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the generation and evaluation of two panels of epitope-matched mouse igg1, igg2a, igg2b and igg3 antibodies specific for plasmodium falciparum and plasmodium yoelii merozoite surface protein 1-19 (msp1(19)).murine immunoglobulin g (igg) plays an important role in mediating protective immune responses to malaria. we still know relatively little about which igg subclasses protect against this disease in mouse models, although igg2a and igg2b are considered to be the most potent and dominate in successful passive transfer experiments in rodent malarias. to explore the mechanism(s) by which the different mouse igg subclasses may mediate a protective effect, we generated mouse igg1, igg2a, igg2b and igg ...201222343045
assessing the adequacy of attenuation of genetically modified malaria parasite vaccine candidates.the critical first step in the clinical development of a malaria vaccine, based on live-attenuated plasmodium falciparum sporozoites, is the guarantee of complete arrest in the liver. we report on an approach for assessing adequacy of attenuation of genetically attenuated sporozoites in vivo using the plasmodium berghei model of malaria and p. falciparum sporozoites cultured in primary human hepatocytes. we show that two genetically attenuated sporozoite vaccine candidates, δp52+p36 and δfabb/f, ...201222342550
proteomic analysis of plasmodium in the mosquito: progress and pitfalls.here we discuss proteomic analyses of whole cell preparations of the mosquito stages of malaria parasite development (i.e. gametocytes, microgamete, ookinete, oocyst and sporozoite) of plasmodium berghei. we also include critiques of the proteomes of two cell fractions from the purified ookinete, namely the micronemes and cell surface. whereas we summarise key biological interpretations of the data, we also try to identify key methodological constraints we have met, only some of which we were ab ...201222336136
the ctla-4 and pd-1/pd-l1 inhibitory pathways independently regulate host resistance to plasmodium-induced acute immune pathology.the balance between pro-inflammatory and regulatory immune responses in determining optimal t cell activation is vital for the successful resolution of microbial infections. this balance is maintained in part by the negative regulators of t cell activation, ctla-4 and pd-1/pd-l, which dampen effector responses during chronic infections. however, their role in acute infections, such as malaria, remains less clear. in this study, we determined the contribution of ctla-4 and pd-1/pd-l to the regula ...201222319445
antimalarial effects of iranian flora artemisia sieberi on plasmodium berghei in vivo in mice and phytochemistry analysis of its herbal extracts.the aim of this study is pharmacochemistry of iranian flora artemisia sieberi and its antimalarial effects on plasmodium berghei in vivo. this is the first application of a. sieberi for treatment of murine malaria. a. sieberi were collected at flowering stage from the khorassan and semnan provinces of iran; the aerial parts were air-dried at room temperature and then powdered. the powder was macerated in methanol, filtered with bokhner hopper and solvent was separated in rotary evaporator. total ...201222315701
antiplasmodial and analgesic activities of clausena anisata.antiplasmodial and analgesic activities of the leaf extract and fractions of clausena anisata (c. anisata) were evaluated for antimalarial and analgesic activities.201222305787
antimalarial plant remedies from burkina faso: their potential for prophylactic use.saye, a combination remedy prepared from cochlospermum planchonii hook.f. (cochlospermaceae), cassia alata l. (fabaceae) and phyllanthus amarus schumach. et thonn. (euphorbiaceae), n'dribala, a cochlospermum planchonii root decoction, and a fruit preparation of azadirachta indica a. juss. (meliaceae) are plant remedies of the folk medicine in burkina faso and are commonly used by traditional healers for the treatment of malaria.201222301449
curcumin-arteether combination therapy of plasmodium berghei-infected mice prevents recrudescence through immunomodulation.earlier studies in this laboratory have shown the potential of artemisinin-curcumin combination therapy in experimental malaria. in a parasite recrudescence model in mice infected with plasmodium berghei (anka), a single dose of alpha,beta-arteether (art) with three oral doses of curcumin prevented recrudescence, providing almost 95% protection. the parasites were completely cleared in blood with art-alone (ae) or art+curcumin (ac) treatments in the short-term, although the clearance was faster ...201222276114
