Intestinal immunity suppresses carrying capacity of rats for the model tapeworm, Hymenolepis diminuta.

Hymenolepis diminuta is a parasitic tapeworm of the rat small intestine and is recognized as a useful model for the analysis of cestode-host interactions. In this study, we analyzed factors affecting the biomass of the tapeworm through use of rat strains carrying genetic mutations, namely X-linked severe combined immunodeficiency (xscid; T, B and NK cells deficiency), nude (rnu; T cell deficiency), and mast cell deficient rats. The worm biomass of F344-xscid rats after infection with 5 cysticercoids was much larger than control F344 rats from 3 to 8 weeks.

Outcome of primary lethal and nonlethal Plasmodium yoelii malaria infection in BALB/c and IFN-γ receptor-deficient mice following chloroquine treatment.

IFN-γ receptor-deficient (IFN-γR(-/-)) mice and control wild-type (WT) mice, with or without chloroquine (CQ) treatment, were infected intraperitoneally with Plasmodium yoelii 17XL (lethal) and P. yoelii 17XNL (nonlethal), and then mouse survival, parasitemia, and antibody production were investigated during the course of infection. Without CQ treatment, both IFN-γR(-/-) and WT mice were susceptible to infection showing 100 % mortality after infection with 1 × 10(5) P.

The course of a primary infection of Plasmodium yoelii 17XL in both 129S1 and IFN-γ receptor-deficient mice.

In the present study, we found that 129S1 mice are resistant to the infection with Plasmodium yoelii 17XL, which is highly virulent and causes lethal infection in various strains of mice. In contrast, IFN-γ receptor-deficient (IFN-γR(-/-)) mice on the 129S1 background were much more susceptible than 129S1 mice with intraperitoneal infection with 1 × 10(5) parasitized erythrocytes. The mortality in 129S1 and IFN-γR(-/-) mice was 11.

Resistance of a rodent malaria parasite to a thymidylate synthase inhibitor induces an apoptotic parasite death and imposes a huge cost of fitness.

Background: The greatest impediment to effective malaria control is drug resistance in Plasmodium falciparum, and thus understanding how resistance impacts on the parasite's fitness and pathogenicity may aid in malaria control strategy.

Methodology/principal Findings: To generate resistance, P. berghei NK65 was subjected to 5-fluoroorotate (FOA, an inhibitor of thymidylate synthase, TS) pressure in mice.

Next-Generation Antimalarial Drugs: Hybrid Molecules as a New Strategy in Drug Design.

Malaria is a disease that affects nearly 40% of the global population, and chemotherapy remains the mainstay of its control strategy. The global malaria situation is increasingly being exacerbated by the emergence of drug resistance to most of the available antimalarials, necessitating search for novel drugs. A recent rational approach of antimalarial drug design characterized as "covalent bitherapy" involves linking two molecules with individual intrinsic activity into a single agent, thus packaging dual-activity into a single hybrid molecule.

Novel rational drug design strategies with potential to revolutionize malaria chemotherapy.

Efforts to develop an effective malaria vaccine are yet to be successful and thus chemotherapy remains the mainstay of malaria control strategy. Plasmodium falciparum, the parasite that causes about 90% of all global malaria cases is increasingly becoming resistant to most antimalarial drugs in clinical use. This dire situation is aggravated by reports from Southeast Asia, of the parasite becoming resistant to the "magic bullet" artemisinins, the last line of defense in malaria chemotherapy.

Plasmodium berghei: efficacy of 5-fluoroorotate in combination with commonly used antimalarial drugs in a mouse model.

Resistance to antimalarial antifolates necessitates a search for new antimetabolites targeting other enzymes of the folate metabolic pathway. In this study, 5-fluoroorotate (FOA), reported to be an inhibitor of thymidylate synthase, was assayed against Plasmodium berghei NK 65 in mice, with(out) an oral uridine supplement. FOA (2.

Possible involvement of IFN-gamma in early mortality of Plasmodium berghei NK65-infected BALB/c mice after febrifugine treatment.

