Publications
| Title | Abstract | Year(sorted descending) Filter | PMID Filter |
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| von willebrand factor a domain-related protein, a novel microneme protein of the malaria ookinete highly conserved throughout plasmodium parasites. | the mosquito-invasive form of the malarial parasite, the ookinete, develops numerous secretory organelles, called micronemes, in the apical cytoplasm. micronemal proteins are thought to be secreted during midgut invasion and to play a crucial role in attachment and motility of the ookinete. we found a novel ookinete micronemal protein of rodent malarial parasite plasmodium berghei, named p. berghei von willebrand factor a domain-related protein (pbwarp), and report it here as a putative soluble ... | 2001 | 11463467 |
| ctl activation is induced by cross-linking of tcr/mhc-peptide-cd8/p56lck adducts in rafts. | to investigate the role of the coreceptor cd8 and lipid rafts in cytotoxic t lymphocyte (ctl) activation, we used soluble mono-and multimeric h-2kd-peptide complexes and cloned s14 ctl specific for a photoreactive derivative of the plasmodium berghei circumsporozoite (pbcs) peptide 252-260 [pbcs(aba)]. we report that activation of ctl in suspension requires multimeric kd-pbcs(aba) complexes co-engaging tcr and cd8. using tcr ligand photo-cross-linking, we find that monomeric kd-pbcs(aba) complex ... | 2001 | 11465114 |
| flow cytometric enumeration of micronucleated reticulocytes: high transferability among 14 laboratories. | this laboratory previously described a single-laser flow cytometric method, which effectively resolves micronucleated erythrocyte populations in rodent peripheral blood samples. even so, the rarity and variable size of micronuclei make it difficult to configure instrument settings consistently and define analysis regions rationally to enumerate the cell populations of interest. murine erythrocytes from animals infected with the malaria parasite plasmodium berghei contain a high prevalence of ery ... | 2001 | 11473389 |
| antimalarial in-vivo activity of bis(9-amino-6-chloro-2-methoxyacridines). | in the fight against malaria, chemotherapy using bisacridines may represent an alternative method to overcoming chloroquine-resistance. eight bis(9-amino-6-chloro-2-methoxyacridines), in which acridine moieties were linked by polyamines substituted with a side chain, were tested for their in-vivo activity upon mice infected by plasmodium berghei. three of the compounds revealed antimalarial activity but no relationship could be deduced from a comparison of in-vitro and in-vivo activities. n-alky ... | 2001 | 11480542 |
| a search for natural bioactive compounds in bolivia through a multidisciplinary approach. part v. evaluation of the antimalarial activity of plants used by the tacana indians. | one hundred and twenty-five extracts of 122 different plant species traditionally used by the tacana, a native community living in lowland forest at the base of the last foothills of the cordillera oriental of the bolivian andes, were screened for antimalarial activity in vitro on plasmodium falciparum chloroquine resistant (d2) and sensitive strains (f32), and were evaluated in vivo on rodent malaria plasmodium berghei. five ethanolic stembark extracts showed marked activity either in vitro or ... | 2001 | 11483383 |
| p25 and p28 proteins of the malaria ookinete surface have multiple and partially redundant functions. | the ookinete surface proteins (p25 and p28) are proven antimalarial transmission-blocking vaccine targets, yet their biological functions are unknown. by using single (sko) and double gene knock-out (dko) plasmodium berghei parasites, we show that p25 and p28 share multiple functions during ookinete/oocyst development. in the midgut of mosquitoes, the formation of ookinetes lacking both proteins (dko parasites) is significantly inhibited due to decreased protection against lethal factors, includ ... | 2001 | 11483501 |
| role of cd40-cvd40l in mouse severe malaria. | we explored the role of cd40-cd40l (cd154) in the severe malaria elicited by plasmodium berghei anka infection in mice. mortality was >90% by day 8 after infection in +/+ mice, but markedly decreased in cd40-/- or in cd40l-/- mice, as well as in +/+ mice treated with anti-cd40l monoclonal antibody. parasitemia was similar in the different conditions. breakdown of the blood-brain barrier was evident in infected +/+, but not in cd40-/- mice. thrombocytopenia was less severe in cd40-/- mice than in ... | 2001 | 11485931 |
| synthesis and in vitro and in vivo antimalarial activity of new 4-anilinoquinolines. | a new series of 4-anilinoquinolines with two proton-accepting side chains has been synthesized. antimalarial activity and levels of cytotoxicity upon both mrc-5 cells and macrophages were found to be highly dependent upon the features of these side chains. several compounds were found to be active in the low nanomolar range, against both chloroquine-sensitive and -resistant strains of plasmodium falciparum in vitro. from among them, a morpholino derivative cured mice infected by plasmodium bergh ... | 2001 | 11495593 |
| superoxide-dependent and -independent pathways are involved in the transmission blocking of malaria. | superoxide plays a crucial role in innate immunity to various pathogens. we examined the role of superoxides in the transmission of malaria using gp91phox knockout (x-cgd) mice that lack the ability to produce superoxide. mosquitoes that fed on x-cgd mice infected intraperitoneally with plasmodium berghei nk65 anka formed more oocysts than did those that fed on control mice at any day after infection. the number of oocysts peaked on day 5 post-infection in x-cgd and control mice and then decreas ... | 2001 | 11510994 |
