ABSTRACT
Searches for dark matter axions involve the use of microwave resonant cavities operating in a strong magnetic field. Detector sensitivity is directly related to the cavity quality factor, which is limited, until recently, to the use of non-superconducting metals by the presence of the external magnetic field. In this paper, we present a cavity of novel design whose quality factor is not affected by a magnetic field. It is based on a photonic structure by the use of sapphire rods. The quality factor at cryogenic temperature is in excess of 5 × 105 for a selected mode.
ABSTRACT
Mycophenolate mofetil (MMF) is a new immunosuppressive agent currently used in organ transplantation and under evaluation in immune-mediated inflammatory disorders such as rheumatoid arthritis. Although MMF was shown to inhibit purine nucleotide synthesis in lymphocytes, it is still unclear whether it might also exert direct antiinflammatory actions in vivo. To address this question, we evaluated the effects of MMF administration on the responses of mice to a single challenge with bacterial lipopolysaccharide (LPS). We observed that MMF treatment inhibits the release of tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) upon LPS injection whereas it promotes IL-10 production. In parallel, MMF was found to protect mice from LPS-induced lethality. Inhibition of TNF-alpha release was also observed in IL-10-deficient mice indicating that it does not exclusively depend on the upregulation of IL-10 endogenous synthesis. In view of the differential effects of MMF on the LPS-induced production of TNF-alpha and NO on one hand and that of IL-10 on the other hand, we conclude that beside its immunosuppressive action at the lymphocyte level, MMF is also endowed with antiinflammatory properties.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Endotoxemia/metabolism , Immunosuppressive Agents/pharmacology , Interleukin-10/biosynthesis , Mycophenolic Acid/analogs & derivatives , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Animals , Endotoxemia/etiology , Interleukin-10/blood , Interleukin-10/deficiency , Lipopolysaccharides/blood , Lipopolysaccharides/toxicity , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mycophenolic Acid/pharmacology , Nitric Oxide/metabolismABSTRACT
We investigated the effects of methotrexate (MTX) on the production of tumor necrosis factor (TNF), nitric oxide (NO) and interleukin-10 (IL-10) in vivo. Administration of low doses of MTX (450 mug/kg once a week for 4 weeks) in Balb/c mice resulted in a significant inhibition of the systemic release of TNF and NO upon LPS challenge, whereas the production of IL-10 remained unchanged. These anti-inflammatory effects of MTX were exerted at the macrophage level since peritoneal macrophages from mice, injected for 4 weeks with MTX produced lower levels of TNF than cells from control mice upon LPS stimulation ex vivo. In parallel, we found that MTX-treated mice were less susceptible to a lethal challenge with LPS and D-galactosamine. MTX did not inhibit TNF release after injection of Concanavalin A (ConA) or anti-CD3 monoclonal antibody (mAb), indicating that MTX does not inhibit TNF production at the T cell level. We conclude that repeated administration of a low dose of MTX in mice is associated with a decreased production of TNF by macrophages upon LPS activation.
