Showing papers on "Plasmodium berghei published in 1991"
Journal Article•
TL;DR: The relatively high percentage of positive results obtained here for "medicinal" plants vs randomly chosen plants demonstrates the effectiveness of the ethnopharmacological approach to drug testing.
Abstract: 1. Ninety-five crude extracts obtained with either organic solvents or water from 48 Brazilian plants or parts of plants were evaluated experimentally as blood schizontocides. Seventy-three extracts were obtained from 33 plants randomly collected using an empirical approach, and 22 from 15 "medicinal" plants. 2. The crude extracts were screened in vivo at up to 1.0 g/kg, po, for 4 days in mice infected with blood forms of Plasmodium berghei and parasitemia was determined on the fifth day. 3. Six plants, 2 randomly collected, Vernonia brasiliana and Eupatorium squalidum, and 4 "medicinal" plants, Acanthospermum australe, Esenbeckia febrifuga, Lisianthus speciosus, and Tachia guianensis, were partly active against the rodent malaria, i.e., they showed 40-50% inhibition of P. berghei multiplication. Forty-two plants whose extracts presented no antimalarial activity are reported. 4. Four extracts with antimalarial activity were also tested in vitro using P. falciparum cultures and two of them, V. brasiliana and A. australe, were active. Extracts of V. brasiliana caused about 50% inhibition of parasite multiplication at relatively low doses (40 ng/ml) as compared to chloroquine (30 ng/ml) and quinine (50 ng/ml). 5. The relatively high percentage of positive results obtained here for "medicinal" plants vs randomly chosen plants demonstrates the effectiveness of the ethnopharmacological approach to drug testing.
167 citations
Journal Article•
TL;DR: Data strongly suggest that the action of IFN-gamma on P. berghei-infected hepatocytes is to induce the production of L-arginine-derived nitrogen oxides that are toxic for the intracellular parasite.
Abstract: 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 addition of arginase to the culture medium blocked the capacity of IFN-gamma to inhibit parasite development in hepatocytes; addition of excess L-arginine to cultures treated with IFN-gamma in the presence of NGMMLA competitively restored IFN-gamma capacity to activate hepatocyte anti-parasite activity. TNF-alpha was neither required for IFN-gamma activity, nor effective at any concentration tested as an inhibitor of schizont development by itself in primary hepatocytes. These data strongly suggest that the action of IFN-gamma on P. berghei-infected hepatocytes is to induce the production of L-arginine-derived nitrogen oxides that are toxic for the intracellular parasite.
165 citations
TL;DR: Analysis of DNA sequences supports the hypothesis that in Plasmodium falciparum, positive Darwinian selection favors diversity in the T-cell epitopes of the CS protein.
Abstract: The circumsporozoite (CS) protein is a cell surface protein of the sporozoite, the stage of the life cycle of malaria parasites (Plasmodium spp.) that infects the vertebrate host. Analysis of DNA sequences supports the hypothesis that in Plasmodium falciparum, positive Darwinian selection favors diversity in the T-cell epitopes (peptides presented to T cells by host MHC molecules) of the CS protein. In gene regions encoding T cell epitopes of P. falciparum, the rate of nonsynonymous nucleotide substitution is significantly higher than that of synonymous substitution, whereas this is not true of other gene regions. Furthermore nonsynonymous nucleotide substitutions in these regions cause a change of amino acid residue charge significantly more frequently than expected by chance. By contrast, in Plasmodium cynomolgi, the same regions show no evidence of positive selection, and residue charge is conserved. The CS protein has a central repeat region, which is the target of host antibodies. In P. falciparum, the amino acid sequence of the repeat region is conserved within and between alleles. In P. cynomolgi, on the other hand, there is evidence that positive selection has favored evolution of two different repeat types within a given allele.
129 citations
TL;DR: It is proposed that CS protein released from the apical end, the leading end of gliding sporozoites, adheres to the sporozoite surface and is translocated posteriorly by a cytochalasin-sensitive and apparently actin-mediated surface motor, which drives gliding motility.