| "one-pot" synthesis and antimalarial activity of formamidine derivatives of 4-anilinoquinoline. | amodiaquine (aq) is an antimalarial which is effective against chloroquino-resistant strains of plasmodium falciparum but whose clinical use is severely restricted because of associated hepatotoxicity and agranulocytosis. "one-pot" synthesis of formamidines likely to be transformed into aq derivatives is reported. compared with aq, the new compounds were devoid of in vitro cytotoxicity upon human embryonic lung cells and mouse peritoneal macrophages. one showed a potent in vivo activity in mice ... | 2001 | 11515580 |
| the role of cerebral oedema in the pathogenesis of cerebral malaria. | it has been suggested that sequestration of parasitized red blood cells might contribute to the pathogenesis of cerebral malaria (cm), by hypoxia causing either: (i) compensatory vasodilatation with a resultant increase in the brain volume; or (ii) enhancing cytokine-induced nitric oxide (no) production via induction of inducible no synthase (inos). available evidence suggests that cerebral oedema is the initiating and probably the most important factor in the pathogenesis of murine cm. the rele ... | 2001 | 11523587 |
| phagocyte-derived reactive oxygen species and the immunology and pathology of murine malaria. | 2001 | 11523600 | |
| synthesis of quinolinyl chalcones and evaluation of their antimalarial activity. | quinolinyl chalcones were synthesized and evaluated for their inhibition of the plasmodium falciparum cystein protease falcipain and their activity against cultured p. falciparum parasites. they were also tested for in vivo efficacy in a rodent p. berghei model. their activity against falcipain and as antimalarials was moderate, but antimalarial activity was probably not due to the inhibition of falcipain and may follow a different mechanism. 1-(2,4-dichlorophenyl)-3-[3-(2-chloro-6,7-dimethoxiqu ... | 2001 | 11525846 |
| antimalarial t-butylperoxyamines. | twelve t-butylperoxyamines (6-17) were synthesized as targeted antimalarials and evaluated for antimalarial activity in vivo against plasmodium berghei in mice and in vitro against both chloroquine sensitive and chloroquine resistant strains of plasmodium falciparum. compound 8 was found to have highest potency with activity at 80 and 160mg/kg dose in vivo and compound 11 exhibited highest efficacy in vitro. | 2001 | 11527712 |
| antimalarial simplified 3-aryltrioxanes: synthesis and preclinical efficacy/toxicity testing in rodents. | a streamlined five-step chemical synthesis of rationally designed, simplified 3-aryltrioxane 8a is described. a noteworthy feature of this synthetic scheme is use of air rather than expensive molecular oxygen as the source of the pharmacologically critical peroxide unit in trioxane 8a. this simplified acetal trioxane carboxylic acid 8a is thermally stable, and it is hydrolytically stable in water even at 40 degrees c and ph 7.4 for at least 7 days. preclinical evaluation of this water-soluble sy ... | 2001 | 11543673 |
| synthesis and evaluation of cryptolepine analogues for their potential as new antimalarial agents. | the indoloquinoline alkaloid cryptolepine 1 has potent in vitro antiplasmodial activity, but it is also a dna intercalator with cytotoxic properties. we have shown that the antiplasmodial mechanism of 1 is likely to be due, at least in part, to a chloroquine-like action that does not depend on intercalation into dna. a number of substituted analogues of 1 have been prepared that have potent activities against both chloroquine-sensitive and chloroquine-resistant strains of plasmodium falciparum a ... | 2001 | 11543688 |
| is ischemia involved in the pathogenesis of murine cerebral malaria? | sequestration of parasitized erythrocytes in the central nervous system microcirculation and increased cerebrospinal fluid lactate are prominent features of cerebral malaria (cm), suggesting that sequestration causes mechanical obstruction and ischemia. to examine the potential role of ischemia in the pathogenesis of cm, plasmodium berghei anka (pba) infection in cba mice was compared to infection with p. berghei k173 (pbk) which does not cause cm (the non-cm model, ncm). cerebral metabolite poo ... | 2001 | 11549603 |
| protection of mice from malaria after co-administration of recombinant mouse granulocyte-macrophage colony- stimulating factor and methionine-enkephalin. | the protective effect of co-administration of recombinant mouse granulocyte-macrophage colony-stimulating factor (rmgm-csf) and synthetic peptide met-enkephalin (m-enk) against blood-induced plasmodium berghei infection in swiss mice was investigated. mice co-administered with rmgm-csf (10.0 mug/kg) and m-enk (2.0 mg/kg) x 3/day, i.p., beginning on day -1 and continuing through day +4 after the initiation of infection, showed significant suppression (p < 0.05) (sometimes even complete eliminatio ... | 2001 | 11566634 |
