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[synthesis of 4-methyl-5-substituted phenoxy-primaquine analogues and preliminary evaluation on their antimalarial activity].on basis of our previous work, seven 4-methyl-5-substituted phenoxy-6-methoxy-8-(1-methyl-4-amino-butylamino)-quinolines (ii2-8) were synthesized and their antimalarial activities were preliminarily evaluated. the target compounds were prepared from 2-nitro-4-methoxy-5-bromo-acetanilide as previously described. the structures of ii2-8 and all of the unknown intermediates were confirmed by elementary and spectral analyses. preliminary biological evaluation revealed that all of ii2-8 exhibited sig ...19947976342
sexual development of malaria parasites is inhibited in vitro by the neem extract azadirachtin, and its semi-synthetic analogues.we have shown that azadirachtin, a compound from the neem tree, azadirachta indica, and selected semi-synthetic derivatives, block the development of the motile male malarial gamete in vitro. changes in the hemiacetal group at position c11 in the molecule result in a loss of activity in this assay. the motility of fully formed male gametes, and other selected flagellated cells, is unaffected by azadirachtin in vitro. these findings raise the possibility of developing azadirachtin-based compounds ...19947980823
antimalarial activity of wr 243251, a dihydroacridinedione.wr 243251 is a dihydroacridinedione that was evaluated for antimalarial blood schizonticidal activity in vitro and in vivo. the in vitro doses calculated to kill 50% of organisms were 11 nm for a chloroquine-susceptible, mefloquine-resistant standard strain and 25 nm for a chloroquine- and pyrimethamine-resistant standard strain. the total dose needed to cure 100% of mice infected with a drug-susceptible strain of plasmodium berghei was 12 to 20 mg/kg of body weight for both oral and subcutaneou ...19947986005
enzymatic amplification of lactate dehydrogenase-elevating virus.to improve the detection of lactate dehydrogenase-elevating virus (ldv), we developed a pcr assay. primers were selected from orf7, encoding nucleocapsid protein vp1. no specific amplification was observed with any other common murine virus or with rnas from the closely related lelystad virus and equine arteritis virus. in experimentally infected mice, ldv could be detected in plasma in both the acute and the persistent phases. ldv was also detected by the pcr in contaminated pools of plasmodium ...19947989557
the small ribosomal subunit rna isoforms in plasmodium cynomolgi.we report the isolation, characterization and analysis of the small subunit rrna genes in plasmodium cynomolgi (ceylon). as in other plasmodium species, these genes are present in low copy number, are unlinked and form two types that are distinct in sequence and are expressed stage specifically. the asexually expressed (type a) genes are present in four copies in the ceylon- and in five copies in the berok-strain. surprisingly, the sexually expressed (type b) gene is present in a single copy. th ...19948005440
subtelomeric structure of plasmodium falciparum chromosomes.previous studies of subtelomeric regions in plasmodium berghei led to the identification of subtelomeric repeats (2.3kb long) present in a variable number at many chromosomal ends. both loss and increase in 2.3kb-repeat copy number are involved in chromosome-size polymorphisms. subtelomeric losses leading to chromosome-size polymorphisms have been described by several authors in p.falciparum where the structure of subtelomeric regions is not known in detail. we therefore undertook their characte ...19947565127
isolation of a distally located gene possibly correlated with gametocyte production ability.previous studies were focussed on the attempt to correlate observable variations in the size of plasmodium berghei chromosomes with the loss of ability to produce viable gametocytes. a temporal coincidence between the appearance of a subtelomeric deletion on p. berghei chromosome 5 and the loss of the ability to produce viable gametocytes was observed in a clone (hpe) directly derived from the high gametocyte-producer clone 8417 during mechanical passages. interestingly enough, three p. berghei ...19947565128
attempted isolation of the gene encoding the 21 kd plasmodium berghei ookinete transmission blocking antigen from plasmodium yoelli and plasmodium vivax.the 21kd ookinete antigen of plasmodium berghei (pbs 21) has been shown to elicit an effective and long lasting transmission blocking immune response in mice. having cloned and sequenced this antigen (paton et al. 1993) the sequence was compared to the genes of the same family previously identified in p. falciparum, p. gallinaceum (kaslow et al. 1989) and p. reichenowi (lal et al. 1990). four conserved areas were identified in this comparison, to which degenerate oligonucleotides were designed. ...19947565129
characterization of the modes of action of anti-pbs21 malaria transmission-blocking immunity: ookinete to oocyst differentiation in vivo.the impact of immune sera, and peripheral blood cells (pbc) from mice immunized with plasmodium berghei ookinetes; and of purified immunoglobulin or fab fragments from anti-pbs21 monoclonal antibody 13.1, upon establishment of oocyst infections in the mosquito was studied. infections were initiated either from gametocyte-infected mice, or membrane feeders which contained either gametocytes or mature ookinetes. pbc from ookinete-immunized mice presented with non-immune serum failed to show any tr ...19947800408
the role of free radicals and antioxidative enzymes in erythrocytes and liver cells in the course of plasmodium berghei and plasmodium vinckei infection of mice.blood schisontocidal test of d0 + d3 type revealed different characteristics of the plasmodium berghei and plasmodium vinckei infection. both types of the rodent plasmodia kill the untreated mice. chloroquine treatment alone does not prevent the death of the p. berghei infected animals and they died at a low level of parasitaemia. the animals cured with chloroquine plus map survive. the infection with p. vinckei produces a high level of parasitaemia and the chloroquine treatment alone prevents t ...19947804719
[histopathologic findings in cd1 albino mice infected with plasmodium berghei in pregnancy. experimental model for pathology of the feto- placental unit in malaria].three study groups of pregnant cd1 albino mice were inoculated intraperitoneally with plasmodium berghei on the 6th (group i), 13th (group ii) and 18th (group iii) day of gestation. two control groups were included, one of non pregnant mice (group iv) and the other of pregnant non inoculated mice. group iv was inoculated in the same day of group i. all mice of these two groups died. of the 20 mice in group ii 8 died, 7 delivered prematurely and 5 gave birth of low birth weight offspring. the 15 ...19947808800
immunoliposomes in vivo.attachment of antibodies to the surface of liposomes was performed to confer specificity for a certain cell or organ expressing the targeted antigenic determinant. these so-called immunoliposomes are expected to be applied as targeted drug carriers. in this article, the literature concerning in vivo studies of the targeting of immunoliposomes to various sites in the body is reviewed. the anatomical, physiological, and pathological constraints and current progress are described. moreover, perspec ...19947820456
