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plasmodium berghei in the white rat: severe malaria of pregnancy does not occur in the progeny of mothers infected during gestation. 199910656044
in vivo antimalarial activities of quassia amara and quassia undulata plant extracts in mice.extracts obtained from two nigerian simaroubaceae plants, quassia amara l. and quassia undulata (giull and perr) d. dietr were screened for antimalarial properties using a total of six extracts. the plant extracts showed significant antimalarial activities in the 4 day suppressive in vivo antimalarial assay in mice inoculated with red blood cells parasitized with plasmodium berghei berghei. plant extracts were studied at 100 mg and 200 mg per kg body weight mouse per day, respectively. at a conc ...199910617067
role of icam-1 (cd54) in the development of murine cerebral malaria.in susceptible mouse strains, infection of mice with plasmodium berghei anka (pba) results in a lethal complication, cerebral malaria. cerebral malaria is due to the immune response induced by the parasite, which results in an increased production of tnf, known to increase the expression of adhesion molecules on the endothelia. to investigate the role of the adhesion molecule icam-1 (cd54), we infected wild-type (+/+) and icam-1-deficient (-/-) mice with pba. while +/+ mice died 6-8 days after i ...199910617927
novel, potent, semisynthetic antimalarial carba analogues of the first-generation 1,2,4-trioxane artemether.ten novel, second-generation, fluorinated ether and ester analogues of the potent first-generation analogues artemether (4a) and arteether (4b) have been designed and synthesized. all of the compounds demonstrate high antimalarial potency in vitro against the chloroquine-sensitive hb3 and -resistant k1 strains of plasmodium falciparum. the most potent derivative 8 was 15 times more potent than artemisinin (2) against the hb3 strain of p. falciparum. in vivo, versus plasmodium berghei in the mous ...199910639291
genome plasticity and sexual differentiation in plasmodium.spontaneous subtelomeric deletions of plasmodium chromosomes have been observed both in natural infections and in laboratory maintained parasites. in the latter case, functions dispensable for asexual parasite multiplication and encoded at the extremities of the chromosomes are easily lost. in particular, spontaneous subtelomeric deletions have been characterised which affect gametocytogenesis both in plasmodium berghei maintained in laboratory animals and in plasmodium falciparum propagated in ...199910697847
plasmodium falciparum cs c-terminal fragment: preclinical evaluation and phase i clinical studies.preclinical evaluation of synthetic peptides corresponding to the c-terminal regions of the circumsporozoite (cs) protein in various plasmodia showed that these preparations were immunogenic and safe upon injection in various animal models. additionally, the corresponding peptide from plasmodium falciparum was widely recognized by sera and pbl obtained from semi-immune adults living in malaria endemic areas. moreover, the cs c-terminal peptide derived from p. berghei conferred protection upon ch ...199910697896
schizontocidal effects of oral artesunate on plasmodium berghei in mice and p knowlesi in monkeys.to study the blood schizontocidal effect of oral artesunate on p berghei in mice and p knowlesi in monkey.199910678113
the chemotherapy of rodent malaria. lvii. drug combinations to impede the selection of drug resistance, part 1: which model is appropriate?the principle has finally been accepted that, whenever possible, antimalarial drugs should be deployed in appropriate combinations in endemic areas, in order to minimize the inevitability that monotherapy will, probably sooner than later, select populations of drug-resistant parasites. which laboratory models can predict the combinations of old or novel compounds that are likely to be of practical value in minimizing this risk? very few relevant data on the use of plasmodium falciparum in vitro ...199910707103
nitric oxide in murine malaria: divergent roles in blood and brain suggested by voltametric measures. 199910717761
[genetic approach to the study of the sporogonic cycle in plasmodium].the development of transformation and mutagenesis techniques of the two species of plasmodium most studied--plasmodium falciparum (human parasite) and plasmodium berghei (rodent parasite)--opens new perspectives for the molecular study on the parasite sporogonic cycle in the insect vector. the parasite's stages that can be genetically transformed (the asexual erythrocytic stages) and gametocytes. the function of proteins coded by genes present in single copy in the genome can thus be studied aft ...199911000961
protective immunity against plasmodium berghei malaria after administration of interleukin-12.interleukin-12 (il-12) has been shown to induce protection in mice against plasmodium cyanomolgi and in rhesus monkey against plasmodium yeolii. this study is to investigate whether recombinant il-12 can induce protection in balb/c mice against plasmodium berghei. five mice were given intraperitoneal injection of 7.5 micrograms/kg body weight recombinant mouse il-12 two days prior to challenge with 5 x 10(4) of p. berghei, while mice in the control group were injected with 0.5 ml of normal salin ...199911068418
immune responses to chloroquine--sensitive and resistant populations of plasmodium berghei in mice.in order to elucidate the role of the host as a factor in the spread of chloroquine resistance, a study of the host's immune responses in chloroquine resistant (cqr) and chloroquine sensitive (cqs) plasmodial infections is essential. course of the infection and the nature of immune responses in mice infected with chloroquine resistant (r) and chloroquine sensitive (s) strains of plasmodium berghei were compared. crude parasite antigen activated t cells from both the groups of mice (r and s) and ...199910810580
role of macrophages in experimental malaria: vi--effect of freund's complete adjuvant in plasmodium berghei infected mice.freund's complete adjuvant (fca) treated group of mice when challenged with lethal plasmodium berghei showed increased survival value; survival period (sp) and median survival day (msd) compared to their respective control groups. k values were affected and mean parasitaemia during infection period was lower than that of control. in general survival rate after 35 days of infection was 10.5% in fca recipients. the survival rate in a particular group of animals which received 0.2 ml fca 3 days bef ...199910810600
