is of vital importance as there are increasing reports of resistance to the currently available therapeutics. in addition, most of the current drugs used for chemoprophylaxis merely act on parasites already replicating in the blood. at this point, a patient might already be suffering from the symptoms associated wi ...201323341167
perturbations of plasmodium puf2 expression and rna-seq of puf2-deficient sporozoites reveal a critical role in maintaining rna homeostasis and parasite transmissibility.malaria's cycle of infection requires parasite transmission between a mosquito vector and a mammalian host. we here demonstrate that the plasmodium yoelii pumilio-fbf family member puf2 allows the sporozoite to remain infectious in the mosquito salivary glands while awaiting transmission. puf2 mediates this solely through its rna-binding domain (rbd) likely by stabilizing or hastening the degradation of specific mrnas. puf2 traffics to sporozoite cytosolic granules, which are negative for severa ...201323356439
efficacy of eosin b as a new antimalarial drug in a murine model.the initial success of any adopted anti-infective strategy to malaria is followed by a descent due to the emergence of resistance to it. the search for new drugs and drug targets is a consistent demand in this disease. eosin b, a common laboratory dye, is reported to have good antiparasitic properties in vitro. it was studied for its antiparasitic effect in vivo on chloroquine-sensitive plasmodium berghei murine malaria. eosin b was administered in 2 different doses by either the oral or parente ...201223365788
isolation, fractionation and evaluation of the antiplasmodial properties of phyllanthus niruri resident in its chloroform fraction.to investigate the antiplasmodial activity of phyllanthus niruri (p. niruri) methanol extract (me) and its fractions in mice.201323375028
in vivo antimalarial activity, toxicity and phytochemical screening of selected antimalarial plants.malaria continues to kill over a million people each year and in many populations affected by malaria, conventional drugs are often unaffordable or inaccessible. historically, plants have been a prominent source of antimalarial drugs. those plants currently used by indigenous people to treat malaria should be documented and investigated as potential sources of new antimalarial drugs.201323376043
expression of cytosolic peroxiredoxins in plasmodium berghei ookinetes is regulated by environmental factors in the mosquito bloodmeal.the plasmodium ookinete develops over several hours in the bloodmeal of its mosquito vector where it is exposed to exogenous stresses, including cytotoxic reactive oxygen species (ros). how the parasite adapts to these challenging conditions is not well understood. we have systematically investigated the expression of three cytosolic antioxidant proteins, thioredoxin-1 (trx-1), peroxiredoxin-1 (tpx-1), and 1-cys peroxiredoxin (1-cys prx), in developing ookinetes of the rodent parasite plasmodium ...201323382676
features of autophagic cell death in plasmodium liver-stage parasites.analyzing molecular determinants of plasmodium parasite cell death is a promising approach for exploring new avenues in the fight against malaria. three major forms of cell death (apoptosis, necrosis and autophagic cell death) have been described in multicellular organisms but which cell death processes exist in protozoa is still a matter of debate. here we suggest that all three types of cell death occur in plasmodium liver-stage parasites. whereas typical molecular markers for apoptosis and ne ...201323388496
in vivo antimalarial activity of a labdane diterpenoid from the leaves of otostegia integrifolia benth.in ethiopian traditional medicine, the leaves of otostegia integrifolia benth. are used for the treatment of several diseases including malaria. in an ongoing search for effective, safe and cheap antimalarial agents from plants, the 80% methanol leaf extract o. integrifolia was tested for its in vivo antimalarial activity, in a 4-day suppressive assay against plasmodium berghei. activity-guided fractionation of this extract which showed potent antiplasmodial activity resulted in the isolation of ...201323401280
experimental cerebral malaria is suppressed by disruption of nucleoside transporter 1 but not purine nucleoside phosphorylase.protozoan parasites rely on purine nucleosides supplied by the host because they are unable to synthesise purine rings denovo. nucleoside transporter 1 (nt1) and purine nucleoside phosphorylase (pnp) play an essential role in purine salvage in plasmodium. it is unclear whether severe pathology, such as cerebral malaria (cm), develops in hosts infected with plasmodium parasites that lack activity of nt1 or pnp. plasmodium berghei (pb) anka-infected mice show features similar to human cm, such as ...201323402751
plasmodium yoelii inhibitor of cysteine proteases is exported to exomembrane structures and interacts with yoelipain-2 during asexual blood-stage development.plasmodium falciparum (pf) blood stages express falstatin, an inhibitor of cysteine proteases (icp), which is implicated in regulating proteolysis during red blood cell infection. recent data using the plasmodium berghei rodent malaria model suggested an additional role for icp in the infection of hepatocytes by sporozoites and during liver-stage development. here we further characterize the role of icp in vivo during infection with plasmodium yoelii (py) and pf. we found that py-icp was refract ...201323421981
[in vivo antiplasmodial activity of mycale laxissima and clathria echinata sponges].the search of new antimalarial compounds comprises, among its challenges, the development of therapeutic alternatives for cerebral malaria; due to the high mortality and neurological deficiencies that persist after treatment with recommended drugs.201223424801
