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[new antimalarial sustained-release formulations based on bioresorbable polymers: therapeutic evaluation using the plasmodium berghei model].chemotherapy keeps an important place in malaria control programme. the development of schizonticidal formulations, which may maintain their efficacy for at least one month after single administration, becomes needful. these formulations should allow to assure a suitable patient compliance and to avoid the disadvantages of high plasmatic peaks. the aim of this study is to evaluate the therapeutic efficacy of implantable bioresorbable reservoir-forms. the use of these polymers allow to avoid the ...19902185357
differences in susceptibility among mouse strains to infection with plasmodium berghei (anka clone) sporozoites and its relationship to protection by gamma-irradiated sporozoites.three inbred mouse strains, c57bl/6 (h-2b), a/j (h-2a), and balb/c (h-2d), and 1 outbred strain, cd-1, demonstrated differences in susceptibility to iv challenge with the anka clone of plasmodium berghei. mice were challenged with 100, 1,000, or 10,000 sporozoites, then evaluated daily beginning on day 4 for patency. cd-1 mice were further evaluated at challenge doses of 12,500, 25,000, and 50,000 sporozoites. c57bl/6 mice were the easiest to infect, with 90% becoming infected with 100 sporozoit ...19902184689
nucleotide sequence of the plasmodium berghei circumsporozoite protein gene from the anka clone 2.34l. 19902183186
purification and characterization of 37-kilodalton proteases from plasmodium falciparum and plasmodium berghei which cleave erythrocyte cytoskeletal components.cytosoluble 100,000 x g extracts from plasmodium berghei or plasmodium falciparum infected red blood cells were shown to hydrolyze erythrocyte spectrin. by fast protein liquid chromatography (fplc), these enzymes were purified and exhibited a pi of 4.5 and mr of 37,000 using sds-page under reducing conditions. an immunochemical enzyme assay using anti-spectrin antibodies was developed. the optimal activity using spectrin as substrate was at ph 5.0, and the enzymes were strongly inhibited by hgcl ...19902183048
organization of subtelomeric repeats in plasmodium berghei.several (but not all) plasmodium berghei chromosomes bear in the subtelomeric position a cluster of 2.3-kilobase (kb) tandem repeats. the 2.3-kb unit contains 160 base pairs of telomeric sequence. the resulting subtelomeric structure is one in which stretches of telomeric sequences are periodically spaced by a 2.1-kb reiterated sequence. this periodic organization of internal telomeric sequences might be related to chromosome-size polymorphisms involving the loss or addition of subtelomeric 2.3- ...19902183034
the effect of bacillus sphaericus upon the susceptibility of anopheles quadrimaculatus to plasmodium berghei.larvae of anopheles quadrimaculatus were exposed to bacillus sphaericus. the surviving adults took blood meals on hamsters infected with plasmodium berghei. fewer mosquitoes were infected than were the paired controls. the inhibitory action appeared to occur during the early stages of the infection in the mosquito gut.19902182774
association of plasmodium berghei proteins with the host erythrocyte membrane: binding to inside-out vesicles.two acidic phosphoproteins of plasmodium berghei origin, of 65 and 46 kda, are associated with the plasma membrane of the host mouse erythrocyte. the 65-kda protein partitions between a soluble and particulate phase upon host cell lysis, whereas the 46-kda protein is localized exclusively in the particulate fraction. both proteins bind to inside-out vesicles derived from erythrocyte ghosts and the conditions of the reassociation reaction indicate that the binding is specific and that the protein ...19902181301
sporontocidal activity of the antimalarial wr-238605 against plasmodium berghei anka in anopheles stephensi.the influence of wr-238605 (8-[(4-amino-1-methyl-butyl) amino]-2,6-dimethoxy-4-methyl-5-[3-tri-fluoromethylphenoxyl] quinoline succinate) on the sporogonic development of a plasmodium berghei anka clone was determined. anopheles stephensi were fed on p. berghei infected mice treated 90 min earlier with 25 or 50 mg wr-238605/kg body weight. mosquitoes engorging on drug-treated mice produced the same number of ookinetes as did those fed on controls; drug-fed mosquitoes produced fewer oocysts/mosqu ...19902180334
glucose-6-phosphate dehydrogenase from plasmodium berghei: kinetic and electrophoretic characterization.evidence is given for the existence of a parasite-specific glucose-6-phosphate dehydrogenase (g6pd) in plasmodium berghei by characterization of its kinetic and electrophoretic properties. from infected rat erythrocytes the parasites were isolated, washed, and lysed. g6pd was purified by affinity chromatography with 2'5'-adp-sepharose 4b, although the separation of the malaria-specific enzyme from that of the host cell was not complete. malarial g6pd significantly differed from the red cell enzy ...19902178950
long insertions within telomeres contribute to chromosome size polymorphism in plasmodium berghei.during prolonged in vivo mitotic multiplication of a plasmodium berghei anka clone (8417hp), parasites that contained an enlarged version of chromosome 4 were observed. restriction mapping and hybridization results demonstrated that the extra dna present in the enlarged chromosome consists of 2.3-kb tandem repeats, known to be normally located in subtelomeric position at several chromosomal ends but absent in the original chromosome. the inserted 2.3-kb units appeared to interrupt one of the ori ...19902174115
possible roles of ca2+ and cgmp as mediators of the exflagellation of plasmodium berghei and plasmodium falciparum.the roles of ca2+ and cyclic nucleotides as secondary, intracellular messengers for exflagellation of plasmodium berghei and plasmodium falciparum were investigated. treatment with ca2+ antagonists such as tmb-8 (an inhibitor of intracellular ca2+ release) or w-7 (a calmodulin inhibitor) strongly inhibited exflagellation induced by alkaline medium at ph 8.0 whereas egta (a ca2+ chelator) or nicardipine and nifedipine (ca2+ channel inhibitors) had no effect. these results may indicate that mobili ...19902172816
endopeptidase activities of streptococcus cremoris. 19902165941
in vitro effects of primaquine and primaquine metabolites on exoerythrocytic stages of plasmodium berghei.the antimalarial activities of primaquine and its metabolites against exoerythrocytic (ee) stages of plasmodium berghei in vitro were compared with their abilities to spontaneously generate activated oxygen. a quantitative relationship between the number of sporozoites and the number of ee merozoites produced was established. the reduction in the number of merozoites was used as an assay of drug activity. the ed50 of primaquine, 3.7-3.9 x 10(-6) m, was the concentration of drug that reduced the ...19902164790