modulation of resistance to chloroquine by ascorbic acid and cyproheptadine in plasmodium berghei in vivo. 19947821987
synthesis and biological evaluation of some potential antimalarials.malaria chemotherapy has been well reviewed. malarial parasites gaining resistance is the major problem in the treatment of the disease. some strains are resistant not only to chloroquine but also to amodiaquine. few new drugs are available or foreseen for the near future. the principal metabolite of cinchona alkaloids appears to be oxidized at c-2. this may result in a loss of activity. pinder and burger suggested that a trifluoromethyl group will prevent this oxidation. so 2-tribromomethyl-6-m ...19947826202
[present status and new approach to anti-parasite therapy].new highly effective molecules have been developed for the treatment of human parasites due to the development resistances and newly described types of parasitosis. in man as in animals, chemoresistant strains of parasites are rare, even for plasmodium species where decreased sensibility has been observed basically due to monotherapies given for too short periods. many resistance mechanisms have been elucidated. most antiparasite drugs are metabolized in the liver and alterations in the mitochon ...19947831211
immunization with irradiated plasmodium berghei sporozoites induces il-2 and ifn gamma but not il-4.protective immunity against plasmodium induced by immunization with irradiated sporozoites (spz) depends on both humoral and cellular responses. although circumsporozoite protein (csp)-specific cytolytic t lymphocyte responses have been established as an effector system, other cell types are required for protection. we have previously demonstrated that although protective immunity and t cell proliferative reactivity to spz are mouse strain- and spz dose-dependent, no correlation between the two ...19947838597
effect of an experimental malaria infection on the metabolism of phenacetin in the rat isolated perfused liver.1. the effect of infection with the rodent malaria parasite plasmodium berghei on the metabolism of phenacetin has been investigated in a rat isolated perfused liver preparation. 2. a bolus dose of phenacetin (10 mg) was introduced into the perfusate reservoir of both control (n = 4) and malaria-infected (n = 4) liver preparations, and samples of bile and perfusate were collected (0-4 h) for hplc analysis of phenacetin, paracetamol and its phase ii metabolites. 3. whereas malaria had no effect o ...19947839701
antimalarial activity of cyclosporins a, c and d.cyclosporin a (csa) is an immunosuppressive drug widely used in organ transplants. it is also accumulated by the erythrocyte, a site that accommodates one of the stages of malaria parasite. we observe that csa and its less potent immunosuppressive analogues csc and csd were as effective as chloroquine in inhibiting p. berghei malaria parasite development in vivo (when administered orally) and p. falciparum parasite in vitro. they were, however, not inhibitory to the liver stages and the gametocy ...19947839946
anti-inflammatory, antipyretic and anti-malarial activities of a west african medicinal plant--picralima nitida.a preliminary pharmacological screening of the methanolic extract of picralima nitida fruit was carried out. the extract showed potent and dose-dependent anti-inflammatory, antipyretic and anti-malarial activities. given intraperitoneally, it inhibited carrageenan-induced rat paw oedema with ic50 of 102mg/kg, and with the highest dose tested (300mg/kg) producing 72.2% inhibition. on the lps-induced pyrexia in rabbits, 50mg/kg of the extract produced a mean percentage antipyrexia of (38.7%) compa ...19947839951
dynamics of telomere turnover in plasmodium berghei.non-uniform composition in telomeric repeats at the extremities of plasmodium chromosomes was exploited in order to obtain data on intraclonal diversification of telomeric sequences, relevant for the study of telomere regeneration dynamics. families of sibling telomeric clones were obtained from several chromosomal ends of plasmodium berghei, and analysed so as to determine the exact points from which individual clones start to diverge. as much as 90% of the telomeric tract appears to be subject ...19947845395
[effect of trifluoroacetoprimaquine on erythrocytic schizonts of rodent malaria].effect of trifluoroacetoprimaquine oxalate (m8506) and primaquine (pq) on blood schizonts of plasmodium berghei were determined using the method of 4-day suppressive test within extended observation period of 60 d. when mice infected with plasmodium berghei anka strain were treated ig with m8506 or pq at a same daily dose of 20 mg/kg for 4 d, the cure rates were 100% and 90%, respectively. the two drugs also showed prominent suppressive effects on chloroquine-resistant p. berghei ns line and pyr ...19947867162
requirements for glycosylphosphatidylinositol attachment are similar but not identical in mammalian cells and parasitic protozoa.the general features of the glycosylphosphatidylinositol (gpi) signal have been conserved in evolution. to test whether the requirements for gpi attachment are indeed the same in mammalian cells and parasitic protozoa, we expressed the prototype gpi-linked protein of trypanosoma brucei, the variant surface glycoprotein (vsg), in cos cells. although large amounts of vsg were produced, only a small fraction became gpi linked. this impaired processing is not caused by the vsg ectodomain, since repl ...19948163550
new, antimalarial, tricyclic 1,2,4-trioxanes: evaluations in mice and monkeys.we have concluded initial preclinical studies with synthetic trioxanes numbered 3-9 and have compared them with artemisinin (numbered 1) using cd-1 mice infected with plasmodium berghei. based on their antimalarial effectiveness in mice, two of these synthetic trioxanes were selected for evaluation in aotus monkeys infected with multidrug-resistant (mdr) p. falciparum. trioxane numbered 8 (12 and 48 mg/kg), trioxane numbered 9 (12 and 48 mg/kg) and arteether (numbered 2, 48 mg/kg) were administe ...19948166360
aminopeptidases from plasmodium falciparum, plasmodium chabaudi chabaudi and plasmodium berghei.using fluorogenic substrates and polyacrylamide gels we detected in cell-free extracts of plasmodium falciparum, plasmodium chabaudi chabaudi and plasmodium berghei only a single aminopeptidase. a comparative study of the aminopeptidase activity in each extract revealed that the enzymes have similar specificities and kinetics, a near-neutral ph optima of 7.2 and are moderately thermophilic. each has an apparent molecular weight of 80,000 +/- 10,000, determined by high performance liquid chromato ...19948167617
studies on the immunogenicity of a recombinant ookinete surface antigen pbs21 from plasmodium berghei expressed in escherichia coli.plasmodium berghei ookinete surface antigen (pbs21), was produced as a fusion product with maltose binding protein (mbp) in escherichia coli and used to induce transmission-blocking immunity in mice. specificity of induced antibody was confirmed by western blotting with native ookinete pbs21, and by the indirect immunofluorescent antibody test on ookinete bloodfilms. immunized mice were infected with p. berghei and transmission to anopheles stephensi mosquitoes determined by both the intensity a ...19948152832
