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stromal cell derived factor 1 synthesis by spleen cells in rodent malaria, and the effects of in vivo supplementation of sdf-1alpha and cxcr4 receptor blocker.the mechanisms of malaria parasite clearance in the host are not well understood, but are ascribed to the intact spleen, the site for parasite clearance. the infection induces a huge increase in spleen volume and cellularity. there is, however, a lack of studies on the splenic production of chemokines, which are small proteins that control homing and activation of immune cells and must be crucial for organized tissue growth. we studied the spleen cell production of sdf-1, a primordial chemokine ...200212057854
identification of two cerebral malaria resistance loci using an inbred wild-derived mouse strain.malaria is a complex infectious disease in which the host/parasite interaction is strongly influenced by host genetic factors. the consequences of plasmodial infections range from asymptomatic to severe complications like the neurological syndrome cerebral malaria induced by plasmodium falciparum in humans and plasmodium berghei anka in rodents. mice infected with p. berghei anka show marked differences in disease manifestation and either die from experimental cerebral malaria (ecm) or from hemo ...200212114535
from noxiustoxin to scorpine and possible transgenic mosquitoes resistant to malaria.scorpion venom contains different types of peptides toxic to a variety of organisms whose molecular targets have been described as mainly ion-channels of excitable cells where they cause impairment of function. based on mouse, cricket, and crustacean bioassays, specific toxins for each group of animals have been found. chromatographic techniques were used to isolate and chemically characterize these peptides. one of the best-studied peptides is noxiustoxin, a 39-amino acid residue-long peptide s ...200212234530
on the pathogenic role of brain-sequestered alphabeta cd8+ t cells in experimental cerebral malaria.cerebral malaria (cm) develops in a small proportion of persons infected with plasmodium falciparum and accounts for a substantial proportion of the mortality due to this parasite. the actual pathogenic mechanisms are still poorly understood, and in humans investigations of experimental cm are unethical. using an established plasmodium berghei-mouse cm model, we have investigated the role of host immune cells at the pathological site, the brain. we report in this study the detailed quantificatio ...200212444144
cam kinase ii-alpha activity, levels and ca/calmodulin dependent phosphorylation of substrate proteins in mice brain during fatal murine cerebral malaria.the activity and levels of cam kinase ii-alpha was investigated in the cytosolic and membrane fraction of mice cerebral cortex and cerebellum using an experimental model of fatal murine cerebral malaria (fmcm). in parallel, ca(2+)/calmodulin dependent phosphorylation of target substrate proteins was studied using syntide-2 as substrate. pathology of fmcm resulted in decreased cam kinase-ii activity in both cortex and cerebellum though western analysis revealed no appreciable changes in the level ...200312499055
heptyl prodigiosin, a bacterial metabolite, is antimalarial in vivo and non-mutagenic in vitro.heptyl prodigiosin was purified from a culture of alpha-proteobacteria isolated from a marine tunicate collected in zamboanga, philippines, as part of a program to screen natural products for antiparasitic activity. an in vitro antimalarial activity similar to that of quinine was found against the chloroquine-sensitive strain plasmodium falciparum 3d7. the in vitro antimalarial activity was about 20 times the in vitro cytotoxic activity against l5178y mouse lymphocytes. a single subcutaneous adm ...200212503881
the effect of 10 alpha-trifluoromethylhydroartemisinin on plasmodium berghei infection and its toxicity in experimental animals.the antimalarial activity of 10 alpha-trifluoromethylhydroartemisinin (tfmha) was compared to that of dihydroartemisinin (dha) in the plamodium berghei mouse model. treatment with tfmha in mice infected with a p. berghei chloroquine-sensitive strain at 25 mg/kg for 3, 5, and 7 d, or dha at the same dose for 7 d showed the parasite was eliminated from the host within 2.6 d. the radical cure and survival rates of these mice up to 60 d after infection were 90-100%. in mice infected with the p. berg ...200212625149
leptin and leptin receptors during malaria infection in mice.leptin, which is involved in a range of physiological processes, could be an important factor in the pathogenesis of malaria. we found that levels of leptin in serum and urine in plasmodium berghei-infected mice increased progressively after infection, reaching a maximum value on day 6 post-infection. serum values were approximately five-fold higher in infected mice than in non-infected controls. a similar relation was found for values of leptin in urine. soluble leptin receptor levels also incr ...200212641196
regulation of murine cerebral malaria pathogenesis by cd1d-restricted nkt cells and the natural killer complex.nkt cells are specialized cells coexpressing nk and t cell receptors. upon activation they rapidly produce high levels of interferon-gamma (ifn-gamma) and interleukin-4 (il-4) and are therefore postulated to influence t(h)1/t(h)2 immune responses. the precise role of the cd1/nkt cell pathway in immune response to infection remains unclear. we show here that cd1d-restricted nkt cells from distinct genetic backgrounds differentially influence t(h)1/t(h)2 polarization, proinflammatory cytokine leve ...200312648456
