Studies on the role of tumor necrosis factor- alpha (TNF-α) in hepatocytes induced apoptosis in vaccinated, Schistosoma mansoni-challenged mice.

Tumour Necrosis Factor-alpha (TNF-α) plays a complex role in pathophysiological changes caused by schistosomiasis in the liver cells as induced apoptosis. So, The highlighted experimentally the role of TNF-α in hepatocytes apoptosis, using that as an assessment of the efficacy of antischistosomal vaccination by mixed crude antigens preparations [Cercarial antigen preparation (CAP) + soluble worm antigen preparation (SWAP) + soluble egg antigen(SEA)] by parasitological, histo-pathological and histochemical studies using Feulgen stain of hepatoytes DNA, a serological study also of serum TNF-α level by ELISA. Fifty two laboratory bred Albino male mice, were used in this study. They were classified into four groups (13 mice in each group), G1: normal control, G2 as infected control while G3 supported by Freund's Adjuvant (F. Adj) then infected and G4 vaccinated with combined antigens (CAP, SWAP and SEA) + F. Adj, then infected. Mice were sacrificed by cervical dislocation 9 weeks post infection, parasitological (Kato-Katz thick smear for egg count), histopathologial {haematoxylin and eosin (H&E) staining of hepatic sections}, histochemical (feulgen staining of hepatocytes DNA) and ELISA to estimate serum TNF-α level were performed. The data showed that vaccination with combined antigens showed protective effect on vaccinated then Schistosoma challenged mice, hepatocytes induced apoptosis was directly proportional with the TNF-α serum level, and the protection degree of potential combined vaccine was inversely proportional with serum TNF-α level and induced apoptosis.

Resistance to praziquantel, effect of drug pressure and stability test.

Various isolates of S. mansoni, originally showed marked diminished susceptibility to PZQ, were used in this work. These isolates were taken from patients not cured after two or three doses of the drug. They were passed in experimental mice and treated with sub-curative doses of PZQ to determine the effect of drug pressure on the offspring of these isolates. Upon treatment of the second generation of these isolates with curative doses of PZQ, they showed significant less response to the drug in terms of both the drug efficacy (percent of worm reduction), and the ED50 (the effective dose that kills 50% of worms). Also, stability test was performed on some S. mansoni isolates. This means repeated treatment of unsusceptible isolates that have been passed for several passages in the lab. and results compared to that of a control susceptible isolate (originally taken from a patient cured after a single dose of PZQ). The results showed that repeated passage of S. mansoni isolates in the lab. does not render them more susceptible to PZQ. Indeed, these resistant isolates showed less susceptibility to the drug than before, or at least they retain their original level of insusceptibility to PZQ.