t lymphocytes from mice immunized with irradiated sporozoites eliminate malaria from hepatocytes.when mice are immunized with radiation-attenuated sporozoites they are solidly protected against sporozoite challenge by an immune response that has been shown to require cd8+ lymphocytes in several strains of mice. the target of this cd8+ t-cell-dependent immunity has not been established. immune balb/c mice were shown to develop malaria-specific, cd8+ t-cell-dependent inflammatory infiltrates in their livers after challenge with plasmodium berghei sporozoites. spleen cells from immune balb/c a ...19902151270
cd4+ cytolytic t cell clone confers protection against murine malaria.a cd4+ t cell clone (a1.6) was derived from spleen cells of mice immunized with irradiated sporozoites. this t cell clone recognizes an antigen that is shared by sporozoites and blood forms of plasmodium berghei and differs from the circumsporozoite protein. clone a1.6 displays cytotoxic activity, produces ifn-gamma and il-2 in vitro, and recognizes the plasmodial antigen in the context of the class ii i-ed molecule. passive transfer of this cd4+ clone into naive mice resulted in a high degree o ...19902146361
quantitative estimation of suppressor/cytotoxic and helper t cells during acute and chronic plasmodium berghei infection.in the present study, the percentage of lymphocyte subpopulations and their relation to t cell subsets was estimated during acute and chronic plasmodium berghei malaria. during acute infection, a decreased percentage of t lymphocytes was observed, whereas no change was observed during chronic infection. however, no change in the percentage of b cells was observed in both types of infection. the t cell population was characterized by an increased percentage of t suppressor cytotoxic (cd8+) cells ...19902146216
changes in hemopoietic and regulator levels in mice during fatal or nonfatal malarial infections. i. erythropoietic populations.erythroid precursors bfu-e and cfu-e and erythroblasts (erb) were monitored in the marrow and spleen of mice during fatal or nonfatal malaria. transient depletions of marrow cfu-e and erb without modification of bfu-e or erythropoietin (epo) levels were found as early events in fatal infections. before anemia development, erythropoiesis was reduced in the bone marrow but increased in the spleen. during the anemic phase, for comparable levels of anemia, plasma epo levels were elevated to a simila ...19902146141
mitogenic activity of soluble preparations from plasmodium berghei-infected erythrocytes to l3t4+, lyt2- and l3t4-, lyt2+ t-cell subsets.the mitogenic activity of soluble preparations of plasmodium berghei-infected erythrocytes (pbep) in cultures of t or non-t cells isolated from spleens of naive mice was investigated. the proportion of cells at each phase in the cell cycle was examined by flow cytometry after incubation with various concentrations of pbep; the proliferation index (pi-cell numbers at s, g2 and m phases/cell numbers at all phases x 100) was calculated. an addition of pbep led to significant increases in the pi lev ...19902144965
regulation of the energy metabolism of plasmodium berghei.energy metabolism of malaria parasites was investigated in p. berghei infected red blood cells of rat. although plasmodia contain mitochondria most of their atp is formed by glycolysis. lactate formation is two orders of magnitude higher than in noninfected erythrocytes. the coupling of respiration and glycolysis is very loose, a pasteur-effect was not found. the key enzymes of glycolysis hexokinase and phosphofructokinase have been partially purified and kinetically characterized. the kinetic p ...19902143651
phosphofructokinase from plasmodium berghei: a kinetic model of allosteric regulation.as in mammalian cells, phosphofructokinase (pfk) is of major regulatory importance in the glucose metabolism of plasmodium berghei. the malarial enzyme shows allosteric properties similar to pfk from various sources; it is activated by fructose-6-phosphate and inhibited by atp, but differs with respect to allosteric regulation. enzyme activity is only marginally increased by amp, a potent activator of many phosphofructokinases. phosphoenolpyruvate, which is reported to inhibit pfk activity, effi ...19902141917
immunosuppression in murine malaria: suppressor role of macrophages and their products during acute and chronic plasmodium berghei infection.marked suppression of igm, igg and iga plaque forming cells was observed in mice immunized with sheep erythocytes (t-dependent antigen) during acute plasmodium berghei infection whereas during chronic infection mild immunosuppression was observed. when mice were immunized with polyvinylpyrrolidone (t-independent antigen), suppression in the number of plaque forming cells was observed at higher parasitaemias only during acute infection whereas during chronic infection the number remained within n ...19902141476
phosphofructokinase from plasmodium berghei. influence of mg2+, atp and mg2(+)-complexed atp.the control enzyme phosphofructokinase is of regulatory significance in the metabolism of glucose by the malarial parasite plasmodium berghei. (1) the enzyme was partially purified from erythrocytic stages of p. berghei by precipitation with poly(ethylene glycol) and chromatography on 2',5'-bisphosphoadenosine-sepharose 4b. (2) similarly to various other phosphofructokinases, the enzyme from p. berghei shows an allosteric behaviour. it is activated by fructose 6-phosphate and inhibited by atp. ( ...19902139776
[the possible therapeutic effect of deferoxamine in experimental infections of mice by plasmodium berghei].deferoxamine is a compound with iron chelating properties. body depletion of this mineral, according to some authors, might influence the metabolism of plasmodia that thrive in the erythrocytes. in order to verify this possibility, we administered daily doses of 300 or 1.000 mg/kg of the compound, for five days and again 15 days, to mice infected with plasmodium berghei. the parameters used to check the activity of deferoxamine were mortality of the animals and the count of blood parasites. the ...19902135836
effect of anti-mosquito antibodies on the infectivity of the rodent malaria parasite plasmodium berghei to anopheles farauti.the effect of mouse anti-mosquito antibodies, present in the bloodmeal, on the infectivity of plasmodium berghei vincke to anopheles farauti laveran was investigated. significantly fewer oocysts developed in mosquitoes feeding on mice immunized with sugar-fed mosquito midgut antigens than in mosquitoes feeding on control mice. mosquitoes feeding on mice immunized with the midgut antigens derived from sugar-fed mosquitoes also showed reduced mortality and had lower infection rates than those fed ...19902132980
cellular mechanisms of nonspecific immunity to intracellular infection: cytokine-induced synthesis of toxic nitrogen oxides from l-arginine by macrophages and hepatocytes.nitric oxide (no) produced by cytokine-treated macrophages and hepatocytes plays a vital role in protective host responses to infectious pathogens. no inhibits iron-sulfur-dependent enzymes involved in cellular respiration, energy production, and reproduction. synthesis of l-arginine-derived nitrite (no2-), the oxidative end product of no, directly correlates with intracellular killing of leishmania major, an obligate intracellular protozoan parasite of macrophages: the level of no2- production ...19902126524
