Micromolar concentrations of estradiol are required to inhibit the oxidation of low-density lipoproteins (LDL) in vitro. Recent evidence suggests that estradiol must be modified before it can become an effective antioxidant at physiological levels. Our aim was to determine other possible conditions under which low concentrations of 17b-estradiol can reduce LDL oxidation. LDL susceptibility to oxidation was monitored by measurements of conjugated diene formation. High levels of 17b-estradiol reduced oxidative modification of LDL. Vitamin C and vitamin E also increased LDL resistance to Cu21-mediated oxidation. More importantly, 10 nM 17b-estradiol, which on its own had no effect, exhibited significant antioxidant actions in the presence of either vitamins C or E. In conclusion, supraphysiological concentrations of 17b-estradiol are required to exert antioxidant effects directly in vitro. However, in the presence of vitamins C and E, concentrations of 17b-estradiol close to physiological levels can also protect LDL from oxidation.

Many cytokines, in particular tumor necrosis factor (TNF)-a have been known to play an important role in the pathogenesis of gastric mucosal lesions caused by various factors such as drugs and Helicobacter pylori infection. Our previous studies have shown that the polysaccharide fractions isolated from the fruiting bodies of Ganoderma lucidum (GLPS) prevented indomethacin- and acetic acid-induced gastric mucosal lesions in the rat. However, the mechanisms remain unclear. This study aimed to investigate whether GLPS had a direct mucosal healing effect in the indomethacin-treated rat, and to explore the possible mechanisms by determining the gastric mucosal mRNA and protein levels of TNF-a and ornithine decarboxylase (ODC) activity. In addition, the effects of GLPS on the cellular proliferation, ODC and c-Myc protein expression and mucus synthesis in the rat gastric cell culture (RGM-1) were examined. The present study demonstrated that GLPS at 250 and 500mg/kg by intragastric input caused ulcer-healing effect in the rat; this was accompanied with a significant suppression of TNF-a gene expression, but with an increased ODC activity. In RGM-1 cells, GLPS at 0.05, 0.25 and 1.0mg/ml significantly enhanced [3H]thymidine incorporation and ODC activity in a concentration-dependent manner. However, these effects were abrogated by the addition of the ODC inhibitor, DL-a-difluoromethyl-ornithine (DFMO). GLPS at 0.25-1.0mg/ml also increased mucus synthesis, as indicated by the increased D-[6-3H]glucosamine incorporation in RGM-1

Background: Thiopurine S-methyltransferase (TPMT) catalyses the S-methylation of thiopurine drugs. Several mutations in the TPMT gene have been identified which correlate with a low activity phenotype. The molecular basis for TPMT deficiency is not well defined in minority Chinese. We investigated differences in the activity of TPMT and the frequencies of mutant TPMT alleles in 4 ethnic groups of Chinese. Method: The frequency of 4 common TPMT mutant alleles, TPMT*2, TPMT*3A, TPMT*3B and TPMT*3C, were determined in healthy subjects from Han (n =312), Jing (n=103), Yao (n=126) and Uygur Chinese (n=160) by allele-specific PCR and PCR-restriction RFLP analysis. TPMT activity in erythrocytes was determined by HPLC. Results: There was no significant difference in the mean TPMT activity between all ethnic groups studied and no subject with TPMT deficiency was found in all populations studied. TPMT*3C was found in 2.2% of Han and 1.9% of Jing Chinese. TPMT*2, TPMT*3B and TPMT*3A alleles were not detected in any of the Han or Jing Chinese tested. In contrast, 3.7% of Uygur Chinese had TPMT*3C and TPMT*3A alleles. Neither allele was detected in Yao Chinese. The overall frequencies of variant TPMT allele in Uygur were higher than in Han or Jing Chinese. However, neither the overall frequency of mutant TPMT alleles nor the genotype frequencies were significantly different between Han, Jing, Yao and Uygur Chinese. Conclusions: The TPMT*3C was the most prevalent allele in Han, Jing and Uygur Chinese, while TPMT*3A is a rare allele in Uygur Chinese who belong to Caucasian. Ethnicity may be an important factor affecting the variability in response to thiopurine chemotherapy.