clotrimazole nanoemulsion for malaria chemotherapy. part ii: stability assessment, in vivo pharmacodynamic evaluations and toxicological studies.the aim of present investigation was to evaluate the potential of clotrimazole as antimalarial drug. due to poor aqueous solubility and high lipophilicity, it was previously formulated in a nanoemulsion based system. the intrinsic effects of nanoemulsion on improvement of antimalarial activity of clotrimazole were assessed in mice infected with plasmodium berghei and compared to its suspension formulation. in four-day suppressive test, mice treated with 10mg/kg clotrimazole nanoemulsion showed t ...201222265913
endoplasmic reticulum stress and neurodegeneration in experimental cerebral malaria.experimental cerebral malaria (ecm) resulting from plasmodium berghei anka (pba) infection in mice results in neuronal cell death. however, the precise mechanisms leading to neuronal cell death in ecm have not been fully elucidated. in the present study, we report the presence of endoplasmic reticulum (er) stress markers and activation of the unfolded protein response (upr) in the brain during the pathogenesis of ecm. specific findings included activation of pkr-like erkinase, inositol-requiring ...201322584375
screening inhibitors of p. berghei blood stages using bioluminescent reporter parasites.we describe two improved assays for in vitro and in vivo screening of inhibitors and chemicals for antimalarial activity against blood stages of the rodent malaria parasite, plasmodium berghei. these assays are based on the determination of bioluminescence in small blood samples that is produced by reporter parasites expressing luciferase. luciferase production increases as the parasite develops in a red blood cell and as the numbers of parasites increase during an infection. in the first assay, ...201322990801
quantitative analysis of plasmodium berghei liver stages by bioluminescence imaging.we describe simple and sensitive in vitro and in vivo assays to analyze plasmodium liver stage development using transgenic p. berghei parasites (pbgfp-luccon), which express the bioluminescent reporter protein, luciferase. in these assays, parasite development in hepatocytes is visualized and quantified by real-time bioluminescence imaging both in culture and in live mice. we also describe quantification of in vitro liver-stage development by measuring luminescence using a microplate reader. re ...201322990796
bioluminescence imaging of p. berghei schizont sequestration in rodents.we describe a technology for imaging the sequestration of infected red blood cells (irbc) of the rodent malaria parasite plasmodium berghei both in the bodies of live mice and in dissected organs, using a transgenic parasite that expresses luciferase. real-time imaging of sequestered irbc is performed by measuring bioluminescence produced by the enzymatic reaction in parasites between the luciferase enzyme and its substrate luciferin injected into the mice several minutes prior to imaging. the b ...201322990791
transfection of rodent malaria parasites.gene manipulation is an invaluable tool to investigate and understand the biology of an organism. although this technology has been applied to both the human and rodent malarial parasites (rmp), plasmodium berghei in particular offers a more robust system due to a higher and more efficient transformation rate. here, we describe a comprehensive transfection and selection protocol using p. berghei including a variant negative selection protocol administering 5-fluorocytosine to the animals in drin ...201322990773
splenocyte apoptosis in plasmodium berghei anka infection: possible role of tnf-α and tgf-β.cerebral malaria is associated with the circulating levels of tumour necrosis factor alpha (tnf-α) and transforming growth factor β (tgf-β), but association between these two cytokines and implications in splenocyte apoptosis remain largely obscured. we have evaluated the outcome of tgf-β and tnf-α production in the context of splenocyte apoptosis during plasmodium berghei anka (pba) infection. blood-stage pba infection confirmed blood-brain barrier disruption, disarray of white pulp, increase i ...201323009201
the evolution and putative function of phosducin-like proteins in the malaria parasite plasmodium.ubiquitous to the proteomes of all living species is the presence of proteins containing the thioredoxin (trx)-domain. the best characterized trx-domain containing proteins include the enzymes involved in cellular redox metabolism facilitated by their cysteine-containing active site. but not all members of the trx-fold superfamily exhibit this catalytic motif, e.g., the phosducin-like (phlp) family of proteins. genome sequencing efforts have uncovered new trx-domain containing proteins, and thei ...201322995278