suppressed expression of hypoxanthine-guanine phosphoribosyltransferase (hgprt) in an irradiation-attenuated plasmodium berghei xat strain.plasmodium berghei xat (xat) is a non-reversible, non-lethal type malaria parasite strain derived from the highly virulent lethal p. berghei nk65 (nk65) by x-irradiation. the difference in polypeptide expression between nk65 and xat was examined in this study. western blot patterns of the parasite polypeptides showed that a 30-kda polypeptide was not detected in xat. in the present paper, we focused the study on the difference in the expression of the 30-kda polypeptide between xat and nk65. alt ...199911269277
[culture of plasmodium berghei with the short life span in mouse erythrocytes: evaluation of chloroquine resistance in three strains of the malaria parasite].this comparative study was made to examine chroloquine inhibition of c14-hypoxanthine incorporation (preferably nucleic acid precursor for plasmodium) in the short-living red blood cell cultures in mice infected with p. berghei strains differently sensitive to the agent 24 hours after incubation. these included 1) chloroquine-sensitive h strain; 2) lnk-65 strain having a spontaneously 2-3-fold decreased sensitivity to the agent; 3) strain lnk-65 chr selected for high resistance to chloroquine. i ...199911221002
myosin a expressions in sporogonic stages of plasmodium. 200011163454
potent in vivo antimalarial activity of 3,15-di-o-acetylbruceolide against plasmodium berghei infection in mice.the antimalarial activity of the o-acylated bruceolide derivative, 3,15-di-o-acetylbruceolide, was evaluated against plasmodium berghei in vivo. the concentration of 3,15-di-o-acetylbruceolide required for 50% suppression (ed50) of p. berghei in mice was 0.46 +/- 0.06 mg/kg/day, whereas bruceolide was only half as effective as 3,15-di-o-acetylbruceolide. two antimalarial drugs used clinically, chloroquine and artemisinin, demonstrated only low activity corresponding to 1/4 and 1/12 of the ed50 v ...200011227768
assessment of the antimalarial potential of tetraoxane wr 148999.the antimalarial peroxide, dispiro-1,2,4,5-tetraoxane wr 148999, was synergistic with chloroquine, quinine, mefloquine, and artemisinin against both d6 and w2 clones of plasmodium falciparum. in consideration of the contrasting antagonism between artemisinin and chloroquine, these drug combination data imply that wr 148999 and artemisinin may not share a common mechanism of action. for plasmodium berghei-infected mice given oral, subcutaneous, and intraperitoneal doses of wr 148999 ranging from ...200011289666
16alpha-bromoepiandrosterone, a dehydroepiandrosterone (dhea) analogue, inhibits plasmodium falciparum and plasmodium berghei growth.dehydroepiandrosterone (dhea) and its analogue, 16alpha-bromoepiandrosterone (alpha-epi-br), may have activity against viral and parasitic infections, including human immunodeficiency virus (hiv) and cryptosporidium parvum. therefore, we evaluated its antimalarial effects on plasmodium falciparum and plasmodium berghei. in vitro, chloroquine (cq)-sensitive and resistant strains of p. falciparum parasitized red blood cells were incubated with escalating doses of alpha-epi-br or cq. in vivo, 62 ra ...200011421378
inhibition of the malaria parasite by experimental co-infection of mice by west nile virus and plasmodium berghei. 200011344791
short report: failure to select for chloroquine- or mefloquine-resistant plasmodium berghei through drug pressure in anopheles stephensi mosquitoes.we investigated whether chloroquine- or mefloquine-resistant plasmodium berghei could be selected through drug pressure applied during continuous cyclical transmission in anopheles stephensi mosquitoes. mosquitoes were infected by feeding them on mice previously inoculated with a drug-sensitive clone of p. berghei anka. mosquitoes ingested mefloquine or chloroquine with the infectious blood-meal, or by feeding on a drug-treated (uninfected) mouse 4 or 10 days after the infectious blood-meal. twe ...200011388501
effects of dihydroartemisinin on fine structure of erythrocytic stages of plasmodium berghei anka strain.the fine structural changes of plasmodium berghei anka strain after treatment with the dihydroartemisinin (datm) were observed.200011324422
role of macrophages in experimental malaria: vii--studies on adoptive transfer of macrophages.adoptive transfer of purified macrophages harvested from normal, plasmodium berghei infected and latent/cured mice and also macrophages exposed to parasites in vitro were carried out to see the role of macrophages in transferring immunity against p. berghei infection. macrophages obtained from mice having high parasitaemia at a dose of one million cells/animal showed significant increase in survival period (sp) and k values, compared to controls. macrophages exposed to low parasite density confe ...200011198398
in vivo antimalarial activity of the beta-carboline alkaloid manzamine a.manzamine a, a beta-carboline alkaloid present in several marine sponge species, inhibits the growth of the rodent malaria parasite plasmodium berghei in vivo. more than 90% of the asexual erythrocytic stages of p. berghei were inhibited after a single intraperitoneal injection of manzamine a into infected mice. a remarkable aspect of manzamine a treatment is its ability to prolong the survival of highly parasitemic mice, with 40% recovery 60 days after a single injection. oral administration of ...200010817722
divergence of noncoding sequences and of insertions encoding nonglobular domains at a genomic region well conserved in plasmodia.to identify conserved features in the rapidly diverging portions of a well-conserved locus, completely sequenced in plasmodium falciparum and plasmodium berghei, a computational method based on recurrence analysis was exploited. at the level of the genomic sequence, in both species, introns and intergenic sequences-though subject to rapid diversification-do not drift without constraints, but rather coevolve, in the sense that they maintain not only an at-rich base composition, but also a consist ...200010824091
the intraperitoneal plasmodium berghei-pasteur infection of swiss mice is not a system that is able to detect the antiplasmodial activity in the pothomorphe plant extracts that are used as antimalarials in brazilian endemic areas.the antimalarial activity of the hexane and methanol extracts derived from the brazilian plants pothomorphe peltata and pothomorphe umbellata-whose leaves are popularly employed in medicinal folk remedies for the treatment of malaria-was assessed through in vivo tests with the peters method. the extracts were delivered to plasmodium berghei-infected mice via the oral or the subcutaneous route. a suppressive effect on the parasitemia seemed to be evident when data regarding the intraperitoneal in ...200010831392
plasmodium berghei: the antimalarial activity of albendazole in rats is mediated via effects on the hematopoietic system. 200010831394
