Mycophenolic acid inhibits PMA-induced activation of the neutrophil respiratory burst.

Mycophenolate mofetil (MMF) is commonly used in immunosuppressive regimens for solid organ transplantation. There is evidence that the hydrolyzed active agent mycophenolic acid (MPA) causes the endothelial depletion of intracellular guanosine 5'-triphosphate (GTP) levels. This depletion may cause inactivation of nicotinamide adenine dinucleotide phosphate oxidase. The purpose of the present study was to examine the impact of MPA on the neutrophil respiratory burst and phagocytic activity using flow cytometry. In whole blood of healthy volunteers, 2 different doses of MPA (1 and 10 mumol/L) did not alter hydrogen peroxide production of neutrophils induced by receptor-dependent activators. In contrast, MPA inhibits the protein kinase C (PKC)-mediated hydrogen peroxide production by phorbol 12-myristate 13-acetate (PMA) in a time-dependent manner (negative: 21.17 +/- 1.64 vs. 120 min: 14.46 +/- 1.28 mean fluorescence intensity, incubation with 1 mumol/L MPA). In conclusion, our results corroborated that the neutrophil respiratory burst activity of healthy volunteers, induced by either formyl-methionyl-leucylphenylalanine (fMLP), priming with tumor necrosis factor alpha followed by fMLP or Escherichia coli and neutrophil phagocytic capacity, were not significantly affected after MPA treatment. We also could demonstrate that the hydrogen peroxide production of neutrophils decreased in response to the PKC activator PMA in a time-dependent manner.

Clinical imaging fluorescence apparatus for the endoscopic photodetection of early cancers by use of Photofrin II.

A fluorescence imaging device applied to the detection of early cancer is described. The apparatus is based on the imaging of laser-induced fluorescence of a dye that localizes in a tumor with a higher concentration than in the surrounding normal tissue after iv injection. Tests carried out in the upper aerodigestive tract, the tracheobronchial tree, and the esophagus with Photofrin II (1 mg/kg of body weight) as the fluorescent agent are reported as examples. The fluorescence is induced by violet (410-nm) light from a continuous-wave (cw) krypton-ion laser. The fluorescence contrast between tumor and surrounding tissue is enhanced by real-time image processing. This is done by the simultaneous recording of the fluorescence image in two spectral domains (470-600 and 600-720 nm), after which these two images are digitized and manipulated with a mathematical operator (look-up table) at video frequency. Among the 7 photodetections performed in the tracheobronchial tree, 6 were successful, whereas it was the case for only 5 of the 15 lesions investigated in squamous mucosa (upper aerodigestive tract and esophagus). The sources of false positives and false negatives are evaluated in terms of the fluorescent dye, tissue optical properties, and illumination optics.