nk cells and conventional dendritic cells engage in reciprocal activation for the induction of inflammatory responses during plasmodium berghei anka infection.cerebral malaria (cm) is the most severe syndrome associated with plasmodium falciparum infections. experimental evidence suggests that disease results from the sequestration of parasitized-red blood cells (prbcs) together with inflammatory leukocytes within brain capillaries. we have previously shown that nk cells stimulate migration of cxcr3(+) t cells to the brain of plasmodium berghei anka-infected mice. here we investigated whether interactions between nk cells and dendritic cells (dcs) are ...201322704523
plasmodium liver load following parenteral sporozoite administration in rodents.one of the bottlenecks in the development of a whole sporozoite malaria vaccine is the route and method of sporozoite administration. immunization and challenge of human volunteers by mosquito bites is effective, but cannot be used as a vaccine. intravenous immunization with sporozoites is effective in rodents and non-human primates, and being studied in humans, but is not yet used for licensed vaccines for infectious diseases. intradermal and subcutaneous immunization regimens show a strong dec ...201323063834
a blood stage fraction of plasmodium berghei induces protective and long lasting immune response in balb/c mice.incorporation of the parasite's subcellular fractions in subunit vaccines can be a possible approach for formulation of vaccine against malaria. in this study, the immunogenicity and protective efficacy of 10,000g fraction of blood stage plasmodium berghei was evaluated in mouse model. this fraction induced higher levels of anti-parasite antibodies and provided complete and long lasting protection as compared to whole parasite antigens. antiserum raised against it was immunoadsorbed on cnbr acti ...201323085043
mechanism-based model of parasite growth and dihydroartemisinin pharmacodynamics in murine malaria.murine models are used to study erythrocytic stages of malaria infection, because parasite morphology and development are comparable to those in human malaria infections. mechanism-based pharmacokinetic-pharmacodynamic (pk-pd) models for antimalarials are scarce, despite their potential to optimize antimalarial combination therapy. the aim of this study was to develop a mechanism-based growth model (mbgm) for plasmodium berghei and then characterize the parasiticidal effect of dihydroartemisinin ...201323147722
brain-derived neurotrophic factor and the course of experimental cerebral malaria.the role of neurotrophic factors on the integrity of the central nervous system (cns) during cerebral malaria (cm) infection remains obscure, but the long-standing neurocognitive sequelae often observed in rescued children can be attributed in part to the modulation of neuronal survival and synaptic plasticity. to discriminate the contribution of key responses in the time-sequence of the pathogenic events that trigger the development of neurocognitive malaria syndrome we defined four stages (i-i ...201323123703
substantiation of the ethnopharmacological use of conyza sumatrensis (retz.) e.h.walker in the treatment of malaria through in-vivo evaluation in plasmodium berghei infected mice.scientific validation of ethnopharmacologically used plants and their utilization for therapeutic interventions can be a source of affordable treatment especially for neglected diseases in endemic areas. conyza sumatrensis is a plant which finds its use in treating malaria like fevers but lacks proper scientific validation. our study has tried to address this gap by authenticating its traditional use for the treatment of malaria.201323123263
synthesis and antimalarial activity of urenyl bis-chalcone in vitro and in vivo.some novel derivatives of bis-chalcone were synthesized and characterized by their physical and spectral data. all the synthesized compounds were subsequently screened for in vitro globin hydrolysis, β-hematin formation, and murine plasmodium berghei, using chloroquine as the reference drug. most of the synthesized compounds exhibited mild to moderate susceptibilities toward the parasite in comparison with the standard. the most active antimalarial compound was 1,1-bis-[(3',4'-n-(urenylphenyl)-3 ...201323094691