| immune-mediated parasite clearance in mice infected with plasmodium berghei following treatment with manzamine a. | manzamine a, a sponge-derived alkaloid, was recently shown to possess in vivo antimalarial activity against the blood stages of the rodent malaria parasite plasmodium berghei. a single intraperitoneal dose of 100 micromol/kg of manzamine a suppressed parasite growth but was followed by parasite recrudescence. forty percent of mice with recrudescing parasites were able to recover and clear the fulminating parasitaemia. examination of sera from these mice revealed that infected mice treated with m ... | 2001 | 11570556 |
| characterization and identification of exflagellation-inducing factor in the salivary gland of anopheles stephensi (diptera: culicidae). | gamete activation factor (gaf) induces exflagellation of plasmodium microgametes. we found gaf in the salivary glands of female mosquitoes, anopheles stephensi. the exflagellation was induced in a concentration-dependent manner in the supernatant of salivary gland's crude homogenate. the exflagellation-inducing activity in the salivary gland was higher than that in the midgut and the head. gaf in the salivary glands was found to be heat stable and low molecular weight (<3000 molecular weight). a ... | 2001 | 11573943 |
| pathogenesis of cerebral malaria: recent experimental data and possible applications for humans. | malaria still is a major public health problem, partly because the pathogenesis of its major complication, cerebral malaria, remains incompletely understood. experimental models represent useful tools to better understand the mechanisms of this syndrome. here, data generated by several models are reviewed both in vivo and in vitro; we propose that some pathogenic mechanisms, drawn from data obtained from experiments in a mouse model, may be instrumental in humans. in particular, tumor necrosis f ... | 2001 | 11585786 |
| nitric oxide and reactive nitrogen intermediates during lethal and nonlethal strains of murine malaria. | the virulence of plasmodia depends partly on the strain of parasite and partly on the host. in this study, plasmodium berghei n/13/1a/4/203 caused the death of mice, whereas plasmodium chabaudi chabaudi as was not lethal. current opinion is that nitric oxide (no) and other reactive nitrogen intermediates (rni) are produced in several host organs during malaria to resist infection or produce tissue damage. no and rni production in blood or plasma, brain, liver and spleen in mf1 mice was investiga ... | 2001 | 11589778 |
| potent antimalarial activities of polyether antibiotic, x-206. | in the course of our screening program to discover antimalarial antibiotics, which are active against drug resistant plasmodium falciparum in vitro and rodents infected with p. berghei in vivo, from the culture broth of microorganisms, we found a selective and potent active substance produced by an actinomycete strain k99-0413. it was identified as a known polyether antibiotic, x-206. we also compared the in vitro antimalarial activities and cytotoxicities of 12 known polyethers with x-206. amon ... | 2001 | 11592502 |
| gambicin: a novel immune responsive antimicrobial peptide from the malaria vector anopheles gambiae. | a novel mosquito antimicrobial peptide, gambicin, and the corresponding gene were isolated in parallel through differential display-pcr, an expressed sequence tag (est) project, and characterization of an antimicrobial activity in a mosquito cell line by reverse-phase chromatography. the 616-bp gambicin orf encodes an 81-residue protein that is processed and secreted as a 61-aa mature peptide containing eight cysteines engaged in four disulfide bridges. gambicin lacks sequence homology with othe ... | 2001 | 11606751 |
| targeting plasmodium ligands on mosquito salivary glands and midgut with a phage display peptide library. | despite vast efforts and expenditures in the past few decades, malaria continues to kill millions of persons every year, and new approaches for disease control are urgently needed. to complete its life cycle in the mosquito, plasmodium, the causative agent of malaria, has to traverse the epithelia of the midgut and salivary glands. although strong circumstantial evidence indicates that parasite interactions with the two organs are specific, hardly any information is available about the interacti ... | 2001 | 11687659 |
| phenoxypropoxybiguanides, prodrugs of dhfr-inhibiting diaminotriazine antimalarials. | a total of 34 analogues of the biguanide ps-15 (5s), a prodrug of the diaminotriazine wr-99210 (8s), have been prepared. several of them, such as 5b (ps-33) and 5m (ps-26), maintain or exceed the in vivo activity of ps-15 while not requiring the use of highly regulated starting materials. the putative diaminotriazine metabolites of these new analogues (compounds 8) have also been prepared and shown to maintain the activity against resistant p. falciparum strains. the structure-activity relations ... | 2001 | 11689078 |
| enhanced immunostimulant activity and protective effect of a synthetic lipopeptide after liposomization against plasmodium berghei infection in mice. | the immunostimulant activity of non-pyrogenic, sugar-free immunomodulator lipopeptide, ala-d-glu(gly-lys-co.c11h23)-nh2 (comp. no 84/201), and its liposomized formulation has been studied. liposomization of this lipopeptide significantly enhanced its antigen specific as well as nonspecific immune responses, as compared to the free lipopeptide. the liposomized formulation of lipopeptide significantly stimulated both the antibody and delayed-type hypersensitivity responses in balb/c mice, and also ... | 2001 | 11697027 |