synthesis and antimalarial efficacy of two-carbon-linked, artemisinin-derived trioxane dimers in combination with known antimalarial drugs.malaria continues to be a difficult disease to eradicate largely because of the widespread populations it affects and the resistance that malaria parasites have developed against once very potent therapies. the natural product artemisinin has been a boon for antimalarial chemotherapy, as artemisinin combination therapy (act) has become the first line of chemotherapy. because the threat of resistance is always on the horizon, it is imperative to continually identify new treatments, comprising bot ...201323425037
marine actinobacterial mediated gold nanoparticles synthesis and their antimalarial activity.streptomyces sp lk-3 (jf710608) mediated gold nanoparticles (au-n-lk3) were found within the size range of 5-50 nm. au-n-lk3 treatment in plasmodium berghei anka (pba) infected mice delayed the parasitemia rise (~6%) compared to pba infection on 8 days post infection. survivability of mice increases to ~85% in au-n-lk3 treated mice in contrast to in pba (~50%) infected mice in 8 dpi with respect to control. during au-n-lk3 treatment in pba infection, histomorphological analysis revealed as such ...201323434675
[antimalarial activity of hydroalcoholic extract from bixa orellana l].bixa orellana l. is one species used in traditional herb medicine in several continents. among the medicinal properties attributed to this plant, the antimalarial action has been included.201123437529
antiplasmodial potential of the african mistletoe: agelanthus dodoneifolius polh and wiens.preparations of agelanthus dodoneifolius have been used in the traditional nigerian medicine to treat malaria and this practice has remained till date without scientific validation. the antiplasmodial property of the water extract of agelanthus dodoneifolius was evaluated in vivo and in vitro against plasmodium berghei and clinical isolates of plasmodium falciparum, respectively. there was a dose-dependent inhibition of parasitaemia in the in vivo antiplasmodial tests likewise, the in vitro scre ...201223441021
the specific, reversible jnk inhibitor sp600125 improves survivability and attenuates neuronal cell death in experimental cerebral malaria (ecm).cerebral malaria (cm) is the most severe complication of plasmodium falciparum in humans and major cause of death. sp600125 is a specific, small molecule inhibitor of jnk that prevents the phosphorylation of c-jun and blocks the expression of proinflammatory cytokines and attenuates neuronal apoptosis in several neurodegenerative disorders. we evaluated the effect of sp600125 treatment on the survival of plasmodium berghei anka (pba)-infected c57bl/6j mice. administration of sp600125 improved su ...201323455938
a perforin-like protein mediates disruption of the erythrocyte membrane during egress of plasmodium berghei male gametocytes.successful gametogenesis of the malaria parasite depends on egress of the gametocytes from the erythrocytes within which they developed. egress entails rupture of both the parasitophorous vacuole membrane and the erythrocyte plasma membrane, and precedes the formation of the motile flagellated male gametes in a process called exflagellation. we show here that egress of the male gametocyte depends on the function of a perforin-like protein, pplp2. a mutant of plasmodium berghei lacking pplp2 disp ...201323461714
alterations in the brain transcriptome in plasmodium berghei anka infected mice.we have used cdna microarrays to compare gene expression profiles in brains from normal mice to those infected with the anka strain of plasmodium berghei, a model of cerebral malaria. for each of three brains in each group, we computed ratios of all quantifiable genes with a composite reference sample and then computed ratios of gene expression in infected brains compared to untreated controls. of the almost 12,000 unigenes adequately quantified in all arrays, approximately 3% were significantly ...201023467761
the plasmodium berghei ca(2+)/h(+) exchanger, pbcax, is essential for tolerance to environmental ca(2+) during sexual development.ca(2+) contributes to a myriad of important cellular processes in all organisms, including the apicomplexans, plasmodium and toxoplasma. due to its varied and essential roles, free ca(2+) is tightly regulated by complex mechanisms. these mechanisms are therefore of interest as putative drug targets. one pathway in ca(2+) homeostatic control in apicomplexans uses a ca(2+)/h(+) exchanger (a member of the cation exchanger family, cax). the p. falciparum cax (pfcax) has recently been characterised i ...201323468629
[application of flow cytometry in the detection of mouse malaria parasites in living cells].peripheral blood samples were obtained from plasmodium berghei-infected mice, and stained with vybrant dyecycle green and anti-mouse cd71 pe. with normal mouse as negative control, the blood samples were tested by flow cytometry at 0, 30, and 60 min after staining. there was no positive signal in the erythrocytes from negative control and the unstained erythrocytes from the infected mouse. however, the positive signal was detected in the stained erythrocytes from the infected mouse. the results ...201223484270
a key role for lipoic acid synthesis during plasmodium liver stage development.the successful navigation of malaria parasites through their life cycle, which alternates between vertebrate hosts and mosquito vectors, requires a complex interplay of metabolite synthesis and salvage pathways. using the rodent parasite plasmodium berghei, we have explored the synthesis and scavenging pathways for lipoic acid, a short-chain fatty acid derivative that regulates the activity of α-ketoacid dehydrogenases including pyruvate dehydrogenase. in plasmodium, lipoic acid is either synthe ...201323490300
a new approach to generate a safe double-attenuated plasmodium liver stage vaccine.recently it has been shown in rodent malaria models that immunisation with genetically attenuated plasmodium parasites can confer sterile protection against challenge with virulent parasites. for the mass production of live attenuated plasmodium parasites for vaccination, safety is a prerequisite. knockout of a single gene is not sufficient for such a strategy since the parasite can likely compensate for such a genetic modification and a single surviving parasite is sufficient to kill an immunis ...201323500072