validation of the hexose transporter of plasmodium falciparum as a novel drug target.chemotherapy of malaria parasites is limited by established drug resistance and lack of novel targets. intraerythrocytic stages of plasmodium falciparum are wholly dependent on host glucose for energy. glucose uptake is mediated by a parasite-encoded facilitative hexose transporter (pfht). we report that o-3 hexose derivatives inhibit uptake of glucose and fructose by pfht when expressed in xenopus oocytes. selectivity of these derivatives for pfht is confirmed by lack of inhibition of hexose tr ...200312792024
pharmacological assessment of the role of nitric oxide in mice infected with lethal and nonlethal species of malaria.this pharmacological investigation sought to determine whether nitric oxide (no) had an antiparasitic effect and/or mediated pathology in mice infected with nonlethal p. chabaudi or lethal p. berghei. nitric oxide synthase (nos) inhibitors were evaluated for their ability to inhibit the rise in reactive nitrogen intermediates (rni) induced by bacterial lipopolysaccharide (lps) in mice. the more effective compound, aminoguanidine (ag) inhibited the rise in rni induced by p. chabaudi and increased ...200312911523
[effects of alcoholism on the development of plasmodium berghei infection in the mouse]. 195613396515
[effect of various diets on the development of plasmodium berghei in the white mouse]. 195514393134
[interferon and protection of the mouse against experimental infestation transmitted by the erythgrocytic forms of plasmodium berghei injected in massive doses. ii. effects of several immunosuppressive agents on protection patterns by a viral interferon inducer]. 19734771733
plasmodium berghei: infectivity of mice to anopheles stephensi mosquitoes.the infectivity of p. berghei-infected to mice to mosquitoes declines rapidly 2 to 5 days after blood inoculation, in spite of rising numbers of gametocytes in the blood. this pattern is typical of many malaria infections and various factors, particularly specific and nonspecific immune responses, have previously been implicated in the decline. here we report that (1) simple physiological changes in the mouse blood, namely, falling ph and bicarbonate levels induced by high parasitaemias, are res ...19968948326
reduced t helper 1 responses in il-12 p40 transgenic mice.to investigate the antagonistic effect of il-12 p40 on il-12 activity in vivo, we generated transgenic (tg) mice in which p40 gene was regulated by a liver-specific promoter. three tg mouse lines were generated, and they expressed the p40 transgene predominantly in liver. serum p40 level was extremely high, and it consisted of mainly monomer and homodimer and also of higher m.w. complexes. these tg mice did not show any apparent phenotypic difference from control littermates in lymphoid cells. e ...19989551892
rheumatoid factor-like igm in plasmodium berghei (apicomplexa: haemosporida) infections of balb/c mice.groups of female balb/c mice infected by intravenous injection with 50 erythrocytes containing plasmodium berghei vincke et lips, 1948 were sacrificed on days 3 through 12 after infection. rheumatoid factor-like igm (rf-igm) and parasite-specific igg levels were determined by enzyme-linked immunosorbent assay in serum specimens and in culture medium removed from spleen cell cultures established at sacrifice. all four mouse igg subisotypes were recognized by rf-igm molecules induced by plasmodium ...200314535342
selection and reversal of plasmodium berghei resistance in the mouse model following repeated high doses of artemether.artemether, a derivative of artemisinin, is effectively used for the treatment of malaria without any clinically relevant resistance to date. artemether has also been developed as an antischistosomal agent, exhibiting highest activity against immature parasites. here, we employ a rodent model and investigate whether the proposed artemether treatment schedule to prevent schistosome-attributable morbidity might select for plasmodium berghei resistance. mice infected with an anka strain of p. bergh ...200414677058
effects of bisphosphonates on the growth of entamoeba histolytica and plasmodium species in vitro and in vivo.the effects of a series of 102 bisphosphonates on the inhibition of growth of entamoeba histolytica and plasmodium falciparum in vitro have been determined, and selected compounds were further investigated for their in vivo activity. forty-seven compounds tested were active (ic(50) < 200 microm) versus e. histolytica growth in vitro. the most active compounds (ic(50) approximately 4-9 microm) were nitrogen-containing bisphosphonates with relatively large aromatic side chains. simple n-alkyl-1-hy ...200414695831
duffy antigen is important for the lethal effect of the lethal strain of plasmodium yoelii 17xl.we studied the potential role of the duffy antigen and glycophorin a as receptors for rodent malaria parasite invasion of erythrocytes. parasitemia increased exponentially after infection with plasmodium berghei nk65, p. chabaudi, and p. vinckei in duffy antigen knockout, glycophorin a knockout, and wild-type mice, indicating that the duffy antigen and glycophorin a are not essential for these malaria parasites. however, parasitemia of the duffy antigen knockout mice infected with p. yoelii 17xl ...200415278442