| plasmodium berghei infection in mice induces liver injury by an il-12- and toll-like receptor/myeloid differentiation factor 88-dependent mechanism. | malaria, caused by infection with plasmodium spp., is a life cycle-specific disease that includes liver injury at the erythrocyte stage of the parasite. in this study, we have investigated the mechanisms underlying plasmodium berghei-induced liver injury, which is characterized by the presence of apoptotic and necrotic hepatocytes and dense infiltration of lymphocytes. although both il-12 and il-18 serum levels were elevated after infection, il-12-deficient, but not il-18-deficient, mice were re ... | 2001 | 11698470 |
| the gametocyte-activating factor xanthurenic acid stimulates an increase in membrane-associated guanylyl cyclase activity in the human malaria parasite plasmodium falciparum. | sex is an obligate step in the life cycle of the malaria parasite and occurs in the midgut of the mosquito vector. with both plasmodium falciparum and plasmodium berghei, the tryptophan metabolite xanthurenic acid induces the release of motile male gametes from red blood cells (exflagellation), a prerequisite for fertilization. the addition of cgmp or phosphodiesterase inhibitors to cultures of mature gametocytes has also been shown to stimulate exflagellation. here, we demonstrate that there is ... | 2001 | 11703675 |
| cd8(+)-t-cell depletion ameliorates circulatory shock in plasmodium berghei-infected mice. | the plasmodium berghei-infected mouse model is a well-recognized model for human cerebral malaria. mice infected with p. berghei exhibit (i) metabolic acidosis (ph < 7.3) associated with elevated plasma lactate concentrations, (ii) significant (p < 0.05) vascular leakage in their lungs, hearts, kidneys, and brains, (ii) significantly (p < 0.05) higher cell and serum glutamate concentrations, and (iv) significantly (p < 0.05) lower mean arterial blood pressures. because these complications are si ... | 2001 | 11705906 |
| a prodrug form of a plasmodium falciparum glutathione reductase inhibitor conjugated with a 4-anilinoquinoline. | glutathione (gsh), which is known to guard plasmodium falciparum from oxidative damage, may have an additional protective role by promoting heme catabolism. an elevation of gsh content in parasites leads to increased resistance to chloroquine (cq), while gsh depletion in resistant p. falciparum strains is expected to restore the sensitivity to cq. high intracellular gsh levels depend inter alia on the efficient reduction of gssg by glutathione reductase (gr). on the basis of this hypothesis, we ... | 2001 | 11708927 |
| cd8beta endows cd8 with efficient coreceptor function by coupling t cell receptor/cd3 to raft-associated cd8/p56(lck) complexes. | the extraordinary sensitivity of cd8+ t cells to recognize antigen impinges to a large extent on the coreceptor cd8. while several studies have shown that the cd8beta chain endows cd8 with efficient coreceptor function, the molecular basis for this is enigmatic. here we report that cell-associated cd8alphabeta, but not cd8alphaalpha or soluble cd8alphabeta, substantially increases the avidity of t cell receptor (tcr)-ligand binding. to elucidate how the cytoplasmic and transmembrane portions of ... | 2001 | 11714755 |
| isolation and biological evaluation of filiformin, plakortide f, and plakortone g from the caribbean sponge plakortis sp. | the bioassay- and spectroscopic-guided fractionation of the antimalarial extract from a jamaican sponge, plakortis sp., resulted in the isolation of three metabolites. the previously reported bromoaromatic filiformin (1) was obtained from our sample of plakortis sp., and the potential origins of this compound are discussed. the peroxide-containing metabolite, plakortide f (2), is a more typical plakortis metabolite and was shown to exhibit significant activity against plasmodium falciparum in vi ... | 2001 | 11720540 |
| virus-like particles as vaccine adjuvants. | virus-like particles (vlps) consist of one or more viral coat proteins that assemble into particles. they can be taken up by antigen presenting cells (apc), peptides derived from them are presented on mhc class i molecules at the cell surface, and thereby prime a cd8+ t cell response, either against the particle-forming protein itself (such as hepatitis b surface antigen) or additional peptide sequences that are produced as fusions with the particle-forming protein. this article describes the pr ... | 2001 | 11725486 |
| antimalarial alkoxylated and hydroxylated chalcones [corrected]: structure-activity relationship analysis. | chalcones with 2',3',4'-trimethoxy, 2',4'-dimethoxy, 4'-methoxy, 4'-ethoxy, 2',4'-dihydroxy, and 4'-hydroxy groups on ring b were synthesized and evaluated in vitro against plasmodium falciparum (k1) in a [3h] hypoxanthine uptake assay. the other ring a was quinoline, pyridine, naphthalene, or phenyl rings with electron-donating or electron-withdrawing substituents of varying lipophilicities. trimethoxy 6 and 27, dimethoxy 7, 8, 29, and methoxy 31 analogues had good in vitro activities (ic(50) < ... | 2001 | 11728189 |
| comparative genomics in plasmodium: a tool for the identification of genes and functional analysis. | comparative genomics allows inferences to be drawn about the coding potential of related genomes, and the evolutionary forces that have influenced genome organisation. early comparisons have indicated that there is significant synteny (conserved physical association of genes) between the human parasite plasmodium falciparum and the malaria parasites of rodents, such as plasmodium berghei. the various plasmodium genome initiatives have now provided the opportunity to perform comparative genomics ... | 2001 | 11738705 |