demonstration of heat-shock protein 70 in the sporozoite stage of malaria parasites.three monoclonal antibodies generated by immunization of mice with plasmodium berghei-infected red blood cells were found to react with the 75-kda heat-shock protein (hsp70) present in liver stages and erythrocytic forms of the parasites. these antibodies were shown to react with a recombinant protein encoding the carboxyl terminal half of pfhsp70 (aa 365-681). differently from earlier results, we clearly demonstrated that hsp70 was also expressed in the sporozoite stage, using these monoclonal ...19948153120
effect of pyrimethamine resistance on sporogony in a plasmodium berghei/anopheles stephensi model.a pyrimethamine-resistant line of plasmodium berghei was derived by treating infected mice with high doses of pyrimethamine and selecting for recrudescence. this resistant line was compared with the parental pyrimethamine-sensitive line in order to ascertain whether drug resistance is associated with a biological advantage. overall, the pyrimethamine-resistant line is quite similar to the sensitive line, except that it proceeds through sporogonic development more slowly than the pyrimethamine-se ...19948119374
photoaffinity labeling of the t cell receptor on cloned cytotoxic t lymphocytes by covalent photoreactive ligand.the interaction of the t cell antigen receptor with a photoreactive antigenic peptide derivative bound covalently to the h-2kd (kd) molecule was studied by photoaffinity labeling on cloned, cd8 positive cytotoxic t lymphocytes. the kd-restricted plasmodium berghei circumsporozoite peptide 253-260 (yips-aeki) was conjugated with iodo-4-azidosalicylic acid at the n terminus and with 4-azidobenzoic acid at the t cell receptor residue lys-259. cell-associated or soluble kd molecules were photoaffini ...19948119892
comparison of in vivo and in vitro antimalarial activity of artemisinin, dihydroartemisinin and sodium artesunate in the plasmodium berghei-rodent model.the in vitro and in vivo antimalarial activity of artemisinin, artesunate and dihydroartemisinin has been compared using the plasmodium berghei-rodent model. drugs were added to synchronized short-term in vitro cultures of the erythrocytic stages and inhibition of parasite development was determined by measuring dna synthesis by flow cytometry. dihydroartemisinin was the most effective drug. ic50 values of artemisinin, artesunate and dihydroartemisinin were 1.9, 1.1 and 0.3 x 10(-8) m, respectiv ...19948082988
possible isozyme-specific effects of experimental malaria infection with plasmodium berghei on cytochrome p450 activity in rat liver microsomes.we have investigated the effect of experimental malaria infection on rat cytochrome p450-mediated drug metabolism using ethoxyresorufin and metoprolol as probe compounds. malaria infection caused a significant reduction in total intrinsic clearance of ethoxyresorufin in both low and high parasitaemia malaria compared with control (control 18.7 +/- 7.2; low parasitaemia 10.5 +/- 4.1; high parasitaemia 4.3 +/- 1.4 ml min-1). however, clearance of metoprolol was unchanged in malaria infection compa ...19948083805
picosecond fluorescence spectroscopy of a single-chain class i major histocompatibility complex encoded protein in its peptide loaded and unloaded states.the tryptophan fluorescence properties of two different peptide complexes of the single-chain h-2kd (sc-kd) were studied by means of the single-photon counting technique. the latter enables time-resolved measurements of fluorescence intensity and anisotropy decay parameters relevant to structural and dynamic properties of proteins. while the isolated sc-kd molecules in their 'original' purified form represent the unloaded state, i.e., containing endogenous low-affinity peptides, the loaded sc-kd ...19948088870
antimalarial activity of dihydroartemisinin derivatives by transdermal application.in addition to artelinic acid, which was demonstrated previously to possess good prophylactic as well as curative antimalarial activity against plasmodium berghei by transdermal administration, seven artemisinin derivatives in a gel formulation were assessed for their antimalarial activities in this study. artemisinin, the parent compound of the series, showed moderate prophylactic but poor curative activity. although methyl artelinate was more active against p. berghei than artelinic acid and s ...19948024074
hemoglobins from plasmodium-infected rat erythrocytes: functional and molecular characteristics.aiming to evaluate the mechanisms responsible for altered o2-transporting properties in blood of plasmodium-infected animals, stripped (cofactor-free) hemoglobin (hb) solutions were prepared from infected erythrocytes (ie) and noninfected erythrocytes (nie) of rats inoculated with plasmodium berghei bergei for functional and structural characterization. at normal intraerythrocytic ph (+/- 7.2), hb from ie showed a higher affinity, a larger bohr effect, and lower sensitivities to 2,3-diphosphogly ...19948025289
remarkable activation of polyamine biosynthesis in hematopoiesis and hyperplasia of spleen in mice with hemolytic anemia caused by infection with plasmodium berghei.ornithine decarboxylase (odc) activity was markedly induced in the spleen of mice infected with plasmodium berghei, showing maximal activity at 8 days after the infection. the increase of spleen weight, on the other hand, reached its peak after 14 days of infection. in the blood of p. berghei-infected mice, no increase of odc activity was observed. this indicated that odc was induced in the spleen cells, but not in the parasites themselves which existed in the blood. polyamines (putrescine, sper ...19948026898
characterization of the effector mechanisms of a transmission-blocking antibody upon differentiation of plasmodium berghei gametocytes into ookinetes in vitro.the transmission-blocking monoclonal antibody 13.1, which recognizes the ookinete surface antigen pbs21 of plasmodium berghei, and an igg2a isotype control antibody 26.37 were purified by caprylic acid and ammonium sulphate precipitation. fab fragments were prepared by papain digestion. igg but not fab from antibody 13.1 reduced ookinete formation by p. berghei in culture by as much as 94% at a concentration of 100 micrograms/ml. there was little difference in antibody efficacy in the range 6.25 ...19948058360
murine aids protects mice against experimental cerebral malaria: down-regulation by interleukin 10 of a t-helper type 1 cd4+ cell-mediated pathology.the retrovirus lp-bm5 murine leukemia virus induces murine aids in c57bl/6 mice that has many similarities with human aids; plasmodium berghei anka causes experimental cerebral malaria in the same strain of mice. the outcome of malaria infection was studied in mice concurrently infected with the two pathogens. the retrovirus significantly reduced the gravity of the neurological manifestations associated with plasmodium berghei anka infection. the protection against experimental cerebral malaria ...19948058763
plasmodium sporozoites possess both positively and negatively charged sites accessible on their surface.studies were conducted on the distribution of anionic and cationic sites on the surface of intact plasmodium berghei and p. yoelii sporozoites. anionic and cationic ferritins were used as probes for electron microscope studies and fluorescein conjugates of the same charged ferritins were used for correlative studies by fluorescence light microscopy. we found that the surfaces of mature sporozoites from mosquito salivary glands possess both negatively and positively charged sites that are accessi ...19948064519
