Moderate skin sensitizers can induce phenotypic changes on in vitro generated dendritic cells.

In the present study, we analyzed the phenotypic alterations induced by several allergens on immature dendritic cells (DC), with the aim to develop a potential in vitro alternative for predicting the sensitizing potential of chemicals. DC were generated from human monocytes cultured in the presence of GM-CSF, IL-4 and TGF-beta1 and treated for 2 or 4 days with different chemicals. Surface marker expression (HLA-DR, CD1a, CD40, CD54, CD83, CD86, CCR7 and E-cadherin) was analyzed by flow cytometry. Results showed that a 2-day treatment with the representative allergens DNCB and NiSO(4) induced significant changes of most antigens while other chemicals such as balm of Peru (strong allergen), kathon (moderate allergen), cinnamic aldehyde (mild allergen) or the irritant SLS had no significant effect. In contrast, the 4-day treatment with allergens substantially improved the results. Indeed, despite a large variability according to the donors, the number of modified antigens was significantly higher with all the tested chemicals, except kathon, as compared to that observed with the irritant SLS. The present study indicates that, in this model, the screening of mild or moderate allergens requires both the consideration of many antigens and a prolonged time of incubation with the chemicals.

Chemical degradation of wastes of antineoplastic agents: cyclophosphamide, ifosfamide and melphalan.

Handling genotoxic compounds commonly used in cancer chemotherapy generates contaminated wastes that require decontamination before disposal. Chemical methods are an alternative and/or a complement to incineration for the treatment of wastes and spills. As part of a program initiated by the International Agency for Research on Cancer (IARC), three chemical methods readily available in the hospital environment, viz sodium hypochlorite (NaOCl, 5.25%), hydrogen peroxide (H2O2, < or = 30%) and Fenton reagent (FeCl2, 2H2O; 0.3 g in 10 ml H2O2, 30%), were tested for the degradation of three alkylating agents (cyclophosphamide, CP; ifosfamide, IF, and melphalan). Pharmaceutical preparations corresponding to the most highly concentrated administration solutions in either NaCl (0.9%) or dextrose (5%) were inactivated by oxidation volume/volume with each of the methods for at least 1 h. The efficiency of degradation was monitored by high-pressure liquid chromatography. The mutagenicity of the degradation residues was tested by means of the Ames test using tester strains of Salmonella typhimurium TA 97a, TA 98, TA 100 and TA 102 with and without an exogenous metabolic activation system. Complete disappearance of CP was observed after 1 h with all degradation methods. However, direct mutagens were generated by the Fenton oxidation technique in the presence of dextrose (5%). IF was completely degraded by the Fenton reagent and NaOCl methods. No mutagenic residues were detected after 1 h of treatment with the Fenton technique, and after 3 h with the NaOCl method. Direct-acting mutagens remained after the H2O2 treatment in the presence of dextrose (5%). Complete degradation of melphalan was achieved in 1 h by each of the three methods, and no mutagenic residues were produced by any of the treatments. The use of NaOCl (5.25%) proved the most efficient system for degradation of the three alkylating agents.

Chemical degradation of wastes of antineoplastic agents. 2: Six anthracyclines: idarubicin, doxorubicin, epirubicin, pirarubicin, aclarubicin, and daunorubicin.

OBJECT: Handling of genotoxic compounds commonly used in cancer chemotherapy generates contaminated wastes that require decontamination before disposal. Chemical methods are an alternative and/or a complement to incineration for the treatment of wastes and spills. METHODS: As part of a program initiated by the International Agency for Research on Cancer (IARC), 3 chemical methods readily available in the hospital environment--sodium hypochlorite (NaOCl, 5.25%), hydrogen peroxide (H2O2, < or = 30%) and Fenton reagent (FeCl2, 2H2O; 0.3 g in 10 ml H2O2, 30%)--are being tested for the degradation of a total of 32 antineoplastic agents. The efficiency of degradation was monitored by high-pressure liquid chromatography. The mutagenicity of the degradation residues were tested by the Ames test using tester strains Salmonella typhimurium TA 97a, TA 98, TA 100, and TA 102 with and without an exogenous metabolic activation system. RESULTS: The first results obtained for the degradation of cyclophosphamide, ifosfamide, and melphalan have been published in this journal. The present manuscript reports the results of the investigation of a series of six anthracyclines (aclarubicin, daunorubicin, doxorubicin, epirubicin, idarubicin, and pirarubicin) commonly used in chemotherapy treatment. Pharmaceutical preparations corresponding to the most concentrated administration solutions in either NaCl (0.9%) or dextrose (5%) were inactivated by oxidation volume/volume with each of the methods for at least 1 h. Complete degradation into nonmutagenic residues of all the tested compounds was observed after 1 h for the NaOCl (5.25%) treatment as previously reported for the first study. CONCLUSION: Sodium hypochlorite (5.25%) is an efficient reagent for the chemical degradation of the nine drugs tested thus far.

[The syndrome of premature ovarian failure]. / Le syndrome d'extinction précoce des ovaires.

The syndrome of early ovarian failure gives rise to several pathogenic and psychological problems because it often condemns the woman to permanent sterility. Because of this a precise diagnosis has to be made, and this is done by: biological examination of serum F.S.H.-L.H., Prolactin, delta 4, 17 O.H.C.S. and 17 C.S., T3 and T4, and T.S.H. and Oestradiol levels. Karyotyping should also be carried out because that allows a dysgenesis to be eliminated. Auto-immune antibodies should be sought and laparoscopy carried out for ovarian biopsy. Finally, karyotyping can be carried out on the ovarian fibroblasts. Primary follicles should also be sought because these alone could theoretically give rise to pregnancy when oestrogen therapy is stopped.