ABSTRACT
BACKGROUND & AIMS: Mycobacterium avium subspecies paratuberculosis has been proposed as a cause of Crohn's disease. We report a prospective, parallel, placebo-controlled, double-blind, randomized trial of 2 years of clarithromycin, rifabutin, and clofazimine in active Crohn's disease, with a further year of follow-up. METHODS: Two hundred thirteen patients were randomized to clarithromycin 750 mg/day, rifabutin 450 mg/day, clofazimine 50 mg/day or placebo, in addition to a 16-week tapering course of prednisolone. Those in remission (Crohn's Disease Activity Index Subject(s)
Anti-Bacterial Agents/administration & dosage
, Clarithromycin/administration & dosage
, Clofazimine/administration & dosage
, Crohn Disease/drug therapy
, Crohn Disease/microbiology
, Mycobacterium Infections/complications
, Mycobacterium avium/classification
, Rifabutin/administration & dosage
, Adult
, Anti-Bacterial Agents/adverse effects
, Anti-Bacterial Agents/therapeutic use
, Clarithromycin/adverse effects
, Clarithromycin/therapeutic use
, Clofazimine/adverse effects
, Clofazimine/therapeutic use
, Double-Blind Method
, Drug Administration Schedule
, Drug Therapy, Combination
, Female
, Glucocorticoids/administration & dosage
, Glucocorticoids/therapeutic use
, Humans
, Male
, Middle Aged
, Patient Compliance
, Prednisolone/administration & dosage
, Prednisolone/therapeutic use
, Rifabutin/adverse effects
, Rifabutin/therapeutic use
, Treatment Failure
Subject(s)
Antibiotic Prophylaxis/adverse effects , Candidiasis/chemically induced , Candidiasis/complications , Hemochromatosis/complications , Liver Cirrhosis/complications , Peritonitis/microbiology , Bacterial Infections/prevention & control , Drug Administration Schedule , Humans , Male , Middle AgedABSTRACT
Cells of Euglena gracilis Klebs, strain z Pringsheim, had high NADPH-glutamate dehydrogenase (GDH) activity when grown on glutamate but activity was repressed completely in cells grown on ammonium (NH4 + ). Subcellular fractionation showed that NADPH-GDH activity was located exclusively in the cytosol, while glutamine synthetase was present in the cytosol and chloroplasts. Despite high NADPH-GDH activity NH4 + assimilation was completely inhibited by methionine sulphoximine (MSO), an inhibitor of glutamine synthetase. With MSO present, cells produced NH4 + and it was shown that greatest NH4 + production occurred with cells containing high levels of NADPH-GDH activity and plentiful carbon supply. It is concluded that NADPH-GDH has a catabolic function in Euglena generating NH4 + from glutamate under conditions of nitrogen limitation.
