A multimodality therapeutic application on Toxoplasma gondii encephalitis utilizing Spiramycin and 'de novo' Ferula asafetida in immunodeficient mice.

This study investigated a 'de Novo' medicinal herb, Ferula asafetida (FA), against toxoplasma encephalitis either alone or combined with spiramycin (SP). Female Swiss-Webster mice (n = 72) were divided into three batches. Batch-I received no DMS to serve as an immunocompetent control, batch-II was immune-suppressed with the DMS (0.25 mg/g/day) for 14 days pre-infection, whilst batch-III was immune-suppressed with the DMS on the same day of infection. All experimental mice were inoculated with Toxoplasma gondii ME49 cysts (n = 75). Each batch was split into four subgroups: Mono-SP, mono-FA, combined drug (SP + FA), or neither. Therapies were administered on day zero of infection in batches (I and II) and 35 days post-infection in batch (III). Treatments lasted for 14 days, and mice were sacrificed 60 days post-infection. Histopathological changes, cysts load, and CD4 and CD8 T-cells were counted in brain tissues. The cyst-load count in mice receiving SP + FA was significantly (p < .0001) the least compared to the mono treatments in all protocols. Interestingly, the combined therapy demolished the T-cell subsets to zero in immunocompetent and immunocompromised infected mice. In conclusion, F. asafetida might be a powerfully natural, safe vehicle of SP in the digestive system and/or across the brain-blood barrier to control toxoplasmosis even through immunodeficient conditions.

Studies on parasitologic and haematologic activities of an enaminone derivative of 4-hydroxyquinolin-2(1H)-one against murine schistosomiasis mansoni.

The activity of a novel enaminone derivative of 4-hydroxyquinoline, BDHQ, was screened for its effectiveness against murine schistosomiasis by electron microscopy and parasitologic studies. The correlation of these studies with serum levels of IFN-gamma and IgE is described. Two groups of 10 mice each were treated with different doses of BDHQ, and their results were correlated with the control and praziquantel (PZQ)-treated groups. Parasitologic study revealed significant reduction in mature worms and tissue egg loads in BDHQ- and PZQ-treated groups, whereas immature worms revealed significant reduction in BDHQ groups only. The group treated with a higher dose of BDHQ showed significant reductions in intestinal ova count when compared with the PZQ-treated group. Ultrastructural examination of the worm revealed significant degeneration of the spines and tegument in all treated groups, while the genital system was affected in BDHQ-treated groups only. BDHQ showed considerable effect on cellular activation where serum levels of IFN-gamma were significantly increased in comparison to control, while anti-soluble worm antigen preparation (SWAP) IgE was significantly increased in comparison to both the control and PZQ-treated groups. Ultrastructural examination revealed cellular activation in buffy coat and the liver in both the BDHQ- and PZQ-treated groups in comparison to the untreated one, whereas in the bone marrow and spleen, evidence of cellular activation was remarkable in the BDHQ-treated groups. In conclusion, BDHQ exhibits high levels of activity against adult and juvenile stages of these parasites, which may be due to its mixed cellular and humoral immunologic mechanisms, as demonstrated by the significant increase of serum levels of IgE and IFN-gamma shown on electron microscopy. Therefore, our results support the comparative advantage that BDHQ has over PZQ.

Parasitological, hematological and ultrastructural study of the effect of COX-2 inhibitor, pyocyanin pigment and praziquantel, on S. mansoni infected mice.

The effect of cyclooxygenase-2 (COX-2) inhibitor, such (as meloxicam, and pyocyanin pigment of Pseudomonas aeruginosa) with and without praziquantel (PZQ) on worms, ova count, bone marrow and blood cells in 7 groups of Schistosoma mansoni infected mice was studied. The results revealed significant decrease of worm burden and ova count in all treated groups as compared to the infected untreated group, while those with combined treatment of PZQ and meloxicam or pyocyanin showed complete eradication of the worm with the highest reduction in the tissue egg load. EM showed extensive swelling and vesiculation of the tegument, completely implanted spines that overlie degenerated muscle layer were obvious in groups treated with either meloxicam or pyocyanin. Hematological study revealed significant increase (P<0.05) of total leucocytic count of PZQ treated group while that treated with either meloxicam or pyocyanin showed significant decrease (P<0.05), but in combination of PZQ with meloxicam or pyocyanin no significant difference as compared to the infected untreated group. The neutrophil was the main cell affected in groups treated with neither meloxicam nor pyocyanin alone with significant decrease (P<0.05), but with significant increase (P<0.05) in combination with PZQ as compared to the infected untreated group. Those treated with PZQ plus meloxicam showed significant increase as compared to that plus pyocyanin. Eosinophil count showed significant decrease (P<0.05) in all treated groups as compared to the infected untreated group. Inverse correlation between serum level of sFas and peripheral neutrophil count was detected. Ultrastructural study of the bone marrow explained the results as groups treated with meloxicam revealed dissociation between nuclear and cytoplasmic development in the neutophils with cytoplasm maintaining primitive appearance despite maturation of the nucleus, that is manifested by the persistent production of immature granules and the still orientation of Golgi cternae and the centriole around the nucleus. Groups treated with pyocyanin pigment revealed many abnormalities in neutophils as hypogranularity or early apoptotic morphology changes as intense perinuclear chromatin aggregation or nucleus fragmentation. In peripheral blood apoptotic morphology changes was detected in both groups treated with meloxicam or pyocyanin while most of cells of mice treated with PZQ were in an active state. Consequently, it is preferable to give meloxicam with PZQ for a short period of time (less side-effect) to eradicate S. mansoni worm completely but with continuous observation of the peripheral neutrophil count and function.