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.

Staphylococcal Enterotoxins and Toxic Shock Syndrome Toxin-1 and Their Association among Bacteremic and Infective Endocarditis Patients in Egypt.

PURPOSE: Infective endocarditis (IE) is a major complication in patients with bacteremia of Staphylococcus (S.) aureus infection. Our aim was to determine the association of the major Staphylococcal superantigens (SAgs), including Staphylococcal enterotoxins (SEs) and toxic shock syndrome toxin-1 (TSST-1), among hospitalized patients diagnosed with bacteremia and those with IE. METHODS: This study was conducted on 88 patients; of these, 84 (95.5%) had two positive blood cultures. Eighteen out of the 84 patients (21.4%) were diagnosed based on the modified Duke criteria by a cardiologist to have IE. The recovered isolates were screened phenotypically using ELISA followed by molecular analysis of sea, seb, sec, sed, see, and tsst-1, the major SAg coding genes, and the obtained findings were statistically analyzed. RESULTS: Phenotypic screening for SE production of 26 selected Staphylococci (15 isolated from the IE patients (10 S. aureus and 5 coagulase negative staphylococci (CoNS)) and 11 from bacteremic patients (10 S. aureus and 1 CoNS)) using ELISA revealed that 12/26 (46%) isolates were SE producers. PCR analysis showed that 19 (73%) isolates were PCR positive for SAg genes with the highest prevalence of the sea gene (79%), followed by seb (63%) and tsst-1 (21%). The least frequent gene was sed (5.3%). Statistical correlations between bacteremic and IE isolates with respect to prevalence of SAgs showed no significant difference (P value = 0.139, effect size = 0.572) indicating no specific association between any of the detected SAgs and IE. CONCLUSION: There is high prevalence of SEs among clinical isolates of Staphylococci recovered from patients suffering bacteremia and those with IE. No significant difference was found among Staphylococcal isolates recovered from patients with bacteremia or IE regarding both phenotypic and genotypic detection of the tested SAgs.

Schistosoma mansoni: effect of dietary zinc supplement on egg granuloma in Swiss mice treated with praziqantel.

Schistosomiasis is one of the most important parasitic diseases in Egypt and chemotherapy is considered the most effective method of control. This study was conducted to assess the effectiveness of zinc administration against Schistosoma mansoni infection by evaluating the activities of arylesterase and paraoxonase (PON1) enzymes, and the degree of liver damage. One hundred and twenty albino mice were divided into two groups; one was an infected control and the other a treated group which was further subdivided into three according to the praziquantel and zinc supplementation given. Blood and liver samples, collected 10 weeks post-infection, were subjected to parasitological, histopathological, and enzyme assays, and immunological studies. The results showed that dietary zinc supplementation led to marked reduction in worm load, and egg deposition in the liver and intestine. Histopathological examination showed marked reduction in the number and diameter of hepatic granulomas in the treated groups. The activity of arylesterase and PON1 enzymes were partially restored in infected animals receiving zinc. IL-10 mRNA expression was higher in the treated groups than in the infection control group. In conclusion, zinc administration could be a promising adjuvant therapy for S. mansoni infection.

Fasciola gigantica: evaluation of the effect of phenyl vinyl sulfone in vitro.

Phenyl vinyl sulfone is a synthetic inhibitor of cysteine protease and has antihelminthic and antiprotozoal properties. Phenyl vinyl sulfone was assayed in vitro for antifasciola activity against adult Fasciola gigantica worms using a well-established culture medium. Worms were treated with phenyl vinyl sulfone for incubation periods ranging from 0 to 12h and its activity was assessed in terms of viability, motility and death of worms. Phenyl vinyl sulfone exhibited a minimum effective concentration of 50 ppm after 12h. Three hundred parts per million concentrations were most potent causing immediate death of adult flukes in vitro. Histopathological studies showed that there was tegumental flattening, rupture of vesicles, and spine loss. Marked reduction in size and number of ova and sperms in the convoluted tubules of the reproductive organs was observed in comparison to the untreated control group. In conclusion, phenyl vinyl sulfone shows potent activity against F. gigantica in vitro, and the authors recommend carrying out more studies to detect its efficacy in vivo.

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.

Amplified Fragment Length Polymorphism Diversity in Cephalosporium maydis from Egypt.

ABSTRACT Cephalosporium maydis, the causal agent of late wilt of maize, was first described in Egypt in the 1960s, where it can cause yield losses of up to 40% in susceptible plantings. We characterized 866 isolates of C. maydis collected from 14 governates in Egypt, 7 in the Nile River Delta and 7 in southern (Middle and Upper) Egypt, with amplified fragment length polymorphism (AFLP) markers. The four AFLP primer-pair combinations generated 68 bands, 25 of which were polymorphic, resulting in 52 clonal haplotypes that clustered the 866 isolates into four phylogenetic lineages. Three lineages were found in both the Nile River Delta and southern Egypt. Lineage IV, the most diverse group (20 haplotypes), was recovered only from governates in the Nile River Delta. In some locations, one lineage dominated (up to 98% of the isolates recovered) and, from some fields, only a single haplotype was recovered. Under field conditions in Egypt, there is no evidence that C. maydis reproduces sexually. The nonuniform geographic distribution of the pathogen lineages within the country could be due to differences in climate or in the farming system, because host material differs in susceptibility and C. maydis lineages differ in pathogenicity.

Relative Competitiveness and Virulence of Four Clonal Lineages of Cephalosporium maydis from Egypt Toward Greenhouse-Grown Maize.

Four clonal lineages of Cephalosporium maydis, a soilborne vascular wilt pathogen that causes late wilt of maize, were differentiated previously with molecular markers. In Egypt, this fungus can cause significant losses in infected susceptible plants. In greenhouse tests of individual isolates we found that these lineages differ in their virulence toward a series of maize accessions commonly used in Egyptian maize breeding programs. We also determined the relative competitiveness of representatives of the four lineages when incorporated into the soil as a mixed inoculum. The lineage (IV) with greatest mean disease incidence (virulence), when tested alone, was the least competitive on susceptible maize accessions when coinoculated as a component of mixed inocula of all four lineages. In these coinoculation experiments, one of the less-virulent lineages (II) dominated (70% of infections) and appeared to be the most competitive. These results suggest that virulence and competitive ability are not the same in this host-pathogen system. These results also suggest that standard protocols that rely on mixed inocula for resistance screening need to be altered, and that the relative proportion of the different lineages of the pathogen recovered in a field may be influenced by the maize variety/hybrid planted.