effects of plasmodium berghei (apicomplexa) on nippostrongylus brasiliensis (nematoda) infection in the mouse, mus musculus.ova and free oxygen radical production and relative peripheral eosinophilia during single and concurrent infections in mice with p. berghei and n. brasiliensis were investigated. prolonged helminth patent periods indicate that nippostrongylus self-cure in concurrently infected mice was suppressed. differential white blood cell determinations showed that the relative number of peripheral blood eosinophils steadily increased (p < or = 0.05) during a nippostrongylus infection when compared to nonin ...19948070956
experiments on the possible role of leeches as vectors of animal and human pathogens: a light and electron microscopy study.the presence and survival of pathogens inside the gut of leeches were studied by means of light and electron microscopy. in african leeches from cameroon, blood was serologically positive for human immunodeficiency virus (hiv) and hepatitis b; blood of hirudo medicinalis bought in german pharmacies contained up to 11 different species of bacteria. in experiments done at low (3 degrees c) and high (22 degrees, 32 degrees c) temperatures, it was shown that ingested red and white blood cells surviv ...19948073013
regular initiation of translation of plasmodium berghei aldolase-2 after pre-mrna splicing.in plasmodium falciparum aldolase a uag or a regular aug codon has been proposed for the initiation of ribosomal protein synthesis. a uag codon present at the beginning of the coding sequence of the aldolase 2 gene (aldo-2) of plasmodium berghei is not recognised in vitro as an initiation codon, which suggests addition of a regular aug codon by mrna splicing. sequence analysis of cdna amplified by the reversed polymerase chain reaction reveals addition of an atg codon with a splice donor consens ...19948008025
inhibitory action of the anti-malarial compound atovaquone (566c80) against plasmodium berghei anka in the mosquito, anopheles stephensi.the activity of atovaquone against plasmodium berghei anka during sporogonic development has been examined. anopheles stephensi mosquitoes were fed on gametocyte infected mice which had been treated 8 h previously with atovaquone or diluent alone. mosquito midguts were examined for oocysts, and salivary gland infections were estimated using an elisa for the circumsporozoite protein (csp). the number of oocysts per midgut fell by at least 97% when mosquitoes were fed on mice dosed with 0.1-10 mg ...19948008451
ro 42-1611 (arteflene), a new effective antimalarial: chemical structure and biological activity.the discovery of the natural peroxides qinghaosu (arteannuin a, artemisinin) (1) and yingzhaosu a (3) from traditional chinese herbal medicines was a major advance in the search for new antimalarials (fig. 1). whereas qinghaosu can be produced from natural sources and has been well studied, yingzhaosu a has never been available for full evaluation as anti-malarial. we have designed a synthesis of the novel ring system present in yingzhaosu a, the 2,3-dioxabicyclo[3.3.1]nonane and prepared a seri ...19947899801
antimalarial activity of the bicyclic peroxide ro 42-1611 (arteflene) in experimental models.the sesquiterpene peroxide ro 42-1611 (arteflene), a synthetic derivative of yingzhaosu, was evaluated extensively against various drug-sensitive and drug-resistant lines of plasmodium falciparum in vitro and p. berghei in vivo in mice. the potential therapeutic and prophylactic activities were studied comparatively with the standard antimalarials chloroquine, mefloquine and quinine, as well as qinghaosu and the derivatives artemether and artesunic acid. experimentally arteflene proved to be a h ...19947899802
immunoglobulin g2a isotype may have a protective role in plasmodium berghei nk65 infection in immunised mice.all cba mice that had been immunised by means of four successive inoculations of plasmodium berghei nk65, each inoculation being followed by chemotherapy, survived an intravenous challenge inoculation of parasite, with 4/12 mice developing patent parasitaemia that resolved within 2 weeks. in contrast, all non-immunised control mice died before the 10th day post-challenge. examination of sera for antibodies revealed that the immunised mice, all of which survived the challenge, had significantly h ...19947886031
mechanisms of pyrimethamine resistance in two different strains of plasmodium berghei. 19947891743
cure with cisplatin (ii) or murine malaria infection and in vitro inhibition of a chloroquine-resistant plasmodium falciparum isolate.antiplasmodium properties of cisplatin [cis-platinum (ii) diamine dichloride], a neoplastic drug, have been assessed in in vivo and in vitro model systems of malarial parasite. a well-tolerated dose of 6 mg/kg body weight of the compound cured the mice infected with plasmodium berghei and the amount of cisplatin required for in vitro inhibition (ic50) of a chloroquine-resistant plasmodium falciparum isolate was smaller than either chloroquine or quinine. the minimum inhibitory concentration (mic ...19947739147
in situ detection of pbs21 mrna during sexual development of plasmodium berghei.the patterns of expression of ribosomal rna and mrna encoding the parasite surface antigen pbs21 have been investigated during the sexual stages of development of the malaria parasite, plasmodium berghei, using the technique of non-radioactive in situ rna hybridisation. an rna probe complementary to a region of the small subunit of p. berghei ribosomal rna hybridised to parasites at all stages of development in a smear of blood taken from mice infected with p. berghei. messenger rna encoding pbs ...19947739665
differential expression in blood stages of the gene coding for the 21-kilodalton surface protein of ookinetes of plasmodium berghei as detected by rna in situ hybridisation.the developmentally regulated transcription of the gene encoding the ookinete surface protein, pbs21, has been investigated in the rodent malaria parasite, plasmodium berghei, by rna in situ hybridisation using fluorescently labelled dna probes. we used a procedure that will allow the visualisation of cytoplasmic mrna in the parasite and of high copy dna repeats in the nucleus. specific hybridisation to pbs21 mrna occurred in the cytoplasm of female gametocytes, zygotes and ookinetes, while asex ...19947739671
conserved location of genes on polymorphic chromosomes of four species of malaria parasites.the number of chromosomes and the chromosomal location and linkage of more than 50 probes, mainly of genes, have been established in four species of plasmodium which infect african murine rodents. we expected that the location and linkage of genes would not be conserved between these species of malaria parasites since extensive inter- and intraspecific size differences of the chromosomes existed and large scale internal rearrangements and chromosome translocations in parasites from laboratory li ...19947739674
nitric oxide: cytokine-regulation of nitric oxide in host resistance to intracellular pathogens.to discover how nitric oxide (no) synthesis is controlled in different tissues as cells within these tissues combat intracellular pathogens, we examined three distinctively different experimental murine models designed for studying parasite-host interactions: macrophage killing of leishmania major; nonspecific protection against tularemia (francisella tularensis) by mycobacterium bovis (bcg); and specific vaccine-induced protection against hepatic malaria with plasmodium berghei. each model para ...19947537721