anti-malarial effect of histone deacetylation inhibitors and mammalian tumour cytodifferentiating agents.the histones of plasmodium falciparum represent a potential new target for anti-malarial compounds. a naturally occurring compound, apicidin, has recently been shown to inhibit the in vitro growth of p. falciparum. apicidin was shown to hyperacetylate histones, suggesting that its mode of action is through histone deacetylase inhibition. we have tested the ability of known histone deacetylase inhibitors, mammalian tumour suppressor compounds, and cytodifferentiating agents to inhibit the in vitr ...200010856511
delayed mortality and attenuated thrombocytopenia associated with severe malaria in urokinase- and urokinase receptor-deficient mice.we explored the role of urokinase and tissue-type plasminogen activators (upa and tpa), as well as the upa receptor (upar; cd87) in mouse severe malaria (sm), using genetically deficient (-/-) mice. the mortality resulting from plasmodium berghei anka infection was delayed in upa(-/-) and upar(-/-) mice but was similar to that of the wild type (+/+) in tpa(-/-) mice. parasitemia levels were similar in upa(-/-), upar(-/-), and +/+ mice. production of tumor necrosis factor, as judged from the plas ...200010858190
plasmodium berghei: cerebral malaria in cba mice is not clearly related to plasma tnf levels or intensity of histopathological changes.plasmodium berghei anka infection in cba/j mice leads to the development of cerebral malaria (cm) that kills 80-90% of the animals in 6-9 days. this model has been used to study the pathogenesis of cm, which is a major cause of morbidity and mortality in plasmodium falciparum-infected individuals. the role of cytokines in the induction of cm in the murine model has been well documented, but most studies have been restricted to the peak of neurological manifestations. here we used a sequential ap ...200010864512
flow cytometry assay for counting micronucleated erythrocytes: development process.development of any new assay proceeds in several phases. when an assay is intended for regular use to support regulatory decision-making, there are significant additional stages in the development process beyond the initial description of the method. in this paper we discuss some of the studies related to the development of a flow cytometric method for counting micronuclei in rodent erythrocytes. studies related to fixation methods and conditions, standardization of dna staining, and antibody st ...200010873482
determination of mosquito bloodmeal ph in situ by ion-selective microelectrode measurement: implications for the regulation of malarial gametogenesis.malarial gametocytes circulate in the peripheral blood of the vertebrate host as developmentally arrested intra-erythrocytic cells, which only resume development into gametes when ingested into the bloodmeal of the female mosquito vector. the ensuing development encompasses sexual reproduction and mediates parasite transmission to the insect. in vitro the induction of gametogenesis requires a drop in temperature and either a ph increase from physiological blood ph (ca ph 7.4) to about ph 8.0, or ...200010874717
experimental erythrocytic malaria infection induces elevated serum amyloid p production in mice.experimental blood-stage malaria infection of nih mice was observed to induce an acute phase response (apr). infection of mice with either p. chabaudi, p. vinckei (both non-lethal) or p. berghei (lethal infection) resulted in elevated serum amyloid p (sap) production, the major acute phase protein in mice. peak production occurred at the peak of the parasitaemia (approximately day 10 post infection). sap isolated from the serum of p. chabaudi infected mice was shown to inhibit the growth of intr ...200010880833
characterization of a differential immunoscreen epitope of plasmodium falciparum using combinatorial agents.a differential serological screening of a lambdagt11 cdna expression library has identified several clones, which react exclusively to sera samples from persons clinically immune to malaria but not to acute malaria patient sera. one such clone, ipf9, has a 315-bp cdna insert, which was found to be conserved in different strains of the human and rodent malarial parasite plasmodium falciparum and plasmodium berghei, respectively. the induced expression product of ipf9 was used to generate polyclon ...200010886717
synthesis and antimalarial activity of sixteen dispiro-1,2,4, 5-tetraoxanes: alkyl-substituted 7,8,15,16-tetraoxadispiro[5.2.5. 2]hexadecanes.sixteen alkyl-substituted dispiro-1,2,4,5-tetraoxanes (7,8,15, 16-tetraoxadispiro[5.2.5.2]hexadecanes) were synthesized to explore dispiro-1,2,4,5-tetraoxane sar and to identify tetraoxanes with better oral antimalarial activity than prototype tetraoxane 1 (wr 148999). the tetraoxanes were prepared either by peroxidation of the corresponding cyclohexanone derivatives in h(2)so(4)/ch(3)cn or by ozonolysis of the corresponding cyclohexanone methyl oximes. those tetraoxanes with alkyl substituents ...200010893313
involvement of ifn-gamma receptor-medicated signaling in pathology and anti-malarial immunity induced by plasmodium berghei infection.ifn-gamma has been implicated in the pathogenesis of experimental cerebral malaria (ecm). we have used mice lacking the alpha chain of the ifn-gamma receptor (ko mice) to define its role in the pathogenesis of ecm. infected ko mice did not develop ecm and showed no leukocyte or parasite sequestration in the brain, and no hemorrhages. the resistance of ko mice to ecm was associated with the absence of any increases of tnf-alpha and icam-1 proteins in the brain, which are both essential for ecm. w ...200010898501
alpha -galactosylceramide-activated valpha 14 natural killer t cells mediate protection against murine malaria.natural killer t (nkt) cells are a unique population of lymphocytes that coexpress a semiinvariant t cell and natural killer cell receptors, which are particularly abundant in the liver. to investigate the possible effect of these cells on the development of the liver stages of malaria parasites, a glycolipid, alpha-galactosylceramide (alpha-galcer), known to selectively activate valpha14 nkt cells in the context of cd1d molecules, was administered to sporozoite-inoculated mice. the administrati ...200010900007
antiplasmodial, analgesic, and anti-inflammatory activities of the aqueous extract of the stem bark of erythrina senegalensis.the in vivo antiplasmodial, analgesic and anti-inflammatory properties of erythrina senegalensis, an ornamental plant commonly used in northern nigeria for the treatment of fevers, was evaluated. aqueous extracts of the stem bark of the plant was used for the study. the in vivo antiplasmodial activity of the aqueous extract against plasmodium berghei was assessed using the suppressive and curative test procedures. analgesic activity was assessed using the acetic acid (0.75%v/v) induced abdominal ...200010904174