fetuin-a, a hepatocyte-specific protein that binds plasmodium berghei thrombospondin-related adhesive protein: a potential role in infectivity.malaria infection is initiated when the insect vector injects plasmodium sporozoites into a susceptible vertebrate host. sporozoites rapidly leave the circulatory system to invade hepatocytes, where further development generates the parasite form that invades and multiplies within erythrocytes. previous experiments have shown that the thrombospondin-related adhesive protein (trap) plays an important role in sporozoite infectivity for hepatocytes. trap, a typical type-1 transmembrane protein, has ...200516113307
gene-expression profiling discriminates between cerebral malaria (cm)-susceptible mice and cm-resistant mice.the development of cerebral malaria (cm) in mice with plasmodium berghei anka infection is under genetic control. brain gene-expression patterns were investigated in well-defined genetically cm-resistant (cm-r; balb/c and dba/2) and cm-susceptible (cm-s; c57bl/6 and cba/j) mice by use of cdna microarrays. by combining transcriptional profiling with rigorous statistical methods and cluster analysis, we identified a set of 69 genes that perfectly discriminated between mouse strains and between cm- ...200616362897
simultaneous increases in immune-competent cells and nitric oxide in the spleen during plasmodium berghei infection in mice.nitric oxide and other reactive nitrogen intermediates (rni) are thought to be important mediators of both immunological and pathological responses of the vertebrate host to malaria infection. the role of rni has been studied most often by assay of stable rni metabolites (nitrites, nitrates) in blood. this study evaluated the nature of the rni response of mice to malaria by analyzing the subsets of immune-competent cells within the organ displaying increased rni in vivo.200616440118
the chemotherapy of rodent malaria. lx. the importance of formulation in evaluating the blood schizontocidal activity of some endoperoxide antimalarials.the activities of artemisinin (qhs) and a number of its semi-synthetic analogues, as well as fenozan b07 (b07), a synthetic 1,2,4-trioxane, and arteflene (atf), a synthetic surrogate of yingzhaosu, were compared in mice infected with drug-sensitive plasmodium berghei or chloroquine-resistant p. yoelii ssp. ns. the studies were stimulated by the observation that b07, in certain aqueous preparations, appears to be equipotent by the subcutaneous (sc) or oral (po) routes in the rodent model but not ...200212396319
ccr5 deficiency decreases susceptibility to experimental cerebral malaria.infection of susceptible mouse strains with plasmodium berghei anka (pba) is a valuable experimental model of cerebral malaria (cm). two major pathologic features of cm are the intravascular sequestration of infected erythrocytes and leukocytes inside brain microvessels. we have recently shown that only the cd8+ t-cell subset of these brain-sequestered leukocytes is critical for progression to cm. chemokine receptor-5 (ccr5) is an important regulator of leukocyte trafficking in the brain in resp ...200312560237
new semisynthetic quassinoids with in vivo antimalarial activity.on the basis of a comparative analysis for stability in mouse serum between 15-o-acetylbruceolide and bruceolide 15-methyl carbonate, several 3,15-dialkyl carbonates of bruceolide were synthesized and their in vitro antimalarial activity was assessed. methyl, ethyl, and isopropyl carbonates with pronounced in vitro activity were further evaluated for in vivo antimalarial potency. both the methyl and ethyl carbonates significantly increased the life span of mice as compared with 3,15-di-o-accetyl ...200312570385
the inhibitory action of some antimalarial drugs and related compounds on the hexokinase of yeast and of plasmodium berghei.of various antimalarial compounds tested, only proguanil failed to inhibit yeast hexokinase. the metabolite of proguanil, 10,580, was an effective inhibitor. some compounds tested which were without antimalarial activity were potent inhibitors of yeast hexokinase. the degree of inhibition increased as the time during which the enzyme had been in contact with the drug increased, and the inhibitory action of mepacrine was reduced when the concentration of atp was raised. the inhibition of yeast he ...195713413145
relationship of chloroquine-induced redistribution of a neutral aminopeptidase to hemoglobin accumulation in malaria parasites.to study the relationship between neutral aminopeptidase activity and hemoglobin accumulation in malaria parasites, we treated mice infected with plasmodium berghei nyu-2 with chloroquine intraperitoneally in doses ranging from 0.3 to 3 micromol per 25 g mouse. preparations of infected erythrocytes (normalized to represent 1000 parasites per 1000 erythrocytes) hydrolyzed 1200 nmol of leucine-p-nitroanilide per minute per milliliter of packed erythrocytes, which was 10x more than that of uninfect ...200312573290
[erythro- and lymphopoiesis in the mouse spleen in plasmodium berghei infection]. 196414247127
competitive relationship between eperythrozoon coccoides and plasmodium berghei in the mouse. 196514281212
[dietetic influence on malaria (plasmodium berghei) in the mouse]. 196414340331