| profiling the malaria genome: a gene survey of three species of malaria parasite with comparison to other apicomplexan species. | we have undertaken the first comparative pilot gene discovery analysis of approximately 25,000 random genomic and expressed sequence tags (ests) from three species of plasmodium, the infectious agent that causes malaria. a total of 5482 genome survey sequences (gsss) and 5582 ests were generated from mung bean nuclease (mbn) and cdna libraries, respectively, of the anka line of the rodent malaria parasite plasmodium berghei, and 10,874 gsss generated from mbn libraries of the salvador i and bele ... | 2001 | 11738710 |
| effects of dna vaccine in murine malaria using a full-length cdna library. | in an attempt to develop a novel malaria vaccine, we constructed a full-length cdna library from the erythrocytic-stage parasites of plasmodium berghei anka strain using the plasmid vector pce-fl, which is driven by an ef321 promoter and a cmv-ie enhancer. here we report the initial trial to screen this library for dna vaccine candidates against malaria parasite infection in mice. the library of p. berghei was divided into five groups, each representing 2,000 independent clones. eight female bal ... | 2001 | 11758646 |
| incidence of apoptosis in the lymphoid organs of normal or malaria infected mice is decreased in cd18 and urokinase-receptor (upar, cd87) deficient mice. | incidence of apoptosis was investigated in the spleen and lymph nodes of +/+, cd18 -/- and urokinase receptor (upar, cd87) -/- mice, untreated or plasmodium berghei anka (pba) infected. in non infected mice, incidence of apoptosis was lower in the lymph nodes of cd18 -/- and upar -/- than in +/+ mice, as seen by facs analysis to count the number of hypodiploid and annexin-v binding cells. infection of mice with pba resulted in a marked increase in the size of spleen and lymph nodes 7-8 days afte ... | 2001 | 11785668 |
| effect of solanum nudum extracts on the liver of mice infected with plasmodium berghei. | the plant solanum nudum has been used by the community of tumaco (nariño, colombia) as a cure for malaria. our group has confirmed the in vitro antimalarial activity against the strain of plasmodium falciparum fcb-2. during our in vivo studies on the therapeutic effect of solanum nudum extracts on mice infected with plasmodium berghei, we observed yellowish tint in the palms of mice treated with the aqueous extract via i.p. at a concentration of 2.4% w/vol. this finding suggested the need to car ... | 2001 | 11789590 |
| multiple display of peptides and proteins on a macromolecular scaffold derived from a multienzyme complex. | the acyltransferase components (e2) from the family of 2-oxo acid dehydrogenase multienzyme complexes form large protein scaffolds, to which multiple copies of peripheral enzymes bind tightly but non-covalently. sixty copies of the e2 polypeptide from the pyruvate dehydrogenase multienzyme complex of bacillus stearothermophilus assemble to form a pentagonal dodecahedral scaffold with icosahedral symmetry. this protein scaffold can be modified to present foreign peptides and proteins on its surfa ... | 2001 | 11124904 |
| synthesis, antimalarial activity, biomimetic iron(ii) chemistry, and in vivo metabolism of novel, potent c-10-phenoxy derivatives of dihydroartemisinin. | the combination of tmsotf and agclo(4) promotes the efficient c-10-phenoxylation of dihydroartemisinin (3) in good chemical yield and excellent stereoselectivity. all of the new phenoxy derivatives have potent in vitro antimalarial activity. on the basis of the excellent yield and stereoselectivity obtained for the p-trifluoromethyl derivative 7b, this compound and the parent phenyl-substituted derivative 5b were selected for in vivo biological evaluation against plasmodium berghei in the mouse ... | 2001 | 11141088 |
| low-complexity regions in plasmodium falciparum proteins. | full-sequence data available for plasmodium falciparum chromosomes 2 and 3 are exploited to perform a statistical analysis of the long tracts of biased amino acid composition that characterize the vast majority of p. falciparum proteins and to make a comparison with similarly defined tracts from other simple eukaryotes. when the relatively minor subset of prevalently hydrophobic segments is discarded from the set of low-complexity segments identified by current segmentation methods in p. falcipa ... | 2001 | 11157785 |
| a central role for p48/45 in malaria parasite male gamete fertility. | fertilization and zygote development are obligate features of the malaria parasite life cycle and occur during parasite transmission to mosquitoes. the surface protein pfs48/45 is expressed by male and female gametes of plasmodium falciparum and pfs48/45 antibodies prevent zygote development and transmission. here, gene disruption was used to show that pfs48/45 and the ortholog pbs48/45 from a rodent malaria parasite p. berghei play a conserved and important role in fertilization. p48/45- parasi ... | 2001 | 11163248 |
| identification of the class xiv myosins pb-myoa and py-myoa and expression in plasmodium sporozoites. | 2001 | 11166399 | |