[casual influence of the stimulation of macrophage production by proteose-peptone, in the experimental infection of mice by plasmodium berghei].proteose-peptone is a known powerful stimulator of macrophages. this stimulation was studied in an experimental malaria infection model, using plasmodium berghei in mice. parasitemia and mortality did not change in stimulated animals, and macrophage mobilization, contrary to other published papers, was not effective to increase either parasite levels in the blood or mortality.19947610336
induction of nitric oxide synthase protects against malaria in mice exposed to irradiated plasmodium berghei infected mosquitoes: involvement of interferon gamma and cd8+ t cells.exposure of balb/c mice to mosquitoes infected with irradiated plasmodium berghei confers protective immunity against subsequent sporozoite challenge. immunized mice challenged with viable sporozoites develop parasitemia when treated orally with substrate inhibitors of nitric oxide synthase (nos). this suggests that the production of nitric oxide (no) prevents the development of exoerythrocytic stages of malaria in liver. liver tissue from immunized mice expressed maximal levels of mrna for indu ...19947516412
antibody-dependent neutrophil-mediated parasite killing in non-lethal rodent malaria.the effects of administrating recombinant human granulocyte colony-stimulating factor (rhg-csf) and passively transferring immune serum on infection with an attenuated variant of plasmodium berghei xat (pb xat), in severe combined immunodeficiency (scid) mice were examined. in immune competent (c.b-17) mice, the attenuated parasite infection was inevitably self-resolving and degenerating forms inside erythrocytes appeared, coinciding with the drop in parasitaemia, whereas scid mice were unable t ...19947532294
flow cytometry in malaria detection. 19947533245
co-localization of inducible-nitric oxide synthase and plasmodium berghei in hepatocytes from rats immunized with irradiated sporozoites.both cd8+ t cells and ifn-gamma (ifn-gamma) are important components in the regulation of inducible-nitric oxide synthase (inos) which contribute to liver stage anti-malarial activity in rodents immunized with irradiated sporozoites. ifn-gamma, provided by malaria-specific cd8+ t cells, stimulates liver cells to produce nitric oxide (no) for the destruction of infected hepatocytes or the parasite within these cells. to identify the cell source of inos in livers from brown norway rats challenged ...19957534796
developmental changes in the circumsporozoite proteins of plasmodium berghei and p. gallinaceum in their mosquito vectors.the circumsporozoite (cs) protein covers the surface of the sporozoite of plasmodia. its role in the development of the malaria parasite in mosquito vectors remains unknown. cs-epitope-containing proteins appear on undifferentiated oocysts on day 7 in plasmodium berghei and on day 5 in p. gallinaceum as demonstrated by indirect fluorescence antibody tests using monoclonal antibodies directed against the cs-protein repeats. the three-dimensional distribution of the cs-epitope-containing proteins ...19957536921
status of hepatic glutathione-s-transferase(s) during plasmodium berghei infection and chloroquine treatment in mastomys natalensis.plasmodium berghei infection in mastomys natalensis impaired the hepatic mitochondrial, microsomal and cytosolic glutathione-s-transferase(s) activity with 1-chloro-2,4-dinitrobenzene as substrate. the enzyme activity was concomitantly decreased with rise in parasitaemia. the decreased enzyme activity due to infection was almost normalized with oral treatment of 16 mg (kg body wt)-1 of chloroquine for 4 days.19957622326
expression of the plasmodium berghei ookinete protein pbs21 in a baculovirus-insect cell system produces an efficient transmission blocking immunogen.a surface protein of plasmodium berghei ookinetes, pbs21, was expressed in a baculovirus-insect cell system in cell culture and in heliothis virescens larvae. groups of balb/c mice received two intraperitoneal inoculations of either i) tris-buffer or homogenized h. virescens larvae infected with wild-type baculovirus; ii) enriched, homogenized ookinetes, or iii) homogenized h. virescens larvae expressing recombinant pbs21 (rpbs21). all animals immunized with ookinetes or with rpbs21 had high tit ...19957624157
plasmodium berghei: implication of intracellular glutathione and its related enzyme in chloroquine resistance in vivo.glutathione (gsh) plays a critical role in the detoxication and the protection of cells against oxidative stress. in the present study we examined the relationship between the intracellular gsh levels as well as glutathione s-transferase (gst), glutathione reductase (gr), and glutathione peroxidase (gpx) activities and how they relate to plasmodium berghei resistance to chloroquine. resistant strains (cqr30 and cqr60) were selected in vivo from a sensitive strain (nk65). marked increases in gsh ...19957628559
plasmodium berghei: selection of mefloquine-resistant parasites through drug pressure in mosquitoes.mefloquine is an antimalarial drug with schizonticidal activity on blood-stage parasites. studies of the role of mefloquine on the development of plasmodium berghei anka in anopheles stephensi have been carried out that showed a dose-dependent effect on the sporogonic cycle of these parasites, with changes in the numbers of oocysts and the extent of sporozoite invasion of salivary glands. in this study, we show that mefloquine-resistant p. berghei anka blood stage parasites could be selected thr ...19957628567
activities of extracts and naphthylisoquinoline alkaloids from triphyophyllum peltatum, ancistrocladus abbreviatus and ancistrocladus barteri against plasmodium berghei (anka strain) in vitro.extracts from three tropical medicinal plant species belonging to the dioncophyllaceae (triphyophyllum peltatum) and the ancistrocladaceae (ancistrocladus abbreviatus and ancistrocladus barteri), and pure naphthylisoquinoline alkaloids derived from these species have been examined for the first time for their activity against asexual blood forms of plasmodium berghei (anka strain) in vitro. these activities were considerable and comparable with those earlier found against erythrocytic forms of p ...19957650949
transgenic mice expressing high levels of soluble tnf-r1 fusion protein are protected from lethal septic shock and cerebral malaria, and are highly sensitive to listeria monocytogenes and leishmania major infections.mice bearing a transgene coding for a soluble tumor necrosis factor receptor type 1 (tnfr1)-fcigg3 fusion protein and placed under the control of the alpha-1-antitrypsin gene promoter were generated. depending on the mouse line, blood levels of the protein ranged from 25 ng/ml to over 100 micrograms/ml; this level of expression was most often transmitted to the transgene-bearing progeny as a relatively stable feature. high-expressor mice were completely resistant to lipopolysaccharide-induced sh ...19957664802
