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effect of fatty acid treatment in cerebral malaria-susceptible and nonsusceptible strains of mice.cerebral malaria-susceptible (c57bl/6) mice infected with plasmodium berghei anka (pba) developed low parasitemia and died from typical neurological symptoms between 8 to 10 days after infection. in contrast, nonsusceptible (balb/c) mice developed high peripheral blood parasitemia and died 22-24 days later without neurological implications. daily injections of fatty acids (fa) during the first 3 days after infection protected c57bl/6 mice from cerebral symptoms but had no effect on balb/c mice. ...19958544078
syntheses and antimalarial activities of n-substituted 11-azaartemisinins.a two-step reaction sequence between artemisinin and methanolic ammonia followed by treatment with amberlyst 15 yielded 11-azaartemisinin in 65% yield. substituting a variety of primary alkyl- and heteroaromatic amines for ammonia in the reaction sequence yields n-substituted 11-azaartemisinins in similar or greater yield. when amberlyst 15 is replaced by a mixture of sulfuric acid/silica gel, both 11-azaartemisinin and the expected metabolite, 10-azadesoxyartemisinin, are formed in 45% and 15% ...19958544181
susceptibility to plasmodium berghei infection in rats is modulated by the acute phase response.brown norway (bn) and sprague dawley (sd) rats are known to differ in their susceptibility to infection with sporozoites of plasmodium berghei, as measured by the density of liver schizonts. because of the known inhibitory effect of non-specific immunomodulators on schizont development, we compared some aspects of the acute phase response in these two rat strains. lps induced il-6 production was measured in supernatants of spleen cells and peritoneal macrophages of both strains. sd rats, which a ...19958552412
effects of artesunate on immune function in mice.to study the effects of artesunate (dihydroartemisinine-12-alpha-succinate, art) on immune function in mice.19958701764
antimalarial properties of soy-bean fat emulsions.intralipid and ivelip are commercial preparations of soy-bean lipid extracts used for intravenous supplementation of lipids in various clinical conditions. they were found to inhibit the growth of plasmodium falciparum in culture with an ic50 of 8.07 +/- 2.13 and 13.32 +/- 2.05 mg.ml-1, respectively. intralipid rapidly and efficiently inhibited nucleic acid synthesis in cultured p. falciparum, exhibiting full inhibitory activity in less than 2 h. ivelip injected intraperitoneally, was found by t ...19958719958
[erythrocyte immunity and regulating factors in mice infected with plasmodium berghei anka strain].after seventy-two icr mice were inoculated with plasmodium berghei anka strain, parasitaemia was revealed in all animals inoculated in two to seven days. during the course the number of malaria parasites increased rapidly from 2.3 +/- 1.3 x 10(3) on d2 to 93.7 +/- 1.8 x 10(3) on d7, the number of erythrocytes increased from 8.2 +/- 0.9 x 10(12)/l on d0 to 11.1 +/- 1.0 x 10(12)/l on d2 and then decreased gradually, reaching 1.9 +/- 0.4 x 10(12)/l on d7, and the number of white blood cells appeare ...19958732077
heme oxygenase and related indices in chloroquine-resistant and -sensitive strains of plasmodium berghei.chloroquine-resistant (cqr) and -sensitive (cqs) plasmodium berghei k173 strains possessed significant activities of heme oxygenase, biliverdin reductase and heme polymerase. heme oxygenase and biliverdin reducatase activities of cqr were significantly higher (7-10 fold) as compared to that of cqs p. berghei, whereas heme polymerase showed a reverse trend (two-fold decrease). however, a 10-fold increase in heme, three-fold increase in ferriprotoporphyrin ix and a two-fold increase in hemozoin le ...19958847167
studies on heme and heme oxygenase during plasmodium berghei infection in golden hamsters.heme and heme degrading enzymes namely heme-oxygenase (ho) and biliverdin reductase (br) were monitored in liver and spleen during plasmodium berghei infection in golden hamsters. there was a sequential rise in the levels of heme and ho with the rise in parasitaemia. br was also significantly increased in these organs following infection.19958786168
plasmodium berghei: the application of cultivation and purification techniques to molecular studies of malaria parasites.species of malaria parasites that infect rodents provide models for the study of the biology of malaria parasites that infect humans. in this article, chris janse and andy waters describe some of the recent advances in the cultivation and purification methodology of one of these species, plasmodium berghei. the improvement of these techniques, and the increasing knowledge about the molecular biology of p. berghei enhance the value of this particular rodent model for the investigation of many asp ...199515275357
effects of endotoxin and dexamethasone on cerebral malaria in mice.cba/t6 and dba/2j mice inoculated with plasmodium berghei anka (pba) develop cerebral involvement 6-8 days post-inoculation, from which the cba mice almost invariably die and the dba mice recover. dexamethasone (dxm; 80 mg/kg) given to inoculated cba mice twice, on day 3 and again within 48 h, reduced the cerebral symptoms and prevented death from cerebral malaria. plasma tumour necrosis factor (tnf) levels, which increased at the time of the cerebral symptoms, were also reduced in these dxm-tre ...199511023408
metabolism of diazepam and ethosuximide in rats with malaria and endotoxin-induced fever.we have investigated the effects of malaria infection with rodent parasite plasmodium berghei and fever induced by escherischia coli endotoxin on the metabolism of diazepam to temazepam by rat liver microsomes, and on the clearance of ethosuximide in vivo in the rat. livers from malaria-infected (parasitaemia =36.8+/- 7.6% endotoxin-treated or saline-treated (control) rats (n=5 per treatment) were used to prepare microsomes. these were incubated with diazepam (10-600ū m) for 10 minutes in an nad ...199617451291
the malaria sporozoite's journey into the liver.perhaps the most challenging event of the malaria parasite's lifecycle is the sporozoite's journey to the hepatocyte. because few parasites are injected by the mosquito, they must be efficiently and rapidly targeted to hepatocytes, where they will invade and develop into merozoites, the form of the parasite infective for red blood cells. little is known about how sporozoites make their way to the liver and subsequently invade hepatocytes. some evidence suggests that they are initially trapped by ...19968805080
antimalarial and toxic effects of the acyclic nucleoside phosphonate (s)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine in plasmodium berghei-infected mice.plasmodium berghei-infected mice died with low levels of parasitemia after repeated intraperitoneal administration (five times at 15 mg kg of body weight-1 every other day) of the in vitro active antimalarial acyclic nucleoside phosphonate (s)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(s)-hpmpa]. toxicological studies showed that the main cause of death resulted from (s)-hpmpa-induced nephrotoxicity. although concomitant intraperitoneal administration of the tubular epithelium transport bl ...19968807044