| triclosan offers protection against blood stages of malaria by inhibiting enoyl-acp reductase of plasmodium falciparum. | the antimicrobial biocide triclosan [5-chloro-2-(2,4-dichlorophenoxy)phenol] potently inhibits the growth of plasmodium falciparum in vitro and, in a mouse model, plasmodium berghei in vivo. inhibition of [14c]acetate and [14c]malonyl-coa incorporation into fatty acids in vivo and in vitro, respectively, by triclosan implicate fabi as its target. here we demonstrate that the enoyl-acp reductase purified from p. falciparum is triclosan sensitive. also, we present the evidence for the existence of ... | 2001 | 11175846 |
| in-vivo antimalarial activity of cassia occidentalis, morinda morindoides and phyllanthus niruri. | the ethanolic, dichloromethane and lyophilized aqueous extracts of cassia occidentalis root bark, morinda morindoides leaves and whole plants of phyllanthus niruri were evaluated for their antimalarial actvity in vivo, in 4-day, suppressive assays against plasmodium berghei anka in mice. no toxic effect or mortality was observed in mice treated, orally, with any of the extracts as a single dose, of 500 mg/kg body weight, or as the same dose given twice weekly for 4 weeks (to give a total dose of ... | 2001 | 11235553 |
| removal of the circumsporozoite protein (csp) glycosylphosphatidylinositol signal sequence from a csp dna vaccine enhances induction of csp-specific th2 type immune responses and improvesprotection against malaria infection. | the c terminus of the circumsporozoite protein (csp) is anchored to the parasite cell membrane by a glycosylphosphatidylinositol (gpi) glycolipid. this gpi signal sequence functions poorly in heterologous eukaryotic cells, causing csp retention within internal cell organelles during genetic immunization. cellular location of antigen has quantitative and qualitative effects on immune responses induced by genetic immunization. removal of the gpi signal sequence had a profound effect on induction a ... | 2001 | 11241272 |
| antibody recognition of rodent malaria parasite antigens exposed at the infected erythrocyte surface: specificity of immunity generated in hyperimmune mice. | in regions where malaria is endemic, inhabitants remain susceptible to repeated reinfection as they develop and maintain clinical immunity. this immunity includes responses to surface-exposed antigens on plasmodium sp.-infected erythrocytes. some of these parasite-encoded antigens may be diverse and phenotypically variable, and the ability to respond to this diversity and variability is an important component of acquired immunity. characterizing the relative specificities of antibody responses d ... | 2001 | 11254617 |
| bacteria expressing single-chain immunotoxin inhibit malaria parasite development in mosquitoes. | single-chain immunotoxins are ideal tools to selectively kill infectious agents. in applying this technology to block transmission of malaria parasites in the mosquito vector, we have constructed a single-chain immunotoxin composed of a single-chain antibody fragment (scfv) directed to pbs2l on the surface of plasmodium berghei ookinetes linked to a lytic peptide, shiva-1. the single-chain immunotoxin was expressed in escherichia coli, and the protein was purified by a ni-nta column. the single- ... | 2001 | 11254957 |
| complementation of plasmodium berghei trap knockout parasites using human dihydrofolate reductase gene as a selectable marker. | previously we have used the plasmodium dihydrofolate reductase thymidylate synthase (dhfr-ts) selectable marker to generate plasmodium berghei trap null mutant parasites. these trap null mutants do not glide and they showed a great reduction in their ability to infect mosquito salivary glands and the hepatocytes of the vertebrate host. thus far, complementation of these knockout parasites was not possible due to the lack of additional selectable markers. recently, a new selectable marker, based ... | 2001 | 11254963 |
| assessing vascular permeability during experimental cerebral malaria by a radiolabeled monoclonal antibody technique. | vascular endothelial integrity, assessed by evans blue dye extrusion and radiolabeled monoclonal antibody leakage, was markedly compromised in the brain, lung, kidney, and heart during plasmodium berghei infection, a well-recognized model for human cerebral malaria. the results for vascular permeability from both methods were significantly (p < 0.001) related. | 2001 | 11292776 |
| functional equivalence of structurally distinct ribosomes in the malaria parasite, plasmodium berghei. | unlike most eukaryotes, many apicomplexan parasites contain only a few unlinked copies of ribosomal rna (rrna) genes. based on stage-specific expression of these genes and structural differences among the rrna molecules it has been suggested that plasmodium spp. produce functionally different ribosomes in different developmental stages. this hypothesis was investigated through comparison of the structure of the large subunit rrna molecules of the rodent malaria parasite, plasmodium berghei, and ... | 2001 | 11292830 |
| in vitro and in vivo antimalarial activity of ferrochloroquine, a ferrocenyl analogue of chloroquine against chloroquine-resistant malaria parasites. | previous studies have shown that ferrochloroquine (fq) exhibited an antimalarial activity against plasmodium spp. the present work confirmed this activity, described the curative effect on p. vinckei and investigated the fq toxicity in vitro and in vivo. the in vitro and in vivo growth inhibition of p. falciparum and p. berghei n, respectively, showed that fq antimalarial activity was 1.5-10 times more potent than chloroquine. fq completely inhibited the in vivo development of both chloroquine-s ... | 2001 | 11293573 |
