The antituberculous activity of 27753-RP (RP), a new semisynthetic derivative of griselimycine, was determined both in vitro and in vivo, and its activity against atypical mycobacteria was also studied in vitro. 1) The minimal inhibitory concentration of RP against H37Rv and its mutants resistant to streptomycin, isoniazide, kanamycin, rifampicin and enviomycin was 0.5 microgram/ml in liquid media, showing no cross-resistance. However, loss of potency occurred in Ogawa's egg media, and 50 micrograms/ml of RP were required for inhibition of growth. 2) In the therapeutic study of experimental tuberculosis in mice, RP was shown to have a remarkable effect. In particular, when treatment was started immediately after infection, RP showed a therapeutic efficacy comparable to that of rifampicin, although a double dose of the drug was required. When treatment was started 3 weeks after infection, RP was inferior to rifampicin in therapeutic efficacy. 3) RP also showed excellent antituberculous activity against experimental tuberculosis in guinea-pigs. Twice-a-week treatment had a therapeutic efficacy comparable to that obtained by daily treatment, but with an increased dosage. 4) Among atypical mycobacteria, RP showed some degree of activity against Mycobacterium kansasii in vitro, while its activity against M. intracellulare appeared to be extremely low.

Animals↗

PubMedDate not supplied

Intragastric administration of ursodeoxycholic acid suppresses immunoglobulin secretion by lymphocytes from liver, but not from peripheral blood, spleen or Peyer's patches in mice.

Ursodeoxycholic acid (UDCA) has been recognized as a therapeutic drug for primary biliary cirrhosis (PBC) and chronic viral hepatitis. As one of the mechanisms by which UDCA improves liver function tests in those patients, its immunomodulatory effect is currently considered important. Although the suppressive effects of UDCA on some cytokine productions, T-cell mediated cytotoxicity and immunoglobulin production were observed from in vitro studies, the immunomodulation in vivo by UDCA remains unclear. In the present study, we investigated the effect of UDCA administration on the number of immunoglobulin secreting cells in liver, peripheral blood, spleen and Peyer's patches in mice using the enzyme linked immunospot assay and assessed whether the UDCA-mediated immunomodulation is liver-specific. It was demonstrated that intragastric administration of UDCA reduced immunoglobulin secretion by lymphocytes from liver, but not from peripheral blood, spleen, or Peyer's patches. However, immunoglobulin production of those lymphocytes cultured in the presence of UDCA was suppressed, irrespective of their distribution sites, in a UDCA dose-dependent manner. When the concentrations of UDCA in portal and peripheral blood were measured using high performance liquid chromatography, UDCA was detectable in the portal blood in UDCA-treated mice, but not in peripheral blood, suggesting that the concentrations of UDCA in the environment surrounding lymphocytes may be an important factor for the modulation of lymphocyte functions.

Adjuvants, Immunologic↗