effects of interruption of apicoplast function on malaria infection, development, and transmission.a chloroplast-like organelle is present in many species of the apicomplexa phylum. we have previously demonstrated that the plastid organelle of plasmodium faciparum is essential to the survival of the blood-stage malaria parasite in culture. one known function of the plastid organelle in another apicomplexan, toxoplasma gondii, involves the formation of the parasitophorous vacuole. the effects of interruption of plastid function on sporozoites and sexual-stage parasites have not been investigat ...200010924753
essential role of cd8 palmitoylation in cd8 coreceptor function.to investigate the molecular basis that makes heterodimeric cd8alphabeta a more efficient coreceptor than homodimeric cd8alphaalpha, we used various cd8 transfectants of t1.4 t cell hybridomas, which are specific for h-2kd, and a photoreactive derivative of the plasmodium berghei circumsporozoite peptide pbcs 252-260 (syipsaeki). we demonstrate that cd8 is palmitoylated at the cytoplasmic tail of cd8beta and that this allows partitioning of cd8alphabeta, but not of cd8alphaalpha, in lipid rafts. ...200010925291
import of host delta-aminolevulinate dehydratase into the malarial parasite: identification of a new drug target.the parasite plasmodium berghei imports the enzyme delta-aminolevulinate dehydratase (alad), and perhaps the subsequent enzymes of the pathway from the host red blood cell to sustain heme synthesis. here we have studied the mechanism of this import. a 65-kda protein on the p. berghei membrane specifically bound to mouse red blood cell alad, and a 93-amino-acid fragment (alad-deltanc) of the host erythrocyte alad was able to compete with the full-length enzyme for binding to the p. berghei membra ...200010932227
tissue distribution of indoleamine 2,3-dioxygenase in normal and malaria-infected tissue.an immunohistochemical method was developed, using a polyclonal antibody, to detect the enzyme indoleamine 2,3-dioxygenase (ido) in normal and malaria-infected tissue. plasmodium berghei anka, a cerebral malaria (cm) model, and p. berghei k173, a non-cerebral malaria (ncm) model, were used. it was found that vascular endothelial cells were the primary site of ido expression in both models of malaria infection and that this response was systemic, with the vascular endothelium of brain, heart, lun ...200010939286
dichloroacetate (dca) reduces brain lactate but increases brain glutamine in experimental cerebral malaria: a 1h-nmr study.recent findings that levels of brain lactate and alanine were elevated in murine cerebral malaria led us to investigate the effect of dichloroacetate (dca; 60 mg/kg), an activator of pyruvate dehydrogenase, on the levels of brain metabolites, and on the survival of mice infected with plasmodium berghei anka which normally causes lethal cerebral malaria. dca significantly reduced brain lactate and alanine levels when administered to infected mice, had no effect on the tca cycle-related metabolite ...200010939296
immunopathology of cerebral malaria: morphological evidence of parasite sequestration in murine brain microvasculature.a murine model that closely resembles human cerebral malaria is presented, in which characteristic features of parasite sequestration and inflammation in the brain are clearly demonstrable. "young" (balb/c x c57bl/6)f(1) mice infected with plasmodium berghei (anka) developed typical neurological symptoms 7 to 8 days later and then died, although their parasitemias were below 20%. older animals were less susceptible. immunohistopathology and ultrastructure demonstrated that neurological symptoms ...200010948166
morphine modulation of plasmodial-antigens-induced colony-stimulating factors production by macrophages.morphine abuse is known to cause immunosuppression and enhanced host susceptibility to malaria. we studied the effect of morphine on the plasmodium berghei total-parasite-antigens soluble in culture medium (p.b.sa)-induced production of colony-stimulating factors (csfs) by mouse peritoneal macrophages, in vitro. morphine exerted a concentration-dependent biphasic modulatory effect; at 1 x 10(-4)-1 x 10 x 10(-6) m it slightly inhibited, whereas at 1 x 10(-8)-1 x 10(-10) m it augmented the product ...200010954037
differential interleukin-10 expression in interferon regulatory factor-1 deficient mice during plasmodium berghei blood-stage infection.mice deficient of functional interferon regulatory factor-1 (irf-1-/-) by targeted gene disruption infected with a lethal murine malaria strain, plasmodium berghei anka survived longer than its wild-type littermates despite the inability to induce appreciable amounts of interferon-gamma (ifn-gamma) and nitric oxide. in addition, infected irf-1-/- mice displayed less organ injury with reduced necrosis and inflammation. both wild-type and irf-1-/- mice treated with exogenous interleukin-12 (il-12) ...200010972849
inhibition of the mosquito transmission of plasmodium berghei by malarone (atovaquone-proguanil).sera from patients treated with atovaquone-proguanil (malarone) have previously been shown to inhibit the mosquito transmission of plasmodium falciparum, though the inhibition was not complete and the effect declined 2 weeks after treatment. in marked contrast, the inhibition of transmission of p. berghei by human sera (fed to mosquitoes, with p. berghei gametocytes, via membrane feeders) from volunteers treated with atovaquone-proguanil was total up to day 28 post-treatment and still very signi ...200010983555
distinct roles for pbs21 and pbs25 in the in vitro ookinete to oocyst transformation of plasmodium berghei.we have developed an in vitro culture system for early sporogonic stages of plasmodium berghei, which can be used to study developmental events normally taking place in the midgut of an infected mosquito. these include penetration of insect cells by the mature ookinete, transformation into oocysts and the early development of the latter, sustained through several rounds of nuclear division. the system, based upon co-culture of enriched ookinetes with several established insect cell lines, was us ...200010984433
targeted terminal deletions as a tool for functional genomics studies in plasmodium.we describe a transfection system that induces terminal deletions at specific chromosome ends in malaria parasites using a linear construct containing telomeric repeats at one end and plasmodial sequences able to drive homologous recombination at the other. a site-specific deletion was generated at one extremity of chromosome 5 of plasmodium berghei, which was stably maintained in the parasite population selected after transfection. the telomeric repeat array introduced with the construct reache ...200010984459