malaria, blood glucose, and the role of tumour necrosis factor (tnf) in mice.hypoglycaemia in falciparum malaria is associated with a poor prognosis and is correlated with mortality. high levels of serum tnf are also correlated with disease severity and mortality, and it has been suggested that tnf may cause the hypoglycaemia. however hypoglycaemia in mice infected with plasmodium chabaudi or the lethal strain of p. yoelii ym is related to hyperinsulinaemia. its development was not prevented by treatments which diminished tnf activity or production without affecting leve ...19968809132
a method for the quantitative assessment of malaria parasite development in organs of the mammalian host.a non-radioactive pcr method was developed to quantify the development of malaria parasites in the infected host. this was achieved by using plasmodium genus-specific primers corresponding to the parasite's small subunit ribosomal rna genes. the quantification of the pcr product was performed by high performance liquid chromatography, and calibration curves were obtained by amplification from defined quantities of purified plasmodium genomic dna. using this method, it was possible to quantify de ...19968813659
sequence analysis of the apical membrane antigen-1 genes (ama-1) of plasmodium yoelii yoelii and plasmodium berghei. 19968813699
re-investigation of the circumsporozoite protein-based induction of sterile immunity against plasmodium berghei infection.although the circumsporozoite protein (csp) of the malaria parasite is the most immunologically characterized protein, the goal of using this protein in an effective vaccine has not yet been realized. monoclonal antibody against the repetitive immunodominant b-epitope of the csp can protect mice from malaria, but vaccines that induce antibody against this epitope do not consistently induce protection. toward developing a rationale for a csp-based effective vaccine, we have re-investigated the ab ...19968817831
identification of a plasmodium berghei antigen sharing common features with p. falciparum and p. chabaudi parasitophorous-vacuole membrane antigens.on the basis of immunological cross-reactivity, we identified a 43-kda plasmodium berghei antigen with homology to the exp-1 antigen from p. falciparium. the p. berghei antigen was recognized by an antibody directed against an epitope on the c-terminus of the p. falciparum exp-1 protein. this antigen is localized on the surface of the parasite and shares peptide sequence homology with the p. chabudi antigen ag3008. to investigate further the role of the p. berghei antigen, we designed antisense ...19968825207
the erythrocytic schizogony of two synchronized strains of plasmodium berghei, nk65 and anka, in normocytes and reticulocytes.by a modified percoll-glucose centrifugation technique the rings and young trophozoites of two strains of plasmodium berghei, nk65 and anka, were separated from the other erythrocytic stages and inoculated into mice. the subsequent infection was followed for anka in normal mice and for nk65 in normal mice and in mice with high-grade reticulocytosis induced by injections of phenylhydrazine. the duration of the erythrocytic schizogony of the nk65 strain was shown to be independent of the age of th ...19968825215
4-aminoquinoline analogs of chloroquine with shortened side chains retain activity against chloroquine-resistant plasmodium falciparum.we have synthesized several 4-aminoquinolines with shortened side chains that retain activity against chloroquine-resistant isolates of plasmodium falciparum malaria (w. hofheinz, c. jaquet, and s. jolidon, european patent 94116281.0, june 1995). we report here an assessment of the activities of four selected compounds containing ethyl, propyl, and isopropyl side chains. reasonable in vitro activity (50% inhibitory concentration, < 100 nm) against chloroquine-resistant p. falciparum strains was ...19968843292
further characterization of a 58 kda plasmodium berghei phosphoprotein as a cochaperone.molecular chaperones are important for proper protein folding during protein biogenesis. this report describes a protein from plasmodium berghei which is 30% identical and 40% similar to a recently described mammalian cochaperone, or heat shock protein 70 interacting protein. the p. berghei cochaperone accumulates throughout the trophozoite stage and decreases during the schizont stage. the stage specific expression is consistent with its presumed role in protein folding or protein-protein inter ...19969010839
synthetic peptides entrapped in microparticles can elicit cytotoxic t cell activity.peptides from plasmodium berghei circumsporozoite protein (cs) and influenza a virus nucleoprotein (np) were entrapped in microparticles prepared from poly (lactide-co-glycolide) polymers, and the microparticles were administered parenterally to mice. after immunization with single or multiple doses, splenocytes were tested for a cytotoxic t cell (ctl) response and high levels of ctl activity were detected. the ctl induced were cd8+, mhc class i restricted, and could recognize virus infected cel ...19969014294
cytotoxic t cell induction with ratchet peptide libraries.immunization with synthetic peptides are used to induce cytotoxic t cell (ctl) responses in vivo. however, ctl peptide vaccines require the use of multiple peptides to overcome genetic diversity associated with mhc restriction, and prior epitope identification from the chosen protein template. we describe here a method whereby all nonamer sequences from a longer template can be synthesized simultaneously in a ratchet peptide library (rpl) covering all potential epitopes within a protein. we synt ...19969032897
synthesis and biological activity of platinum group metal complexes of o-vanillin thiosemicarbazones.o-vanillin-(4-methylthiosemicarbazone), o-vanillin-(4-phenylthiosemicarbazone) and some of their metal complexes of the platinum group have been synthesized, characterized by chemical and spectral methods and studied for their antibacterial, antifungal and amoebicidal activity in vitro. the platinum group metal chelates exibited significant activity against a wide spectrum of microorganisms at different concentrations. the pt(ii) and ru(iii) chelates derived from o-vanillin-(4-phenylthiosemicarb ...19969050213
induction of anti-malarial transmission blocking immunity with a recombinant ookinete surface antigen of plasmodium berghei produced in silkworm larvae using the baculovirus expression vector system.we have studied pbs21, a major ookinete surface protein of plasmodium berghei, for the development of a model transmission blocking immunogen. in the mouse, recombinant pbs21 expressed in the escherichia coli expression system (ecrpbs21) is not as effective in inducing transmission blocking antibodies as native pbs21 (npbs21), possibly because of differences in post-translational processing between ecrpbs21 and npbs21. in an attempt to improve the efficacy of the recombinant molecule, we describ ...19968852407
upregulation of reactive oxygen and nitrogen intermediates in plasmodium berghei infected mice after rescue therapy with chloroquine or artemether.plasmodium berghei anka infected c57b1/6 mice develop cerebral malaria at a parasitaemia of 15-25%. when parasitaemia reached 10%, p. berghei infected mice were treated with artemether, chloroquine or clindamycin in order to prevent the occurrence of cerebral malaria. artemether and chloroquine were highly efficient. functional tests revealed that zymosan stimulated spleen cells from untreated mice with cerebral malaria showed a slight decrease in their capacity to produce reactive oxygen interm ...19968858461