immune response to plasmodium berghei sporozoite antigens. i. evaluation of murine t cell repertoire following immunization with irradiated sporozoites.the plasmodium berghei sporozoite antigen-specific t cell repertoire was analyzed in c57bl/6 (h-2b), balb/c (h-2d) and c3h/hen (h-2k) mice following immunization with irradiated sporozoites. proliferative responses were correlated with the protective status of each strain. proliferative reactivities to sporozoite antigens were compared in cultures containing either cd4+ t cells, cd8+ t cells, or total splenic lymphocytes. cd8+ t cells had no proliferative activity to sporozoite antigens; cd4+ t ...19902122748
interleukin 6 production in experimental cerebral malaria: modulation by anticytokine antibodies and possible role in hypergammaglobulinemia.the production of interleukin 6 (il-6) was studied during experimental cerebral malaria (ecm) induced by plasmodium berghei anka (pba) infection. il-6 is present in the serum of mice with ecm, the highest concentrations being observed in mice with full-blown neurological syndrome. high il-6 levels were also observed, however, in the absence of pathology in nonlethal malaria infection. these data suggest that il-6 is produced in large amounts during malaria infection, but does not play a major ro ...19902121890
[synthesis of 2-formyl (acetyl) substituted quinoline thiosemicarbazones].a series of 2-formyl (acetyl) substituted quinoline thiosemicarbazones (iii, xii, xiii) were prepared in order to evaluate their antimalarial activity. oxidation of substituted quinolines (iv) with selenium dioxide gave 2-formyl substituted quinolines (v). 2-acetyl substituted quinoline (ix) was obtained from iv by oxidation, esterification, claisen condensation and decarboxylation. iii1-9 were synthesized by two methods; one was by condensation of 2-formyl (acetyl) substituted quinolines with m ...19902104472
implications of cytokines in immunopathology: experimental and clinical data. 19902104242
spectrophotometric assay of the interaction between malaria erythrocyte lysates with methylene blue and neutral red dyes.changes of oxidative processes induced in mouse erythrocytes by plasmodium berghei were studied in the presence of methylene blue, neutral red or of both cationic redox dyes. the results are discussed in terms of redox and metachromatic modifications of the dyes which are produced by malarial and normal erythrocyte lysates.19902101204
use of adjuvants in modulating the behaviour of plasmodium berghei.different adjuvants were assessed for their role in conferring protection against the rodent malarial parasite p. berghei and compared with the classical freund's complete adjuvant (fca). pretreatment of mice with trehalose dimycolate (tdm) mixed with antigen (ag), sulpholipids (sl) mixed with ag, muramyl dipeptide (mdp) alone, liposomes containing ag and phosphomannoinositides (pim) mixed with ag were ineffective in conferring protection. however, mdp given with squalane (sq) and ag, mdp with i ...19902099325
three-dimensional reconstruction of the feeding process of the malaria parasite.the use of serial sectioning followed by three-dimensional (3d) reconstruction is a convenient way to study the spatial morphology of any structure (organ, cell, organelle). this method was applied to the study of the feeding mechanism of some strains of murine and human plasmodium and enabled clarification of morphological features of this process. the feeding and digestive system of plasmodium is polymorphic: in single sections, it shows rounded or elongated vesicles or vacuoles of very differ ...19902096983
c-reactive protein and the liver stage of plasmodium vivax and p. berghei. 19902096504
role of circumsporozoite protein-specific t-cells in protective immunity against plasmodium berghei.the plasmodium berghei circumsporozoite (cs) protein-specific t-cell repertoire was analysed in c57bl/6 (h-2b), balb/c (h-2d), and c3h/hen (h-2k) mice immunized with irradiated sporozoites and the proliferative responses were correlated with the protective status of each strain. splenic lymphocytes responded to the priming antigen, but the responses varied according to both murine strain and immunization schedule. analysis of cytolytic t lymphocyte (ctl) responses in mice immunized with irradiat ...19902094596
plasmodium sporozoite-host cell interactions during sporozoite invasion.in vitro and in vivo studies were performed to clarify the nature of some interactions between plasmodium berghei sporozoites and rodent host cells. videomicroscopic observations were made on in vitro interactions between sporozoites and cultured host cells (rodent peritoneal macrophages, w138 human lung fibroblasts, and hepg2 human hepatoma cells). the results showed a diversity of dynamic interactions and sporozoite activities, including active sporozoite penetration, often followed by sporozo ...19902094594
pre-erythrocytic stage malaria parasites: non-circumsporozoite protein antigens.a series of non-circumsporozoite proteins found in pre-erythrocytic parasites are being developed as putative vaccine candidates. it is anticipated that these will be useful in addition to, rather than instead of, the cs (circumsporozoite) vaccines. it is likely that a greater understanding of the basic biology of malaria parasite-host relationships will lead to development of improved malarial vaccines.19902094584
a liver-stage specific antigen of p. berghei identified by a monoclonal antibody.stage-specific immunity (to the sporozoite, the asexual blood-stages and the sexual stages of malaria) has been well documented and antigens from each stage are being tested for their potential as vaccine candidates. recently it has become clear that the liver stage can also be the target of protective immune responses; however, only the circumsporozoite protein has been identified as a protective liver antigen. it is critical for vaccine evaluation and development to identify other liver antige ...19902094583
delayed-type hypersensitivity and protection in mice following immunization with plasmodium berghei sporozoites.the measurement of footpad swelling (fps) following the inoculation of sporozoite antigen (ag) into the hind footpad (hfp) of outbred mice was used as an in vivo test of delayed-type hypersensitivity (dth) to attenuated sporozoite immunization. an attempt was made to correlate dth with protective antisporozoite immunity. the optimum time for testing dth following a single intravenous immunization was four days. the optimum sensitizing dose was 1 x 10(5) attenuated sporozoites. a single immunizat ...19902094579
