Antioxidants to reduce sperm DNA fragmentation: an unexpected adverse effect.

Reactive oxygen species (ROS) have a negative impact on sperm DNA, leading to the formation of oxidative products such as 8-oxo-7,8-dihydroxyguanosine. This compound causes fragmentation and, thus, has a mutagenic effect. Patient treatment with oral antioxidant vitamins is, therefore, standard practice for male infertility, in an attempt to decrease formation of ROS and improve fertility. In this study, the DNA fragmentation index and the degree of sperm decondensation were measured using the sperm chromatin structure assay before and after 90 days treatment with antioxidant vitamins associated with zinc and selenium. Antioxidant treatment led to a decrease in sperm DNA fragmentation (-19.1%, P < 0.0004), suggesting that at least part of the decay was linked to ROS. However, it also led to an unexpected negative effect: an increase in sperm decondensation with the same order of magnitude (+22.8%, P < 0.0009). The opening of interchain disulphide bridges in protamines may explain this aspect, as antioxidant vitamins, especially vitamin C, are able to open the cystin net, thus interfering with paternal gene activity during preimplantation development. This observation might explain the discrepancy observed concerning the role of these antioxidant treatments in improving male fertility.

Treatment of peritoneal carcinomatosis in patients with digestive cancers with combination of intraperitoneal hyperthermia and mitomycin C.

Peritoneal carcinomatosis in patients with digestive cancer carries a poor prognosis, with a majority of patients dying within 6 months. Mitomycin C has been reported to have some antitumor efficacy in this setting. We performed combination intraperitoneal hyperthermia and mitomycin to potentiate the effect of mitomycin C in 83 patients with peritoneal involvement due to digestive cancers. Eighty six IPCH procedures were performed using inflow temperature 46 to 49 degrees Celsius, using a closed circuit, during 90 minutes. Mitomycin C was administered as a perfusate at 10 mg/l. Primary tumors were essentially gastric (42) and colorectal (27). Mortality and morbidity rates were 3/83 and 5/83 respectively. For resectable tumors, the median survival time was 16 months in stage 1 and 2 carcinomatosis (malignant granulations less than 5 mm in diameter). For resectable gastric cancers with stage 1 and 2 carcinomatosis, one, two and three year actuarial survival rates were 80, 61 and 41% respectively. In conclusion, IPCH appears to be an interesting therapeutic option in patients with digestive cancers and small malignant peritoneal granulations (stage 1 and 2).