D-2-Hydroxyglutarate Inhibits Calcineurin Phosphatase Activity to Abolish NF-AT Activation and IL-2 Induction in Stimulated Lymphocytes.

Gliomas expressing mutant isocitrate dehydrogenases excessively synthesize d-2-hydroxyglutarate (D2HG), suppressing immune surveillance. A portion of this D2HG is released from these tumor cells, but the way environmental D2HG inhibits lymphocyte function is undefined. We incubated human PBLs or Jurkat T cells with D2HG at concentrations present within and surrounding gliomas or its obverse l-2-hydroxyglutarate (L2HG) stereoisomer.

Why Does Doxycycline Pose a Relatively Low Risk for Promotion of Infection?

Background: Clinical studies suggest that doxycycline poses a low risk for promotion of infection, but the microbiologic explanation for this finding is unclear.

Methods: Mice treated with oral doxycycline, oral azithromycin, subcutaneous ceftriaxone, doxycycline plus ceftriaxone, or azithromycin plus ceftriaxone were challenged with 10 colony-forming units of 2 different strains on day 2 of 5 of treatment. The concentration of was measured in stool 2 and 5 days after challenge.