systemic release of high mobility group box 1 (hmgb1) protein is associated with severe and fatal plasmodium falciparum malaria.severe falciparum malaria (sm) pathogenesis has been attributed, in part, to deleterious systemic host inflammatory responses to infection. high mobility group box 1 (hmgb1) protein is an important mediator of inflammation implicated in sepsis pathophysiology.201323506269
antimalarial and hepatoprotective effects of crude ethanolic extract of lingzhi or reishi medicinal mushroom, ganoderma lucidum (w.curt.:fr.)p.karst. (higher basidiomycetes), in plasmodium berghei-infected mice.this study was aimed at investigating the in vivo antimalarial activity (using some biochemical indices) of crude aqueous extracts of the fruiting bodies of ganoderma lucidum, a mushroom with well-established medicinal properties. a rodent malaria parasite, plasmodium berghei (1 × 107), was inoculated intraperitoneally into swiss albino mice. the test groups were administered g. lucidum extract and chloroquine (cq, as standard drug), while the control groups were administered the same amount of ...201223510214
il-27 receptor signaling regulates cd4+ t cell chemotactic responses during infection.il-27 exerts pleiotropic suppressive effects on naive and effector t cell populations during infection and inflammation. surprisingly, however, the role of il-27 in restricting or shaping effector cd4(+) t cell chemotactic responses, as a mechanism to reduce t cell-dependent tissue inflammation, is unknown. in this study, using plasmodium berghei nk65 as a model of a systemic, proinflammatory infection, we demonstrate that il-27r signaling represses chemotaxis of infection-derived splenic cd4(+) ...201323536628
transgenic parasites stably expressing full-length plasmodium falciparum circumsporozoite protein as a model for vaccine down-selection in mice using sterile protection as an endpoint.circumsporozoite protein (csp) of plasmodium falciparum is a protective human malaria vaccine candidate. there is an urgent need for models that can rapidly down-select novel csp-based vaccine candidates. in the present study, the mouse-mosquito transmission cycle of a transgenic plasmodium berghei malaria parasite stably expressing a functional full-length p. falciparum csp was optimized to consistently produce infective sporozoites for protection studies. a minimal sporozoite challenge dose wa ...201323536694
plasmodium berghei mapk1 displays differential and dynamic subcellular localizations during liver stage development.mitogen-activated protein kinases (mapks) regulate key signaling events in eukaryotic cells. in the genomes of protozoan plasmodium parasites, the causative agents of malaria, two genes encoding kinases with significant homology to other eukaryotic mapks have been identified (mapk1, mapk2). in this work, we show that both genes are transcribed during plasmodium berghei liver stage development, and analyze expression and subcellular localization of the pbmapk1 protein in liver stage parasites. li ...201323544094
evidence of trna cleavage in apicomplexan parasites: half-trnas as new potential regulatory molecules of toxoplasma gondii and plasmodium berghei.several lines of evidence demonstrated that organisms ranging from bacteria to higher animals possess a regulated endonucleolytic cleavage pathway producing half-trna fragments. in the present study, we investigated the occurrence of this phenomenon in two distantly related apicomplexan parasites, toxoplasma gondii, the agent of toxoplasmosis, and the rodent malaria parasite plasmodium berghei. a low-scale molecular characterization of the small rna fraction of t. gondii revealed the endonucleol ...201323557708
malaria parasite carbonic anhydrase: inhibition of aromatic/heterocyclic sulfonamides and its therapeutic potential.plasmodium falciparum (p. falciparum) is responsible for the majority of life-threatening cases of human malaria, causing 1.5-2.7 million annual deaths. the global emergence of drug-resistant malaria parasites necessitates identification and characterization of novel drug targets and their potential inhibitors. we identified the carbonic anhydrase (ca) genes in p. falciparum. the pfca gene encodes anα-carbonic anhydrase, a zn(2+)-metalloenzme, possessing catalytic properties distinct from that o ...201123569766
antiplasmodial and antiulcer activities of melanthera scadens.to evaluate the antimalarial and antiulcerogenic activities of leaf extract and fractions of melanthera scandens (m. scandens).201223569827
comparative study of chloroquine and quinine on malaria rodents and their effects on the mouse testis.to evaluate the effects of quinine and chloroquine against male mice infected with plasmodium berghei and their adverse effects on the mice testes.201223569921
substituted imidazopyridazines are potent and selective inhibitors of plasmodium falciparum calcium-dependent protein kinase 1 (pfcdpk1).a series of imidazopyridazines which are potent inhibitors of plasmodium falciparum calcium-dependent protein kinase 1 (pfcdpk1) was identified from a high-throughput screen against the isolated enzyme. subsequent exploration of the sar and optimisation has yielded leading members which show promising in vitro anti-parasite activity along with good in vitro adme and selectivity against human kinases. initial in vivo testing has revealed good oral bioavailability in a mouse pk study and modest in ...201323570789
ifnar1 controls progression to cerebral malaria in children and cd8+ t cell brain pathology in plasmodium berghei-infected mice.development of cerebral malaria (cm), a severe and fatal form of clinical plasmodium falciparum infection, results from a damaging cascade of vascular, inflammatory, and immunological host responses that leads to brain injury. progression to cm can be modified by host genetic factors. our case-control study in angolan children aimed at highlighting the role of ifn (α, β) receptor 1 (ifnar1) in progression to cm. we report a robust association between ifnar1 and cm protection, as well as detailed ...201323585679