an exploration of the structure-activity relationships of 4-aminoquinolines: novel antimalarials with activity in-vivo.the structure-activity relationships of bisquinolines, a potentially important group of novel antimalarial drugs, were studied. the high-temperature (180-250 degrees c) synthesis of 4-aminoquinolines, including bisquinolines, by nucleophilic displacement was both fast and efficient several bisquinolines including (+/-)-trans-n1,n2-bis(7-trifluoroquinolin-4-yl)cyclohexane-1, 2-diamine and 1r,2r-(-)-, 1s,2s-(+)-, (+/-)-trans- and cis-n1, n2-bis(7-chloroquinolin-4-yl)cyclohexane-1,2-diamine exhibit ...19968887736
a chromatin-associated protein is encoded in a genomic region highly conserved in the plasmodium genus.a single copy gene, pbb7, encoding a putative 26 kda acidic protein has been isolated from plasmodium berghei and appears to be part of a genomic region well conserved within the plasmodium genus. the deduced amino acid sequence exhibits significant blocks of similarity with nucleosome assembly proteins from yeast and man. the nuclear localization of the natural protein and its close association with chromatin during the entire erythrocytic cycle of the parasite have been demonstrated using spec ...19968892296
release of malaria circumsporozoite protein into the host cell cytoplasm and interaction with ribosomes.to date, the circumsporozoite (cs) protein has been implicated in guiding malaria sporozoites to the liver [cerami et al., cell 70, 1992, 1021-1033]. here we show that shortly after invasion, p. berghei and p. yoelii sporozoites lie free in the invaded cell and release considerable amounts of cs protein into the cytoplasm. the intracytoplasmic deposition of cs protein begins during the attachment of the sporozoite to the host cell surface and reaches its peak during the first 4-6 h after invasio ...19968898331
recombinant plasmodium falciparum dihydrofolate reductase-based in vitro screen for antifolate antimalarials.we describe the system for screening the effective antifolate antimalarials that uses the recombinant plasmodium falciparum dhfr domain of the bifunctional dhfr-ts expressed in escherichia coli, and were designed with amino acid alterations found in the dhfr genes of the antifolate resistant strains. the validity of the screen was verified by the subsequent examination of several substituted pyrrolo[2,3-d]pyrimidines for their antimalarial activity. among the 120 chemical derivatives, 5 compound ...19968898337
correlation between enhanced vascular permeability, up-regulation of cellular adhesion molecules and monocyte adhesion to the endothelium in the retina during the development of fatal murine cerebral malaria.the relationships between increased vascular permeability to protein, monocyte adherence to the endothelium, and expression of the cell adhesion molecules, intercellular adhesion molecule-1 (icam-1) and vascular cell adhesion molecule-1 (vcam-1) in the central nervous system microvasculature were studied during the progression of fatal murine cerebral malaria. cba mice were inoculated with plasmodium berghei anka, and changes in the retinal microvasculature were examined on days 3, 5, and 7 post ...19968909263
facilitation of rift valley fever virus transmission by plasmodium berghei sporozoites in anopheles stephensi mosquitoes.certain mosquito species are susceptible to viral infection but cannot transmit the virus due to a salivary gland barrier. we hypothesized that such species could transmit virus if the mosquito were infected with both virus and malaria parasites. malaria sporozoites disrupt the integrity of mosquito salivary glands and, in so doing, may destroy salivary gland barriers to viral transmission. to examine this postulate, the model system of rift valley fever (rvf) virus and a rodent parasite, plasmo ...19968916797
apicidin: a novel antiprotozoal agent that inhibits parasite histone deacetylase.a novel fungal metabolite, apicidin [cyclo(n-o-methyl-l-tryptophanyl-l -isoleucinyl-d-pipecolinyl-l-2-amino-8-oxodecanoyl)], that exhibits potent, broad spectrum antiprotozoal activity in vitro against apicomplexan parasites has been identified. it is also orally and parenterally active in vivo against plasmodium berghei malaria in mice. many apicomplexan parasites cause serious, life-threatening human and animal diseases, such as malaria, cryptosporidiosis, toxoplasmosis, and coccidiosis, and n ...19968917558
molecular electronic properties of a series of 4-quinolinecarbinolamines define antimalarial activity profile.a detailed computational study on a series of 4-quinolinecarbinolamine antimalarials was performed using the semiempirical austin model 1 (am1) quantum chemical method to correlate the electronic features with antimalarial activity and to illuminate more completely the fundamental molecular level forces that affect the function and utility of the compounds. ab initio (3-21g level) calculations were performed on mefloquine, the lead compound in this series, to check the reliability of the am1 met ...19968917651
experimental congenital toxocariasis: effect on foetal future immune response.congenital parasitic infections may not lead to any overt clinical effects but could modulate the foetal future immune response to the same parasite depending on whether sensitization or tolerance has occurred in utero. in this study, pregnant female mice were infected with toxocara canis eggs at different gestational age, then the offspring were next challenged with toxocara eggs 6 weeks after birth and their immune response was assessed by estimation of the eosinophilic count and serum ige con ...19968918035
cell surface glycosaminoglycans are not obligatory for plasmodium berghei sporozoite invasion in vitro.the malaria circumsporozoite (cs) protein binds to glycosaminoglycan chains from heparan sulfate proteoglycans present on the basolateral surface of hepatocytes and hepatoma cells in vitro. when injected into mice, cs protein is rapidly cleared from the blood circulation by hepatocytes. the binding region for the hspgs is the evolutionarily conserved region ii-plus of the cs protein. here we have asked whether the presence of glycosaminoglycans on the plasma membrane of target cells is required ...19968920011
dual interaction of the malaria circumsporozoite protein with the low density lipoprotein receptor-related protein (lrp) and heparan sulfate proteoglycans.speed and selectivity of hepatocyte invasion by malaria sporozoites have suggested a receptor-mediated mechanism and the specific interaction of the circumsporozoite (cs) protein with liver-specific heparan sulfate proteoglycans (hspgs) has been implicated in the targeting to the liver. here we show that the cs protein interacts not only with cell surface heparan sulfate, but also with the low density lipoprotein receptor-related protein (lrp). binding of 125i-cs protein to purified lrp occurs w ...19968920859
a one-step lysis procedure for 18s ribosomal rna-based diagnosis of infection by plasmodium species. 19968921197