in vitro and in vivo efficacy and in vitro metabolism of 1-phenyl-3-aryl-2-propen-1-ones against plasmodium falciparum.investigation of a series of 1-phenyl-3-aryl-2-propen-1-ones resulted in the identification of nine inhibitors with submicromolar efficacy against at least one plasmodium falciparum strain in vitro. these inhibitors were inactive when given orally in a plasmodium berghei infected mouse model. significant compound degradation occurred upon their exposure to a liver microsome preparation, suggesting metabolic instability may be responsible for the lack of activity in vivo.200616908136
the use of transgenic plasmodium berghei expressing the plasmodium vivax antigen p25 to determine the transmission-blocking activity of sera from malaria vaccine trials.p25 is a major surface protein of plasmodium ookinetes. antibodies against p25 prevent the formation of oocysts in the mosquito and thereby block transmission of the parasite through an endemic population. plasmodium vivax transmission-blocking vaccines based on pv25 have undergone human trials and inhibit transmission significantly. the current assay to determine transmission-blocking activity (tba) of these sera, the 'standard membrane feeding assay', is complex and can be performed by few gro ...200717049690
antimalarial activity of traditionally used western ghats plants from india and their interactions with chloroquine against chloroquine-tolerant plasmodium berghei.an ethnopharmacological investigation was undertaken on western ghats plants traditionally used to treat malaria; 50 plants were very carefully selected from total of 372 plants, and 216 extracts were prepared and tested for in vivo antiplasmodial activity alone and in combination with chloroquine (cq) against cq-tolerant plasmodium berghei (strain nk65). in in vivo antiplasmodial activity when plant extract alone is used, 81 extracts (or 37.5%) gave 52.90% significant parasitemia inhibition on ...201120846029
cd4+ cd25+ regulatory t cells suppress cd4+ t-cell function and inhibit the development of plasmodium berghei-specific th1 responses involved in cerebral malaria pathogenesis.the infection of mice with plasmodium berghei anka constitutes the best available mouse model for human plasmodium falciparum-mediated cerebral malaria, a devastating neurological syndrome that kills nearly 2.5 million people every year. experimental data suggest that cerebral disease results from the sequestration of parasitized erythrocytes within brain blood vessels, which is exacerbated by host proinflammatory responses mediated by cytokines and effector cells including t lymphocytes. here, ...200717325053
magnetic resonance spectroscopy reveals an impaired brain metabolic profile in mice resistant to cerebral malaria infected with plasmodium berghei anka.malaria is a major cause of morbidity and mortality with an annual death toll exceeding one million. severe malaria is a complex multisystem disorder, including one or more of the following complications: cerebral malaria, anemia, acidosis, jaundice, respiratory distress, renal insufficiency, coagulation anomalies, and hyperparasitemia. using a combined in vivo/in vitro metabolic-based approach, we investigated the putative pathogenic effects of plasmodium berghei anka on brain, in a mouse strai ...200717369263
iron deficiency influences the course of malaria in plasmodium berghei infected mice.iron deficiency accelerates suicidal erythrocyte death, which is evident from phosphatidylserine exposure. the present study explored whether iron deficiency compromises intraerythrocytic growth of plasmodium and enhances death of infected erythrocytes thus influencing the course of malaria. as a result, phosphatidylserine exposure is increased in plasmodium falciparum infected human erythrocytes, an effect significantly more marked in iron deficiency. moreover, iron deficiency impairs in vitro ...200717445762
recombinant human ifn-alpha inhibits cerebral malaria and reduces parasite burden in mice.most c57bl/6 mice infected i.p. with plasmodium berghei anka (pba) die between 7 and 14 days with neurologic signs, and the remainder die later (>15 days) with severe anemia. daily i.p. injections of a recombinant human ifn-alpha (active on mouse cells) prevented death by cerebral malaria (87% deaths in the control mice vs 6% in ifn-alpha-treated mice). the mechanisms of this ifn-alpha protective effect were multiple. ifn-alpha-treated, pba-infected mice showed 1) a marked decrease in the number ...200717475871
aquaporin 9 is the major pathway for glycerol uptake by mouse erythrocytes, with implications for malarial virulence.human and rodent erythrocytes are known to be highly permeable to glycerol. aquaglyceroporin aquaporin (aqp)3 is the major glycerol channel in human and rat erythrocytes. however, aqp3 expression has not been observed in mouse erythrocytes. here we report the presence of an aquaglyceroporin, aqp9, in mouse erythrocytes. aqp9 levels rise as reticulocytes mature into erythrocytes and as neonatal pups develop into adult mice. mice bearing targeted disruption of both alleles encoding aqp9 have eryth ...200717636116
induction of experimental cerebral malaria is independent of tlr2/4/9.the contribution of the toll-like receptor (tlr) cascade to the pathogenesis of cerebral malaria (cm) is controversially discussed. tlr2 and tlr9 were reported to be involved in the induction of cm in a study while recently tlr signaling was shown to be dispensable for the development of cm. using plasmodium berghei anka (pba) infection of mice as a model of cm, we demonstrate here that the induction of cm is independent of tlr2, 4 and 9. using triple tlr2/4/9-deficient mice, we exclude synergis ...200817668237