the development and routine application of high-density exoerythrocytic-stage cultures of plasmodium berghei.methods are reviewed for the culture of the exoerythrocytic stages of plasmodium berghei wherein development reproducibly reflects growth observed in vivo in laboratory rodents. the combination of these methods with the culture of both asexual and sexual blood stages has allowed the completion of the entire vertebrate phase of malaria development in vitro. the development of new methods for high-density exoerythrocytic-stage culture combined with robust statistical analysis of parasite growth by ...19902094577
plasmodium sporozoite interactions with macrophages in vitro: a videomicroscopic analysis.studies of in vitro interactions between plasmodium berghei sporozoites and peritoneal macrophages from mice and rats were performed. a videomicroscopic analysis was made of interactions observed by phase-contrast microscopy. our results showed a diversity of dynamic interactions between sporozoites and macrophages that included no interaction, surface interaction without sporozoite interiorization, active sporozoite penetration, active penetration with subsequent sporozoite escape, macrophage d ...19902086782
a cytochemical ultrastructural study of the lysosomal system of different species of malaria parasites.we have used ultrastructural techniques in different malarial species to demonstrate a lysosomal system. first, we have tried to localize acid phosphatase, a typical lysosomal label. its activity was localized in the endoplasmic reticulum and in endocytic vesicles, and in dense-cored vesicles near the digestive vacuoles, especially in plasmodium falciparum (fcr3 strain). then, we have studied the different cellular compartments of the malarial parasite by the zinc iodide-osmium tetroxide techniq ...19902086778
evaluation of the antimalarial activity of new compounds against plasmodium falciparum in vitro, and plasmodium berghei in vivo.various hydrazones of thiophene carboxaldehyde were tested in vitro on two plasmodium falciparum strains and in vivo on mice experimentally infected with plasmodium berghei. these hydrazones were obtained by condensation of appropriate hydrazines with thiophene-2-carboxaldehyde (series 1), thiophene-3- carboxaldehyde (series 2) and 5-nitrothiophene-2-carboxaldehyde (series 3). compounds of series 3, 5-nitrothiophene-2-carboxaldehyde presented significant effects in vitro. in vivo tests confirmed ...19902086754
evolutionary relationships of avian eimeria species among other apicomplexan protozoa: monophyly of the apicomplexa is supported.direct, reverse transcriptase-mediated, partial sequencing of the small-subunit (16s-like) ribosomal rna (srrna) of eimeria tenella and e. acervulina was performed. sequences were aligned by eye with six previously published, partial or complete srrna sequences of apicomplexan protists (plasmodium berghei, theileria annulata, cryptosporidium sp., toxoplasma gondii, sarcocystis muris, and s. gigantea). six eukaryotic protists (a slime mold, a yeast, two dinoflagellates, and two ciliates) acted as ...19912072862
[the computer processing of experimental research data on malaria. 1. the primary processing of the dynamic indices of malarial infection].universal computer software for primary statistical and graphic analysis of data on malaria dynamics in patients and in the experiment has been suggested. the analysis of the results of investigations on rodent malaria model in based on graded parasitemia assessment according to moshkovskiÄ­ [correction of mashkovsky].19912067496
[the sensitivity of a plasmodium berghei strain resistant to artemisinin and other antimalarial preparations].the development of p. berghei resistance to artemisin has been studied. the narrs p. berghei strain which has 200 times lower sensitivity to artemisin was formed. different degree cross-resistance was established with quinine, chloroquine, dabequine, mefloquine; a high fansidar's efficacy in respect to narrs was observed.19912067477
[an experimental study of the effect of different biologically active substances on the susceptibility of mosquitoes to the causative agent of malaria. 1. insect development regulators].it has been shown on the model pair ae. aegypti-p. gallinaceum that dimilin, an inhibitor of insect chitin synthesis has practically no effect on female sensitivity to malaria agent. an analogue of the juvenile hormone juvemon at a concentration of 0.001-0.002 mg/l, causing death of 35% of insects, produces a 7-17% decrease in sporozoite index value. in concentration of 0.004-0.05 mg/l, there is a tendency towards an increase in the vector capacity of the survived female individuals. no differen ...19912067470
[in vitro cultivation of the exoerythrocytic stage of plasmodium berghei].this paper reports on an in vitro culture system for the exoerythrocytic (ee) stage of plasmodium berghei (p.b.) using embryonic lung cells. the system was first developed by our laboratory in china. the embryonic lung cells were isolated by trypsin digestion of a human embryonic lung obtained from a therapeutic abortion case and was designated as cell line elu 8801. anopheles stephensi mosquitoes were infected by biting p.b. anka strain infected kunming mice and after 18-21 days were dissected ...19912065449
stimulation by adjuvants of cell-mediated immune response in plasmodium berghei infected mice.immunological adjuvants (alum, liposomes and saponin) were utilized to stimulate cell-mediated immune response in plasmodium berghei infected balb/c mice. it was shown that malaria antigen mixed with adjuvant induced appreciably delayed type hypersensitivity and production of migration inhibition factor compared to antigen alone.19912055600
the effect of malaria infection on paracetamol disposition in the rat.the effect of plasmodium berghei infection, a rodent malarial model, on the disposition of paracetamol (50 mg/kg, i.v.) was investigated in rats. malaria infection (mi) resulted in a significant decrease in clearance (control: 21.6 +/- 5.5 vs test: 11.8 +/- 2.9 ml/min/kg, p less than 0.005) with no change in volume of distribution and a significant prolongation of the elimination half-life (control: 30.7 +/- 6.3 vs 53.3 +/- 12.1 min, p less than 0.005) of paracetamol in malaria infected rats. th ...19912043159
[the effect of an extract from cochlospermum angolense ("burututu") on plasmodium berghei in the mouse malaria suppression test].often existing cross-resistance to structure analogous antimalarials causes the need to find new active compounds against malaria parasites. for this purpose the traditional medicine of tropical countries has proved to be a treasury. a root extract of cochlospermum angolense showed in vitro a remarkable activity against plasmodium berghei in the dna synthesis measurement with 3h-labelled hypoxanthine. this effect could be reproduced under in vivo conditions with the "4-day suppressive test" of r ...19912039095