inhibition of plasmodium berghei liver schizont development and reduction of cytokine production capacity in rats by dietary fish oil supplementation.experimental primary infection with plasmodium berghei in rats is known to be influenced by several cytokines. dietary supplementation of n-3 fatty acids has been shown to influence cytokine production capacity and to protect mice from cerebral malaria. we investigated the effect of dietary fish oil (fo) supplementation on cytokine and nitric oxide production and liver schizont development in male brown norway rats. control groups were fed either a corn oil-supplemented diet (co) or standard lab ...19957677226
monopalmitic acid-peptide conjugates induce cytotoxic t cell responses against malarial epitopes: importance of spacer amino acids.cytolytic t cells (ctl) play a critical role in providing protection against the liver stage of malaria infection. previous investigations have shown that induction of ctl against peptide or proteins can be achieved by attachment of lipids. in the present study, we used the plasmodium berghei circumsporozoite protein ctl epitope (syipsaeki (pl76)). this peptide with cysteine-serine (cs) as spacer amino acids was coupled to palmitic acid (pa). the same ctl epitope containing only an extra serine ...19957540640
effect of mosquito age and reproductive status on melanization of sephadex beads in plasmodium-refractory and -susceptible strains of anopheles gambiae.malaria-refractory and -susceptible strains of the mosquito vector, anopheles gambiae, differ in their response to negatively-charged sephadex cm-25 beads. cm-25 beads elicit a much stronger melanization reaction in refractory mosquitoes than in susceptible mosquitoes. light microscopic and scanning electron microscopic studies documented a progression from early stages with small spots of melanin adhering to cm-25 beads to late stages where spots had grown and coalesced to form a dark dense cap ...19957544819
[relationship between tumour necrosis factor and anemia of malaria].in this paper, the relation between the level of the reactive oxygen species (ros) and relevant free radicals in the blood plasma of the balb/c mice infected with plasmodium berghei anka strain and their erythrocytic deformability (ed), and the relation between the ed and the hb indices of these mice were studied by chemiluminescence (cl), induced cl (icl) and laser diffraction method. the results indicated that the ed decreased with the increase of the level of ros and free radicals in blood pl ...19957554164
attenuated immunogenic parasites are essential in the transfer of immunity to virulent plasmodium berghei.a less virulent parasite of plasmodium berghei k173 was isolated that induced immunity against the more virulent parasite. immunity to this parasite but not to the virulent one, could be transferred by immune spleen cells but not by immune lymph node cells. however, the immune spleen cells did transfer immunity to the virulent strain if accompanied by infection with viable parasites of the less virulent strain, but only if they were allowed to proliferate for a period of 1 week before challenge ...19957558142
enhanced depletion of glutathione and increased liver oxidative damage in aflatoxin-fed mice infected with plasmodium berghei.the effect of dietary aflatoxins b1 and g1 and plasmodium berghei infection on glutathione (gsh) levels and liver status in mice was investigated. three days after intraperitoneal injection of 0.1 x 10(6) parasitized red blood cells into the mice, there was a significant fall in blood glutathione levels accompanied by a significant increase in serum cholinesterase and liver malonic dialdehyde levels in the mice fed aflatoxin compared with those in the control group. the results suggested that ma ...19957747309
use of synthetic peptide libraries for the h-2kd binding motif identification.to identify kd-binding peptides, an approach based on small peptide libraries has been developed. these peptide libraries correspond to all possible single-amino acid variants of a particular kd-binding peptide, syipsaeyi, an analog of the plasmodium berghei 252-260 antigenic peptide syipsaeki. in the parent sequence, each position is replaced by all the genetically encoded amino acids (except cysteine). the multiple analog syntheses are performed either by the divide couple and recombine method ...19957756754
effect of a cecropin-like synthetic peptide (shiva-3) on the sporogonic development of plasmodium berghei.the effect of a synthetic cecropin-like peptide, shiva-3, on in vitro ookinete development and on the early sporogonic stages of plasmodium berghei in the midgut of anopheles albimanus was investigated. peptide concentrations of 75 and 100 microm were effective (p < 0.05) in reducing ookinete production and the number of infected mosquitoes in almost all experiments. these peptide concentrations in the midgut were not toxic for the survival of the mosquitoes. complete inhibition was obtained if ...19957758540
plasmodium berghei infection: dichloroacetate improves survival in rats with lactic acidosis.the kinetics of plasmodium berghei infection and the development of lactic acidosis, hypoglycemia, and anemia were defined in young wistar rats. this model of metabolic dysfunction, which is similar to that of severe human malaria, was used to test the hypothesis that dichloroacetate, a treatment for lactic acidosis, prolonged survival in rats receiving a single antimalarial dose of quinine (20 mg/kg). rats with hyperlactatemia (lactate > 5 mmol/liter, n = 183) were randomized to receive either ...19957758543
stable transfection of malaria parasite blood stages.genetic manipulation of malaria parasites would revolutionize the study of this group of pathogens and have implications for vaccine and drug development. this report describes the stable, drug-selectable genetic transformation of the clinically relevant intracellular blood stages of a malaria parasite. a plasmid transfection vector carrying the gene locus that encodes a drug-resistant form of the bifunctional enzyme dihydrofolate reductase-thymidylate synthase from the rodent malaria parasite p ...19957761856
characterization of a sporozoite antigen common to plasmodium falciparum and plasmodium berghei.previous studies demonstrated that immunization with plasmodium falciparum sporozoites protected mice against plasmodium berghei sporozoite infection and that this cross-protection was mediated, at least in part, by anti-sporozoite antibody. the experiments presented in this report show that serum and monoclonal antibodies derived from these protected mice identify a novel 42/54-kda antigen (designated circumsporozoite protein 2 or csp-2) in both p. falciparum and p. berghei sporozoites. anti-cs ...19957770087
detection of 54-kda protein overexpressed by chloroquine-resistant plasmodium berghei anka strain in pyronaridine-resistant p berghei anka strain.a 54-kda protein overexpressed by chloroquine-resistant (cr) plasmodium berghei anka strain was first reported by us. this study is conducted to detect the protein in pyronaridine-resistant (pr) p berghei anka strain.19957771189
inhibitory activity of the anti-malarial atovaquone (566c80) against ookinetes, oocysts, and sporozoites of plasmodium berghei.ookinete formation from mature plasmodium berghei gametocytes in vitro was partially inhibited by 0.05-0.1 microm atovaquone and almost totally blocked at a concentration of 0.25 microm. microgametocyte exflagellation was not affected by atovaquone at concentrations up to 300 microm. ookinete formation was also inhibited in culture when addition of 0.20 microm atovaquone was delayed by 4 hr, by which time dna replication was likely to have been completed. inhibition of ookinete formation by atov ...19957776134