characterisation and expression of pbs25, a sexual and sporogonic stage specific protein of plasmodium berghei.following gametogenesis and fertilisation in the bloodmeal within the mosquito midgut, the newly formed zygotes of the malaria parasite develop into motile invasive ookinetes. during this development, surface molecules are synthesised de novo including molecules of 21-28 kda from the zygote-ookinete stages. an antiserum recognising a 26 kda protein of plasmodium berghei was used to clone the corresponding gene from a cdna library, which was shown to be identical to the reported pbs25 gene sequen ...200010989152
hematin polymerization assay as a high-throughput screen for identification of new antimalarial pharmacophores.hematin polymerization is a parasite-specific process that enables the detoxification of heme following its release in the lysosomal digestive vacuole during hemoglobin degradation, and represents both an essential and a unique pharmacological drug target. we have developed a high-throughput in vitro microassay of hematin polymerization based on the detection of (14)c-labeled hematin incorporated into polymeric hemozoin (malaria pigment). the assay uses 96-well filtration microplates and require ...200010991837
genetic vaccination against malaria infection by intradermal and epidermal injections of a plasmid containing the gene encoding the plasmodium berghei circumsporozoite protein.the circumsporozoite protein (csp) from the surface of sporozoite stage plasmodium sp. malaria parasites is among the most important of the malaria vaccine candidates. gene gun injection of genetic vaccines encoding plasmodium berghei csp induces a significant protective effect against sporozoite challenge; however, intramuscular injection does not. in the present study we compared the immune responses and protective effects induced by p. berghei csp genetic vaccines delivered intradermally with ...200010992502
molecular interactions between anopheles stephensi midgut cells and plasmodium berghei: the time bomb theory of ookinete invasion of mosquitoes.we present a detailed analysis of the interactions between anopheles stephensi midgut epithelial cells and plasmodium berghei ookinetes during invasion of the mosquito by the parasite. in this mosquito, p. berghei ookinetes invade polarized columnar epithelial cells with microvilli, which do not express high levels of vesicular atpase. the invaded cells are damaged, protrude towards the midgut lumen and suffer other characteristic changes, including induction of nitric oxide synthase (nos) expre ...200011080150
toxoplasma gondii homologue of plasmodium apical membrane antigen 1 is involved in invasion of host cells.proteins with constitutive or transient localization on the surface of apicomplexa parasites are of particular interest for their potential role in the invasion of host cells. we describe the identification and characterization of tgama1, the toxoplasma gondii homolog of the plasmodium apical membrane antigen 1 (ama1), which has been shown to elicit a protective immune response against merozoites dependent on the correct pairing of its numerous disulfide bonds. tgama1 shows between 19% (plasmodi ...200011083833
pfsbp1, a maurer's cleft plasmodium falciparum protein, is associated with the erythrocyte skeleton.antibodies from hyperimmune monkey sera, selected by absorption to plasmodium falciparum-infected erythrocytes, and elution at acidic ph, allowed us to characterize a novel parasite protein, pfsbp1 (p. falciparum skeleton binding protein 1). pfsbp1 is an integral membrane protein of parasite-induced membranous structures associated with the erythrocyte plasma membrane and referred to as maurer's clefts. the carboxy-terminal domain of pfsbp1, exposed within the cytoplasm of the host cell, interac ...200011087921
a role for linoleic acid in erythrocytes infected with plasmodium berghei.unesterified fatty acids were measured in mouse erythrocytes infected either with chloroquine-susceptible (cs) or with chloroquine-resistant (cr) lines of plasmodium berghei. this work was undertaken to identify candidates for the lipid involved in ferriprotoporphyrin ix (fp) polymerization. linoleic, oleic, palmitic, and stearic acids were quantified by gas chromatography/mass spectrometry. in total, they increased 4-fold with cs infections and 6-fold with cr infections. treating infected mice ...200011113630
scant parasitemia in balb/c mice with congenital malaria infection.balb/c mice were examined to determine whether or not they transmitted rodent malaria, plasmodium berghei, to their fetuses. on the 15th day of pregnancy, mice were inoculated with approximately 3 x 10(6) p. berghei-infected erythrocytes by peritoneal injection. the blood from 27 adult females and 196 neonates was examined using a sensitive polymerase chain reaction (pcr) method with a detection level of approximately 1 parasite/microl blood. the average parasitemia of females at delivery was 8. ...200011128475
plasmodium yoelii: efficient in vitro invasion and complete development of sporozoites in mouse hepatic cell lines. 200011162379
the synthetic, oxidized c-terminal fragment of the plasmodium berghei circumsporozoite protein elicits a high protective response.a polypeptide of 69 amino acids (pbcs 242-310) encompassing the c-terminal region of the circumsporozoite protein of plasmodium berghei (pbcs) was generated using solid-phase peptide synthesis. the immunological and protective properties of peptide pbcs 242-310 were studied in balb/c mice (h-2d). two subcutaneous injections, in the presence of ifa at the base of the tail, generated (i) high titers of anti-peptide antibodies which also recognized the native p. berghei cs protein, (ii) cytolytic t ...200011009102
oxygenated chalcones and bischalcones as potential antimalarial agents.oxygenated chalcones (3a,b) and bischalcones (4a-j) have been synthesized and evaluated for antimalarial activity against chloroquine sensitive and resistant strains of plasmodium berghei in mice. some of the screened compounds, 3a, 4c, 4e, 4f and 4i, have shown significant activity at 100 mg/kg dose against sensitive strain.200011012019
the roles of the glycosylphosphatidylinositol anchor on the production and immunogenicity of recombinant ookinete surface antigen pbs21 of plasmodium berghei when prepared in a baculovirus expression system.malarial ookinetes express an immunodominant surface protein (p28) that is a priority candidate for the development of transmission-blocking vaccines. the full length p28 gene from plasmodium berghei [pbs21(1-213)] and a deletion construct [pbs21(1-188)] encoding a protein that lacks the 25 c-terminal amino acids, including the glycosylphosphatidylinositol (gpi) anchor signal, were expressed in insect cells using baculovirus vectors. pbs21(1-213) protein is strongly hydrophobic, found in the cyt ...200011012975