evaluation of merocyanine 540-sensitized photoirradiation as a method for purging malarially infected red cells from blood.the photosensitizing dye merocyanine 540 (mc 540) was evaluated as a means for purging malarially infected red cells from murine blood using the rodent malarial pathogens, plasmodium yoelii and plasmodium berghei, as models of human malaria. malarially infected red cells bound more mc 540 and were more sensitive to mc 540-sensitized photoirradiation than were noninfected erythroid cells. extracorporeal exposure of infected red cells to the dye and white light prevented the transmission of the di ...19912037797
specific binding of antigenic peptides to cell-associated mhc class i molecules.t lymphocytes recognize antigen in the form of peptides that associate with specific alleles of class i or class ii major histocompatibility (mhc) molecules. by contrast with the clear mhc allele-specific binding of peptides to purified class ii molecules purified solubilized class i molecules either bind relatively poorly or show degenerate specificity. using photo-affinity labelling, we demonstrate here the specific interaction of peptides with cell-associated mhc class i molecules and show th ...19912027386
morphological characteristics of intracerebral arterioles in clinical (plasmodium falciparum) and experimental (plasmodium berghei) cerebral malaria.spastic constriction of intracerebral arterioles was identified in clinical (p. falciparum) and experimental (p. berghei) cerebral malaria. morphological criteria were used to characterize pathologically spastic constriction of arterioles. the significance of spastic constriction of intracerebral arterioles for microcirculatory disturbance in relation to development of cerebral malaria is discussed.19912027026
plasmodium berghei: quantitation of in vitro effects of antimalarial drugs on exoerythrocytic development by a ribosomal rna probe.a stage-specific ribosomal rna probe has been used to quantitate exoerythrocytic development of plasmodium berghei in primary cultures of mouse hepatocytes. parasite rrna could be detected as soon as 6 hr after sporozoite invasion and was increased during schizogony to a maximum at 48 hr, when mature schizonts were identified by microscopy. as few as 10 exoerythrocytic schizonts could be detected by filter blot hybridization, followed by autoradiography and liquid scintillation counting. by hybr ...19912026219
intraerythrocytic parasites and red cell deformability: plasmodium berghei and babesia microti.in the studies reported here, we examined the effects of two intraerythrocytic parasites (plasmodium berghei and babesia microti) on the deformability of their host red cells. red cell deformability was assessed by three criteria: 1) the prevalence of tank-treading (the tank-tread-like movement of the red cell membrane around its cytoplasmic contents), 2) elongation under fluid shear stress (the steady-state length: width ratio), and 3) the time required for the red cell to reduce its steady-sta ...19912018857
the effect of malaria infection on antipyrine metabolite formation in the rat.we have shown that malaria infection can impair selectively the formation of antipyrine metabolites in the rat. during malaria, a significant increased urinary levels of unchanged antipyrine was observed (control: 1.7 +/- 0.4 vs test: 8.1 +/- 1.1% of dose, p less than 0.001). this was associated with significantly decreased excretion of 3-hydroxymethylantipyrine (control: 24.5 +/- 1.2 vs test: 21.4 +/- 0.7%, p less than 0.001) and 4-hydroxyantipyrine (control: 20.1 +/- 0.9 vs test: 15.5 +/- 1.3% ...19912009102
antimalarial polyamine analogues.a series of novel tetraamines of the general formula rnh(ch2)xnh(ch2)ynh(ch2)xnhr was synthesized and examined for activity against growth of plasmodium falciparum in vitro. within the series, dibenzyl analogues (r = benzyl) were found to be the most effective growth inhibitors, with ic50 values of about 10(-6) m. further modifications of the tetraamine provided the optimum chain length for antimalarial activity of y = 7, x = 3. compound 8 (mdl 27,695) with the structure y = 7, x = 3, r = benzyl ...19911995879
plasmodium berghei: ionic regulation and the induction of gametogenesis.the role of ionic regulation in the induction of gametogenesis of plasmodium berghei at 20 degrees c was investigated. a potent inhibitor of na+/h+ exchange, amiloride, strongly inhibited exflagellation and subsequent ookinete formation induced by rpmi 1640 with 10% fetal calf serum at ph 8.0, whereas na+ or k+ channel inhibitors, h(+)-atpase inhibitors, and a protonophore had no significant effect. amiloride-treated 'activated' microgametocytes synthesized dna to levels consistent with the expe ...19911993463
analysis of immunity induced by the affinity-purified 21-kilodalton zygote-ookinete surface antigen of plasmodium berghei.by using affinity-purified ookinete surface antigen from the rodent malaria parasite plasmodium berghei, a transmission-blocking immunity was induced in mice. groups of mice were immunized via different routes, with total quantities of antigen ranging from 0.5 to 40 micrograms (with or without freund adjuvant). vaccination by the intramuscular route with 20 micrograms of antigen in the absence of adjuvant and boosted once with the same amount of protein induced a total transmission blockade. imm ...19911987051
the chemotherapy of rodent malaria. xlv. reversal of chloroquine resistance in rodent and human plasmodium by antihistaminic agents.the inherent blood schizontocidal activities of five antihistaminic compounds, cyproheptadine hydrochloride (cyp), ketotifen hydrogen fumarate (ket), pizotyline hydrogen maleate (piz), azatadine maleate (azat) and loratadine (lor) were examined against the following organisms: chloroquine-sensitive (cs) plasmodium berghei and chloroquine-resistant (cr) p. yoelii ssp. ns in mice; and cs tak 9 clone 96 and cr k1 strain of p. falciparum in vitro. chloroquine, verapamil and desipramine were used as ...19901981663
the effect of malaria infection on the disposition of quinine and quinidine in the rat isolated perfused liver preparation.the effect of malaria on the disposition of quinine and quinidine was studied in livers isolated from young rats infected with merozoites of plasmodium berghei, a rodent malaria model, and non-infected controls. following bolus administration of quinine (1 mg) or quinidine (1 mg) to the 100 ml recycling perfusion circuit, perfusate was sampled (0-4 h) and plasma assayed for quinine and quinidine by hplc. higher quinine (auc:6470 +/- 1101 vs 3822 +/- 347 ng h ml-1, p less than 0.001) and quinidin ...19901979624
pyrimidine biosynthesis in parasitic protozoa: purification of a monofunctional dihydroorotase from plasmodium berghei and crithidia fasciculata.dihydroorotase (dhoase) catalyzes the reversible cyclization of n-carbamoyl-l-aspartate (l-ca) to l-5,6-dihydroorotate (l-dho), which is the third enzyme in de novo pyrimidine biosynthesis. the enzyme was purified from two parasitic protozoa, crithidia fasciculata (about 16,000-fold) and plasmodium berghei (about 790-fold). the c. fasciculata enzyme had a native molecular weight (mr) of 42,000 +/- 5000, determined by gel filtration chromatography, and showed a single detectable protein band on s ...19901976382