malaria-infected mice are cured by oral administration of new artemisinin derivatives.in four or five chemical steps from the 1,2,4-trioxane artemisinin, a new series of 23 trioxane dimers has been prepared. eleven of these new trioxane dimers cure malaria-infected mice via oral dosing at 3 x 30 mg/kg. the clinically used trioxane drug sodium artesunate prolonged mouse average survival to 7.2 days with this oral dose regimen. in comparison, animals receiving no drug die typically on day 6-7 postinfection. at only 3 x 10 mg/kg oral dosing, seven dimers prolong the lifetime of mala ...200818232653
clotrimazole scaffold as an innovative pharmacophore towards potent antimalarial agents: design, synthesis, and biological and structure-activity relationship studies.we describe herein the design, synthesis, biological evaluation, and structure-activity relationship (sar) studies of an innovative class of antimalarial agents based on a polyaromatic pharmacophore structurally related to clotrimazole and easy to synthesize by low-cost synthetic procedures. sar studies delineated a number of structural features able to modulate the in vitro and in vivo antimalarial activity. a selected set of antimalarials was further biologically investigated and displayed low ...200818278860
cxcr3 determines strain susceptibility to murine cerebral malaria by mediating t lymphocyte migration toward ifn-gamma-induced chemokines.cerebral malaria (cm) results from the binding of infected erythrocytes and leukocytes to brain endothelia. the precise mechanisms underlying lymphocyte recruitment and activation in cm remain unclear. therefore, the expression of various chemokines was quantified in brains of mice infected with plasmodium berghei anka (pba). several chemokines attracting monocytes and activated t-lymphocytes were expressed at high levels. their expression was almost completely abrogated in ifn-gamma ligand and ...200818383042
mast cell-mediated immune responses through ige antibody and toll-like receptor 4 by malarial peroxiredoxin.in this study, 2-cys plasmodium berghei anka (pba) peroxiredoxin (prx) was identified as an antigenic protein recognized by an anti-pba ige antibody using two-dimensional polyacrylamide gel electrophoresis and proteomic analysis. innate immune responses to pbaprx were examined using cells from mice deficient in toll-like receptors (tlr) or related molecules, and it was demonstrated that responses were severely impaired in tlr4(-/-), myd88(-/-) and md-2(-/-) mice, but not in toll/il-1 receptor do ...200818398934
immunological profile of a plasmodium vivax ama-1 n-terminus peptide-carbon nanotube conjugate in an infected plasmodium berghei mouse model.we have covalently conjugated an n-terminus plasmodium vivax apical membrane antigen-1 (ama-1) peptide to functionalized carbon nanotubes (f-cnt). immunological characterization of this molecular conjugate revealed that the immunogen-ama-1 peptide was appropriately presented after being conjugated to cnts as well as being recognized by balb/c polyclonal antibodies. subsequent experiments lead us to assess the ama-1 peptide alone, as well as the cnt-peptide conjugate regarding rodent malarial inf ...200818771700
antiplasmodial activity of root extract and fractions of croton zambesicus.antiplasmodial activity of root extract and fractions of croton zambesicus were evaluated to ascertain the folkloric claim of its antimalarial activity and elucidate its antiplasmodial mechanism of action.200918996464
perforin mediated apoptosis of cerebral microvascular endothelial cells during experimental cerebral malaria.cerebral malaria is a serious complication of plasmodium falciparum infection. we have investigated the role of perforin in the pathogenesis of cerebral malaria in a murine model (plasmodium berghei anka (pba) infection). c57bl/6 mice demonstrated the typical neuropathological symptoms of experimental cerebral malaria infection from day 5p.i. and became moribund on day 6p.i. this pathology was not seen in pba-infected, perforin-deficient (pfp-/-) mice. from days 5-6p.i. onwards there was a signi ...200616500656
rhop-3 protein conservation among plasmodium species and induced protection against lethal p. yoelii and p. berghei challenge.in the present study, rhop-3 polymorphism among plasmodium falciparum field and laboratory isolates and among rodent plasmodium species was investigated and identified. the rhop-3 gene was found in all plasmodium species so far tested. the overall structure of the rhop-3 protein was found conserved among p. falciparum, plasmodium yoelii, and plasmodium berghei. however, it was more conserved among rodent plasmodium species than between p. falciparum and plasmodium vivax. the most conserved regio ...200616541261
cerebral malaria: role of microparticles and platelets in alterations of the blood-brain barrier.brain lesions of cerebral malaria (cm) are characterised by a sequestration of plasmodium falciparum-parasitised red blood cells (prbc), leucocytes and platelets within brain microvessels, by an excessive release of pro-inflammatory cytokines as well as by disruption of the blood-brain barrier (bbb). we evaluated the possibility that prbc and platelets interact and induce functional alterations in brain endothelium. using an in vitro model of endothelial lesion, we showed that platelets can act ...200616600245