impact of methylene blue and atorvastatin combination therapy on the apparition of cerebral malaria in a murine model.proveblue®, a methylene blue dye that complies with european pharmacopoeia and contains limited organic impurities and heavy metals of recognized toxicity, showed in vitro synergy against plasmodium falciparum when combined with atorvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme a reductase. the objective of this study was to evaluate the in vivo efficacy of proveblue® when combined with atorvastatin in a murine model of experimental cerebral malaria.201323587099
the survival of memory cd8 t cells that is mediated by il-15 correlates with sustained protection against malaria.ag-specific memory t cell responses elicited by infections or vaccinations are inextricably linked to long-lasting protective immunity. studies of protective immunity among residents of malaria endemic areas indicate that memory responses to plasmodium ags are not adequately developed or maintained, as people who survive episodes of childhood malaria are still vulnerable to either persistent or intermittent malaria infections. in contrast, multiple exposures to radiation-attenuated plasmodium be ...201323589611
quantitative bioluminescent imaging of pre-erythrocytic malaria parasite infection using luciferase-expressing plasmodium yoelii.the liver stages of plasmodium parasites are important targets for the development of anti-malarial vaccine candidates and chemoprophylaxis approaches that aim to prevent clinical infection. analyzing the impact of interventions on liver stages in the murine malaria model system plasmodium yoelii has been cumbersome and requires terminal procedures. in vivo imaging of bioluminescent parasites has previously been shown to be an effective and non-invasive alternative to monitoring liver stage burd ...201323593316
wild anopheles funestus mosquito genotypes are permissive for infection with the rodent malaria parasite, plasmodium berghei.malaria parasites undergo complex developmental transitions within the mosquito vector. a commonly used laboratory model for studies of mosquito-malaria interaction is the rodent parasite, p. berghei. anopheles funestus is a major malaria vector in sub-saharan africa but has received less attention than the sympatric species, anopheles gambiae. the imminent completion of the a. funestus genome sequence will provide currently lacking molecular tools to describe malaria parasite interactions in th ...201323593423
susceptibility to lethal cerebral malaria is regulated by epistatic interaction between chromosome 4 (berr6) and chromosome 1 (berr7) loci in mice.in humans, cerebral malaria is a rare but often lethal complication of infection with plasmodium parasites, the occurrence of which is influenced by complex genetic factors of the host. we used a mouse model of experimental cerebral malaria (ecm) with plasmodium berghei anka to study genetic factors regulating appearance of neurological symptoms and associated lethality. in a genome-wide screen of n-ethyl-n-nitrosourea-mutagenized mice derived from c57bl/6j (b6) and 129s1/svimj (129) mouse strai ...201323594960
mechanisms of protective immune responses induced by the plasmodium falciparum circumsporozoite protein-based, self-assembling protein nanoparticle vaccine.a lack of defined correlates of immunity for malaria, combined with the inability to induce long-lived sterile immune responses in a human host, demonstrate a need for improved understanding of potentially protective immune mechanisms for enhanced vaccine efficacy. protective sterile immunity (>90%) against the plasmodium falciparum circumsporozoite protein (csp) has been achieved using a transgenically modified plasmodium berghei sporozoite (tg-pb/pfcsp) and a self-assembling protein nanopartic ...201323607541
liver or blood-stage arrest during malaria sporozoite immunization: the later the better?so far, the best immunization strategies to achieve high levels of protection against malaria are based on whole parasites. complete sterile protection can be obtained in rodent models after immunization with sporozoites and chemoprophylaxis, or with sporozoites attenuated either genetically or by radiation. these approaches target specific stages, with arrests occurring at different time-points of the parasite life cycle. here, we review these different approaches in relation to their capacity ...201323608185
the utility of plasmodium berghei as a rodent model for anti-merozoite malaria vaccine assessment.rodent malaria species plasmodium yoelii and p. chabaudi have been widely used to validate vaccine approaches targeting blood-stage merozoite antigens. however, increasing data suggest the p. berghei rodent malaria may be able to circumvent vaccine-induced anti-merozoite responses. here we confirm a failure to protect against p. berghei, despite successful antibody induction against leading merozoite antigens using protein-in-adjuvant or viral vectored vaccine delivery. no subunit vaccine approa ...023609325
efficacy of proveblue (methylene blue) in an experimental cerebral malaria murine model.although 100% of untreated mice infected with plasmodium berghei died with specific signs of cerebral malaria and 100% of mice treated with 3 mg/kg dihydroartemisinin, the active metabolite of artesunate, which is used as the first-line treatment for severe malaria, also died but showed no specific signs of cerebral malaria, 78% of mice treated with 10 mg/kg proveblue (methylene blue) and 78% of mice treated with a combination of 3 mg dihydroartemisinin and 10 mg/kg proveblue survived and showed ...201323612202
slow and continuous delivery of a low dose of nimodipine improves survival and electrocardiogram parameters in rescue therapy of mice with experimental cerebral malaria.human cerebral malaria (hcm) is a life-threatening complication caused by plasmodium falciparum infection that continues to be a major global health problem despite optimal anti-malarial treatment. in the experimental model of cerebral malaria (ecm) by plasmodium berghei anka, bolus administration of nimodipine at high doses together with artemether, increases survival of mice with ecm. however, the dose and administration route used is associated with cardiovascular side effects such as hypoten ...201323617605