Abstract: Plasmodium sporozoites, the causative agents of malaria, release circumsporozoite (CS) protein into medium when under conditions simulating those that the parasites encounter in the bloodstream of the vertebrate host. CS protein of the rodent parasite, Plasmodium berghei, is released as the lower molecular weight form, Pb44. This release is substratum- and antibody-independent. Previous studies show that CS protein is released at the trailing, posterior end of motile sporozoites. Video and electron microscopic studies now demonstrate that CS protein is released at the apical end of cytochalasin b-immobilized sporozoites. We propose that CS protein released from the apical end, the leading end of gliding sporozoites, adheres to the sporozoite surface and is translocated posteriorly by a cytochalasin-sensitive and apparently actin-mediated surface motor, which drives gliding motility. This model explains the mechanism of both the circumsporozoite precipitation (CSP) reaction and formation of the CS protein trail by gliding sporozoites.
104 citations
TL;DR: Northern blot analysis of TNF mRNA from stimulated macrophages showed that pentoxifylline inhibited TNF expression at the transcription level, and TNF bioactivity in supernatants was strongly depressed, which makes pentoxifyinglline a potential candidate for study as a supportive agent in human CM.
Abstract: 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 pentoxifylline-treated mice, serum tumor necrosis factor (TNF) bioactivity was nondetectable, whereas control mice had high TNF levels on day 6 after infection. These findings were supported by in vitro investigations of malaria antigen-induced TNF synthesis. Northern blot analysis of TNF mRNA from stimulated macrophages showed that pentoxifylline inhibited TNF expression at the transcription level, and TNF bioactivity in supernatants was strongly depressed. These findings make pentoxifylline a potential candidate for study as a supportive agent in human CM.
81 citations
01 Feb 1991
TL;DR: Alcoholic extracts of 44 plants were screened in vivo and in vitro for antimalarial activity against the NK 65 strain of Plasmodium berghei and found to possess schizontocidal activity (50% and above) in vivo as well as in vitro.
Abstract: Alcoholic extracts of 44 plants were screened in vivo and in vitro for antimalarial activity against the NK 65 strain of Plasmodium berghei. Jurinea macrocephala, Artemisia scoparia, Nyctanthes arbor-tristis, Enicostema hyssopifolium, Aegle marmelos, Cinnamomum tamala, Momordica dioica and Prunus persica were found to possess schizontocidal activity (50% and above) in vivo as well as in vitro at a dose of 1 gm/kg × 4 days and 100 μg/ml respectively, whereas 12 other plant extracts were active only in vivo and 3 plant extracts in in vitro only.
72 citations
TL;DR: The data strongly suggest that the BALB/c-P.
Abstract: 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 inflammatory response against P. berghei is initiated soon after sporozoite injection; by 24 h, substantial histopathological changes have developed within the liver. There is considerably less of a cellular inflammatory response against P. yoelii; significant histopathological changes within the liver are not observed until well after hepatic schizonts have begun to rupture at around 44 h postinjection of sporozoites. These differences in the cellular inflammatory response against two different, closely related species of sporozoites are of considerable interest. The data strongly suggest that the BALB/c-P. berghei sporozoite system is a relatively poor biological model for sporozoite immunization studies. Images
70 citations
TL;DR: Anti‐LFA‐1 treatment did not result in a substantial decrease in the monocyte accumulation observed in cerebral vessels of susceptible mice, suggesting its efficacy may be related to the broader roles of L FA‐1 in cell‐cell interactions important in the later pathogenic stages of the immune response to the parasite.