reduction of malaria transmission by transgenic mosquitoes expressing an antisporozoite antibody in their salivary glands.we have previously developed a robust salivary gland-specific expression system in transgenic anopheles stephensi mosquitoes. to establish transgenic mosquito lines refractory to plasmodium falciparum using this system, we generated a transgenic mosquito harbouring the gene encoding an anti-p. falciparum circumsporozoite protein (pfcsp) single-chain antibody (scfv) fused to dsred in a secretory form (mdsred-2a10 scfv). fluorescence microscopy showed that the mdsred-2a10 scfv was localized in the ...201323176559
proteomic and genetic analyses demonstrate that plasmodium berghei blood stages export a large and diverse repertoire of proteins.malaria parasites actively remodel the infected red blood cell (irbc) by exporting proteins into the host cell cytoplasm. the human parasite plasmodium falciparum exports particularly large numbers of proteins, including proteins that establish a vesicular network allowing the trafficking of proteins onto the surface of irbcs that are responsible for tissue sequestration. like p. falciparum, the rodent parasite p. berghei anka sequesters via irbc interactions with the host receptor cd36. we have ...201323197789
liver-specific protein 2: a plasmodium protein exported to the hepatocyte cytoplasm and required for merozoite formation.the liver stage is the first stage of the malaria parasite that replicates in the vertebrate host. however, little is known about the interplay between the parasite liver stage and its host cell, the hepatocyte. in this study, we identified an exported protein that has a critical role in parasite development in host hepatocytes. expressed sequence tag analysis of plasmodium berghei liver-stage parasites indicated that transcripts encoding a protein with an n-terminal signal peptide, designated l ...201323216750
antimalaria action of antiretroviral drugs on plasmodium berghei in mice.malaria parasitemia enhances replication of human immunodeficiency virus. antiretroviral drugs that possess antiplasmodial activity may reverse such an effect. activity of the antiretroviral drugs lamivudine (l), zidovudine (z), nevirapine (n), and stavudine (s) against plasmodium berghei inoculated into 70 adult albino mice was investigated. eight groups of five animals each were treated with different drugs as either curative or prophylactic regimens. these regimens were also given to four gro ...201323208888
antimalarial and safety evaluation of extracts from toddalia asiatica (l) lam. (rutaceae).toddalia asiatica (l) lam. (rutaceae) is a medicinal plant traditionally used in kenya by many communities for the treatment of malaria and other ailments. all parts of the plant are claimed to have medicinal value, but the root bark in particular is believed to be more potent. decoctions or infusions of the roots are taken orally to treat malaria, fever and stomach ache.201323207061
the c-type lectin receptor dcir is crucial for the development of experimental cerebral malaria.cerebral malaria (cm) is the most severe complication of malaria. the murine plasmodium berghei anka (pba) infection model has helped to identify crucial players in the pathogenesis of cm. however, the role of pattern recognition receptors in innate immunity to cm induction is still poorly understood. c-type lectin receptors (clrs) represent a family of pattern recognition receptors that recognize carbohydrate structures on pathogens and self-ags often in a ca(2+)-dependent manner. in this study ...201323918990
a novel chitosan based antimalarial drug delivery against plasmodium berghei infection.chitosan is a natural polysaccharide that has attracted significant scientific interest during the last two decades and chitosan based nanodrug delivery systems seem to be a hopeful and viable strategy for improving disease treatment. this study aims to evaluate the potency of the polymer based nanochloroquine in application for attenuation of plasmodium berghei infection in swiss mice and effectiveness against the parasite induced oxidative stress and deoxyribo nucleic acid (dna) damage in lymp ...201323906613
evaluation of effectiveness of ethanolic extract of artemisia aucheri, individually and in combination with chloroquine, on chloroquine - sensitive strain of plasmodium berghei in sourian mice.drug resistance in malaria parasites is extending in the world particularly in chemical synthesized drugs such as 4- aminoquinolines and aminoalcoholes. employing herbal extracts is encouraged by who in the malarious areas. in this study, the effectiveness of ethanolic extract of artemisia aucheri individually and in combination with chloroquine, has been considered against chloroquine - sensitive strain of plasmodium berghei.201326056643
