[AIDS: ethics and scientific investigation on human beings]. / Sida: éthique et investigation scientifique sur l'être humain.

The experimentation on human beings of one or several therapeutic molecules discovered in laboratory is necessary and important because it helps to find new treatments or new diagnostic methods. But, it presents serious ethical problems. In this article we are analysing the example of the HIV infection. We are succinctly describing the research methods in laboratory for therapeutic molecules, first the experimentation on animals and then on human being in clinical trials. We will then try to show, with several examples, how during these last 25 years of HIV infection, the research of new molecules has not always respected the ethical rules set out in Helsinki declaration, "Code de la santé publique" or "Guide de bonnes pratiques cliniques-ICH" etc. We are discussing here the way to avoid these irregularities.

Amelioration of type II collagen induced arthritis in rats by treatment with sodium diethyldithiocarbamate.

OBJECTIVE: Sodium diethyldithiocarbamate (Ditiocarb, DDTC), which is used in the treatment of heavy metal poisoning, effectively inhibits NF-kappaB activation and cytokine secretion in vitro. To investigate the antiinflammatory and immunosuppressive potency of DDTC, we examined its influence on the course of collagen induced arthritis in rats. METHODS: Arthritis was induced in female DA rats by injection of rat collagen type II emulsified in incomplete Freund's adjuvant into the tail base. After onset of arthritis, the animals received DDTC or vehicle by intraperitoneal injections or subcutaneous infusion using osmotic pumps. Disulfiram, which is cleaved into DDTC within the gastrointestinal tract, was administered orally via gastric gavage. The course of arthritis was followed by clinical scoring and measurement of joint swelling. RESULTS: Collagen induced arthritis was significantly ameliorated by intraperitoneal injection (2 x 300 mg/kg/day) and subcutaneous infusion (120 mg/kg/day) of DDTC and by enteral administration of disulfiram (200 and 300 mg/kg/day). CONCLUSION: Dithiocarbamates may provide an effective new approach for the treatment of arthritis and other inflammatory diseases.

Role of glutathione in the antiulcer effect of hot water extract of black tea (Camellia sinensis).

The role of a hot water extract of black tea (Camellia sinensis (L). O. Kuntze Theaceae) in the gastric cytoprotective mechanisms was studied using gastric mucosal lesions produced by various ulcerogens in rats as an experimental model. Prior oral administration of black tea extract (BTE) at 20 ml/kg, i.g. once a day for 7 days significantly reduced the incidence of gastric erosions and severity induced by ethanol, diethyldithiocarbamate (DDC) and diethylmaleate (DEM). This treatment also favorably altered the changes in acid and peptic activity of gastric juice in these ulcerogen-treated animals. Singular administration of succimer (60 mg/kg, i.g.), the standard sulfhydryl containing antiulcer drug used as a reference drug, was also effective. The levels of glutathione and glutathione peroxidase were significantly decreased after treatment with ethanol, DDC and DEM, and this decrease was prevented by BTE pretreatment in the aforesaid manner. Other major features of BTE-induced reversal of ulcerogenic agents include a significant decrease in the protein content and a marked increase in hexosamine and sialic acid content. These results suggest a major role for glutathione, an endogenous antioxidant, in the cytoprotection against ulceration afforded by BTE.

Sodium dithiocarb as adjuvant immunotherapy for high risk breast cancer: a randomized study.

Sixty-four patients with non metastatic high risk breast cancer were randomized in a double blind trial of adjuvant immunotherapy with sodium dithiocarb (DDC) versus placebo. All patients underwent prior surgery (mammectomy according to Patey) then adjuvant FAC chemotherapy +/- DDC. With a median follow-up of 5 years we observed 6 relapses and 5 deaths in DDC group; 13 relapses and 12 deaths in control group. At 6 years, overall survival is 81% in DDC group versus 55%. Disease free survival (DFS) is 76% in DDC group versus 55%. DDC associated to chemotherapy and locoregional treatment can improve survival and probably DFS in this high risk breast cancer subgroup.