Synthesis and anti-BVDV activity of novel δ-sultones in vitro: implications for HCV therapies.

In this study we report the synthesis and activity against bovine viral diarrhea virus (BVDV) of a novel series of bicycle δ-sultones containing γ-lactones. BVDV is responsible for major losses in cattle. Some of the synthesized δ-sultones showed pronounced anti-BVDV activity with EC50 values of 0.12-1.0µM and no significant cytotoxicity. Among them, the ortho bromosubstituted derivative 4f (EC50=0.12µM) showed better antiviral activity than other derivatives and was 10 fold more that of than positive control ribavirin (EC50=1.3µM). BVDV is also considered to be a valuable surrogate for the hepatitis C virus (HCV) in antiviral drug studies. The above results provided a novel candidate for the development of anti-HCV agents.

[Expression and clinical significance of COX-2 and BCL-2 in distal transitional mucosa adjacent to rectal carcinoma].

OBJECTIVE: To investigate the expression of COX-2 and BCL-2 in transitional mucosa adjacent to rectal carcinoma, and to determine whether precursor event exists in the transitional mucosa. METHODS: Mucin histochemical method (HID/AB) was used to determine the distal mucosa 2 cm away from rectal carcinoma in 54 patients with rectal cancer. Immunohistochemical method was employed to detect the expression of BCL-2 and COX-2 in the rectal cancer specimen, transitional mucosa (TM), non-transitional mucosa (NTM), and 20 cases of normal rectal mucosa. Student's t-test and Chi-square test were preformed. RESULTS: Nineteen patients with positive TM were found. COX-2 expression was identified in 81.5% of cancer tissue, 21.1% of TM, 17.1% of NTM, and 10.0% in normal mucosa. BCL-2 protein was found in 77.8% of cancer tissue, 21.1% of TM, 22.9% of NTM, and 5.0% of normal mucosa. The expressions of COX-2 and BCL-2 in TM were significantly different from tumor tissue[(0.737±0.895) versus (3.519±1.998), and (0.632±0.955) versus (2.833±1.756), all P<0.01]. However, there were no significant differences between TM and NTM or normal mucosa. CONCLUSIONS: Expressions of COX-2 and BCL-2 are non-specific in the transitional mucosa at the distal rectum. Evidence is not available in TM being precursor lesion.