Abstract: CBA/Ca mice injected with Plasmodium berghei develop cerebral malaria (CM) characterized by ataxia and progressive paralysis leading to death 7-9 days after experimental infection. The development of cerebral symptoms is a function of the immune response in susceptible strains, and depends on cell-cell interactions involving T helper cells and mononuclear phagocytes. Here we ask whether antibodies to cell adhesion receptors of the immune system can influence the development of CM in this mouse model. When administrated on day 6 after infection, antibody to the leukocyte integrin leukocyte function-antigen-1 (LFA-1) but not antibodies to MAC-1, LECAM-1 (the MEL-14 antigen), alpha 4 integrin or ICAM-1 dramatically reduced the incidence of CM, leading to survival of most mice until the later onset of anemia. Anti-LFA-1 treatment did not result in a substantial decrease in the monocyte accumulation observed in cerebral vessels of susceptible mice. Its efficacy may be related to the broader roles of LFA-1 in cell-cell interactions important in the later pathogenic stages of the immune response to the parasite. Perturbation of immune cell function through interference with cell adhesion mechanisms may offer an important therapeutic tool in acute, life-threatening immune-mediated disorders.
67 citations
TL;DR: Seven alkaloids isolated from Strychnos usambarensis have been assessed for in vitro activities against Entamoeba histolytica and Plasmodium falciparum and for in vivo activity against Plas modium berghei in mice.
Abstract: Seven alkaloids isolated from Strychnos usambarensis have been assessed for in vitro activities against Entamoeba histolytica and Plasmodium falciparum and for in vivo activity against Plasmodium berghei in mice. Strychnopentamine and 3',4'-dihydrousambarensine were highly active against P. falciparum in vitro, but were inactive and non-toxic against P. berghei in vivo. Usambarensine, usambarine, and 18,19-dihydrousambarine were highly active against E. histolytica in vitro, but were less active against P. falciparum in vitro. Nb-Methylusambarensine was less active against both protozoa than was usambarensine, and akagerine possessed little antiprotozoal activity. Structure-activity relationships are discussed in the context of the reported cytotoxic and pharmacological properties of these alkaloids.
64 citations
TL;DR: The requirement of the long-chain ubiquinones for activity supports the hypothesis of the linkage of pyrimidine biosynthesis to the electron transport system and oxygen utilization in malaria by DHODase via ubiquinONES.
Abstract: 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, contains 2.022 mol of iron and 1.602 acid-labile sulfurs per mole of enzyme, and does not contain a flavin cofactor. The purified DHODase exhibits optimal activity at pH 8.0 in the presence of the ubiquinone coenzyme CoQ6, CoQ7, CoQ9, or CoQ10. The Km values for L-DHO and CoQ6 are 7.9 +/- 2.5 microM and 21.6 +/- 5.5 microM, respectively. The kcat values for both substrates are 11.44 min-1 and 11.70 min-1, respectively. The reaction product orotate and an orotate analogue, 5-fluoroorotate, are competitive inhibitors of the enzyme-catalyzed reaction with Ki values of 30.5 microM and 34.9 microM, respectively. The requirement of the long-chain ubiquinones for activity supports the hypothesis of the linkage of pyrimidine biosynthesis to the electron transport system and oxygen utilization in malaria by DHODase via ubiquinones [Gutteridge, W. E., Dave, D., & Richards, W. H. G. (1979) Biochim. Biophys. Acta 582, 390-401].
45 citations
TL;DR: The temporal presence of amplifiable circumsporozoite gene sequences in the infected mosquitomidgut lumen, midgut endothelium, and salivary glands corresponded directly to the visual identification of ookinetes, oocysts, and Salivary gland sporozoites, respectively.
TL;DR: A series of novel tetraamine compounds synthesized and examined for activity against growth of Plasmodium falciparum in vitro found dibenzyl analogues (R = benzyl) to be the most effective growth inhibitors.
Abstract: 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, in combination with the ornithine decarboxylase inhibitor alpha-(difluoromethyl)ornithine, resulted in radical cures when tested against experimental Plasmodium berghei infections in mice. The structure-activity relationships of the series are discussed.
TL;DR: A PGP-specific monoclonal antibody was used to determine the presence of PGP genes in resistant and sensitive Plasmodium and Leishmania parasites and suggested that a correlation existed between the degree of antimony susceptibility and the concentration of the moiety recognized by C219 in two L. panamensis clones.
