Dietary docosahexaenoic acid suppresses inflammation and immunoresponses in contact hypersensitivity reaction in mice.

This study was designed to examine the immunomodulatory effects of dietary docosahexaenoic acid (DHA) in the absence of eicosapentaenoic acid (EPA). We investigated the effects of feeding dietary DHA ethyl ester (DHA-Et) (97% pure) at levels of 4.8 wt% of the total diet and of feeding EPA ethyl ester (EPA-Et) (99% pure) at 4.8 wt% on the inflammatory response in the challenge phase of the contact hypersensitivity reaction (CHR) in the ears of mice sensitized with 2,4-dinitro-1-fluorobenzene (DNFB). The effect of DHA-Et on T lymphocytes at the CHR site was examined using anti-CD4 antibodies. Furthermore, we examined the cytokines formed at the CHR site on the mRNA level. It was found that 24 h after the challenge, DHA-Et but not EPA-Et reduced the ear swelling. Infiltration of inflammatory cells, in particular, CD4-positive T lymphocytes, into the ears in the challenge phase of CHR was observed. DHA-Et reduced the infiltration of CD4-positive T lymphocytes into the ears. DHA-Et also decreased the expression of interferon-gamma, interleukin (IL)-6, IL-1beta, and IL-2 mRNA in ears. These observations suggest that DHA, but not EPA, may exert an antiinflammatory and immunosuppressive effect. The immunosuppressive effectiveness of fish oil may be attributed mainly to DHA.

Effect of oral adsorbent AST-120 on cyclosporin absorption in rats.

The oral adsorbent AST-120 is used to inhibit the progression of renal failure by adsorbing uraemic toxins in the gastrointestinal tract. When AST-120 is administered to patients receiving immunosuppressive medicines, it is important to study the effect of AST-120 on the amount of these and other drugs absorbed. We have, therefore, studied the in-vitro adsorption of cyclosporin by AST-120 and investigated the effect of oral administration of AST-120 on the absorption of cyclosporin in rats. The in-vitro adsorption ratios of AST-120 for cyclosporin were more than 80%. When pure cyclosporin powder was administered with AST-120, blood cyclosporin concentrations were significantly higher than when cyclosporin was administered alone. When cyclosporin dissolved in medium-chain triglyceride was administered to rats by intramuscular injection there was no significant difference in the blood cyclosporin concentration of rats given combined AST-120 and cyclosporin and those given cyclosporin alone. There was no significant difference between the serum concentration of total bile acids, in rats receiving combined oral AST-120 and cyclosporin dissolved in olive oil, and those receiving orally solely a solution of cyclosporin dissolved in olive oil. These results suggest that oral administration of AST-120 accelerates the absorption of orally administered cyclosporin from the gastrointestinal tract and does not affect the metabolism of cyclosporin. When a solution of cyclosporin in olive oil is administered orally, however, oral administration of AST-120 has no influence on cyclosporin absorption and does not affect the enterohepatic circulation of bile acids.

[Studies on hyperthermia and radiation treatment of uterine cancer using multicellular tumor spheroid].

Anticancer effects of hyperthermia and radiation on uterine cancer cells were studied using multicellular tumor spheroids and monolayer cultured cells. Cell lines used were SKG-3a(uterine cervical epidermoid carcinoma), HeLa-S3 (uterine cervical adenocarcinoma) and HEC-59 (uterine corpus adenocarcinoma). All cell lines grown in monolayer culture have similar growth rates, but as spheroids, their growth rate are HeLa-S3 greater than HEC-59 greater than SKG-3a cells. The radiosensitivity of all cell lines in monolayer are as follows according to dose-survival relationships. :HEC-59 greater than HeLa-S3 greater than SKG-3a cells. Survival assay to hyperthermia on SKG-3a and HEC-59 cells resulted in no response from 37 degrees to 41 degrees C and in cytotoxicity over 42 degrees C. There is no difference in sensitivity to hyperthermia between the two types of cells. The responses of three cell lines grown as spheroids in hyperthermia and radiation demonstrated that the combination therapy is not effective on the SKG-3a cell, but induced a 1.3-fold effectiveness ratio in HEC-59 and 1.6-fold in HeLa-S3 cells, i.e. more cytotoxicity than with radiation alone. These results suggests that hyperthermia and radiation employed together may be more effective on radioresistant adenocarcinoma cells than on radiosensitive epidermoid carcinoma cells.