a search for natural bioactive compounds in bolivia through a multidisciplinary approach. part iv. is a new haem polymerisation inhibition test pertinent for the detection of antimalarial natural products?the search for new antimalarial agents in plant crude extracts using traditional screening tests is time-consuming and expensive. new in vitro alternative techniques, based on specific metabolic or enzymatic process, have recently been developed to circumvent testing of antimalarial activity in parasite culture. the haem polymerisation inhibition test (hpia) was proposed as a possible routine in vitro assay for the detection of antimalarial activity in natural products. a total of 178 plant extr ...200011025165
some in vitro invasion inhibition of red cells by in vivo nonprotective anti-ldh antibodies of plasmodium berghei.in plasmodium berghei, sephadex g-200 purified lactate dehydrogenase (ldh) fraction immunized mice did not exhibit protection when challenged with 1 x 10(6) p. berghei-parasitized erythrocytes. however, ldh immunized mice seroconverted and showed an antibody titre of 1:2048 by indirect haemagglutination (iha) and 1:160 by indirect fluorescent antibody (ifa) assays. fluorescence was distributed evenly on p. berghei-parasitized red cells showing no specific location of parasite ldh. anti-ldh antib ...200011048428
anti-malarial activity of leaf-extract of hydrangea macrophylla, a common japanese plant.to find a new anti-malarial medicine derived from natural resources, we examined the leaves of 13 common japanese plants in vitro. among them, a leaf-extract of hydrangea macrophylla, a common japanese flower, inhibited the parasitic growth of plasmodium falciparum. the ic50 of hydrangea macrophylla leaf extract to plasmodium falciparum was 0.18 microg/ml. the ic50 to nih 3t3-3 cells, from a normal mouse cell line, was 7.2 microg/ml. thus, selective toxicity was 40. for the in vivo test, we inoc ...200011061572
the chemotherapy of rodent malaria. lviii. drug combinations to impede the selection of drug resistance, part. 2: the new generation--artemisinin or artesunate with long-acting blood schizontocides.the search for combinations of antimalarial drugs that will impede the selection of drug resistance, especially in plasmodium falciparum, is currently focused on the use of a member of the artemisinin family, with a short half-life, in association with a relatively long-acting blood schizontocide. experiments with such 'third-generation' combinations, in mice infected either with chloroquine-sensitive p. berghei or p. chabaudi, or chloroquine-resistant p. yoelii ssp. ns, have produced interestin ...200010723521
acidocalcisomes and a vacuolar h+-pyrophosphatase in malaria parasites.plasmodium berghei trophozoites were loaded with the fluorescent calcium indicator, fura-2 acetoxymethyl ester, to measure their intracellular ca(2+) concentration ([ca(2+)](i)). [ca(2+)](i) was increased in the presence of the sarcoplasmic/endoplasmic reticulum ca(2+)-atpase inhibitor, thapsigargin. trophozoites also possess a significant amount of ca(2+) stored in an acidic compartment. this was indicated by: (1) the increase in [ca(2+)](i) induced by bafilomycin a(1), nigericin, monensin, or ...200010727425
oxidative phosphorylation, ca(2+) transport, and fatty acid-induced uncoupling in malaria parasites mitochondria.respiration, oxidative phosphorylation, calcium uptake, and the mitochondrial membrane potential of trophozoites of the malaria parasite plasmodium berghei were assayed in situ after permeabilization with digitonin. adp promoted an oligomycin-sensitive transition from resting to phosphorylating respiration. respiration was sensitive to antimycin a and cyanide. the capacity of trophozoites to sustain oxidative phosphorylation was additionally supported by the detection of an oligomycin-sensitive ...200010734123
the mosquito transmission of malaria: the effects of atovaquone-proguanil (malarone) and chloroquine.despite its recognized importance, the prevention of patients with malaria from continuing to infect mosquitoes after treatment is not always achieved in practice. an inevitable consequence of the prolonged life-span and relative metabolic stasis of the mature gametocytes of plasmodium falciparum is that they are not cleared by most antimalarials, and few antimalarials block infection in the mosquito vector. previous research on the constituents of malarone, a new 'combined antimalarial', sugges ...200010748906
neutrophils play a critical role in the pathogenesis of experimental cerebral malaria.the role of neutrophils in experimental cerebral malaria (ecm) is not well understood. in this study we used a moab, rb6-8c5, to deplete the peripheral neutrophils of ecm-susceptible cba/nslc mice 24 h before plasmodium berghei anka (pba) infection. we found that early neutrophil depletion prevented the development of ecm and dramatically decreased the sequestration of monocytes and microhaemorrhage in the brain. the depletion of neutrophils also down-regulated tumour necrosis factor-alpha, inte ...200010759773
molecular characterization of a prophenoloxidase cdna from the malaria mosquito anopheles stephensi.some refractory anopheline mosquitoes are capable of killing plasmodium, the causative agent of malaria, by melanotic encapsulation of invading ookinetes. phenoloxidase (po) appears to be involved in the formation of melanin and toxic metabolites in the surrounding capsule. a cdna encoding anopheles stephensi prophenoloxidase (ans-propo) was isolated from a cdna library screened with an amplimer produced by reverse transcriptase polymerase chain reaction (rt-pcr) with degenerate primers designed ...200010762420
scorpine, an anti-malaria and anti-bacterial agent purified from scorpion venom.a novel peptide, scorpine, was isolated from the venom of the scorpion pandinus imperator, with anti-bacterial activity and a potent inhibitory effect on the ookinete (ed(50) 0.7 microm) and gamete (ed(50) 10 microm) stages of plasmodium berghei development. it has 75 amino acids, three disulfide bridges with a molecular mass of 8350 da. scorpine has a unique amino acid sequence, similar only to some cecropins in its n-terminal segment and to some defensins in its c-terminal region. its gene was ...200010767415