nyctanthes arbor-tristis positively affects immunopathology of malaria-infected mice prolonging its survival.in order to search for new products that display antimalarial and immunomodulatory mechanisms that complement direct antiparasitic activity, a set of in vitro and in vivo experiments were designed to evaluate the effect of nyctanthes arbor-tristis in plasmodium berghei infected mice. three extracts of n. arbor-tristis leaves from varying concentrations of alcohol and water were considered for their potential to suppress expression of pro-inflammatory mediators from macrophages primed with lipopo ...201323624584
in vitro and in vivo antimalarial efficacies of optimized tetracyclines.with increasing resistance to existing antimalarials, there is an urgent need to discover new drugs at affordable prices for countries in which malaria is endemic. one approach to the development of new antimalarial drugs is to improve upon existing antimalarial agents, such as the tetracyclines. tetracyclines exhibit potent, albeit relatively slow, action against malaria parasites, and doxycycline is used for both treatment (with other agents) and prevention of malaria. we synthesized 18 novel ...201323629719
measurement of the uniaxial mechanical properties of rat brains infected by plasmodium berghei anka.degenerative and demyelinating diseases are known to alter the mechanical properties of brain tissue. while few studies have characterized these biomechanical changes, it is clear that accurate characterization of the mechanical properties of diseased brain tissue could be a substantial asset to neuronavigation and surgery simulation through haptic devices. in this study, samples of brain tissue from rats infected with plasmodium berghei anka, an african murine malaria parasite, are evaluated us ...201323637271
global analysis of apicomplexan protein s-acyl transferases reveals an enzyme essential for invasion.the advent of techniques to study palmitoylation on a whole proteome scale has revealed that it is an important reversible modification that plays a role in regulating multiple biological processes. palmitoylation can control the affinity of a protein for lipid membranes, which allows it to impact protein trafficking, stability, folding, signalling and interactions. the publication of the palmitome of the schizont stage of plasmodium falciparum implicated a role for palmitoylation in host cell i ...201323638681
malaria infection does not affect the sensitivity of peripheral receptor neurons in anopheles stephensi.mosquitoes transmit many important diseases including malaria, dengue and yellow fever. disease transmission from one vertebrate host to another depends on repeated blood feedings by single mosquitoes. in order for the mosquito to acquire the blood that it needs to complete oogenesis, the insect must locate a suitable host. olfactory cues (including carbon dioxide) released by the host and detected by the mosquito are the primary signals that vector insects use for host location. previous studie ...201323642231
angiotensin ii is a new component involved in splenic t lymphocyte responses during plasmodium berghei anka infection.the contribution of t cells in severe malaria pathogenesis has been described. here, we provide evidence for the potential role of angiotensin ii (ang ii) in modulating splenic t cell responses in a rodent model of cerebral malaria. t cell activation induced by infection, determined by 3 to 4-fold enhancement in cd69 expression, was reduced to control levels when mice were treated with 20 mg/kg losartan (ic₅₀ = 0.966 mg/kg/d), an at₁ receptor antagonist, or captopril (ic₅₀ = 1.940 mg/kg/d), an i ...201323646169
transmission-blocking interventions eliminate malaria from laboratory populations.transmission-blocking interventions aim to reduce the prevalence of infection in endemic communities by targeting plasmodium within the insect host. although many studies have reported the successful reduction of infection in the mosquito vector, direct evidence that there is an onward reduction in infection in the vertebrate host is lacking. here we report the first experiments using a population, transmission-based study of plasmodium berghei in anopheles stephensi to assess the impact of a tr ...023652000
antimalarial potential of china 30 and chelidonium 30 in combination therapy against lethal rodent malaria parasite: plasmodium berghei.homeopathy is a therapeutic method based on the application of similia principle, utilizing ultra-low doses of medicinal substances made from natural products. the present study has been designed to evaluate the efficacy of cinchona officinalis (chin.) 30c and chelidonium majus (chel.) 30c in combination therapy against lethal murine malaria. five groups having twelve balb/c mice each were administered orally with 0.2 ml/mouse/day of different drugs, and their antimalarial potential was evaluate ...201323652641
expression of tim-1 and tim-3 in plasmodium berghei anka infection.cerebral malaria (cm) is a serious and often fatal complication of plasmodium falciparum infections; however, the precise mechanisms leading to cm is poorly understood. mouse malaria models have provided insight into the key events in pathogenesis of cm. t-cell immune response is known to play an important role in malaria infection, and members of the t-cell immunoglobulin- and mucin-domain-containing molecule (tim) family have roles in t-cell-mediated immune responses. tim-1 and tim-3 are expre ...201323653017