Abstract: Multidrug-resistance (MDR) in neoplastic cells is frequently characterized by the overexpression of P-glycoprotein (PGP), a 170 kDa transmembrane glycoprotein that binds multiple cytotoxic drugs as well as calcium channel antagonists. Chloroquine resistance in Plasmodium falciparum appears to be analogous to MDR in neoplastic cells, where the induction of resistance with one drug confers resistance to other structurally and functionally unrelated drugs. To test the hypothesis that chloroquine resistance in P. falciparum and antimony resistance in Leishmania is mediated by a similar mechanism of MDR in mammalian neoplastic cells, a PGP-specific monoclonal antibody (C219) was used to determine the presence of PGP genes in resistant and sensitive Plasmodium and Leishmania parasites by indirect immunofluorescence assays and Western blotting procedures. These PGP-like components were detected in both drug-sensitive and -resistant Plasmodium and Leishmania cells. A 40-42 kDa component was observed to be greater in a chloroquine-resistant P. berghei (C line) than in a chloroquine-susceptible P line. Differences observed between Pentostam-resistant and -sensitive Leishmania promastigote clones and isolates included the increased expression of 96-106 and 23-25 kDa peptides in drug-resistant L. enrietti, and increased amounts of two different peptides in two drug-resistant L. panamensis clones (i.e., 96-106 and 43-45 kDa in WR-746-CL4, and 53 and 23-25 kDa in kDa) in amastigotes as in MDR KB carcinoma cells (KB-V1). Comparative indirect immunofluorescent studies suggested that a correlation existed between the degree of antimony susceptibility and the concentration of the moiety recognized by C219 in two L. panamensis clones. Binding of the C219 monoclonal antibody to the PGP-like component of Leishmania was blocked by Pentostam, while the binding of C219 to multiple-drug resistant KB-V1 PGP was not inhibited by Pentostam, regardless of the PGP concentration. This suggests some degree of specificity in the binding of Pentostam to the Leishmania PGP-like components. In addition, these studies have demonstrated that drug-sensitive Leishmania accumulate two to five times more 125Sb-Pentostam than resistant clones.
TL;DR: By using affinity-purified ookinete surface antigen from the rodent malaria parasite Plasmodium berghei, a transmission-blocking immunity was induced in mice and immunoblot analysis confirmed that immune sera invariably recognized Pbs21 antigen.
Abstract: 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. Immunoblot analysis confirmed that immune sera invariably recognized Pbs21 antigen. The isotype and titer of the anti-Pbs21 immunoglobulin G (IgG) response was determined by enzyme-linked immunosorbent assay. The antibody isotype was predominantly IgG1. The concentration of specific anti-Pbs21 IgG reached a peak of 182.45 +/- 92.13 micrograms/ml by week 7 postimmunization and fell progressively to 38 micrograms/ml at week 34 (at which time the transmission was still inhibited by 98%).
TL;DR: The inhibition by HPMPApp is competitive with dATP, strongly suggesting that Plasmodium DNA polymerases are targets for this class of nucleotide analogue.
TL;DR: Data are consistent with published evidence which indicates that a reduction in parasitaemia may cause an increase in infectivity of gametocytes to the mosquito vector and the impact of strategies aiming to control asexual parasites is re-examined.
Abstract: In the rodent malarial parasite Plasmodium berghei sexual parasites are produced in a single major wave with maximal numbers between day 7 and day 16. Irrespective of their time of appearance during infection these sexual parasites are equally fertile in vitro. In contrast, in vivo infectivity to the mosquito is maximal at day 3-5 when gametocyte numbers are only 9% of the peak levels seen between days 7 and 16. Up to 96% of natural potential infectivity of gametocytes for the mosquito is therefore suppressed. The suppression is humoral, reversible and correlates with the appearance of an effective host response to the initial rapid increase in asexual parasitaemia. These data are consistent with published evidence which indicates that a reduction in parasitaemia may cause an increase in infectivity of gametocytes to the mosquito vector. Therefore the impact of strategies aiming to control asexual parasites is re-examined. Inefficient strategies might be predicted to increase and not suppress malaria transmission.
TL;DR: The significance of spastic constriction of intracerebral arterioles for microcirculatory disturbance in relation to development of cerebral malaria is discussed.