development of severe pathology in immunized pregnant mice challenged with lethal malaria parasites.pregnant women are highly susceptible to malaria infection because of their low immunity and are at increased risk of maternal illness or death, in addition to spontaneous abortion, stillbirth, premature delivery, and low birth weight. however, the detailed pathogenesis of maternal malaria remains unclear. in this study, we evaluated a mouse model that shows similar severe pathological features of pregnant women during plasmodium falciparum infection and investigated the pathogenesis of maternal ...201323897619
role of il-10-producing regulatory b cells in control of cerebral malaria in plasmodium berghei infected mice.cerebral malaria (cm) is a neurological syndrome often occurring in severe malaria. although cm is known as an immunopathology in brain tissue mediated by excessive proinflammatory cytokines, the immunoregulatory mechanism is poorly understood. here, we investigated the role of il-10-producing regulatory b (breg) cells in modulating cm development in a murine model of plasmodium berghei anka infection. we observed that blood-stage p. berghei induced expansion of il-10-producing breg cells in c57 ...201323893352
3,5-bis(benzylidene)-4-piperidones and related n-acyl analogs: a novel cluster of antimalarials targeting the liver stage of plasmodium falciparum.drug resistance is a major challenge in antimalarial chemotherapy. in addition, a complete cure of malaria requires intervention at various stages in the development of the parasite within the host. there are only a few antimalarials that target the liver stage of the plasmodium species which is an essential part of the life cycle of the malarial parasite. we report a series of antimalarial 3,5-bis(benzylidene)-4-piperidones and related n-acyl analogs 1-5, a number of which exhibit potent in vit ...201324139941
cerebral tissue oxygenation impairment during experimental cerebral malaria.ischemia and hypoxia have been implicated in cerebral malaria (cm) pathogenesis, although direct measurements of hypoxia have not been conducted. c57bl/6 mice infected with plasmodium berghei anka (pba) develop a neurological syndrome known as experimental cerebral malaria (ecm), whereas balb/c mice are resistant to ecm. in this study, intravital microscopy methods were used to quantify hemodynamic changes, vascular/tissue oxygen (o₂) tension (po₂), and perivascular ph in vivo in ecm and non-ecm ...201324128424
evaluation of novel lipid based formulation of β-artemether and lumefantrine in murine malaria model.the present investigation aims at formulating lipid based drug delivery system of β-artemether and lumefantrine and comparative pharmacological evaluation with innovator formulation. commercial modified oil and indigenous natural fatty acids comprised the oily phase in developing lipidic formulation of β-artemether and lumefantrine. the developed system was characterized for mean globule size, stability by freeze thaw cycles, and birefringence. developed formulation and innovator formulation wer ...201323886650
in vitro and in vivo antimalarial activity and cytotoxicity of extracts and fractions from the leaves, root-bark and stem-bark of triclisia gilletii.to evaluate the in vitro antiplasmodial activity and cytotoxicity, and the in vivo activity of extracts and fractions from the leaves, root-bark and stem-bark of triclisia gilletii (de wild) staner (menispermaceae), used in traditional medicine against malaria.201323876596
antimalarial, hematological, and antioxidant effects of methanolic extract of terminalia avicennioides in plasmodium berghei-infected mice.terminalia avicennioides guill. & perr. (combretaceae) is used traditionally to treat malaria in nigeria. to establish its efficacy, methanolic extract of t. avicennioides bark was investigated for antimalarial activity against plasmodium berghei (nk-65) in mice. twenty-five mice in five groups were used for this study. group 1 was uninfected normal control. twenty mice infected with p. berghei were grouped as untreated negative control (group 2), 5 mg/kg b.w. p.o. artesunate-treated positive co ...201323873616
glutathione peroxidase contributes with heme oxygenase-1 to redox balance in mouse brain during the course of cerebral malaria.oxidative stress has been attributed both a key pathogenic and rescuing role in cerebral malaria (cm). in a plasmodium berghei anka murine model of cm, host redox signaling and functioning were examined during the course of neurological damage. host antioxidant defenses were early altered at the transcriptional level indicated by the gradually diminished expression of superoxide dismutase-1 (sod-1), sod-2, sod-3 and catalase genes. during severe disease, this led to the dysfunctional activity of ...201323872112