in silico screening on the three-dimensional model of the plasmodium vivax sub1 protease leads to the validation of a novel anti-parasite compound.widespread drug resistance calls for the urgent development of new antimalarials that target novel steps in the life cycle of plasmodium falciparum and plasmodium vivax. the essential subtilisin-like serine protease sub1 of plasmodium merozoites plays a dual role in egress from and invasion into host erythrocytes. it belongs to a new generation of attractive drug targets against which specific potent inhibitors are actively searched. we characterize here the p. vivax sub1 enzyme and show that it ...201323653352
the exported protein pbcp1 localises to cleft-like structures in the rodent malaria parasite plasmodium berghei.protein export into the host red blood cell is one of the key processes in the pathobiology of the malaria parasite plasmodiumtrl falciparum, which extensively remodels the red blood cell to ensure its virulence and survival. in this study, we aimed to shed further light on the protein export mechanisms in the rodent malaria parasite p. berghei and provide further proof of the conserved nature of host cell remodeling in plasmodium spp. based on the presence of an export motif (r/kxlxe/q/d) terme ...201323658610
enterobacter-activated mosquito immune responses to plasmodium involve activation of srpn6 in anopheles stephensi.successful development of plasmodium in the mosquito is essential for the transmission of malaria. a major bottleneck in parasite numbers occurs during midgut invasion, partly as a consequence of the complex interactions between the endogenous microbiota and the mosquito immune response. we previously identified srpn6 as an immune component which restricts plasmodium berghei development in the mosquito. here we demonstrate that srpn6 is differentially activated by bacteria in anopheles stephensi ...201323658788
mesenchymal stem cells play an important role in host protective immune responses against malaria by modulating regulatory t cells.plasmodium spp. parasites, the causative agents of malaria, survive and replicate in human hosts by modulating host protective immune responses. in a rodent model, malaria manifests as a severe splenomegaly, with infiltration of cells and lympho-proliferation as major contributing factors of the immunopathology. however, the cellular contents and the functions of these cells have not been well studied. here, we report that plasmodium berghei infection of mice leads to massive recruitment of mese ...201323670483
identification of targets of cd8⁺ t cell responses to malaria liver stages by genome-wide epitope profiling.cd8⁺ t cells mediate immunity against plasmodium liver stages. however, the paucity of parasite-specific epitopes of cd8⁺ t cells has limited our current understanding of the mechanisms influencing the generation, maintenance and efficiency of these responses. to identify antigenic epitopes in a stringent murine malaria immunisation model, we performed a systematic profiling of h(2b)-restricted peptides predicted from genome-wide analysis. we describe the identification of plasmodium berghei (pb ...201323675294
therapeutic effects of various solvent fractions of alstonia boonei (apocynaceae) stem bark on plasmodium berghei-induced malaria.malaria, the most important parasitic disease afflicting man is the leading cause of mortality and morbidity in the world. chemotherapy remains the mainstay for the treatment and prevention of the disease in the absence of an effective vaccine. the incidence of resistance of malaria parasites to chemotherapy is increasing and complicated. this study was therefore undertaken in order to evaluate the therapeutic effects of fractions of the stem bark of a. boonei on p. berghei-induced malaria using ...201223678633
effects of low protein diet and pregnancy on course of plasmodium berghei infection in mice.pregnancy and malnutrition influence the severity or trend of malaria especially in sub-saharan africa where parasitic infections are highly predominant. this study was used to evaluate the combined effects of low protein diet and pregnancy on the course of plasmodium berghei infection in mice. thirty female balb/c mice were divided into six groups viz: non-infected mice fed on normal diet (nind), infected mice fed on normal diet (ind), noninfected mice fed on low protein diet (nilp), infected m ...201223678649
brain microvessel cross-presentation is a hallmark of experimental cerebral malaria.cerebral malaria is a devastating complication of plasmodium falciparum infection. its pathogenesis is complex, involving both parasite- and immune-mediated events. cd8(+) t cells play an effector role in murine experimental cerebral malaria (ecm) induced by plasmodium berghei anka (pba) infection. we have identified a highly immunogenic cd8 epitope in glideosome-associated protein 50 that is conserved across rodent malaria species. epitope-specific cd8(+) t cells are induced during pba infectio ...201323681698
ficolin-a enhances inhibition of the c-terminal 19 kda region of merozoite surface protein-1 of plasmodium berghei using test in vivo.malaria remains a serious public health problem with significant morbidity and mortality. this study was conducted to identify whether ficolin-a could play an active role of against malaria infection.201323682257
translational repression controls temporal expression of the plasmodium berghei lccl protein complex.plasmodium lccl proteins comprise a family of six proteins that function as a protein complex and have essential roles in sporozoite transmission. in plasmodium berghei, family members pblap1, pblap2 and pblap3 have been shown to be expressed in gametocytes and, following gametogenesis and fertilization, to be targeted to distinctive multivesicular organelles termed crystalloids that form in the ookinete. here, we show by gfp-tagging that pblap4, pblap5 and pblap6, like their family members, are ...201323684590
synthesis and antimalarial testing of neocryptolepine analogues: addition of ester function in sar study of 2,11-disubstituted indolo[2,3-b]quinolines.this report describes the synthesis, and in vitro and in vivo antimalarial evaluations of certain ester-modified neocryptolepine (5-methyl-5h-indolo[2,3-b]quinoline) derivatives. the modifications were carried out by introducing ester groups at the c2 and/or c9 position on the neocryptolepine core and the terminal amino group of the 3-aminopropylamine substituents at the c11 position with a urea/thiourea unit. the antiplasmodial activities of our derivative agents against two different strains ( ...201323685569