antimalarial activity of novel ring-contracted artemisinin derivatives.bromoacetal 2 undergoes a novel ring-contracted reaction to give the aldehyde 3 in the presence of dbu or triethylamine. the aldehyde 3 is reduced to the alcohol 4 and oxidized to the carboxylic acid 5. the alcohol 4 reacts with dihydroartemisinin to give the two diastereoisomers 38 and 39. all the compounds were tested for antimalarial activity in mice infected with chloroquine sensitive plasmodium berghei. if the activity of a compound was comparable to that of the standard compound, such as a ...19957783124
chloroquine encapsulated in malaria-infected erythrocyte-specific antibody-bearing liposomes effectively controls chloroquine-resistant plasmodium berghei infections in mice.the suitability of liposomes as drug carriers in the treatment of drug-resistant rodent malaria was examined after covalently attaching f(ab')2 fragments of a mouse monoclonal antibody (mab), mab f10, raised against the host cell membranes isolated from the plasmodium berghei-infected mouse erythrocytes, to the liposome surface. the antibody-bearing liposomes thus formed specifically recognized the p. berghei-infected mouse erythrocytes under both in vitro and in vivo conditions. no such specifi ...19957695303
the effect of chemical substitution on the metabolic activation, metabolic detoxication, and pharmacological activity of amodiaquine in the mouse.the adverse reactions associated with the antimalarial amodiaquine (aq), agranulocytosis and hepatotoxicity, have been attributed to the bioactivation of the drug to a quinone imine metabolite. therefore the effect of chemical modification on the metabolism of aq was studied, with particular reference to the prevention of bioactivation and the introduction of glucuronidation. glutathione conjugates of aq and desethylaq were eliminated in bile after intraportal administration of [3h]aq (54 mumol/ ...19957714794
chaperonin-like repeats in a 34-kda plasmodium berghei phosphoprotein. 19957731926
long-term survival of plasmodium sporozoites in vitro. 19957731930
maintenance of protective immunity against malaria by persistent hepatic parasites derived from irradiated sporozoites.immunization of rodents and humans with irradiation-attenuated malaria sporozoites confers preerythrocytic stage-specific protective immunity to challenge infection. this immunity is directed against intrahepatic parasites and involves t cells and interferon gamma, which prevent development of exoerythrocytic stages and subsequent blood infection. the present study was undertaken to determine how protective immunity is achieved after immunization of rodent hosts with irradiated plasmodium berghe ...19957732032
plasmodium falciparum and plasmodium berghei: effect of magnesium on the development of parasitemia.the in vitro growth of plasmodium falciparum was reduced by 35 and 43% through high concentrations (5 mmole/liter) of magnesium in rpmi medium and magnesium-free medium, respectively, after 48 hr, whereas no significant inhibition could be observed under these conditions after 24 hr cultivation in the respective medium. levels of magnesium between 0.5 and 3 mmole/liter showed no inhibitory effect on the in vitro growth of p. falciparum even after long-term exposure for 7 days. the 50 and 90% chl ...19957895830
decrease in platelet survival and total platelet sialic acid concentration in rats infected with plasmodium bergei bergei.suckling wistar rats aged 3-5 weeks were infected through their dorsal tail vein with p. berghei berghei passed in swiss albino mice. platelet recovery and platelet survival using 51cr-labelled heterologous platelets obtained from adult wistar rats were determined in the infected animals on different post-infection days and on a group of non-infected rats as controls. total platelet sialic acid was also determined in the same groups of animals. the results showed reduced platelet recovery, short ...19957495199
synthesis and biological activity of novel metal complexes of 2-acetylpyridine thiosemicarbazones.2-acetylpyridine-(2-methylthiosemicarbazone), 2-acetylpyridine-(4-methylthiosemicarbazone), 2-acetylpyridine-(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. they were studied also for their antimalarial activity and for toxicity in vivo. the platinum metal chelates exhibited significant activity against a wide ...19957495474
experimental cerebral malaria: possible new mechanisms in the tnf-induced microvascular pathology.in order to contribute to the prevention of malaria morbidity and mortality, especially in endemic zones, we have carried out a series of studies on cytokine interactions in an experimental model of cerebral malaria (cm). this rapidly lethal syndrome develops, in some strains of mice, upon infection with plasmodium berghei anka (pba). a crucial mediator of neurovascular lesions appears to be tnf, found in high amounts in relation with cerebral complications, in both experimental and human cm. in ...19957900436
activity of azithromycin as a blood schizonticide against rodent and human plasmodia in vivo.we compared the efficacy of azithromycin to the clinical antimalarial doxycycline in plasmodium berghei-infected mice and in p. falciparum-infected aotus monkeys. when mice were administered drug orally twice a day for three days, the minimum total dose of azithromycin that cured all mice was 768 mg/kg. doxycycline at a dose of 1,536 mg/kg cured no mice. the efficacy of fast-acting blood schizonticides (quinine, halofantrine, artemisinin) against p. berghei was augmented by azithromycin. in monk ...19957872444
plasmodium berghei: production and quantitation of hepatic stages derived from irradiated sporozoites in rats and mice.immunization with irradiated-attenuated malaria sporozoites has been shown to protect both rodents and humans against a homologous sporozoite challenge. irradiated-attenuated sporozoites retain their capacity to invade hepatocytes and transform into trophozoites without undergoing complete schizogony. as a result, the minute size of these trophozoites (4-8 microns) makes their detection by conventional microscopy difficult. an additional problem lies in obtaining sufficient quantities of exoeryt ...19957876979
protection against murine cerebral malaria by dietary-induced oxidative stress.feeding 20% (w/w) menhaden-fish oil in a standard laboratory chow diet for 4 wk partially protected cba/caj mice from the central nervous system consequences of infection with plasmodium berghei (anka). full protection (complete survival for 14 days postinfection) could be obtained by feeding a purified pro-oxidant vitamin e-deficient diet containing 4% (w/w) menhaden oil (mo - ve diet). the purified pro-oxidant mo - ve diet also exerted a pronounced suppressive effect against the parasite (depr ...19957876987
structure-activity relationships of lactone ring-opened analogs of the antimalarial 1,2,4-trioxane artemisinin.1,2,4-trioxane benzylic ethers 8a-e were prepared as simplified, tricyclic versions of the clinically used tetracyclic antimalarial drug artemisinin (1). five additional artemisinin analogs (9-11) were prepared. neither water solubility (analogs 8e and 11b) nor chelating ability (analogs 9 and 10), however, produced trioxanes of especially high in vitro antimalarial activity. trioxane fluorobenzyl ether 8b is the most active in this series (more active than artemisinin) against plasmodium falcip ...19957861408
