thioguanine-anhydrous and Granuloma

Three cases of allergic granulomatosis (Churg-Strauss syndrome) are reported. The patients all presented 2-10 years after the onset of pulmonary symptoms with a mononeuritis multiplex, accompanied by sharp pain in the extremities involved. In one patient, the neurological findings improved under treatment with corticoids and cyclophosphamide; the other two patients responded to treatment with thioguanine and cytarabine. In the first patient, the diagnosis was confirmed by a biopsy specimen of the sural nerve.

Topics: Adrenal Cortex Hormones; Adult; Antigen-Antibody Complex; Axons; Cyclophosphamide; Cytarabine; Demyelinating Diseases; Female; Granuloma; Humans; Hypersensitivity; Middle Aged; Muscles; Neuromuscular Diseases; Sural Nerve; Syndrome; Thioguanine; Vasculitis

The mutagenic activity of the natural plant product aristolochic acid (AA) was tested in the Granuloma Pouch Assay, which detects gene mutations induced in a subcutaneous granuloma tissue of rats. After direct exposure of the target tissue, AA induced high frequencies of mutants at a relatively low cytostatic/cytotoxic level. AA was more potent that N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) at equimolar doses. After oral application of AA, a dose-dependent mutagenic activity was seen. In contrast a very weak and inconsistent mutagenic effect was seen after systemic application of MNNG. These observations suggest that after oral application AA is not detoxified efficiently and can exert its mutagenic activity in extrahepatic tissues whereas MNNG is detoxified to a large extent at the site of administration.

Topics: Administration, Oral; Animals; Aristolochic Acids; Drug Resistance; Granuloma; Hypoxanthine Phosphoribosyltransferase; Inactivation, Metabolic; Male; Methylnitronitrosoguanidine; Mutagenicity Tests; Mutagens; Phenanthrenes; Rats; Rats, Inbred Strains; Thioguanine

Topics: Animals; Azathioprine; Dactinomycin; Fluocinolone Acetonide; Granuloma; Methotrexate; Mice; Schistosoma; Thioguanine