localization of ribosomal rna and pbs21-mrna in the sexual stages of plasmodium berghei using electron microscope in situ hybridization.a reproducible technique for the ultrastructural localization of rnas in malaria parasites has been developed which combines excellent structural preservation with high hybridization signals. signals obtained following in situ hybridization with an antisense rrna probe which recognizes all forms of small subunit (ssu) rrna correlate with the density of ribosomes in the parasite cytoplasm and show that a) the male gametocyte has only 12 to 25% the ribosomes found in the female cell and asexual pa ...19968929565
mitochondrial heme oxygenase of mastomys coucha.while studying the fate of heme generated during malaria infection, it was observed that mitochondrial preparations were highly enriched with heme compared to other subcellular particles. with this background, the present study aimed to determine the status of mitochondrial heme oxygenase and compare it with the microsomal enzyme. mitochondrial and microsomal preparations were obtained from liver, spleen, kidney and brain of normal, inducer (cobalt chloride and hemin)-treated and plasmodium berg ...19968930130
synthesis and immunostimulant activity of novel analogs of human casein fragment (54-59).structural analogs of the hexapeptide sequence 54-59 (a) human casein, reported to stimulate immune response, were synthesized and evaluated for immunostimulant activity. hexapeptide 91/409 (c), 90/649 (d) and 91/361 (e) stimulated higher antibody titre and delayed type of hyper-sensitivity (dth) response than the natural casein hexapeptide in balb/c mice-sheep red blood cells (srbc) and guinea pig-ovalbumin models. these peptides also induced higher stimulation of non-specific immune response a ...19968933167
molecular cloning and antigenic mapping of heat-shock protein 70 from the malaria species plasmodium berghei.we have isolated a 70-kd heat-shock protein (hsp-70) cdna from plasmodium berghei. a cdna clone encoding the p. berghei hsp-70 was isolated and sequenced, demonstrating that it is highly homologous with other plasmodium hsp-70s. one of the common features is a series of ggmp amino acid repeats at the carboxy terminus; there is also a long, at-rich 5' untranslated region, a hallmark of other malarial rnas. hydropathy and antigenicity analyses suggest the presence of two hydrophilic domains. recom ...19968940993
heat-labile and heat-stimulable heme polymerase activities in plasmodium berghei. 19968946392
plasmodium berghei: infectivity of mice to anopheles stephensi mosquitoes.the infectivity of p. berghei-infected to mice to mosquitoes declines rapidly 2 to 5 days after blood inoculation, in spite of rising numbers of gametocytes in the blood. this pattern is typical of many malaria infections and various factors, particularly specific and nonspecific immune responses, have previously been implicated in the decline. here we report that (1) simple physiological changes in the mouse blood, namely, falling ph and bicarbonate levels induced by high parasitaemias, are res ...19968948326
[effect of momordica charantia l. in mice infected with plasmodium berghei].according to the world health organization malaria is one of the major public health problems in brazil and all over developing countries, where 80% of the population use traditional medicine to solve their primary medical problems. both treatment and control of this parasitosis have become difficult, because of parasite strains that are resistant to conventional drugs, such as chloroquine. that makes the search for new antimalarial drugs not only important but urgent. we aimed therefore at eval ...19968966309
cd8 beta increases cd8 coreceptor function and participation in tcr-ligand binding.to study the role of cd8 beta in t cell function, we derived a cd8 alpha/beta-(cd8-/-) t cell hybridoma of the h-2kd-restricted n9 cytotoxic t lymphocyte clone specific for a photoreactive derivative of the plasmodium berghei circumsporozoite peptide pbcs 252-260. this hybridoma was transfected either with cd8 alpha alone or together with cd8 beta. all three hybridomas released interleukin 2 upon incubation with l cells expressing kd-peptide derivative complexes, though cd8 alpha/beta cells did ...19968976201
induction of sustained and elevated immune responses to weakly immunogenic synthetic malarial peptides by encapsulation in biodegradable polymer microspheres.biodegradable microspheres (ms) based on poly(d,l-lactide) and poly(d,l-lactide-coglycolide) have the capacity to release encapsulated antigens over defined lengths of time depending on their composition and to elicit and sustain strong and long-lasting immune responses to protein antigens. in the present study, two synthetic multiple antigenic peptides (map), p30b2 and (nanp)6p2p30, were incorporated into ms of different compositions. p30b2 and (nanp)6p2p30 are composed of one or two universal ...19968994320
comparison of adjuvant formulations for cytotoxic t cell induction using synthetic peptides.we have investigated the capacity of synthetic peptides delivered in different adjuvant formulations to induce cytotoxic t lymphocyte (ctl) responses to a class i h-2kd-restricted plasmodium berghei circumsporozoite epitope, cs 252-260. using three immunogen formulations: soybean emulsion; montanide isa720; and lipopeptide (p3-cs), we first evaluated the effects of immunization routes on ctl induction. no ctl response was induced in mice immunized s.c. or i.p. with cs peptide formulated in soybe ...19968735553
pyrrolo[2,3-d]pyrimidines and pyrido[2,3-d]pyrimidines as conformationally restricted analogues of the antibacterial agent trimethoprim.conformationally restricted analogues of the antibacterial agent trimethoprim (tmp) were designed to mimic the conformation of drug observed in its complex with bacterial dihydrofolate reductase (dhfr). this conformation of tmp was achieved by linking the 4-amino function to the methylene group by one- and two-carbon bridges. a pyrrolo[2,3-d]pyrimidine, a dihydro analogue, and a tetrahydropyrido[2,3-d]pyrimidine were synthesized and tested as inhibitors of dhfr. one analogue showed activity equi ...19968735847
immunity to plasmodium berghei exoerythrocytic forms derived from irradiated sporozoites.the nature of immunity generated by plasmodium berghei exoerythrocytic (ee) stages developing from irradiated sporozoites was studied using in vivo parameters of host protection on immunization with irradiated sporozoites and in vitro parameters of inhibition of sporozoite invasion and ee form development by serum antibodies from immunized mice. on in vivo challenge of immunized mice by sporozoites, protection was observed in an irradiation-dose-dependent manner. this finding stresses that prote ...19968740544
participation of lymphocyte subpopulations in the pathogenesis of experimental murine cerebral malaria.we determined the requirement for selected lymphocyte subsets and cytokines in the pathogenesis of experimental murine cerebral malaria (cm) by using gene-targeted knockout and mab-suppressed mice. plasmodium berghei anka infection induced cm in a 0/0 mice, which lack expression of surface mhc class ii glycoproteins and consequently express a severe and chronic reduction in numbers of cd4+ t cells. however, when a 0/0 mice, which are on a c57bl/6 x 129 genetic background, or immune-intact c57bl/ ...19968759747