Parasitemia patterns, survival and cytokine levels of Plasmodium berghei NK65-infected BALB/c mice, treated orally with the alkaloidal mixture of febrifugine and isofebrifugine at a dose of 1 mg/kg twice a day for 4 consecutive days were monitored. Whereas the untreated mice showed a progressive increase in parasitemia and ultimate death, the alkaloid mixture-treated group showed a transient suppression of parasitemia during the course of treatment. However, the parasitemia increased on discontinuation of treatment, leading to earlier death of mice in the treated group than in the infected but untreated controls.

Plasmodium berghei: lack of antimalarial activity of an analogue of folate precursor, 2,4-diamino-6-hydroxymethylpteridine in a mouse model.

It was earlier hypothesized that the malarial parasite may convert precursors of folate analogues to synthesize de novo inhibitors toxic to itself, but not to the mammalian cell. It was suggested that one such analogue, 2,4-diamino-6-hydroxymethylpteridine (DAP) may be converted to aminopterin (AMP), a known dihydrofolate reductase inhibitor. In the present study, we evaluated the ability of DAP to inhibit proliferation of Plasmodium berghei NK65 in mice, with(out) folinic acid rescue.

Antiplasmodial triterpenoids from Ekebergia capensis.

From the stem bark of Ekebergia capensis, 10 new triterpenoid compounds, ekeberins A (1), B (2), C1 (3), C2 (4), C3 (5), D1 (6), D2 (7), D3 (8), D4 (9), and D5 (10), were isolated together with 17 known compounds. The structures of these new compounds were elucidated on the basis of the results of spectroscopic analysis, and the absolute configuration of compounds 6-10 were determined by partial synthesis from known compounds and using the Mosher ester method. Several of these compounds were screened in vitro against both chloroquine (CQ)-sensitive and -resistant Plasmodium falciparum isolates and were found to exhibit moderate antiplasmodial activity, with compounds 20 (7-deacetoxy-7-oxogedunin) and 27 (2-hydroxymethyl-2,3,22,23-tetrahydroxy-2,6,10,15,19,23-hexamethyl-6,10,14,18-tetracosatetraene) showing IC50 values of 6 and 7 microM, respectively.

In Vivo antimalarial activity of aqueous extracts from Kenyan medicinal plants and their chloroquine (CQ) potentiation effects against a blood-induced CQ-resistant rodent parasite in mice.

Hot water extracts from eight medicinal plants representing five families, used for malaria treatment in Kenya were screened for their in vivo antimalarial activity in mice against a chloroquine (CQ) resistant Plasmodium berghei NK65, either alone or in combination with CQ. Extracts of three plants, Toddalia asiatica (root bark), Rhamnus prinoides (leaves and root bark) and Vernonia lasiopus (root bark) showed high chemosuppression in the range 51%-75%. Maytenus acuminata, M.

Antimalarial activity of methanolic extracts from plants used in Kenyan ethnomedicine and their interactions with chloroquine (CQ) against a CQ-tolerant rodent parasite, in mice.

Methanolic extracts from 15 medicinal plants representing 11 families, used traditionally for malaria treatment in Kenya were screened for their in vivo antimalarial activity in mice against a chloroquine (CQ)-tolerant Plasmodium berghei NK65, either alone or in combination with CQ. The plant parts used ranged from leaves (L), stem bark (SB), root bark (RB), seeds (S) and whole plant (W). When used alone, extracts from seven plants, Clerodendrum myricoides (RB), Ficus sur (L/SB/RB), Maytenus acuminata (L/RB), Rhamnus prinoides (L/RB), Rhamnus staddo (RB), Toddalia asiatica (RB) and Vernonia lasiopus (RB) had statistically significant parasitaemia suppressions of 31.

Chloroquine efficacy in Plasmodium berghei NK65-infected ICR mice, with reference to the influence of initial parasite load and starting day of drug administration on the outcome of treatment.

We examined whether the initial number of parasites inoculated and the starting day of medication post-infection influenced the antimalarial efficacy of chloroquine (CQ) against Plasmodium berghei NK65 infection in ICR mice. Male ICR mice were inoculated intraperitoneally with 1 x 10(5), 1x10(6), 1 x 10(7), 1 x 10(8) P. berghei NK65-parasitized erythrocytes (pRBC).

Chromosomal mapping of host resistance loci to Trichinella spiralis nematode infection in rats.