| gene targeting in the rodent malaria parasite plasmodium yoelii. | it is anticipated that the sequencing of plasmodium falciparum genome will soon be completed. rodent models of malaria infection and stable transformation systems provide powerful means of using this information to study gene function in vivo. to date, gene targeting has only been developed for one rodent malaria species, plasmodium berghei. another rodent species, plasmodium yoelii, however, is favored to study the mechanisms of protective immunity to the pre-erythrocytic stages of infection an ... | 2001 | 11295181 |
| aldolase genes of plasmodium species. | 2001 | 11295188 | |
| cd1d-restricted nk t cells are dispensable for specific antibody responses and protective immunity against liver stage malaria infection in mice. | immunization with a single dose of irradiated sporozoites is sufficient to induce protection against malaria in wild-type mice. although this protection is classically attributed to conventional cd4+ and cd8+ t cells, several recent reports have suggested an important role for cd1-restricted nk t cells in immunity to malaria. in this study, we directly compared the ability of c57bl/6 wild-type and cd1-deficient mice to mount a protective immune response against plasmodium berghei sporozoites. ou ... | 2001 | 11309137 |
| of mice and malaria mutants: unravelling the genetics of drug resistance using rodent malaria models. | it is well recognized that drug resistance is the most significant obstacle to gaining effective malaria control. despite the enormous advances in the knowledge of the biochemistry and molecular biology of malaria parasites, only a few genes determining resistance to the commonly used drugs have been identified. the idea that rodent malaria parasites should be exploited more widely for such work, in view of the practical problems of studying this subject experimentally in human malaria, is prese ... | 2001 | 11323308 |
| glucose-6-phosphate dehydrogenase-6-phosphogluconolactonase. a novel bifunctional enzyme in malaria parasites. | plasmodium falciparum glucose 6-phosphate dehydrogenase (pf glc6pd), compared to other glc6pds has an additional 300 amino acids at the n-terminus. they are not related to glc6pd but are similar to a family of proteins (devb) of unknown function, some of which are encoded next to glc6pd in certain bacteria. the human devb homologue has recently been shown to have 6-phosphogluconolactonase (6pgl) activity. this suggests pf glc6pd may be a bifunctional enzyme, the evolution of which has involved t ... | 2001 | 11277923 |
| biomagnetic separation of contaminating host leukocytes from plasmodium-infected erythrocytes. | carlton, j. m-r., yowell, c. a., sturrock, k. a., and dame, j. b. 2001. biomagnetic separation of contaminating host leukocytes from plasmodium-infected erythrocytes. experimental parasitology 97, 111-114. | 2001 | 11281708 |
| protective cd8+ t cell responses against the pre-erythrocytic stages of malaria parasites: an overview. | cd8+ t cells have been implicated as critical effector cells in protection against the pre-erythrocytic stage of malaria in mice and humans following irradiated sporozoite immunization. immunization experiments in animal models by several investigators have suggested different strategies for vaccination against malaria and many of the targets from liver stage malaria antigens have been shown to be immunogenic and to protect mice from the sporozoite challenge. several prime/boost protocols with r ... | 2001 | 11285500 |
| anopheles gambiae laminin interacts with the p25 surface protein of plasmodium berghei ookinetes. | laminin is a major constituent of the basal lamina surrounding the midgut of the malaria vectors that has been implicated in the development of the plasmodium oocyst. in this report we describe the cloning of the anopheles gambiae gene encoding the laminin gamma 1 polypeptide and follow its expression during mosquito development. to further investigate the putative role of laminin in the transmission of the malaria parasite we studied the potential binding of the p25 surface protein of plasmodiu ... | 2001 | 11223130 |
| the plasmodium falciparum knob-associated pfemp3 antigen is also expressed at pre-erythrocytic stages and induces antibodies which inhibit sporozoite invasion. | the expression of the pfemp3 gene and the corresponding pfemp3 knob-associated protein in the pre-erythrocytic stages of plasmodium falciparum was demonstrated by rt-pcr, western blots, ifat and iem. the antigen was found on the surface of the sporozoite and in the cytoplasm of mature hepatic stage parasites. immunological cross-reactivity was observed with sporozoites from the rodent malaria parasites plasmodium yoelii yoelii and plasmodium berghei and was exploited to assess a potential role o ... | 2001 | 11223132 |
| a critical role of fc receptor-mediated antibody-dependent phagocytosis in the host resistance to blood-stage plasmodium berghei xat infection. | plasmodium berghei xat is an irradiation-induced attenuated variant derived from the lethal strain p. berghei nk65, and its blood-stage parasites are spontaneously cleared in immune competent mice. in the present study, we studied the mechanism of host resistance to blood-stage malaria infection using p. berghei xat. infection enhanced ab-dependent phagocytosis of prbc by splenic macrophages in wild-type c57bl/6 mice. in contrast, fcr gamma-chain knockout (fcrgamma(-/-)) mice, which lack the abi ... | 2001 | 11342646 |