TL;DR: The enlargement of the CTD of the human parasite by six heptapeptide repeats is most likely generated by a recent amplification of a specific repeat unit.
TL;DR: The data suggest that important pathways of drug detoxification may be compromised by MI in a relatively selective fashion and the relevance of these findings to the clinical use of drugs eliminated by these pathways merits further study.
TL;DR: None of the recombinant virus-immunized animals could be protected from a challenge of sporozoites even at the lowest dose of parasite used.
TL;DR: In this article, the authors found evidence of inflammatory cells (eosinophils) infiltrating hepatic schizonts as early as 40 hours post-injection with sporozoites.
Abstract: 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 mount an inflammatory response is age-dependent. Young (4 weeks) rats had weak inflammatory responses against hepatic schizonts, whereas older (8–10 weeks) rats mounted a strong response. Older rats had many granulomatous reactions within the liver; eosinophils represented a pioneer component of the cellular infiltrate. There was a reduction in the numbers of surviving hepatic schizonts in the older rats, suggesting that these granulomatous and eosinophilic reactions had effectively destroyed some of the hepatic schizonts. We found clear evidence of inflammatory cells (eosinophils) infiltrating hepatic schizonts as early as 40 hours post-injection with sporozoites, a time well before any hepatic schizonts could have burst within the liver. This presents histological evidence that inflammatory cells can recognize and infiltrate intact hepatocytes containing schizonts in immunologically naive animals.
TL;DR: Results indicate that chloroquine delivery in antibody targeted liposomes may help in the successful treatment of the chloroquines resistant malarial infections.
Abstract: Suitability of anti-erythrocyte F(ab')2-bearing liposomes as vehicles for chloroquine in the treatment of chloroquine resistant Plasmodium berghei infections in mice has been examined. Free chloroquine or chloroquine encapsulated in antibody-free liposomes failed to show much effect on the resistant infections, but the same doses of this drug after being encapsulated in antibody-bearing liposomes exhibited a significant inhibitory effect on this infection. These results indicate that chloroquine delivery in antibody targeted liposomes may help in the successful treatment of the chloroquine resistant malarial infections.
Journal Article•
TL;DR: These results, together with the recent evidence of manganese-superoxide dismutase activity in malarial mitochondria, suggest that the production of superoxide radical may occur in vivo.
Abstract: Dihydroorotate dehydrogenase purified from mitochondria of Plasmodium berghei, a rodent malaria parasite, mediates production of superoxide radical during oxidation of dihydroorotate to orotate. Reduction of dichlorophenolindophenol or cytochrome c or nitroblue tetrazolium was significantly inhibited by superoxide dismutase or theonyltrifluoroacetone, a specific iron chelator of the enzyme. These results, together with the recent evidence of manganese-superoxide dismutase activity in malarial mitochondria [Ranz, A., and Meshnick, S.R. (1989) Exp. Parasitol. 69, 125-128], suggest that the production of superoxide radical may occur in vivo.
TL;DR: A method has been developed which detects malaria parasites in the salivary glands of live Anopheles stephensi by exploiting the sugar feeding behaviour of the mosquito and requires only routine Western blotting techniques on nitrocellulose membrane (NCM).
Abstract: A method has been developed which detects malaria parasites in the salivary glands of live Anopheles stephensi. The method exploits the sugar feeding behaviour of the mosquito and requires only routine Western blotting techniques on nitrocellulose membrane (NCM). Infectivity can be determined without any direct manipulation of individual mosquitoes. Female A. stephensi were infected with the rodent malaria parasite, Plasmodium berghei, and after 14-16 d were starved of fructose overnight (12-18 h), then resupplied with fructose presented through a small piece of NCM. Mosquitoes were allowed to probe the membrane for several hours; the NCM was then removed and subjected to a standard immunoblotting protocol using an anti-P. berghei circumsporozoite protein (CSP) monoclonal antibody as the primary reagent, and a horseradish peroxidase-coupled secondary antibody. NCMs taken from cages containing infected mosquitoes showed a variable number of small black dots where individual females had probed and deposited either CSP or sporozoites. Infectivity could be detected easily from 13-14 d after feeding, and in as few as 10 mosquitoes at 19 d after infection; in one instance, infection in a single mosquito was clearly determined. After blocking with goat serum, the NCMs could be stored for 3-4 months and still provided positive reactions, offering some potential for applicability to field research studies.