naphthylisoquinoline alkaloids exhibit strong growth-inhibiting activities against plasmodium falciparum and p. berghei in vitro--structure-activity relationships of dioncophylline c.the growth-inhibiting activities of naturally occurring naphthylisoquinoline alkaloids against asexual blood stages of plasmodium falciparum (nf 54, clone a1a9) and p. berghei (anka) were studied in vitro. three of the alkaloids [7-epi-dioncophylline a (8b), dioncolactone a (4), and 5'-o-demethyl-8-o-methyl-7-epidioncophylline a (11)] displayed good activities against both parasites, with median inhibitory concentrations (ic50) of 1-5 micrograms/ml. dioncophylline c (2), however, was even better ...19968762401
comparison of numerous delivery systems for the induction of cytotoxic t lymphocytes by immunization.a variety of vaccine delivery systems including peptides with various adjuvants, recombinant particles, live recombinant viruses and bacteria and plasmid dna were tested for their ability to induce cd8+ cytotoxic t lymphocytes (ctl) against a well-defined epitope (amino acids 252-260) from the circumsporozoite (cs) protein of plasmodium berghei. we compared routes of immunization that would be applicable for the administration of a malaria vaccine in humans. the majority of these vaccines did no ...19968765044
antimalarial activity of novel arylene bis(methylketone) compounds.because of the spread of drug-resistant plasmodium species, there is an urgent need for novel effective antimalarial agents. a series of arylene bis(methylketone) compounds were screened in vitro against a number of plasmodium falciparum clones and in vivo against plasmodium berghei. 2-amino-4-(3,5-diacetylphenyl)amino-1,6-dimethylpyrimidinium chloride (cytokine network inc. [cni]-h0294) was the most effective of the compounds in vitro, with an ic50 of 1.5-4.0 microm against parasite clones with ...19968769633
the large difference in infectivity for mice of plasmodium berghei and plasmodium yoelii sporozoites cannot be correlated with their ability to enter into hepatocytes.sporozoites of p. yoelii nigeriensis are 50-100-times more infective to mice than the strain nk65 of p. berghei. to study the mechanisms involved in this striking difference in the infectivity of these closely related species of malaria parasites, we have developed a quantitative pcr targeted to parasite-specific ribosomal rna. using this method, we detect rna from a single sporozoite, and exo-erythorcytic forms of rna in the livers of mice injected with 200 sporozoites. we find that 20 h after ...19968784767
the course of plasmodium berghei, p. chabaudi and p. yoelii infections in beta-thalassaemic mice.in order to study the effects of acclimatization of plasmodium in beta-thalassaemic mice, we used a mouse model of beta-thalassaemia (dba/2j/beta-thal/beta-thal), similar to that observed in humans. we acclimatized 3 rodent malarias (p. berghei, p. chabaudi and p. yoelii) in dba/2j and dba/2j/beta-thal mice lines, by 4 intraperitoneal serial transfers. all 3 rodent malarias developed in red blood cells of beta-thalassaemic mice without losing their virulence. there was no delay in infection and ...19968728990
patterns of haemozoin accumulation in tissue.a sensitive fluorometric method for assaying malarial pigment, haemozoin, has been developed and used to determine the haemozoin content of blood and tissue samples. plasmodium falciparum rings and trophozoites were found to contain 23 and 339 ng haemozoin/10(6) parasitized red blood cells (prbcs), respectively. unsynchronized plasmodium berghei nk65 or anka parasites from infected mice contained 27 and 61 ng haemozoin/10(6) prbcs, respectively. an exponential accumulation of haemozoin within 18 ...19968728992
the within-host cellular dynamics of bloodstage malaria: theoretical and experimental studies.the properties of a mathematical model of bloodstage infection with a single strain of malaria were investigated. analysing the cell population dynamics in the absence of a host immune response we demonstrate a relationship between host and parasite parameters that defines a criterion for the successful invasion and persistence of the parasite. important parameters are the rates of merozoite production and death and those of erythrocyte production, death and invasion. we present data from experi ...19968710412
[malaria parasite dna and rna changes connected with acquired resistance to chloroquine]. 19968714121
expression of a plasmodium gene introduced into subtelomeric regions of plasmodium berghei chromosomes.targeted integration of exogenous dna into the genome of malaria parasites will allow their phenotype to be modulated by means of gene disruption or the stable expression of foreign and mutated genes. described here is the site-specific integration through reciprocal exchange, and subsequent expression, of a selectable marker gene into the genome of the pathogenic, bloodstage forms of the rodent malaria parasite plasmodium berghei. stable integration of a single copy of the marker gene (retained ...19968571132
sulfated polyanions inhibit invasion of erythrocytes by plasmodial merozoites and cytoadherence of endothelial cells to parasitized erythrocytes.sulfated proteoglycans have been shown to be involved in the binding of sporozoites of malaria parasites to hepatocytes. in this study, we have evaluated the effect of sulfated glycosaminoglycans on the invasion of erythrocytes by plasmodium falciparum merozoites and cytoadherence of parasitized erythrocytes (prbc) to endothelial cells. invasion of erythrocytes by hb3ec-6 (an hb3 line selected for high binding to endothelial cells) was inhibited by dextran sulfate 500k, dextran sulfate 5k, sulfa ...19968606103
attenuated vaccinia virus-circumsporozoite protein recombinants confer protection against rodent malaria.nyvac-based vaccinia virus recombinants expressing the circumsporozoite protein (csp) were evaluated in the plasmodium berghei rodent malaria model system. immunization of mice with a nyvac-based csp recombinant elicited a high level of protection (60 to 100%). protection did not correlate with cs repeat-specific antibody responses and was abrogated by in vivo cd8+ t-cell depletion. protection was not enhanced by modification of the subcellular localization of csp. these results suggest the pote ...19968613376
mhc class i-dependent presentation of exoerythrocytic antigens to cd8+ t lymphocytes is required for protective immunity against plasmodium berghei.t lymphocytes are believed to play a major role in protection against malaria. previous experiments using in vivo depletion of cd8+ t cells, reconstitution with cd8+ t splenic cells, and adoptive transfer of cd8+ ctl clones demonstrated that protection against the exoerythrocytic stage of the murine strain, plasmodium berghei malaria, was cd8+ t cell-dependent. despite evidence for the critical role of cd8+ ctl, neither the cellular nor the molecular requirements for cd8+ t cell induction or for ...19968617963
dietary iron supplementation does not aggravate experimental malaria in young rats.the hypotheses that iron-deficient hosts are less susceptible to severe malaria and that iron supplementation aggravates infection have been supported by some clinical and experimental evidence. in the present study, the course of plasmodium berghei infection was monitored in an experimental model of dietary iron deficiency and iron supplementation. weanling wistar rats were fed purified diets with different iron concentrations: 20 mg/kg (group d, n = 24), 50 mg/kg (group n, n = 24) and 100 mg/k ...19968632220