| malaria sporozoites actively enter and pass through rat kupffer cells prior to hepatocyte invasion. | malaria sporozoites have to cross the layer of sinusoidal liver cells to reach their initial site of multiplication in the mammalian host, the hepatocytes. to determine the sinusoidal cell type sporozoites use for extravasation, endothelia or kupffer cells, we quantified sporozoite adhesion to and invasion of sinusoidal cells isolated from rat liver. in vitro invasion assays reveal that plasmodium berghei and p. yoelii sporozoites attach to and enter kupffer cells, but not sinusoidal endothelia. ... | 2001 | 11343244 |
| haptoglobin and malaria. | haptoglobin gene knockout mice and wild-type controls were infected with plasmodium berghei anka or plasmodium chabaudi. the peak parasitaemia and parasite burden were higher in hp-/- mice than in hp+/+ mice. the increase in spleen weight following malaria infection was smaller in hp-/- mice than in hp+/+ animals. the occurrence of cerebral malaria in p. berghei anka infection was not different in hp gene knockout mice and their controls. | 2001 | 11865983 |
| [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. | 2001 | 12571939 |
| [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. | 2001 | 12571949 |
| [the antimalarial mechanism of artemisinin and its derivatives]. | 2001 | 12571953 | |
| [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. | 2001 | 12572020 |
| rodent malaria in the natural host--irradiated sporozoites of plasmodium berghei induce liver-stage specific immune responses in the natural host grammomys surdaster and protect immunized grammomys against p. berghei sporozoite challenge. | the choice of the host in studying host-parasite interactions is of crucial importance, and the use of a natural host is most appropriate in answering pertinent questions related to human malaria. the grammomys surdaster is the natural host and reservoir of the rodent malaria parasite plasmodium berghei. this natural host is difficult to protect by irradiated sporozoite immunization, a situation comparable to what has been observed in humans with p. falciparum. this is in contrast to the complet ... | 2001 | 14513935 |
| [cytoadherence in cerebral malaria as particular example of pathology in host--parasite system]. | cerebral malaria in man and in animals is the consequence of a cascade of events, involving the patological changes, leading to the amplification of the expression of the receptors for cytoadherence on brain capillary endothelial cells. sequestration is the process by which erytrocytes infected with the mature forms of the malaria parasite plasmodium falciparum disappear from circulation and accumulate within venules and capillaries of various organs and tissues. the molecular mechanism in seque ... | 2001 | 16886392 |
| [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. | 2000 | 12567636 |
| [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. | 2000 | 12567637 |
| 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. | 2000 | 12567659 |
| [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. | 2000 | 12567686 |
| [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). | 2000 | 12567719 |
| inhibition of the malaria parasite by experimental co-infection of mice by west nile virus and plasmodium berghei. | 2000 | 11344791 | |
| 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 ... | 2000 | 11227768 |
| 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 ... | 2000 | 11289666 |
| 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. | 2000 | 11324422 |
| 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 ... | 2000 | 11198398 |
| myosin a expressions in sporogonic stages of plasmodium. | 2000 | 11163454 | |
| plasmodium yoelii: efficient in vitro invasion and complete development of sporozoites in mouse hepatic cell lines. | 2000 | 11162379 | |
| 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. ... | 2000 | 11128475 |
| 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, ... | 2000 | 10708974 |
| 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 ... | 2000 | 10817722 |
| 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 ... | 2000 | 10824091 |
| 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 ... | 2000 | 10831392 |
| plasmodium berghei: the antimalarial activity of albendazole in rats is mediated via effects on the hematopoietic system. | 2000 | 10831394 | |
| 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 ... | 2000 | 10856511 |
| 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 ... | 2000 | 10858190 |
| 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 ... | 2000 | 10864512 |
| 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 ... | 2000 | 10873482 |
| 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 ... | 2000 | 10874717 |
| 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 ... | 2000 | 10880833 |
| 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 ... | 2000 | 10886717 |
| 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 ... | 2000 | 10893313 |
| 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 ... | 2000 | 10898501 |
| 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 ... | 2000 | 10900007 |