Latent toxoplasmosis has been previously found to cause behavioural and personality changes in humans, which are specific for each gender. Here we tested the stress hypothesis of these gender differences based on the assumption that latent toxoplasmosis causes long-term subliminal stress. In line with this hypothesis, the gender difference will appear specifically in situations with interpersonal context because in contrast to the typical individualistic coping style of men, women have a tendency to express elevated prosocial behaviour under stress.
The antimalarial compound qinghaosu (artemisinin) was tested in vitro for the ability to inhibit plaque formation by Toxoplasma gondii in fibroblasts. Qinghaosu at 0.4 microgram/ml for 5 days eliminated all plaques and microscopic foci of T. gondii. At 1.3 micrograms/ml for 14 days, qinghaosu completely eliminated T. gondii. Pretreatment of host cells or T. gondii with qinghaosu had no effect on T. gondii growth. There was no apparent toxicity to human fibroblasts in long-term studies.
The in vitro effect of the following antimicrobial agents on Toxoplasma gondii tachyzoites were studied: artemisinin ether (arteether), cycloguanil hydrochloride (cycloguanil), mefloquine, primaquine phosphate, and quinine sulfate, as well as the calcium channel blocker verapamil and the calmodulin inhibitor trifluoperazine hydrochloride. Arteether at > or = 0.5 micrograms/ml and cycloguanil at > or = 1.0 micrograms/ml inhibited T. gondii in vitro. Cycloguanil (2.5 micrograms/ml) combined with a noninhibitory concentration of sulfadiazine (25 micrograms/ml) inhibited T.
Toxoplasma gondii infection, like malaria, is sensitive to inhibition by artemisinin (ART). Mechanisms of action for ART in malaria treatment have been proposed, but little is known about its effects in T. gondii infection. To better understand its inhibitory effects on T. gondii, mutants resistant to ART were selected by progressive culture in permissive levels of the drug. Five clonal isolates were established and characterized.
The American Journal of Tropical Medicine and Hygiene
The effect of artesunate and its metabolite dihydroartemisinin against the cerebral cysts of Toxoplasma gondii was studied. In vitro experiments were performed with the THP-1 cell line and showed an inhibition of parasite growth of approximately 70% with 0.1-0.5 microg/ml of dihydroartemisinin for 96 hr. However, with artesunate, dihydroartemisinin, or a combination (50:50) of them, the number of tachyzoites decreased approximately 40-50% and they appeared motionless. Fifty-eight to 72 hr after washing of the tachyzoites and THP-1 cells in culture, parasitized cells reappeared.
A cDNA of 1.1 kb comprising the gene encoding the peroxiredoxin of Toxoplasma gondii (TgPrx) has been cloned. The open reading frame of 591 bp was translated into a protein of 196 amino acids with a molecular mass of 25 kDa. Conserved 2 cysteine domains of Phe-Val-Cys-Pro and Glu-Val-Cys-Pro indicated TgPrx belonged to 2-Cys Prx families. TgPrx showed the highest homology with that of Arabidopsis thaliana by 53.9% followed by Entamoeba histolytica with 39.5% by the amino acid sequence alignment. Polyclonal antibody against recombinant TgPrx detected 25 kDa band in T.
Toxoplasmosis, caused by the protozoan Toxoplasma gondii, is medically important and distributed worldwide. Currently available medications are limited in terms of efficacy and side effects. We synthesized novel, nonacetal, hydrolytically stable derivatives of artemisinin and showed that they inhibit the replication of Toxoplasma gondii in cell culture.
Artemisinin is a plant sesquiterpene lactone that has become an important drug for combating malaria, especially in regions where resistance to other drugs is widespread. While the mechanism of action is debated, artemisinin has been reported to inhibit the sarcoplasmic endoplasmic reticulum Ca(2+) ATPase (SERCA) in the malaria parasite. Artemisinin is also effective against Toxoplasma in vitro and in vivo, although it is less potent and, hence, is generally not used therapeutically to treat toxoplasmosis.
Intracellular calcium controls several crucial cellular events in apicomplexan parasites, including protein secretion, motility, and invasion into and egress from host cells. The plant compound thapsigargin inhibits the sarcoplasmic-endoplasmic reticulum calcium ATPase (SERCA), resulting in elevated calcium and induction of protein secretion in Toxoplasma gondii. Artemisinins are natural products that show potent and selective activity against parasites, making them useful for the treatment of malaria.
OBJECTIVES: We sought to improve upon the usefulness of artemisinins as anti-Toxoplasma agents by synthesizing new unsaturated, carba derivatives and then testing them for in vitro efficacy against three steps of the lytic cycle of Toxoplasma gondii tachyzoites. METHODS: Novel derivatives of ART were synthesized and then tested for in vitro antiparasitic activity using T. gondii tachyzoites constitutively expressing beta-galactosidase and human fibroblast host cells.