trafficking of plasmodium chabaudi adami-infected erythrocytes within the mouse spleen.plasmodium chabaudi adami causes a nonlethal infection in mice. we found that crisis, the time of rapidly dropping parasitemia, was abrogated by splenectomy, indicating the role of spleen in parasite killing. the factors that mediate spleen-dependent immunity are not known. an earlier study in plasmodium berghei-infected rats showed an association between increased clearance of heat-treated erythrocytes and the onset of crisis [wyler, d. j., quinn, t. c. & chen, l.-t. (1982) j. clin. invest. 67, ...19968643449
efficient binding to the mhc class i k(d) molecule of synthetic peptides in which the anchoring position 2 does not fit the consensus motif.peptides eluted from the mhc class i k(d) molecule are generally nonamers that display a strong preference for tyr in position 2 and ile or leu in position 9. we investigated the binding ability of several synthetic peptides which did not fit this consensus motif. in our peptides, tyr(2) was substituted by other amino acids, i.e. leu, ile or met. these peptides were variants of the 252-260 k(d)-restricted peptide syipsaeki derived from the plasmodium berghei circumsporozoite protein. they bound ...19968654564
plasmodium berghei mouse model: antimalarial activity of new alkaloid salts and of thiosemicarbazone and acridine derivatives.sixteen compounds were synthesized and evaluated on plasmodium berghei in cd1 mouse. the nature of the salt associated to the active principle can give some advantages in the field of activity, bioavailability and toxicity. beta-resorcylic acid was chosen in this study because of its previously described antimalarial activity and its expected enhancement of quinine antimalarial activity. while treatment with subcutaneous quinine sulphate at 1 mmol/kg cured 6/10 mice, quinine beta-resorcylate cur ...19968673843
toward a novel metal-based chemotherapy against tropical diseases. 2. synthesis and antimalarial activity in vitro and in vivo of new ruthenium- and rhodium-chloroquine complexes.chloroquine free base (cq) reacts with [rh(cod)cl]2 (cod = 1,5-cyclooctadiene) and rucl3.-3h2o/zn to yield rh(cod)(cq)cl (1) and [rucl2(cq)]2 (2), respectively. the two novel metal- cq complexes, which were characterized mainly by 1d and 2d nmr spectroscopy, were tested against plasmodium berghei. the in vitro activity of 1 was comparable to that of chloroquine diphosphate (cqdp), whereas 2 was about 5 times more active. in in vivo tests at equivalent concentrations of free cq, cqdp reduced the ...19968676344
wistar rat-plasmodium berghei model does not approximate human congenital malaria.until recently, congenital malaria was thought to be rare. now, several reports suggest that more than 10% of newborns in some settings are parasitemic. the pathophysiology of transplacental transmission of plasmodium is not well understood, and no animal model of congenital malaria exists. a rodent model of malaria in pregnant females, however, has been developed. in an effort to test the usefulness of this model in the study of congenital malaria, wistar rats were injected intraperitoneally wi ...19968691374
[ca++ ion transport blockers as reversants of the drug resistance of malarial parasites. 1. the effect of verapamil on the resistance to chloroquine in vivo of plasmodium berghei and in vitro of plasmodium falciparum].the reversing action of verapamil on the effect of chloroquine was found in in vivo experiments by using a model p. berghei resistant to chloroquine, an lnk65 isolate having a naturally lower resistance to the agent, and its polyresistant strain with the acquired resistance to chloroquine and fansidar, as well as by employing the chlorine-resistant p. falciparum isolates from the south of the socialist republic of vietnam. the magnitude of this effect was related to the dose of verapamil, the fr ...19968700004
synthesis and antiprotozoal activities of some new triazine derivatives including a new antitrypanosomal agent: sipi-1029.two series of compounds, 1,2-dihydro-2,2-dimethyl-4, 6-diamino-1-(omega-haloalkyloxy)-s-triazines and o, o'-bis (4, 6-diamino-1, 2-dihydro-2, 2-disubstituted-s-triazin-l-yl) alkanediols were synthesized and tested against plasmodium berghei and trypanosoma evansi in mice. most title compounds showed good antimalarial activity and compounds iic-e showed good antitrypanosomal effect. after further studies on pharmacology, toxicology, pharmacokinetics and efficacy on infected cattles compound iie ( ...19969863252
[chemical and biological evaluation of the effect of plant extracts against plasmodium berghei].extracts from thirteen species of plants were evaluated by "in vivo" antimalarial test against plasmodium berghei effects. significant activities were observed in the ethyl acetate and aqueous extracts, elaborated of cedrela tonduzii leaves, trichilia havanensis and trichilia americana barks, neurolaena lobata and gliricidia sepium leaves and duranta repens fruits. compounds identified include flavanoids, coumarins, mellilotic acid and iridoids which some kind of biodynamic activity has previous ...19969246360
temporary appearance of a circulating granulocyte-macrophage colony-stimulating factor in lethal murine malaria.infection of mice with plasmodium berghei engendered a temporary appearance of granulocyte-macrophage colony-stimulating factor (gm-csf) in the serum. the peak of gm-csf levels was detected at day 2 post-infection, and then gradually decreased. on the other hand, the number of committed stem cells for granulocytes and macrophages (cfu-gm) in bone marrow transiently decreased at day 2 post-infection, and then increased and peaked at day 6 post-infection. when the serum of p. berghei-infected mice ...19969185264
nitric oxide synthase activity in malaria-infected mice.nitric oxide (no) is implicated in a variety of major cellular functions including defence from invasion by microbical pathogens. evidence has been presented suggesting that it is an important mediator of protection in the early non-specific responses to malaria in mice infected with plasmodium chabaudi (taylor-robinson et al. 1993). other data from in vitro studies on the asexual stages of human parasite plasmodium falciparum indicated that while nitric oxide itself may not be inhibitory to par ...19969226691
protection of rats against malaria by a transplanted immune spleen.a number of reports have suggested that the spleen plays a key role in the regulation of immunity to malaria but the role, if any, of other tissues is less clear. furthermore, numerous functional changes occur in the spleen following malaria infection and it is not known whether the spleen's role relates primarily to its content of malaria-specific lymphocytes or to the altered structure and function that has occurred. to address these issues we have generated splenic chimeras by transplanting s ...19969229385
epitope mapping on the ookinete surface antigen pbs21 of plasmodium berghei: identification of the site of binding of transmission-blocking monoclonal antibody 13.1.the ookinete surface protein of plasmodium berghei pbs21 belongs to a class of sexual stage antigens able to induce in the vertebrate host a transmission-blocking immune response. the effectors of this transmission-blocking immunity are antibody molecules directed against particular protein epitopes. the anti-pbs21 monoclonal antibody 13.1 is known to bind a linear stretch of amino acids within the primary sequence of pbs21 and to efficiently block the development of p. berghei in the mosquito g ...19969257345