polymorphism of the parasite lactate dehydrogenase gene from plasmodium vivax korean isolates.assaying for the parasitic lactate dehydrogenase (pldh) is widely used as a rapid diagnostic test (rdt), but the efficacy of its serological effectiveness in diagnosis, that is antibody detection ability, is not known. the genetic variation of korean isolates was analysed, and recombinant protein pldh was evaluated as a serodiagnostic antigen for the detection of plasmodium vivax malaria.201323688062
broad-spectrum antimalarial activity of peptido sulfonyl fluorides, a new class of proteasome inhibitors.despite declining numbers of cases and deaths, malaria remains a major public health problem in many parts of the world. today, case management relies heavily on a single class of antimalarial compounds: artemisinins. hence, development of resistance against artemisinins may destroy current malaria control strategies. beyond malaria control are elimination and eradication programs that will require drugs with good activity against acute infection but also with preventive and transmission-blockin ...201323689711
quinolin-4(1h)-imines are potent antiplasmodial drugs targeting the liver stage of malaria.we present a novel series of quinolin-4(1h)-imines as dual-stage antiplasmodials, several-fold more active than primaquine in vitro against plasmodium berghei liver stage. among those, compounds 5g and 5k presented low nanomolar ic50 values. the compounds are metabolically stable and modulate several drug targets. these results emphasize the value of quinolin-4(1h)-imines as a new chemotype and their suitable properties for further drug development.201323701465
comparison of antimalarial activity of artemisia turanica extract with current drugs in vivo.the purpose of this study was to compare antimalarial activity of artemisia turanica krasch as iranian flora with current antimalarial drugs against plasmodium berghei in vivo in mice.201323703440
development of a chimeric plasmodium berghei strain expressing the repeat region of the p. vivax circumsporozoite protein for in vivo evaluation of vaccine efficacy.the development of vaccine candidates against plasmodium vivax-the most geographically widespread human malaria species-is challenged by technical difficulties, such as the lack of in vitro culture systems and availability of animal models. chimeric rodent plasmodium parasites are safe and useful tools for the preclinical evaluation of new vaccine formulations. we report the successful development and characterization of chimeric plasmodium berghei parasites bearing the type i repeat region of p ...201323716612
antibody to a conserved antigenic target is protective against diverse prokaryotic and eukaryotic pathogens.microbial capsular antigens are effective vaccines but are chemically and immunologically diverse, resulting in a major barrier to their use against multiple pathogens. a β-(1→6)-linked poly-n-acetyl-d-glucosamine (pnag) surface capsule is synthesized by four proteins encoded in genetic loci designated intercellular adhesion in staphylococcus aureus or polyglucosamine in selected gram-negative bacterial pathogens. we report that many microbial pathogens lacking an identifiable intercellular adhe ...201323716675
cd19(+) b cells confer protection against experimental cerebral malaria in semi-immune rodent model.in african endemic area, adults are less vulnerable to cerebral malaria than children probably because of acquired partial immunity or semi-immune status. here, we developed an experimental cerebral malaria (ecm) model for semi-immune mice. c57bl/6 (b6) mice underwent one, two and three cycles of infection and radical treatment (1-cure, 2-cure and 3-cure, respectively) before being finally challenged with 10(4) plasmodium berghei anka without treatment. our results showed that 100% of naïve (0-c ...201323724100
anti-malarial property of steroidal alkaloid conessine isolated from the bark of holarrhena antidysenterica.in the face of chronic and emerging resistance of parasites to currently available drugs and constant need for new anti-malarials, natural plant products have been the bastion of anti-malarials for thousands of years. moreover natural plant products and their derivatives have traditionally been a common source of drugs, and represent more than 30% of the current pharmaceutical market. the present study shows evaluation of anti-malarial effects of compound conessine isolated from plant holarrhena ...201323758861
pharmacodynamic evaluation for antiplasmodial activity of holarrhena antidysentrica (kutaja) and azadirachta indica (neemb) in plasmodium berghei infected mice model.to investigate in-vivo anti-plasmodial activity of aqueous extracts of plants selected based on the symptomology mentioned in ayurveda.201323768822
morphogenesis of plasmodium zoites is uncoupled from tensile strength.a shared feature of the motile stages (zoites) of malaria parasites is a cortical cytoskeletal structure termed subpellicular network (spn), thought to define and maintain cell shape. plasmodium alveolins comprise structural components of the spn, and alveolin gene knockout causes morphological abnormalities that coincide with markedly reduced tensile strength of the affected zoites, indicating the alveolins are prime cell shape determinants. here, we characterize a novel spn protein of plasmodi ...201323773015
type i interferons contribute to experimental cerebral malaria development in response to sporozoite or blood-stage plasmodium berghei anka.cerebral malaria is a severe complication of plasmodium falciparum infection. although t-cell activation and type ii ifn-γ are required for plasmodium berghei anka (pba)-induced murine experimental cerebral malaria (ecm), the role of type i ifn-α/β in ecm development remains unclear. here, we address the role of the ifn-α/β pathway in ecm devel-opment in response to hepatic or blood-stage pba infection, using mice deficient for types i or ii ifn receptors. while ifn-γr1⁻/⁻ mice were fully resist ...201323780878