influence of paclitaxel on parasitemia and survival of plasmodium berghei infected mice.paclitaxel triggers suicidal erythrocyte death or eryptosis, characterized by exposure of phosphatidylserine at the erythrocyte surface and cell shrinkage. eryptosis of infected erythrocytes may delay development of parasitemia and thus favourably influence the course of malaria. the present study explored whether paclitaxel influences in vitro parasite growth and eryptosis of plasmodium falciparum infected human erythrocytes and in vivo parasitemia and survival of plasmodium berghei infected mi ...200919255513
characterization of cerebral malaria in the outbred swiss webster mouse infected by plasmodium berghei anka.plasmodium berghei anka (pba) infection in susceptible inbred mouse strains is the most commonly used experimental model to study pathogenesis of cerebral malaria (cm). indeed, many concepts on mechanisms related to this complication have arisen from works using this model. although inbred strains present several advantages and are indicated for most studies, the use of outbred models can show unique usefulness in a number of approaches such as fine post-quantitative trait loci mapping and disco ...200919335550
construction of transgenic plasmodium berghei as a model for evaluation of blood-stage vaccine candidate of plasmodium falciparum chimeric protein 2.9.the function of the 19 kda c-terminal region of the merozoite surface protein 1 (msp1-19) expressed by plasmodium has been demonstrated to be conserved across distantly related plasmodium species. the green fluorescent protein (gfp) is a reporter protein that has been widely used because it can be easily detected in living organisms by fluorescence microscopy and flow cytometry.200919727400
determination of the expression of lymphocyte surface markers and cytokine levels in a mouse model of plasmodium berghei.this study aimed to determine the changes in lymphocyte surface markers and cytokine profiles during a malarial infection in a mouse model of malaria. mononuclear cells obtained from the spleens of the mice infected with plasmodium berghei (p. berghei) were stained with anti-mouse cd3, anti-mouse cd4, anti-mouse cd8, anti-mouse cd19, anti-mouse cd152, anti-mouse pan natural killer (nk), anti-mouse cd80 monoclonal antibodies and expression of surface markers was evaluated by flow cytometry. in th ...200919845111
synthesis, in vitro and in vivo antimalarial assessment of sulfide, sulfone and vinyl amide-substituted 1,2,4-trioxanes prepared via thiol-olefin co-oxygenation (toco) of allylic alcohols.thiol-olefin co-oxygenation (toco) methodology has been applied to the synthesis of a small library of weak base and polar 1,2,4-trioxanes. the 1,2,4-trioxane units synthesised exhibit remarkable stability as they survive base catalysed hydrolysis and mixed anhydride/amine coupling reactions. this unique stability feature has enabled a range of novel substitution patterns to be incorporated within the spiro 1,2,4-trioxane unit. selected analogues express potent in vitro nm antimalarial activity, ...201020401383
protein kinase c θ deficiency increases resistance of c57bl/6j mice to plasmodium berghei infection-induced cerebral malaria.protein kinase c θ (pkcθ) functions as a core component of the immunological synapse and serves as a key protein in the integrated t-cell antigen receptor (tcr)/cd28-induced signaling cascade leading to t-cell activation. however, the involvement of pkcθ in host-mediated immune responses to pathogens has not been thoroughly investigated. we tested the consequences of pkcθ ablation on the host response to infection by plasmodium berghei anka (pba). we found that both pkcθ(+/+) and pkcθ(-/-) c57bl ...201020660606
plasmodium berghei k173: selection of resistance to naphthoquine in a mouse model.naphthoquine (nq), as a component of arco® which composed of nq and artemisinin, is a new 4-aminoquinoline antimalarial synthesized by our institute. here, a naphthoquine-resistant line of rodent malaria parasite was selected through exposing plasmodium berghei keyberg 173 strain to progressively increased drug pressure. the selected strain showed a more than 200-fold decreased susceptibility to nq with a stable resistance phenotype after 10 serial passages without drug pressure or when cryopres ...201020868687
a rapid murine coma and behavior scale for quantitative assessment of murine cerebral malaria.cerebral malaria (cm) is a neurological syndrome that includes coma and seizures following malaria parasite infection. the pathophysiology is not fully understood and cannot be accounted for by infection alone: patients still succumb to cm, even if the underlying parasite infection has resolved. to that effect, there is no known adjuvant therapy for cm. current murine cm (mcm) models do not allow for rapid clinical identification of affected animals following infection. an animal model that more ...201020957049