effect of tryptophan-n-formylated gramicidin on growth of plasmodium berghei in mice.the effect of tryptophan-n-formylated gramicidin (nfg) on the growth of plasmodium berghei in mice was tested in three different experiments. nfg was shown to be capable of inhibiting the growth of the parasite in a dose-dependent way, although its action did not result in elimination of the parasite and was only temporary, preventing mice from early death, presumably due to cerebral malaria, but not from fatal generalized malaria. intriguingly, a similar observation was made with two other drug ...19979257760
trap is necessary for gliding motility and infectivity of plasmodium sporozoites.many protozoans of the phylum apicomplexa are invasive parasites that exhibit a substrate-dependent gliding motility. plasmodium (malaria) sporozoites, the stage of the parasite that invades the salivary glands of the mosquito vector and the liver of the vertebrate host, express a surface protein called thrombospondin-related anonymous protein (trap) that has homologs in other apicomplexa. by gene targeting in a rodent plasmodium, we demonstrate that trap is critical for sporozoite infection of ...19979267031
heme biosynthesis by the malarial parasite. import of delta-aminolevulinate dehydrase from the host red cell.the mouse and human malarial parasites, plasmodium berghei and plasmodium falciparum, respectively, synthesize heme de novo following the standard pathway observed in animals despite the availability of large amounts of heme, derived from red cell hemoglobin, which is stored as hemozoin pigment. the enzymes, delta-aminolevulinate dehydrase (alad), coproporphyrinogen oxidase, and ferrochelatase are present at strikingly high levels in the p. berghei infected mouse red cell in vivo. the isolated p ...19979268315
purification and characterisation of the hexokinase of plasmodium berghei, a murine malaria parasite.hexokinase (ec 2.7.1.1) activity in cell-free plasmodium berghei was 35 and 5 times higher as compared to normal and p. berghei-infected mouse erythrocytes, respectively. maximal enzyme activity was present in the cytosolic fraction of the isolated parasite. manifold purification of parasite hexokinase was achieved with sephadex g-200. sodium dodecyl sulphate polyacrylamide gel electrophoresis (sds-page) revealed parasite enzyme subunit in the molecular weight range of 47 kda with atp (adenosine ...19979270135
in vitro inhibition of liver forms of the rodent malaria parasite plasmodium berghei by naphthylisoquinoline alkaloids--structure-activity relationships of dioncophyllines a and c and ancistrocladine.naphthylisoquinoline alkaloids are derived from dioncophyllaceae and ancistrocladaceae species and comprise a new class of promising antimalarials with a demonstrated potential against asexual erythrocytic plasmodium falciparum and p. berghei stages in vitro. we report herein the pronounced activity of pure naphthylisoquinoline alkaloids against exoerythrocytic malaria parasites. p. berghei-infected human hepatoma cells (hep g2) were incubated with culture medium containing selected alkaloids at ...19979272557
the roles of temperature, ph and mosquito factors as triggers of male and female gametogenesis of plasmodium berghei in vitro.developmentally arrested malarial gametocytes undergo gamete formation in the mosquito midgut immediately after ingestion of the infected bloodmeal. in the rodent malaria parasite plasmodium berghei male gametogenesis (exflagellation) can be induced in vitro by a temperature decrease (from 39 degrees c in the vertebrate host to 20 degrees c) and a concomitant ph increase (from 7.3 in mouse blood to 8.0). we report the presence of additional gametocyte activating factor(s) (gaf) present in anophe ...19979280891
leukocytes in a plasmodium falciparum-infected blood meal reduce transmission of malaria to anopheles mosquitoes.mosquitoes are infected with plasmodium falciparum by taking a blood meal from a gametocyte carrier. since a mosquito takes a volume of 1 to 2 microl, a blood meal may contain 1 x 10(4) to 3 x 10(4) leukocytes (wbc). the majority of wbc are composed of neutrophils which may phagocytose and kill developing gametes inside the mosquito midgut. phagocytosis was measured in vitro by a luminol-dependent chemiluminescence (cl) assay. in the presence of p. falciparum gametes, sera from areas of endemici ...19979284160
inhibition of nitric oxide interrupts the accumulation of cd8+ t cells surrounding plasmodium berghei-infected hepatocytes.the elimination of liver-stage malaria parasites by nitric oxide (no)-producing hepatocytes is regulated by t cells. both cd8+ and cd4+ t cells, which surround infected hepatocytes, are evident by 24 h after sporozoite challenge in brown norway rats previously immunized with irradiated plasmodium berghei sporozoites. while the number of cd4+ t cells remained the same beyond 24 h postchallenge, the number of cd8+ t cells increased three- and sixfold by 31 and 44 h, respectively. this increase in ...19979284167
infection with plasmodium berghei alters benzodiazepine receptor in rat brain.the purpose of this study was to assess the effect of malaria infection on benzodiazepine binding in rat brain. young male wistar rats were infected with the rodent parasite plasmodium berghei, while age-matched control rats (n = 5) received normal saline intraperitoneally. parasitemia was determined in blood of infected animals. animals were killed after two weeks, and synaptosomal brain membrane homogenate was prepared from cerebral cortex. membrane homogenate was incubated in duplicate with 3 ...19979291643
the diversity of antigen-specific tcr repertoires reflects the relative complexity of epitopes recognized.antigen-selected t cell receptor (tcr) repertoires vary in complexity from very limited to extremely diverse. we have previously characterized two different cd8 t cell responses, which are restricted by the same mouse major histocompatibility complex (mhc) class i molecule, h-2 kd. the tcr repertoire in the response against a determinant from plasmodium berghei circumsporozoite protein (pbcs; region 252-260) is very diverse, whereas tcrs expressed by clones specific for a determinant in region 1 ...19979297530
erythrocyte binding protein homologues of rodent malaria parasites.erythrocyte invasion by malaria parasites requires specific molecular interactions between the merozoite and erythrocyte surface receptors. a well-conserved, functionally important family of erythrocyte binding proteins is the ebp family. the ebp family includes the plasmodium vivax, p. knowlesi duffy binding protein (dbp) family and the p. falciparum erythrocyte binding antigen-175 (eba-175). the ebp are transmembrane proteins, characterized by two conserved cysteine-rich domains, expressed in ...19979297707
induction of a cytotoxic t lymphocyte response by immunization with a malaria specific ctl peptide entrapped in biodegradable polymer microspheres.we have previously reported that biodegradable polymer microspheres (ms) are capable of eliciting strong and long-lasting antibody and t cell proliferative responses for either natural protein antigens or synthetic peptides. in this study, we investigated the possibility of inducing antigen-specific cytotoxic t lymphocyte (ctl) responses in vivo with a short synthetic peptide from the circumsporozoite (cs) protein of plasmodium berghei (pb) 252-260 by using different ms formulations. we show tha ...19979302752