cd8 modulation of t-cell antigen receptor-ligand interactions on living cytotoxic t lymphocytes.thymocytes and class i major histocompatibility complex (mhc)-restricted cytotoxic t lymphocytes express predominantly heterodimeric alpha/beta cd8. by interacting with non-polymorphic regions of mhc class i molecules cd8 can mediate adhesion or by binding the same mhc molecules that interact with the t-cell antigen receptor (tcr) function as coreceptor in tcr-ligand binding and t-cell activation. using tcr photoaffinity labelling with a soluble, monomeric photoreactive h-2kd-peptide derivative ...19957830771
cd8+ cell activation to a major mastocytoma rejection antigen, p815ab: requirement for tum- or helper peptides in priming for skin test reactivity to a p815ab-related peptide.delayed-type hypersensitivity (dth) responses, mediated by cd8+ cells and detected by skin test assay, occur in sensitized mice in response to challenge with class i-restricted antigenic peptides of mutagenized (tum-) p815 mastocytoma cells. in contrast, a nonapeptide related to a tumor rejection antigen, p815ab, failed in this study to elicit dth after sensitization of mice with irradiated tumor cells or adoptive transfer of p815ab-pulsed dendritic cells. unresponsiveness, however, could be ove ...19957589074
cd8+ t-cell protective immunity induced by immunization with plasmodium berghei cs protein-derived synthetic peptides: evidence that localization of peptide-specific ctls is crucial for protection against malaria.immunization of balb/c mice (h-2d) with a mixture of major histocompatibility complex (mhc) class i- and mhc class ii-restricted synthetic peptides emulsified in incomplete freund's adjuvant (ifa) induced a high level of specific cytotoxic t lymphocyte (ctl) activity. peptides 249-260 or 252-260, derived from the circumsporozoite protein of plasmodium berghei and representing a h-2kd-restricted ctl epitope, were injected twice subcutaneously or intraperitoneally in balb/c mice in combination wit ...19957590920
a conserved peptide sequence of the plasmodium falciparum circumsporozoite protein and antipeptide antibodies inhibit plasmodium berghei sporozoite invasion of hep-g2 cells and protect immunized mice against p. berghei sporozoite challenge.minutes after injection into the circulation, malaria sporozoites enter hepatocytes. the speed and specificity of the invasion process suggest that it is receptor mediated. the region ii sequence of plasmodium falciparum circumsporozoite (cs) protein includes a nonapeptide (wspcsvtcg) which is highly conserved in all of the cs proteins sequenced to data, including the one from plasmodium berghei. we have found that two peptides based on the p. falciparum region ii sequence, p18 (ewspcsvtcgngiqvr ...19957591073
efficient binding of reduced peptide bond pseudopeptides to major histocompatibility complex class i molecule.reduced peptide bond pseudopeptide analogues have been examined for their ability to bind murine class i molecules of the major histocompatibility complex (mhc). eight pseudopeptide analogues of an antigenic peptide derived from plasmodium berghei (h-ser252-tyr-ile-pro-ser-ala-glu-lys-ile260-oh) were obtained by systematically replacing one peptide bond at a time by a reduced peptide bond psi (ch2-nh). the resulting analogues were then tested for their binding to a recombinant single chain sc-kd ...19957592803
isolation and analysis of nephritic-producing immune complexes in plasmodium berghei-infected mice.a nephritic condition was developed by infecting swiss webster albino mice with the malarial parasite plasmodium berghei nk 65. these animals were tested for urinary protein and the presence of circulating immune complexes using reagent strips and a polyethylene glycol (peg) precipitation assay. the circulating immune complexes were isolated from the sera using both affinity chromatography and peg precipitation and from the kidney by acid elution. the isolated complexes were dissociated into the ...19959583966
plasmodium berghei: sensitivity of chloroquine-resistant and chloroquine-sensitive strains to irradiation and the effect of irradiated malaria parasites on cytochrome p450-dependent monooxygenases.differences in sensitivities of chloroquine-sensitive and chloroquine-resistant strains of plasmodium berghei were observed following irradiation of the parasites. a dose of 15 kilorads from a cobalt-60 source killed the erythrocytic stages of the chloroquine-sensitive strain and no parasitemias were observed when mice were injected with these irradiated parasites. in contrast, when the chloroquine-resistant strain was irradiated with the same dose of cobalt-60 and injected into mice, an infecti ...19958581351
interferon-gamma and the induction of protective igg2a antibodies in non-lethal plasmodium berghei infections of mice.mice treated with anti-ifn-gamma monoclonal antibodies were unable to recover from infection with an attenuated variant of p. berghei (pb xat) which causes non-lethal malaria in normal mice. on the other hand, treatment with anti-il-4 monoclonal antibodies had no effect on the course of infection. ifn-gamma was produced by spleen cells in vitro during the early phase of the infection. treatment with anti-ifn-gamma suppressed development of an anti-plasmodial igg2a immunoglobulin isotype in the s ...19958587787
proteolysis of a 34 kda phosphoprotein coincident with a decrease in protein kinase activity during the erythrocytic schizont stage of the malaria parasite.protein phosphorylation events may play important roles in the replication and differentiation of the malarial parasite. investigations into the lability of a plasmodium protein kinase revealed that a 34 kda parasite phosphoprotein is rapidly converted into a 19 kda fragment. coincident with this conversion is a nearly total loss of a protein kinase activity, as determined from the phosphorylation of endogenous protein substrates. both the conversion of the 34 kda protein to the 19 kda protein a ...19958520577
evaluation of resistant-reversal, cdri compound 87/209 and its possible mode of action in rodent experimental malaria.the resurgence of malaria in form of resistance against chloroquine (cq) has decreased the importance of the drug as a chemotherapeutic agent. if an agent in combination with cq can make cq resistant plasmodia susceptible to cq, the problem of drug resistance may then be solved. use of conventional drugs like verapamil, desipramine along with cq suggested the feasibility of this approach. this report is concerned with a new class of compound, cdri compound 87/209 (15 mg/kg b. wt.) which is given ...19958525290
antimalarial activity of oxidized starch and cellulose imine derivatives.with the purpose of screening potential antimalarial agents, oxidized starch imine derivatives of sulfonamides or pyrimidine - derivatives of sulfisoxazole (ml8), sulfameter (ml11) and trimethoprim (ml13) - and oxidized cellulose imine derivatives of dapsone (ml14), sulfadiazine (ml17), sulfamethoxazole (ml18), sulfisoxazole (ml19), sulfamethoxypyridazine (ml20) and sulfameter (ml22) were submitted to in vivo biological assays with mice infected with plasmodium berghei. only ml11 was 100% curati ...19958527105
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