marked biological differences between insecticide resistant and susceptible strains of anopheles funestus infected with the murine parasite plasmodium berghei.anopheles funestus is one of the major malaria vectors in africa but research on this species has been restricted due to the lack of viable laboratory colonies. the vectorial capacity of natural populations of an. funestus is well known but its ability to host plasmodium in the laboratory and the development cycle of the parasite within this mosquito species was, until very recently, unknown. in this study we compared laboratory strains of an. funestus that were resistant and susceptible to pyre ...201323782642
the metabolism of primaquine to its active metabolite is dependent on cyp 2d6.the efficacy of the 8-aminoquinoline (8aq) drug primaquine (pq) has been historically linked to cyp-mediated metabolism. although to date no clear evidence exists in the literature that unambiguously assigns the metabolic pathway or specific metabolites necessary for activity, recent literature suggests a role for cyp 2d6 in the generation of redox active metabolites.201323782898
costs of crowding for the transmission of malaria parasites.the utility of using evolutionary and ecological frameworks to understand the dynamics of infectious diseases is gaining increasing recognition. however, integrating evolutionary ecology and infectious disease epidemiology is challenging because within-host dynamics can have counterintuitive consequences for between-host transmission, especially for vector-borne parasites. a major obstacle to linking within- and between-host processes is that the drivers of the relationships between the density, ...201323789029
brine shrimp toxicity and antimalarial activity of some plants traditionally used in treatment of malaria in msambweni district of kenya.in kenya, most people especially in rural areas use traditional medicine and medicinal plants to treat many diseases including malaria. malaria is of national concern in kenya, in view of development of resistant strains of plasmodium falciparum to drugs especially chloroquine, which had been effective and affordable. there is need for alternative and affordable therapy. many antimalarial drugs have been derived from medicinal plants and this is evident from the reported antiplasmodial activity.201323791809
in vivo antimalarial activity of keetia leucantha twigs extracts and in vitro antiplasmodial effect of their constituents.the west african tree keetia leucantha (rubiaceae) is used in traditional medicine in benin to treat malaria. the twigs dichloromethane extract was previously shown to inhibit in vitro plasmodium falciparum growth with no cytotoxicity (>100µg/ml on human normal fibroblasts).201323792125
antimalarial activity of bergenia ciliata (haw.) sternb. against plasmodium berghei.the emergence of resistance against most of the drugs in current use against malaria has aggravated the disease burden in endemic regions. several plants species have been used for treatment of malaria in traditional/cultural health systems. bergenia ciliata, used traditionally for treatment of fever by local communities in the himalayan region, was evaluated for its plausible role as an antimalarial. phytochemical screening of the ethanolic leaf extract of b. ciliata (elebc) revealed the presen ...201323793360
in vivo antimalarial activity of trichilia megalantha harms extracts and fractions in animal models.the crude methanol extracts of leaf, stem bark, root bark and stem bark fractions of trichilia megalantha (meliaceae) were screened for in vivo antimalarial activities in mice against a chloroquine resistant plasmodium berghei berghei anka clone using the 4-day suppressive test procedure. chloroquine diphosphate was used as the positive control. the extracts demonstrated intrinsic antimalarial property. of all the seven extracts studied, the stem bark gave the highest activity. at 200 mg/kg of m ...201323801363
experimental genetics of plasmodium berghei nfu in the apicoplast iron-sulfur cluster biogenesis pathway.eukaryotic pathogens of the phylum apicomplexa contain a non-photosynthetic plastid, termed apicoplast. within this organelle distinct iron-sulfur [fe-s] cluster proteins are likely central to biosynthesis pathways, including generation of isoprenoids and lipoic acid. here, we targeted a nuclear-encoded component of the apicoplast [fe-s] cluster biosynthesis pathway by experimental genetics in the murine malaria parasite plasmodium berghei. we show that ablation of the gene encoding a nitrogen f ...201323805304
potential of lichen secondary metabolites against plasmodium liver stage parasites with fas-ii as the potential target.chemicals targeting the liver stage (ls) of the malaria parasite are useful for causal prophylaxis of malaria. in this study, four lichen metabolites, evernic acid (1), vulpic acid (2), psoromic acid (3), and (+)-usnic acid (4), were evaluated against ls parasites of plasmodium berghei. inhibition of p. falciparum blood stage (bs) parasites was also assessed to determine stage specificity. compound 4 displayed the highest ls activity and stage specificity (ls ic50 value 2.3 μm, bs ic50 value 47. ...201323806111
nitric oxide synthase dysfunction contributes to impaired cerebroarteriolar reactivity in experimental cerebral malaria.cerebrovascular dysfunction plays a key role in the pathogenesis of cerebral malaria. in experimental cerebral malaria (ecm) induced by plasmodium berghei anka, cerebrovascular dysfunction characterized by vascular constriction, occlusion and damage results in impaired perfusion and reduced cerebral blood flow and oxygenation, and has been linked to low nitric oxide (no) bioavailability. here, we directly assessed cerebrovascular function in ecm using a novel cranial window method for intravital ...201323818850
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