survival and antigenic profile of irradiated malarial sporozoites in infected liver cells.exoerythrocytic (ee) stages of plasmodium berghei derived from irradiated sporozoites were cultured in vitro in hepg2 cells. they synthesized several antigens, predominantly but not exclusively those expressed by normal early erythrocytic schizonts. after invasion, over half the intracellular sporozoites, both normal and irradiated, appeared to die. after 24 h, in marked contrast to the normal parasites, ee parasites derived from irradiated sporozoites continued to break open, shedding their ant ...19901974886
generation of chromosome size polymorphism during in vivo mitotic multiplication of plasmodium berghei involves both loss and addition of subtelomeric repeat sequences.extensive chromosome size polymorphism arises in plasmodium berghei during in vivo mitotic multiplication. size differences between homologous chromosomes involve rearrangements occurring in the subtelomeric portions while internal chromosomal regions do not contribute significantly to chromosome size polymorphism. differences in the copy number of a 2.3-kb subtelomeric repeated unit are shown to correlate with size variations, and in at least one case to account completely for the size differen ...19901974695
sfii and noti polymorphisms in theileria stocks detected by pulsed field gel electrophoresis.dnas of theileria parva parva, t. p. lawrencei, t. p. bovis and theileria mutans stocks, from kenya, uganda, zanzibar and zimbabwe were digested with either sfii or noti and analysed using contour-clamped homogeneous electric field (chef) and field-inversion gel electrophoresis (fige). the sfii-digested t. parva genomic dna resolved into approximately 30 fragments while the noti digestion produced between 4-7 bands. the summation of the sizes of sfii fragments gave an estimate of 9-10 x 10(6) ba ...19901972977
[preliminary studies on the diagnosis of plasmodium falciparum malaria by monoclonal antibody sandwich dot-immunogold silver staining assay].in this report, the blood samples from 30 falciparum malaria patients with parasitemia 0.015-0.58% and the blood samples from 30 healthy persons were examined by monoclonal antibody (mcab) sandwich dot-immunogold silver staining assay (dot-igssa). when the mcab 11g5, 13a2 and 13a1 were used for sandwich dot-igssa with mcab 14d9 labeled with colloidal gold respectively, the 0.0001% of parasitemia could be detected and the mcab 11g5, 13a1 and 14d9 labeled with colloidal gold could also be used to ...19911959167
[antimalarial activity of deoxoqinghaosu].compound 3 (deoxoqinghaosu) and compound 4 (deoxocarbaqinghaosu) were synthesized from arteannuic acid (2). primary exploration of their antimalarial effect against k173 strain of plasmodium berghei shows that compound 3 is somewhat more effective than the natural compound--qinghaosu. however, the carba-analogue compound 4 is almost ineffective. the enhanced activity of compound 3 is supposedly ascribed to its higher lipophilicity and, hence, higher affinity for plasmodial membrane. further stud ...19911957665
transdermal artelinic acid: an effective treatment for plasmodium berghei-infected mice.artelinic acid, a derivative of the naturally occurring antimalarial artemisinin, has been incorporated into a gel suitable for transdermal administration. the formulation was tested for efficacy in plasmodium berghei-infected mice for both curative and prophylactic properties by application to their partially denuded backs, beginning on days 3 and 0, respectively, after injection of parasitized erythrocytes. in the curative experiments, rapid elimination of the parasitemia and 60-day survival o ...19911951870
nucleotide sequence variation in the beta-tubulin genes from plasmodium berghei and plasmodium falciparum. 19911944421
antimalarial activity and cytotoxicity of evodia fatraina stem bark extracts.stem bark extracts of evodia fatraina (rutaceae) were tested for antimalarial activity in vitro on plasmodium falciparum using an isotopic semi-microtest and in vivo on plasmodium berghei in mice. ethyl acetate extract showed moderate antimalarial activity in vitro (ic50 = 8.5 micrograms ml-1). however, ethanolic extract exhibited significant potency in vivo (65% suppression of parasitaemia). moreover, low toxicity against hela cells and l 929 fibroblasts was observed with ethanolic extract (ic5 ...19911921419
plasmodium berghei ookinete densities in three anopheline species.plasmodium berghei ookinete kinetics and densities were examined in the blood meals of 3 species of anopheles mosquitoes fed simultaneously from a gametocytemic mouse. simple techniques were developed for estimating relative and absolute ookinete densities within individual mosquito blood meals. the kinetics of ookinete formation were similar in all 3 species, with peak ookinete densities occurring from 12 to 24 hr postingestion. ookinete densities consistently were lower in anopheles stephensi ...19911919925
18s rrna sequences of leishmania enriettii promastigote and amastigote.dideoxy sequencing with reverse transcriptase and universal primers was used to obtain partial sequences of the 18s rrnas from the promastigote and amastigote life-cycle stages of l. enriettii. approximately 1400 nucleotides of sequence from the two stages were compared. unlike plasmodium berghei, in which 18s rrnas from the mosquito stage and the mammalian stage of the life cycle are only 96.5% similar, the amastigote and promastigote rrnas of l. enriettii are identical. in addition, a comparis ...19911917290
effect of plasmodium berghei infection and chloroquine on the hepatic drug metabolizing system of mice.the hepatic microsomal mixed-function oxidase (mfo) system was markedly impaired during plasmodium berghei infection in mice. cytochrome p-450 and other mono-oxygenases, viz. aniline hydroxylase, aminopyrine-n-demethylase and benzo(a)pyrene hydroxylase, were significantly decreased while microsomal heme showed a four-fold increase at peak parasitemia (greater than 50%). oral treatment with chloroquine (16 mg kg-1 body wt for 4 days) of p. berghei-infected mice cleared the parasitemia within 72 h ...19911917287
antimalarial effect of cyclosporin-a on murine p. berghei and human p. falciparum.the effects of cyclosporin-a (csa) on the growth of plasmodia were investigated in an experimental murine model in vivo and on human malaria in vitro. mice were inoculated with plasmodium berghei and then treated with different doses of csa at the patent period. the development and course of this normally lethal parasitaemia in mice was affected by treatment with csa which is a known immunosuppressant. the drug showed complete protection at a dose of 20 mg/kg wt/day without any recrudescence. an ...19911915980