the plasmodium translocon of exported proteins (ptex) component thioredoxin-2 is important for maintaining normal blood-stage growth.plasmodium parasites remodel their vertebrate host cells by translocating hundreds of proteins across an encasing membrane into the host cell cytosol via a putative export machinery termed ptex. previously ptex150, hsp101 and exp2 have been shown to be bona fide members of ptex. here we validate that ptex88 and trx2 are also genuine members of ptex and provide evidence that expression of ptex components are also expressed in early gametocytes, mosquito and liver stages, consistent with observati ...201323869529
age-related cd4(+)cd25(+)foxp3(+) regulatory t-cell responses during plasmodium berghei anka infection in mice susceptible or resistant to cerebral malaria.different functions have been attributed to cd4(+)cd25(+)foxp3(+) regulatory t-cells (tregs) during malaria infection. herein, we describe the disparity in treg response and pro- and anti-inflammatory cytokines during infection with plasmodium berghei anka between young (3-week-old) and middle-aged (8-month-old) c57bl/6 mice. young mice were susceptible to cerebral malaria (cm), while the middle-aged mice were resistant to cm and succumbed to hyperparasitemia and severe anemia. the levels of pro ...201323864739
improved efficacy of fosmidomycin against plasmodium and mycobacterium species by combination with the cell-penetrating peptide octaarginine.cellular drug delivery can improve efficacy and render intracellular pathogens susceptible to compounds that cannot permeate cells. the transport of physiologically active compounds across membranes into target cells can be facilitated by cell-penetrating peptides (cpps), such as oligoarginines. here, we investigated whether intracellular delivery of the drug fosmidomycin can be improved by combination with the cpp octaarginine. fosmidomycin is an antibiotic that inhibits the second reaction in ...201323856773
phytochemical screening, antimalarial and histopathological studies of allophylus africanus and tragia benthamii.the anti-malarial potential of different parts of allophylus africanus p. beauv and tragia benthamii baker were determined in vivo for suppressive, curative and cytotoxic activities in mice receiving 0.2 ml of a standard inoculum size of 1 × 10(7) infected erythrocytes of plasmodium berghei (nk-65) intraperitoneally. the a. africanus extracts suppressed parasitaemia following administration to infected mice by 92.82%-97.81% on day 7 post-infection against 96.81% for chloroquine. the infected ext ...201323845545
il-23 protection against plasmodium berghei infection in mice is partially dependent on il-17 from macrophages.although il-12 is believed to contribute to protective immune responses, the role played by il-23 (a member of the il-12 family) in malaria is elusive. here, we show that il-23 is produced during infection with plasmodium berghei nk65. mice deficient in il-23 (p19ko) had higher parasitemia and died earlier than wild-type (wt) controls. interestingly, p19ko mice had lower numbers of il-17-producing splenic cells than their wt counterparts. furthermore, mice deficient in il-17 (17ko) suffered high ...201323843079
plasmodium berghei anka (pba) infection of c57bl/6j mice: a model of severe malaria.the term "severe malaria" refers to a wide spectrum of syndromes in plasmodium-infected humans including cerebral malaria (cm), respiratory distress, severe anemia, liver dysfunction, and hypoglycemia. mouse models have been employed to further our understanding of the pathology and immune responses that occur during plasmodium infection. evidence of brain, liver, lung, and spleen pathology, as well as anemia and tissue-sequestration of parasites, has been reported in various strains of inbred m ...201323824903
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
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
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 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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
the role of platelet-activating factor receptor (pafr) in lung pathology during experimental malaria.malaria-associated lung pathology has been a neglected area in the study of malaria complications. platelet-activating factor (paf) is an inflammatory mediator involved in lung inflammation. using mice lacking the paf receptor (pafr(-/-)) we investigated the relevance of signaling through the pafr for the lung inflammatory process triggered by plasmodium berghei anka (pba) strain infection. in pafr(-/-) mice, pulmonary inflammation was markedly reduced as demonstrated by histology, production of ...201323260771
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