dematin, a component of the erythrocyte membrane skeleton, is internalized by the malaria parasite and associates with plasmodium 14-3-3.the malaria parasite invades the terminally differentiated erythrocytes, where it grows and multiplies surrounded by a parasitophorous vacuole. plasmodium blood stages translocate newly synthesized proteins outside the parasitophorous vacuole and direct them to various erythrocyte compartments, including the cytoskeleton and the plasma membrane. here, we show that the remodeling of the host cell directed by the parasite also includes the recruitment of dematin, an actin-binding protein of the er ...201021084299
antimalarial activity of novel 5-aryl-8-aminoquinoline derivatives.in an attempt to separate the antimalarial activity of tafenoquine (3) from its hemolytic side effects in glucose-6-phosphate dehydrogenase (g6pd) deficiency patients, a series of 5-aryl-8-aminoquinoline derivatives was prepared and assessed for antimalarial activities. the new compounds were found metabolically stable in human and mouse microsomal preparations, with t(1/2) > 60 min, and were equal to or more potent than primaquine (2) and 3 against plasmodium falciparum cell growth. the new age ...201021141892
the functional domain of gcs1-based gamete fusion resides in the amino terminus in plant and parasite species.fertilization is one of the most important processes in all organisms utilizing sexual reproduction. in a previous study, we succeeded in identifying a novel male gametic transmembrane protein gcs1 (generative cell specific 1), also called hap2 (hapless 2) in the male-sterile arabidopsis thaliana mutants, as a factor critical to gamete fusion in flowering plants. interestingly, gcs1 is highly conserved among various eukaryotes covering plants, protists and invertebrates. of these organisms, chla ...201021209845
artemether and artesunate show the highest efficacies in rescuing mice with late-stage cerebral malaria and rapidly decrease leukocyte accumulation in the brain.the murine model of cerebral malaria (ecm) caused by plasmodium berghei anka (pba) infection in susceptible mice has been extensively used for studies of pathogenesis and identification of potential targets for human cm therapeutics. however, the model has been seldom explored to evaluate adjunctive therapies for this malaria complication. a first step toward this goal is to define a treatment protocol with an effective antimalarial drug able to rescue mice presenting late-stage ecm. we evaluate ...201121220531
small-scale in vitro culture and purification of plasmodium berghei for transfection experiment.the standard protocol for genetic modification of the rodent malaria parasite plasmodium berghei requires infected blood from one or more laboratory mice, followed by large-scale in vitro parasite culture and purification of mature schizonts. here, protocols are described for small-scale in vitro culture from 20 µl of mouse tail blood and purification of mature p. berghei schizonts sufficient for a single transfection experiment. all procedures are performed in 1.5-ml microcentrifuge tubes. we c ...201121291917
in vivo and in vitro antimalarial activity of 4-nerolidylcatechol.4-nerolidylcatechol (4-nc) isolated from piper peltatum l. (piperaceae) was evaluated for in vitro antiplasmodial activity against plasmodium falciparum (cultures of both standard cqr (k1) and cqs (3d7) strains and two amazonian field isolates) and for in vivo antimalarial activity using the plasmodium berghei-murine model. 4-nc exhibits significant in vitro and moderate in vivo antiplasmodial activity. 4-nc administered orally and subcutaneously at doses of 200, 400 and 600?mg/kg/day suppressed ...201121302338
aminoindoles, a novel scaffold with potent activity against plasmodium falciparum.this study characterizes aminoindole molecules that are analogs of genz-644442. genz-644442 was identified as a hit in a screen of ~70,000 compounds in the broad institute's small-molecule library and the iccb-l compound collection at harvard medical school. genz-644442 is a potent inhibitor of plasmodium falciparum in vitro (50% inhibitory concentrations [ic50s], 200 to 285 nm) and inhibits p. berghei in vivo with an efficacy of > 99% in an adapted version of peters' 4-day suppressive test (w. ...201121422215
plasmodium cysteine repeat modular proteins 3 and 4 are essential for malaria parasite transmission from the mosquito to the host.the plasmodium cysteine repeat modular proteins (pcrmp) are a family of four conserved proteins of malaria parasites, that contain a number of motifs implicated in host-parasite interactions. analysis of mutants of the rodent parasite plasmodium berghei lacking expression of pcrmp1 or 2 showed that these proteins are essential for targeting of p. berghei sporozoites to the mosquito salivary gland and, hence, for transmission from the mosquito to the mouse.201121453484
cd4+ natural regulatory t cells prevent experimental cerebral malaria via ctla-4 when expanded in vivo.studies in malaria patients indicate that higher frequencies of peripheral blood cd4(+) foxp3(+) cd25(+) regulatory t (treg) cells correlate with increased blood parasitemia. this observation implies that treg cells impair pathogen clearance and thus may be detrimental to the host during infection. in c57bl/6 mice infected with plasmodium berghei anka, depletion of foxp3(+) cells did not improve parasite control or disease outcome. in contrast, elevating frequencies of natural treg cells in vivo ...201021170302