The differences in host response among strains of rats to intestinal nematode parasite Trichinella spiralis infection could provide a powerful benefit for further elucidation of molecular interactions between the host and the parasite. Using several strains of rats, we previously observed that DA strain is a strong responder and F344 strain is a weak responder with respect to expulsion of the adult worm. To identify the host resistance loci, quantitative trait loci (QTLs) analysis in F2 population from crosses between DA and F344 strains was performed.

Cytokine and antibody production during the course of resolution in Plasmodium yoelii 17XL-infected BALB/c mice treated with febrifugine and isofebrifugine mixture from leaves of Hydrangea macrophylla var. Otaksa.

Cytokine and antibody production was investigated during the course of resolution of primary infection in Plasmodium yoelii 17XL-infected BALB/c mice treated with a mixture of febrifugine and isofebrifugine. The infected mice in an untreated control group showed a progressively increasing parasitemia, leading to mouse death. In contrast, infected mice given the mixture orally showed low parasitemia levels during administration.

Combination effects of chloroquine with the febrifugine and isofebrifugine mixture against a blood-induced infection with chloroquine-resistant Plasmodium berghei NK65 in ICR mice.

The combination effects of chloroquine with a mixture of febrifugine and isofebrifugine were evaluated against a blood-induced infection with chloroquine-resistant P. berghei NK65 in ICR mice. Mice in the untreated control showed a progressively increasing parasitemia leading to mouse death.

Different responses of three rodent Plasmodia species, Plasmodium yoelii 17XL, P. berghei NK65 and P. chabaudi AS on treatment with febrifugine and isofebrifugine mixture from Hydrangea macrophylla var. Otaksa leaf in ICR mice.

The antimalarial activity of Hydrangea macrophylla var. Otaksa alkaloids was evaluated against Plasmodium yoelii 17XL, P. berghei NK65 and P.

Comparison of antimalarial activity of the alkaloidal fraction of Hydrangea macrophylla var. Otaksa leaves with the hot-water extract in ICR mice infected with Plasmodium yoelii 17 XL.

The antimalarial activity of the fractions isolated from the leaves of Hydrangea macrophylla Seringe var. Otaksa Makino was evaluated against Plasmodium yoelii 17 XL in mice. Four different fractions were prepared in the usual manner to obtain an alkaloid fraction.

Hymenolepis pseudodiminuta Tenora et al. 1994 from Apodemus speciosus and H. diminuta: a comparison of experimental infections in rats.

The successful maintenance of Hymenolepis pseudodiminuta, isolated from Apodemus speciosus, is described for the first time. In the laboratory, the flour beetle, Tribolium confusum, and F344 rats could serve as intermediate and definitive hosts, respectively. In single worm infections with H.

Intestinal granuloma formation in normal and SCID BALB/c mice infected with Angiostrongylus costaricensis.

We studied the histomorphology of granuloma formation and cytokine production in Angiostrongylus costaricensis-infected immunocompetent and immunodeficient BALB/c mice. Histological examination of the infected intestine showed well developed granulomas in BALB/c mice. In contrast, in SCID mice, clusters of eggs and larvae and a progression of infiltration of inflammatory cells were also observed, but little fibroblastic activity was seen.

A brief survey of free-living amebae in Thailand and Hamamatsu District, Japan.

The aim of this study was to determine the presence of free-living amebae in aquatic habitats of human environments in Thailand and Hamamatsu district, Japan. Genus identification was based on the morphology of cyst and trophozoite forms and a flagellation test for genus Naegleria. The pathogenic potential was tested in mice by nasal instillation for genus Naegleria and Acanthameba.

Chromosomal mapping of the host resistance locus to rodent malaria (Plasmodium yoelii) infection in mice.

The disease outcome in malaria caused by the protozoan parasite Plasmodium is influenced by host genetic factors. To identify host genes conferring resistance to infection with the malaria parasite, we undertook chromosomal mapping using a whole-genome scanning approach in cross-bred mice. NC/Jic mice all died with high parasitemia within 8 days of infection with 1 x 10(5) parasitized erythrocytes.

Chromosomal mapping of host susceptibility loci to Angiostrongylus costaricensis nematode infection in mice.

Angiostrongylus costaricensis is a nematode found mainly as a rodent parasite. Laboratory mice were experimentally infected with this parasite. It is known that there is great variability in mortality among inbred mouse strains after infection with this nematode.