detection of polymerase chain reaction-amplified malarial dna in infected blood and individual mosquitoes.chelex treatment of plasmodium falciparum and p. berghei infected tissues, in lieu of organic extraction, was followed directly by polymerase chain reaction amplification of primed circumsporozoite gene sequences. the amplified dna products were detected in stained gels and hybridization blots of extracts from individual infected mosquitoes and dissected mosquito tissues as well as small volumes of infected blood. parasite development, within the mosquito midgut and salivary gland, was also moni ...19911915745
ribosomal rna sequences of sarcocystis muris, theileria annulata and crypthecodinium cohnii reveal evolutionary relationships among apicomplexans, dinoflagellates, and ciliates.sarcocystis muris is a coccidium with a two-host life cycle involving the domestic cat and the mouse, mus musculus. s. muris and theileria annulata belong to the phylum apicomplexa, but the latter organism is a tick-borne protozoon in the subclass piroplasmea and causes tropical theileriosis in cattle. the small-subunit ribosomal rna (16s-like rrna) coding regions of these organisms as well as that of the free living dinoflagellate crypthecodinium cohnii were amplified using polymerase chain rea ...19911904987
purification and characterization of dna polymerases from plasmodium berghei.dna polymerases from the malaria parasite plasmodium berghei were purified more than 50-fold. several distinct enzymatic activities were isolated that could be distinguished by the use of various specific dna polymerase inhibitors. in particular, subdivision into an aphidicolin-sensitive and an aphidicolin-resistant group was possible. further analysis allowed a better comparison with host dna polymerases and indicated that one aphidicolin-sensitive dna polymerase resembled dna polymerase alpha ...19911903844
ifn-gamma inhibits development of plasmodium berghei exoerythrocytic stages in hepatocytes by an l-arginine-dependent effector mechanism.primary cultures of balb/cj hepatocytes treated with 10(3) u/ml rifn-gamma consistently inhibited intracellular plasmodium berghei liver schizont development by 50 to 70%. monomethyl-l-arginine (ngmmla), the competitive inhibitor of l-arginine as substrate for production of nitric oxides by hepatocytes, reversed the activity of ifn-gamma on these malaria-infected cells. reversal of ifn-gamma activity by ngmmla was dose dependent and was maximal at 0.5 mm ngmmla. depletion of l-arginine by additi ...19911903415
interferon-gamma enhances the effect of antimalarial chemotherapy in murine plasmodium vinckei malaria.most nonimmune patients with plasmodium falciparum infection are no longer cured by such standard antimalarial drugs as chloroquine. thus, alternative treatment regimens are necessary. a combination therapy was tested consisting of a subcurative dose of chloroquine and interferon-gamma (ifn-gamma) in balb/c mice with lethal plasmodium vinckei malaria. treatment with either agent alone prolonged median survival by 1-2 days compared with placebo-treated mice. however, a combination of 80 microgram ...19911902249
plasmodium berghei: lactic acidosis and hypoglycaemia in a rodent model of severe malaria; effects of glucose, quinine, and dichloroacetate.fulminant malaria infections are characterised by hypoglycaemia and potentially lethal lactic acidosis. in young adult wistar rats (n = 26) infected with plasmodium berghei (anka strain), hyperparasitaemia (greater than 50%), anaemia (pcv 19.6 +/- 5.3%; mean +/- sd) hypoglycaemia (1.04 +/- 0.74 mmol/litre), hyperlactataemia (13.2 +/- 2.20 mmol/litre), hyperpyruvicaemia (0.51 +/- 0.12 mmol/litre) and metabolic acidosis (arterial ph 6.96 +/- 0.11) developed after approximately 14 days of infection ...19911901269
the evolution of plasmodial stage-specific rrna genes is dominated by gene conversion.plasmodium species exhibit the unprecedented situation of distinct, stage-specific rrna sequences. we present an analysis of two pairs of sequences of the small rrna subunit (plasmodium falciparum and plasmodium berghei) and show that these genes do not evolve independently and that in fact their evolution is dominated by gene conversion. this analysis also shows that no extensive stage-specific sequences are conserved in the two species, thus rendering unlikely that the existence of stage-speci ...19911901094
monoterpenic fragment analogues of aplasmomycin as potential antimalarial.seven analogues of monoterpenic fragment of aplasmomycin were synthesized as targeted antimalarial agents. the potency of the compound 6 was comparable with the sesquiterpene lactone artemisinin and the antibiotic aplasmomycin in vivo against plasmodium berghei yoelli.19911895301
deet and permethrin as protectants against malaria-infected and uninfected anopheles stephensi mosquitoes.deet and permethrin were evaluated as protectants against plasmodium falciparum-infected, p. berghei-infected and uninfected anopheles stephensi mosquitoes. deet 50% effective dose (ed50) values were 3.2 micrograms/cm2 for p. falciparum-infected and 1.9 micrograms/cm2 for uninfected mosquitoes; permethrin values were 0.5 micrograms/cm2 and 0.6 micrograms/cm2, respectively. deet ed50 values were 2.3 micrograms/cm2 for p. berghei-infected and 1.3 micrograms/cm2 for uninfected mosquitoes; the perme ...19911895090
lack of h-2 restriction of the plasmodium falciparum (nanp) sequence as multiple antigen peptide.the major surface antigen of malaria sporozoites, the circumsporozoite protein, contains a region of tandem amino acid repeats, which in the case of the human malaria parasite plasmodium falciparum, consist of four amino acids asn-ala-asn-pro (nanp) repeated up to about 40 times. this repetitive sequence has been considered as the basis for the development of subunit vaccines against p. falciparum malaria. we and others had previously shown that synthetic and recombinant nanp peptides were immun ...19911889465
[a titrographic method for determining the glycolysis flow rate with plasmodium berghei-infected red blood cells].a procedure is described for the elucidation of the glycolytic flux rate of red blood cells infected with the malarial parasite plasmodium berghei. it is based on the titration of the protons originating from the glycolytic lactate accumulation. compared with traditional methods of biochemical measurements of glucose consumption or accumulation of lactate the proposed procedure shows the following advantages: continuously measurement is possible; constancy of the ph-value during the measurement; ...19911888075
multiple display of foreign peptides on a filamentous bacteriophage. peptides from plasmodium falciparum circumsporozoite protein as antigens.we describe here two systems for encoding foreign amino acid sequences in the exposed n-terminal segment of the major coat protein of bacteriophage fd. small peptides can be encoded directly; larger peptides are encoded in hybrid bacteriophage particles, in which the capsid is formed from a mixture of wild-type and modified coat proteins. in both cases, the peptides are present in multiple copies per phage particle. peptides that represent the circumsporozoite protein, the major surface antigen ...19911880799