matrix metalloproteinases, tissue inhibitors of mmps and tace in experimental cerebral malaria.cerebral malaria (cm) is a life-threatening disorder and a major medical problem in developing countries. it is caused by the sequestration of malaria-infected erythrocytes onto brain endothelia, followed by blood-brain barrier (bbb) damage and neurological deficit. in the present study, matrix metalloproteinases (mmps) were analysed in a mouse model of cm with plasmodium berghei anka. increased numbers of gelatinase b (mmp-9)-positive cells, which were also cd11b(+), were detected in the brain. ...200616865090
caspase-1 activation of interleukin-1{beta} (il-1{beta}) and il-18 is dispensable for induction of experimental cerebral malaria.malaria infection is initiated by sporozoite invasion of hepatocytes and asexual reproduction of liver stages, processes that are regarded to be "clinically and diagnostically silent." merozoites, which egress from hepatocytes, infect erythrocytes in periodic cycles and induce disease. how the host innate immune system contributes to disease outcomes and to the induction of effector cells during malaria remains unclear. likewise, how the initial liver stages may shape responses to blood-stage pa ...201121708993
Triterpenoids as inhibitors of erythrocytic and liver stages of Plasmodium infections.Bioassay-guided fractionation of the methanol extract of Momordica balsamina led to the isolation of two new cucurbitane-type triterpenoids, balsaminol F (1) and balsaminoside B (2), along with the known glycosylated cucurbitacins, cucurbita-5,24-diene-3ß,23(R)-diol-7-O-ß-d-glucopyranoside (3) and kuguaglycoside A (4). Compound 1 was acylated yielding two new triesters, triacetylbalsaminol F (5) and tribenzoylbalsaminol F (6). The structures were elucidated based on spectroscopic methods includi ...201122071523
Protection from experimental cerebral malaria with a single dose of radiation-attenuated, blood-stage Plasmodium berghei parasites.Whole malaria parasites are highly effective in inducing immunity against malaria. Due to the limited success of subunit based vaccines in clinical studies, there has been a renewed interest in whole parasite-based malaria vaccines. Apart from attenuated sporozoites, there have also been efforts to use live asexual stage parasites as vaccine immunogens.201121935405
analgesic and antimalarial activities of crude leaf extract and fractions of acalypha wilkensiana.antiplasmodial and analgesic activities of leaf extract and fractions of acalypha wilkensiana were evaluated to ascertain the folkloric claim of its antimalarial and analgesic activities.201019892007
antimalarial and antitubercular nostocarboline and eudistomin derivatives: synthesis, in vitro and in vivo biological evaluation.the synthesis of nine nostocarboline derivatives with substitutions of the 2-methyl group by alkyl, aryl and functionalized residues, 10 symmetrical bis cationic dimers linking 6-cl-norharmane through the 2-position and fifteen derivatives of the marine alkaloids eudistomin n and o is reported. these compounds were evaluated in vitro against four parasites (trypanosoma brucei rhodesiense stib 900, trypanosoma cruzi tulahuen c2c4, leishmania donovani mhom-et-67/l82 axenic amastigotes, and plasmod ...201020133138
lead optimization of aryl and aralkyl amine-based triazolopyrimidine inhibitors of plasmodium falciparum dihydroorotate dehydrogenase with antimalarial activity in mice.malaria is one of the leading causes of severe infectious disease worldwide; yet, our ability to maintain effective therapy to combat the illness is continually challenged by the emergence of drug resistance. we previously reported identification of a new class of triazolopyrimidine-based plasmodium falciparum dihydroorotate dehydrogenase (pfdhodh) inhibitors with antimalarial activity, leading to the discovery of a new lead series and novel target for drug development. active compounds from the ...201121517059
the ifn-+¦-inducible gtpase, irga6, protects mice against toxoplasma gondii but not against plasmodium berghei and some other intracellular pathogens.clearance of infection with intracellular pathogens in mice involves interferon-regulated gtpases of the irg protein family. experiments with mice genetically deficient in members of this family such as irgm1(lrg-47), irgm3(igtp), and irgd(irg-47) has revealed a critical role in microbial clearance, especially for toxoplasma gondii. the in vivo role of another member of this family, irga6 (iigp, iigp1) has been studied in less detail. we investigated the susceptibility of two independently gener ...201121698150
bioinformatics analysis and prediction for structure and function of nitric oxide synthase and similar proteins from plasmodium berghei.to search and analyze nitric oxide synthase (nos) and similar proteins from plasmodium berghei(pb).201121771405
prevention of experimental cerebral malaria by flt3 ligand during infection with plasmodium berghei anka.dendritic cells are the most potent antigen-presenting cells, but their roles in blood-stage malaria-infection are not fully understood. we examined the effects of flt3 ligand, a cytokine which induces dendritic cell production, in vivo on the course of infection with plasmodium berghei anka. mice treated with flt3 ligand showed preferential expansion of cd8(+) dendritic cells and granulocytes, lower parasitemia, and were protected from the development of lethal experimental cerebral malaria (ec ...201121807908
cerebral malaria: human versus mouse studies. 201020382077
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