The activity of ketoconazole against
Candida albicans
in Sabouraud glucose medium was markedly influenced by pH. Minimum inhibitory concentrations of this imidazole against both a standard strain and clinical isolates ranged from 40 μg/ml at pH 3 to 0.02 μg/ml at pH 7, a greater than 1,000-fold difference.
Induction of endogenous tumor necrosis factor (TNF) by administration of Bordetella pertussis vaccine (BPV) as a triggering agent and its therapeutic effect against MM46 carcinoma were investigated in C3H/He mice. Test triggering agents were injected intravenously into mice after intravenous injection of 4‐fold dilution of macrophage activating factor (MAF) or 104 units of murine interferon‐γ (Mu‐IFN‐γ). Then sera were obtained from the mice, and their TNF activities were assayed on L‐929 cells by the method of Ruff and Gifford. The triggering activity of BPV was the highest among those of conventional triggers, such as lipopolysaccharide (LPS) of Escherichia coli, and OK‐432. The levels of serum TNF activity triggered by BPV (4 × 109 cells), LPS of E. coli (3 μg) and OK‐432 (3 KE) were 5350, 85 and 102 units/ml, respectively. Growth of MM46, a spontaneous mammary carcinoma cell line of C3H/He was observed for 35 days after tumor inoculation and was suppressed significantly by intravenous injection of MAF and BPV (4 × 109 cells). On local injection of BPV (2 × 109 cells) into murine tumors, complete regression was observed in 67% of the mice tested with or without MAF priming on day 25 after tumor inoculation, and intratumoral TNF activity was observed even in the case of the single injection of BPV.
Summary Intratumoral induction of tumour necrosis factor (TNF) by administration of Bordetella pertussis vaccine (BPV) as compared with that by the agent OK-432 was investigated in mice. Two hours after such administration tumour tissues tested were resected from the mice, homogenised, and the TNF activities in the homogenate were assayed using a L-929 fibroblast assay. Intravenous injection of BPV into mice bearing the MM46 carcinoma resulted in a greater concentration of TNF in the tumour homogenate than in the serum. With OK-432, however, there was a greater concentration of TNF in the serum than in the tumour homogenates. A high level of intratumoral TNF induction by BPV was also observed in mice bearing Meth A fibrosarcoma or Lewis lung carcinoma. The therapeutic effect against the Meth A fibrosarcoma was in parallel with the intratumoral TNF activity. Intratumoral TNF activity is therefore believed to be a good index of therapeutic effect.
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