eosinophil-rich, granulomatous inflammatory response to plasmodium berghei hepatic schizonts in nonimmunized rats is age-related.inflammatory responses to plasmodium hepatic schizonts within the livers of non-immunized animals have long been assumed to be initiated only after the parasites have matured and begun to burst. however, recent reports of inflammatory responses around hepatic schizonts suggested a re-examination of this issue. we injected norway-brown rats of various ages intravenously with plasmodium berghei sporozoites and studied subsequent liver histopathology. we found that the ability of these rats to moun ...19911877714
dextran sulfate induced suppression of plasmodium berghei parasitaemia.effect of dextran sulfate (ds, mr 500,000) on parasitaemia in mice (balb/c) infected with erythrocytic stage of p. berghei was investigated. intraperitoneal injection of ds caused marked suppression of patent parasitaemia and also enhanced the survival time of the infected animals.19911874546
recent studies on antimalarial efficacy of piperaquine and hydroxypiperaquine.piperaquine and hydroxypiperaquine seem to be successful candidates of antimalarial drugs in china. their antimalarial efficacy, experimental resistance, combination, mode of antimalarial action and clinical trials are described briefly.19911874015
pentoxifylline prevents murine cerebral malaria.pentoxifylline, a widely used methylxanthine, was tested for its capacity to prevent cerebral malaria (cm) in plasmodium berghei anka-infected cba/ca mice. nine of 12 control mice developed neurologic signs and died from cm approximately 2 weeks after infection. all 12 mice treated with daily intraperitoneal pentoxifylline (1 mg) for 10 days after infection did not develop cm. all surviving mice developed high parasitemia and severe anemia and died 2 weeks later without neurologic signs. in pent ...19911869848
immune response to plasmodium berghei sporozoite antigens. i. evaluation of murine t cell repertoire following immunization with irradiated sporozoites. 19911858962
inhibition of the growth of plasmodium falciparum and plasmodium berghei by the dna polymerase inhibitor hpmpa.the acyclic adenosine analogue (s)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [hpmpa] belongs to a class of nucleoside analogues originally described as having potent activity against a broad spectrum of dna viruses. we examined the effects of this class of drugs on the growth of cultured plasmodium falciparum. strong inhibition was observed by hpmpa (id50 = 47 nm) at concentrations more than 1000-fold less than the cytotoxic dose for human cells. 3-deaza-hpmpa was even more strongly inhibit ...19911857384
role of host cellular response in differential susceptibility of nonimmunized balb/c mice to plasmodium berghei and plasmodium yoelii sporozoites.we found balb/c mice to be on the order of 2,000 times more susceptible to plasmodium yoelii than plasmodium berghei sporozoites, as measured by the ability of these sporozoites to differentiate into microscopically detectable hepatic schizonts in the livers of immunologically naive mice. one of the factors that determine the relative insusceptibility of mice to p. berghei sporozoites is the innate cellular inflammatory response that the mice mount after injection with sporozoites. the cellular ...19911855974
cyclic amp level in red blood cells of plasmodium berghei-infected mastomys natalensis.the present report describes the changes in cyclic amp level which occur upon parasitization of red cells by plasmodium berghei. parasitized erythrocytes were separated from the non-parasitized population by percoll density-gradient centrifugation. an increase in the cyclic amp content of both non-parasitized and parasitized erythrocytes of infected animals compared with that of uninfected animals was observed. the patterns of physiological response to isoproterenol in normal, parasitized and no ...19911849086
purification and characterization of dihydroorotate dehydrogenase from the rodent malaria parasite plasmodium berghei.dihydroorotate dehydrogenase (dhodase) has been purified 400-fold from the rodent malaria parasite plasmodium berghei to apparent homogeneity by triton x-100 solubilization followed by anion-exchange, cibacron blue f3ga-agarose affinity, and gel filtration chromatography. the purified enzyme has a molecular mass of 52 +/- 2 kda on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and of 55 +/- 6 kda by gel filtration chromatography, and it has a pi of 8.2. it is active in monomeric form, ...19911847078
[evaluation of the possible therapeutic effect of the plant rubim in plasmodium berghei experimental infection in mice]. 19911845014
comparative and sequential histopathology of plasmodium chabaudi-infected balb/c mice.1. rodent experimental models have been useful to study severe malaria but few serial and controlled studies have been conducted. in the present investigation, we describe the histopathology of lethal and non-lethal rodent malaria induced by plasmodium berghei and p. chabaudi. p. berghei malaria shows a uniformly lethal course, while p. chabaudi malaria produces a non-lethal acute infection with recovery and periodical recrudescences. sequential histopathological changes were also characterized ...19911843871
comparative evaluation of blood schizontocidal activity of quinine and quinidine against drug resistant rodent malaria.blood schizontocidal activity of quinine and quinidine has been compared against sensitive as well as chloroquine/mefloquine/quinine resistant strains of plasmodium berghei and a multiple resistant strain of p. yoelii nigeriensis in swiss mice. evaluation of results on ed50/ed90 basis has shown distinct superiority of quinidine over quinine against sensitive as well as drug resistant strain of rodent malaria.19911842807
antimalarial chemotherapy with natural products and chemically defined molecules.in the present work we have described the in vivo antimalarial activity of six different plants. two of them (vernonia brasiliana and eupatorium squalidum) were tested in a randomic approach among 273 crude extracts from plants; four (acanthospermum australe, esenbeckia febrifuga, lisianthus speciosus and tachia guianensis) were selected after screening 22 crude extracts from different medicinal plants used in brazil against fever and/or malaria. we also studied chemically defined molecules and ...19911841997
screening of the antimalarial activity of plants of the cucurbitaceae family.crude ethanolic extracts (cees) from two species of cucurbitaceae, cucurbita maxima and momordica charantia (commonly called "abóbora moranga" and "melão de são caetano", respectively) were assayed for antimalarial activity by the 4-d suppressive test. the cee of dry c. maxima seeds showed strong antimalarial activity following oral administration (250 and 500 mg/kg), reducing by 50% the levels of parasitemia in plasmodium berghei-infected mice. treatment of normal animals with 500 mg/kg of the ...19911841996
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