Reference

In vitro and in vivo activities of new rifamycin derivatives against mycobacterial infections

In vitro and in vivo activities of new rifamycin derivatives against mycobacterial infections. Lounis, N.; Roscigno, G. (Faculte de Medecine Pitie-Salpetriere, Paris, Fr. 61379-65-5 and 129791-92-0 are cas registry numbers. These chemicals are also mentioned in this article.). Current Pharmaceutical Design, 10(26), 3229-3238 (English) 2004 Bentham Science Publishers Ltd. CODEN: CPDEFP. ISSN: 1381-6128. DOCUMENT TYPE: Journal; General Review CA Section: 1 (Pharmacology) A review. Several rifamycin derivs. have been developed during the last 15 yr for the treatment of mycobacterial infections. For tuberculosis, rifabutin (RFB) showed strong activity and seemed to be suitable when tuberculosis patients were also treated for their AIDS infection. Rifapentine (RPT) was evaluated in patients with or without AIDS for its intermittent use. It displayed promising activity but must be strengthened in situations, such as AIDS or patients without AIDS but with cavities. Rifalazil (RLZ) has been evaluated in mice but the dosages used were much higher than those tolerated by patients. Regarding Mycobacterium avium infections, RFB showed significant prophylactic activity in humans, RPT displayed some activity in mice and RLZ showed modest activity in mice. .

Effects of benzoxazinorifamycin KRM-1648 on cytokine production at sites of Mycobacterium avium complex infection induced in mice

Effects of benzoxazinorifamycin KRM-1648 on cytokine production at sites of Mycobacterium avium complex infection induced in mice. Tomioka, Haruaki; Sato, Katsumasa; Shimizu, toshiaki; Sano, Chiaki; Akaki, Tatsuya; Saito, Hajime; Fujii, Kenji; Hidaka, Takayoshi (Dep. Microbiol. Immunol., Shimane Med. Univ., Izumo 693, Japan). Antimicrobial Agents and Chemotherapy, 41(2), 357-362 (English) 1997 American Society for Microbiology. CODEN: AMACCQ. ISSN: 0066-4804. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 14 Although various antimicrobial agents exhibit appreciable microbicidal activity in the early phase (weeks 2 to 4) of Mycobacterium avium complex (MAC) infection induced in mice, progressive bacterial regrowth subsequently occurs. To clarify the reason for this pattern of changes, the authors studied changes in the levels of various cytokines in tissue at sites of infection (spleens and lungs) of MAC-infected mice which were or were not given a benzoxazinorifamycin, KRM-1648 (KRM). Levels of the proinflammatory cytokines tumor necrosis factor alpha (TNF-a) and gamma interferon (IFN-g) in tissues temporarily increased at around weeks 2 to 4 after infection, rapidly decreased thereafter, and returned to normal by week 8. Similar but somewhat delayed changes were noted for levels of interleukin 10 (IL-10) and transforming growth factor beta (TGF-b), immunosuppressive cytokines with macrophage (MF)-deactivating activity, in tissue, except that TGF-b levels in the spleen remained high during weeks 4 to 8.Several substances like 129791-92-0 may be metioned in this study. KRM treatment blocked the increase in the levels of all of those cytokines in tissue in the early phase of infection, most strongly at week 4. IL-6 levels were beneath the limit of detection throughout the observation period. Bacterial loads in the visceral organs decreased during the first 2 wk, and KRM treatment markedly promoted this decrease. However, regrowth of MAC organisms began at weeks 2 to 4 and continued thereafter, even in KRM-treated mice. Splenocytes and splenic MFs of MAC-infected mice (week 2) produced and/or released into the culture fluid significant amts. of TNF-a (in a cell-bound form), IFN-g and IL-10, but not TGF-b, during 3 days of cultivation. A substantial amt. of TGF-b was produced during 2 wk of cultivation of peritoneal MFs. KRM itself did not significantly affect the IL-10- and TGF-b-producing ability of cultured MFs. These findings suggest that IL-10 and TGF-b play important roles in the regrowth of MAC organisms seen during the course of KRM treatment. .