direct immunization of malaria dna vaccine into the liver by gene gun protects against lethal challenge of plasmodium berghei sporozoite.the liver is the first target organ for malaria parasites immediately after the bite of an infected mosquito. we studied local immunization of malaria dna vaccines at the site of the liver using a gene gun as a useful tool for in vivo transfection of foreign genes. a malaria dna vaccine consisting of the plasmodium berghei circumsporozoite protein (pbcsp) gene plus the mouse il-12 gene was bombarded directly by a gene gun into mouse liver once or into the skin twice. a marked protective effect w ...200010777689
isolation of antigen from the circulating immune complex in mice infected with plasmodium berghei.circulating immune complex (cic) is known to play a role in pathological glomerular alterations in malaria. however, the nature of the antigens comprising the cic is still not fully understood. we report here the isolation of the antigen in cic and its localisation in mice infected with plasmodium berghei nk65. the antigen was successfully isolated from cic extracted from the blood of mice infected with p. berghei, by using c1q-coated microplates. the molecular mass of the antigen separated from ...200010779574
optimisation of flow cytometric measurement of parasitaemia in plasmodium-infected mice.mouse malaria is often used as a model for drug testing. the results of drug trials are monitored by tedious (and consequently, sometimes inaccurate) microscopic counting of blood smears, or by flow cytometry. we suggest an improved, accurate and time-saving flow cytometric method for determination of parasitaemias in mice infected with plasmodium vinckei petteri or plasmodium berghei. the method involves collection of drops of blood from the tail vein, fixation, storage, permeabilisation, stain ...200010779580
synthesis and antimalarial activity of artemisinin derivatives containing an amino group.in search of water-soluble artemisinin derivatives that are more stable than sodium artesunate, over 30 derivatives containing an amino group (compounds 3-5) were synthesized and tested in mice. all products tested (except 5a and 5b) are the beta isomers. these basic compounds combined with organic acids (oxalic acid, maleic acid, etc. ) to yield the corresponding salts. generally, the maleates have better solubility in water than the corresponding oxalates. the aqueous solutions of these salts ...200010780920
cutting edge: the igg response to the circumsporozoite protein is mhc class ii-dependent and cd1d-independent: exploring the role of gpis in nk t cell activation and antimalarial responses.biochemical analysis has suggested that self gpi anchors are the main natural ligand associated with mouse cd1d molecules. a recent study reported that valpha14+ nk t cells responded to self as well as foreign (parasite-derived) gpis in a cd1d-dependent manner. it further reported that the igg response to the plasmodium berghei malarial circumsporozoite (cs) protein was severely impaired in cd1d-deficient mice, leading to a model whereby nk t cells, upon recognition of cd1d molecules presenting ...200010799852
the role of intrahepatic lymphocytes in mediating protective immunity induced by attenuated plasmodium berghei sporozoites.exposure to irradiated plasmodium sporozoites (gamma-spz) results in protection against malaria. like infectious spz, gamma-spz colonize hepatocytes to undergo maturation. disruption of liver stage development prevents the generation of protection, which appears, therefore, to depend on liver stage antigens. although some mechanisms of protection have been identified, they do not include a role for intrahepatic mononuclear cells (ihmc). we demonstrated that p. berghei gamma-spz-immune murine ihm ...200010807512
[time course of serum nuclease activity in mice infected with plasmodium berghei].the present paper shows that murine serum nuclease activity increases following p.berghei infection. dna activity begins increasing just 48 hours after infection. following 78 hours, it achieves the maximum, by exceeding the baseline level by 6 times. then dna activity starts decreasing and following 94 hours after infection it is just thrice higher than the baseline. serum rna activity shows only 30% increases 72 hours after infection and returns to the baseline following 94 hours. microscopic ...200010808713
enumeration of micronucleated reticulocytes in rat peripheral blood: a flow cytometric study.micronuclei (mn) are routinely enumerated in mouse peripheral blood to index genotoxicity. recent data from the collaborative study group for the micronucleus test (csgmt) [csgmt (the collaborative study group for the micronucleus test), evaluation of the rat micronucleus test with bone marrow and peripheral blood: summary of the 9th collaborative study by csgmt/jems mms, environ. mol. mutagen. 32 (1998) 84-100] suggest that rat peripheral blood may also be appropriate for the enumeration of mn, ...200010708974
a search for natural bioactive compounds in bolivia through a multidisciplinary approach. part i. evaluation of the antimalarial activity of plants used by the chacobo indians.thirty extracts of plants traditionally used by the chacobos, a native community living in the amazonian part of bolivia, were screened in vitro and/or in vivo for antimalarial activity. two of the four species designated as antimalarial, geissospermum laeve and maquira coriacea, displayed rather good activity, corroborating their traditional uses. however, they did show a rather high toxicity in vivo. among twelve species used to cure symptoms relevant to malaria, five showed good activity: apu ...200010687869
phenyl beta-methoxyacrylates: a new antimalarial pharmacophore.phenyl beta-methoxyacrylates, linked to an aromatic ring via an olefinic bridge, have been identified as novel, potentially inexpensive, antimalarial agents. the compounds are believed to exert their activity by inhibition of mitochondrial electron transport at the cytochrome bc(1) complex. a series of compounds have been synthesized to define structure-activity relationships affecting antimalarial activity. it was found that the beta-methoxyacrylate was required ortho to the linker and the opti ...200010691682
the selectable marker human dihydrofolate reductase enables sequential genetic manipulation of the plasmodium berghei genome.genetic transformation of malaria parasites has been limited by the number of selectable markers available. for the rodent malaria parasite, plasmodium berghei, only a single selection marker has been at hand, utilising the dihydrofolate reductase-thymidylate synthase gene from either p. berghei or toxoplasma gondii to confer resistance to the anti-malarial drug pyrimethamine. here we report the use of the human dihydrofolate reductase (hdhfr) gene as a new selectable marker, which confers resis ...200010699250