plasmodium activates the innate immune response of anopheles gambiae mosquitoes.innate immune-related gene expression in the major disease vector mosquito anopheles gambiae has been analyzed following infection by the malaria parasite, plasmodium berghei. substantially increased levels of mrnas encoding the antibacterial peptide defensin and a putative gram-negative bacteria-binding protein (gnbp) are observed 20-30 h after ingestion of an infected blood-meal, at a time which indicates that this induction is a response to parasite invasion of the midgut epithelium. the indu ...19979321391
molecular immune responses of the mosquito anopheles gambiae to bacteria and malaria parasites.immune responses of the malaria vector mosquito anopheles gambiae were monitored systematically by the induced expression of five rna markers after infection challenge. one newly isolated marker encodes a homologue of the moth gram-negative bacteria-binding protein (gnbp), and another corresponds to a serine protease-like molecule. additional previously described markers that respond to immune challenge encode the antimicrobial peptide defensin, a putative galactose lectin, and a putative serine ...19979326640
recognition of the parasite infected cell surface determinants by homologous antiserum raised against infected cell membranes.identification of neo-antigenic determinant(s) on parasite infected cell surface is important to control intracellular infections. such determinant(s) on the surface of intact plasmodium berghei infected erythrocytes have not been conclusively demonstrated. to generate polyclonal antiserum selectively recognizing the parasite infected cell surface determinant(s), in natural state, we have examined the efficacy of the homologous immunizations, in balb/c mice, with the membrane rich preparation of ...19979342738
cytokine profile suggesting that murine cerebral malaria is an encephalitis.cerebral malaria (cm) remains a poorly understood and life-threatening complication of malaria caused by the parasite plasmodium falciparum. the discovery that murine cm caused by plasmodium berghei anka and human cm are both characterized by production of inflammatory cytokines, especially tumor necrosis factor alpha (tnf-alpha), led to a revival of the suggestion that p. berghei cm may have value as a model of the human disease. in this study, quantitative reverse transcription-pcr was used to ...19979353082
a protein particle vaccine containing multiple malaria epitopes.ty virus-like particles consist of a single protein species that can be produced in yeast. recombinant ty-vlps carrying a string of up to 15 defined cytotoxic t lymphocyte (ctl) epitopes from plasmodium species prime protective ctl responses in mice following a single administration without adjuvant. effective processing of epitopes from the string was demonstrated in vitro and in vivo and was not affected by flanking sequences.19979359112
the novel oxygenated chalcone, 2,4-dimethoxy-4'-butoxychalcone, exhibits potent activity against human malaria parasite plasmodium falciparum in vitro and rodent parasites plasmodium berghei and plasmodium yoelii in vivo.previous studies have shown that licochalcone a, an oxygenated chalcone, exhibits antileishmanial and antimalarial activities. the present study was designed to examine the antimalarial activity of an analog of licochalcone a, 2,4-dimethoxy-4'-butoxychalcone (2,4mbc). 2,4mbc inhibited the in vitro growth of both a chloroquine-susceptible (3d7) and a chloroquine-resistant (dd2) strain of plasmodium falciparum in a [3h]hypoxanthine uptake assay. the in vivo activity of 2,4mbc was tested in mice in ...19979359735
ctl induction using synthetic peptides delivered in emulsions--critical role of the formulation procedure.emulsions have been used with variable degrees of success to deliver antigen to stimulate immune responses. we have investigated three different ways of incorporating peptide antigen into soybean emulsions to induce ctl responses in mice. two of these emulsions (oil-in-water, o/w, and water-in-oil-in-water, w/o/w) had peptide incorporated at the formulation stage, while the third had peptide added to a pre-formed o/w emulsion. high levels of ctl activity were induced when peptide was dispersed i ...19979364682
malaria toxins from p. chabaudi chabaudi as and p. berghei anka cause dyserythropoiesis in c57bl/6 mice.the lack of correlation between parasitaemia and anaemia in severe malaria indicates that factors in addition to schizont rupture or erythrophagocytosis contribute to anaemia. we asked whether malaria toxin (mt) from plasmodium berghei or p. chabaudi might impair erythropoiesis. daily intraperitoneal injection of mt into c57bl/6 mice induced a transient reduction of rbc values by 25-30% after about 2 weeks, followed by increased haematopoiesis in the spleen as compared to mice receiving uninfect ...19979368897
malaria toxins: effects on murine spleen and bone marrow cell proliferation and cytokine production in vitro.the ability of deproteinated malaria exoantigens from plasmodium falciparum (pf-mt) and p. berghei anka (pba-mt) to activate murine haematopoietic cells was analysed in vitro. malaria toxins (mt) of both plasmodium species induced cell proliferation and the production of ifn-gamma in overnight and long-term (5 days) spleen and bone marrow cultures and a reduction of the number of tnf-alpha spot forming cells (sfc). when added to cells of malaria-experienced animals, mt decreased the number of il ...19979368898
expression of major histocompatibility complex antigens on mouse brain microvascular endothelial cells in relation to susceptibility to cerebral malaria.the physiopathology of experimental cerebral malaria (cm), an acute neurological complication of plasmodium berghei anka (pba) infection, involves interferon-gamma (ifn-gamma) and tumour necrosis factor-alpha (tnf-alpha), two cytokines that are known to modulate major histocompatibility complex (mhc) molecule expression. the aim of this study was to evaluate whether the genetic susceptibility to cm is related to the constitutive or ifn-gamma-induced expression of mhc molecules on brain microvess ...19979370924
synthesis and antimalarial activity in vitro and in vivo of a new ferrocene-chloroquine analogue.the antimalarial activities of ferrocenic compounds mimicking chloroquine and active upon chloroquine-resistant strains of plasmodium falciparum were evaluated. four 7-chloro-4-[[[2-[(n,n-substituted amino)methyl]ferrocenyl]methyl]amino]quinoline derivatives have been synthesized; one of them, 1a, showed high potent antimalarial activity in vivo on mice infected with plasmodium berghei n. and plasmodium yoelii ns. and was 22 times more potent against schizontocides than chloroquine in vitro agai ...19979371235
regulation of heme polymerizing activity and the antimalarial action of chloroquine.mice infected with plasmodium berghei served as donors of erythrocytes with a high level of parasitemia for the study of ferriprotoporphyrin ix (fp) polymerization. six hours after treatment of these mice with 3 micromol of chloroquine per 25 g of body weight, there were significant losses of heme polymerase i (hpa i). for chloroquine-susceptible (cs) p. berghei, the rate of fp polymerization decreased from 541 +/- 42 (mean +/- standard deviation; n = 12) to 51 +/- 19 (n = 8) nmol of fp polymeri ...19979371350
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