TL;DR: 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 Plas modium berghei, as models of human malaria.
Abstract: 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 disease in a transfusion model. P. berghei-infected red cells were more resistant to the antimalarial activity of MC 540 than were P. yoelii-infected cells, presumably because P. berghei preferentially infects reticulocytes whereas P. yoelii infects mature red cells. The possibility of using photoirradiation sensitized by MC 540 or related dyes to purge malarially infected donor blood is discussed.
TL;DR: A 34-year-old black man presented with high fever, diarrhea, and severe disorientation, and the clinical diagnosis of falciparum malaria was confirmed by the finding of ^ parasitemia with Plasmodium falcIParum.
Abstract: Colleagues?Recent reports suggest that tumor necrosis factor (TNF) [1] is an important component of host response in malaria. Elevated concentrations of TNF have been noted in patients with cerebral malaria. Levels of TNF ^1 pg/ml were associated with a high fatality rate [2, 3]. Treatment with antiTNF antibodies protected mice from cerebral complications of Plasmodium berghei infection. In an animal murine malaria model, pentoxifylline inhibited the evolution of cerebral malaria [4]. A 34-year-old black man presented with high fever ^390C), diarrhea, and severe disorientation. He had been sick ~ 1 week after a 2-week visit to Nigeria. The clinical diagnosis of falciparum malaria was confirmed by the finding of ^ parasitemia with Plasmodium falciparum. Treatment was started with quinine (20 mg/kg) and continued with quinine (10 mg/kg every 8 h) and clindamycin [5] (10 mg/kg every 12 h) intravenously for 7 days. On admission concentrations of TNF and interleukin-6 (IL-6) [6] were 158 pg/ml and 147 pg/ml, respectively. The next morning the patient was precomatose and responded only to massive irritation. TNF rose to 195 pg/ml and IL-6 to 197 pg/ml. Be-
TL;DR: The combination of chemotherapy with the cytokine IFN-gamma leads to substantial improvement of antimalarial treatment and to a rapid development of strain-specific immunity in murine P. vinckei malaria.
Abstract: 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 micrograms of chloroquine given at the time of infection plus 1 x 10(4) units of IFN-gamma/day for 11 days (starting 3 days before infection) cured 83% of infected mice. Moreover, these mice showed solid immunity when challenged with the homologous strain of P. vinckei. However, when these mice were infected with the heterologous strain of Plasmodium berghei, the same degree of parasitemia developed as did in P. berghei-infected control mice. Thus, the combination of chemotherapy with the cytokine IFN-gamma leads to substantial improvement of antimalarial treatment and to a rapid development of strain-specific immunity in murine P. vinckei malaria.
TL;DR: The hepatic microsomal mixed-function oxidase (MFO) system was markedly impaired during Plasmodium berghei infection in mice and oral treatment with chloroquine cleared the parasitemia within 72 h and almost normalized the altered levels of MFO indices, a week after cessation of treatment.
TL;DR: Stem bark extracts of Evodia fatraina (Rutaceae) showed significant potency in vivo (65% suppression of parasitaemia) and low toxicity against HeLa cells and L 929 fibroblasts was observed with ethanolic extract.
TL;DR: Iloprost, a synthetic prostacyclin analog, successfully prevents the development of cerebral malaria in mice and northern analysis of TNF mRNA revealed that malaria antigen-induced TNF expression was suppressed at the transcription level.
Abstract: Iloprost, a synthetic prostacyclin analog, successfully prevents the development of cerebral malaria in mice. Malaria antigen-induced tumor necrosis factor (TNF) production could be inhibited by iloprost in vitro and in vivo. Northern analysis of TNF mRNA revealed that malaria antigen-induced TNF expression was suppressed at the transcription level.