reactive changes of retinal microglia during fatal murine cerebral malaria: effects of dexamethasone and experimental permeabilization of the blood-brain barrier.microglial activation and redistribution toward blood vessels are some of the earliest observable events occurring within the central nervous system (cns) during fatal murine cerebral malaria (fmcm). to investigate stimuli that might modulate microglial reactivity during fmcm we have performed two experimental manipulations and observed microglial responses in retinal whole mounts. first, to determine whether increased blood-brain barrier (bbb) permeability in the absence of the malaria parasite ...200010702421
analysis of a malaria sporozoite protein family required for gliding motility and cell invasion. 200010707054
molecular characterization of five serine protease genes cloned from anopheles gambiae hemolymph.we identified five new serine protease cdnas from the hemolymph of the malaria vector, anopheles gambiae. all five show sequence similarity to genes thought to be involved in vertebrate or invertebrate defense responses. sp14a, sp14d2 and sp22d demonstrate changes in transcript abundance in response to bacteria injections. sp14a and sp14d2, as well as the previously characterized sp14d1, are induced by infection with the malaria parasite, plasmodium berghei. these three proteases, along with sp1 ...200010646969
malaria-infected erythrocytes serve as biological standards to ensure reliable and consistent scoring of micronucleated erythrocytes by flow cytometry.a procedure for optimizing the configuration of flow cytometers for enumerating micronucleated erythrocytes is described. the method is based on the use of a biological model for micronucleated erythrocytes, the malaria parasite plasmodium berghei. p. berghei endows target cells of interest (erythrocytes) with a micronucleus-like dna content. unlike micronuclei, parasitized red blood cells have a homogenous dna content, and can be very prevalent in circulation. these characteristics make malaria ...200010648906
the effect of nitric oxide on the growth of plasmodium falciparum, p. chabaudi and p. berghei in vitro.protective immune mechanisms to the asexual erythrocytic stages of the malaria parasite plasmodium chabaudi as strain include antibody-independent mechanisms. nitric oxide (no) is produced during the infection and indirect evidence suggests that it can contribute to the antiparasitic mechanisms. we examined the effect of an no producer, s-nitroso-acetyl-penicillamine (snap), on the growth and survival in vitro of p. chabaudi as, p. berghei and p. falciparum. growth of the parasites was monitored ...200010652122
covalent binding of polyethylene glycol to the surface of red blood cells as detected and followed up by cell electrophoresis and rheological methods.cyanuric chloride activated polyethylene glycol (peg)-5000 was covalently coupled to murine and human red blood cells (pegylated rbc). our purpose was to camouflage rbc receptors, which is necessary for parasite invasion, a process essential to sustain parasitemia. cell electrophoretic mobility analysis (cem) of pegylated rbc distinguished a new population of cells bearing characteristic cem. pegylation of rbc also modified their rheological properties, which were documented by evaluation of cel ...200010675005
characterization of the merozoite surface protein 4/5 gene of plasmodium berghei and plasmodium yoelii.the genes encoding merozoite surface protein 4/5 (msp4/5) from plasmodium berghei and plasmodium yoelii have been cloned and completely sequenced. comparisons of the predicted protein sequences with those of plasmodium chabaudi msp4/5 and plasmodium falciparum msp4 and msp5 show general structural similarities. all predicted proteins contain hydrophobic signal sequences, potential gpi attachment sequences and a single epidermal growth factor (egf)-like domain at the c-terminus. the amino acid se ...200010613706
the rodent malaria parasite plasmodium berghei does not contain a typical o-type small subunit ribosomal rna gene. 200010613710
[studies on pharmacokinetics of chloroquine in mice infected with chloroquine-resistant strain of plasmodium berghei].to compare the pharmacokinetic differences of chloroquine in normal mice and the mice infected with the n and the rc strains of plasmodium berghei.200012567636
[effect of nippostrongylus brasiliensis induced alterations in t helper cell subsets on plasmodium berghei infection in mice].to observe the anti-p. berghei ability of c57bl/6 mice after infected with nippostrongylus brasiliensis alterations in t helper cell subsets in the course of plasmodium infection, and the effect of the alteration on host's prognoses.200012567637
the schizontocidal activity of daphnetin against malaria parasites in vitro and in vivo.to investigate the in vitro and in vivo schizontocidal activity of daphnetin.200012567659
[role of tnf-alpha and icam-1 in pathogenesis of cerebral malaria].to investigate the role of tnf-alpha and icam-1 in the pathogenesis of cerebral malaria.200012567686
[the synergistic action of guanghuoxiang volatile oil and sodium artesunate against plasmodium berghei and reversal of sa-resistant plasmodium berghei].to study the synergistic action of a combination of guanghuoxiang volatile oil (b) and sodium artesunate (sa) against plasmodium berghei (p. b) and the resistance-reversal activity against sa-resistant p. b (p. b sa-r).200012567719
analysis of immune responses against t- and b-cell epitopes from plasmodium falciparum liver-stage antigen 1 in rodent malaria models and malaria-exposed human subjects in india.liver-stage antigen 1 (lsa-1) is a potential vaccine candidate against preerythrocytic stages of malaria. we report here the immunogenicity of linear synthetic constructs delineated as t(h)-cell determinants from the nonrepeat regions of plasmodium falciparum lsa-1 in murine models and human subjects from areas where malaria is endemic in rajasthan state, india. seven peptide constructs (ls1.1 to ls1.7) corresponding to predicted t-cell sites from both the n- and c-terminal regions and peptide l ...200010603380
[partial sequence of sporogony stage-specific 18s ribosomal dna of plasmodium yoelii and its application for detection of parasites].to determine sequence of sporogony stage-specific (s type) 18s ribosomal rna gene of plasmodium yoelii (p. y) by265 strain, and by using it to detect the malaria parasites within vector mosquito.200112571939
[analysis on karyotypes of anka strain of plasmodium berghei].to analyze the molecular karyotypes of anka strain of plasmodium berghei and demonstrate the size and number of chromosomes.200112571949
[the antimalarial mechanism of artemisinin and its derivatives]. 200112571953
[effect of daphnetin on the exo-erythrocytic stage of rodent malaria].to investigate the activity of daphnetin(dpnt) against the exo-erythrocytic stage of rodent malaria.200112572020
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