Susceptibility of Biomphalaria alexandrina to the plant Azolla pinnata and some herbicides in relation to infection with Schistosoma mansoni miracidia.

Molluscicidal activity of the herebicides 2,4-D and Graminol, as well as both extracts and dry powder of the plant Azolla pinnata were evaluated against B. alexandrina snails. It was observed that 2,4-D proved to be the most toxic compound among he tested ones, showing LC90 of 52 ppm after 24 h of exposure. Ethanol extract of Azolla showed the highest molluscicidal activity against the tested snails compared with the other extracts and dry powder (LC90 = 3300 ppm). Ethanol extract at 6600 ppm after 3 h of exposure killed 100% and 19.4% of S. mansoni miracidia and cercariae, respectively. The molluscicidal activity of 2,4-D was not influenced by the presence of Azolla (900 plants/liter) for 7 days, while Graminol effect was significantly reduced. However, the infectivity of S. mansoni miracidia to B. alexandrina snails was not affected by Azolla existence.

Effect of the plant Azolla pinnata on survival, growth rate, fecundity and hatchability of egg-masses of Biomphalaria alexandrina snails.

Data indicated that Azolla pinnata plants variously reduce the growth rate of Biomphalaria alexandrina snails expressed as net increase in shell diameter (direct or indirect exposure). The plant density played an important role in this respect. The higher the plant density was the lower the growth rate and vice versa. Too, indirect exposure of newly hatched B. alexandrina resulted from exposed treated eggs reduced the growth rate of these snails. Data revealed that direct and/or indirect exposure to the abnormal high density (50,000 plants/L) resulted in complete kill of B. alexandrina snails after two weeks from continuous exposure. Snails exposed directly to Azolla at 50,000 and 25,000 plants/L failed to lay eggs. On the other hand, sanils exposed to 10,000 plants/L laid few eggs, resulted in low reproductive rate (57.94) compared with unexposed ones (110.6). The same trend of results was recorded with hatchability of Biomphalaria eggs.

Effect of X-ray on the snails of schistosomiasis in Egypt.

Biomphalaria alexandrina and Bulinus truncatus snails were exposed to sublethal doses 0.2, 3, 5, 10 and 20 rad of X-ray. The survival and reproductive rates of these snails were highly affected by these doses. The maximum survival periods of laboratory populations of Biomphalaria snails were less than those of field ones which means a high sensitivity of laboratory snails to X-ray. The reproductive capacity of irradiated Biomphalaria and Bulinus snails was highly suppressed and this will interrupt Schistosomiasis transmission. A deleterious effect of gametogenesis of irradiated Biomphalaria was histologically proved. After 3 weeks of snail irradiation with high dose (40 rad) the hermaphrodite gland became completely evacuated.

Eukaryotic DNA topoisomerases mediated DNA cleavage induced by a new inhibitor: NSC 665517.

A compound with a novel structure, NSC 665517, was tested in the National Cancer Institute Preclinical Drug Discovery Screen. With the COMPARE algorithm, the pattern of differential cytotoxicity for NSC 665517 most closely resembled those of known topoisomerase II (top2) inhibitors. In vitro data showed that NSC 665517 induced DNA cleavage in the presence of top2 and topoisomerase I (top1) (at a higher concentration). The minimum concentration required to induce top2 cleavage was 0.5 microM. A substantial decrease in top2-induced cleavage by NSC 665517 was seen when the reaction mixtures were shifted to elevated temperature (55 degrees), suggesting that top2-induced cleavage occurs through the mechanism of stabilizing the reversible enzyme/DNA complex and inhibiting religation. The DNA cleavage pattern induced by NSC 665517 with top2 was different than that of other known top2 inhibitors, including etoposide, mitoxantrone, anthracyclines, amsacrine, and ellipticine. top2 cleavage sites induced by NSC 665517 showed strong preference for G located 3' to the top2-mediated DNA cleavage (position +1). NSC 665517 produced limited DNA unwinding at high drug concentration. DNA damage analyzed in KB cells by alkaline elution showed that NSC 665517 induced strand break. Data from the cytotoxicity in KB-V1 overexpressing P-glycoprotein and COMPARE analysis with rhodamine efflux assay indicated that NSC 665517 is a substrate of P-glycoprotein. These results strongly suggest that NSC 665517 is a novel topoisomerase-targeted drug. Preclinical evaluation of NSC 665517 as an antitumor agent is under way.