Clinical pharmacokinetics of mycophenolic acid and its metabolites in solid organ transplant recipient

Mycophenolate mofetil (MMF), an ester prodrug of the immunosuppressant mycophenolic acid (MPA), is widely used for maintenance immunosuppressive therapy and prevention of renal allograft rejection in renal transplant recipients.MPA inhibits inosine monophosphate dehydrogenase (IMPDH), an enzyme involved in the “de novo” synthesis of purine nucleotides, thus suppressing both T-cell and B-cell proliferation. MPA shows a complex pharmacokinetics with considerable interand intra- patient by between- and within patient variabilities associated to MPA exposure. Several factors may contribute to it. The pharmacokinetic modeling according to the population pharmacokinetic approach with the non-linear mixed effects models has shown to be a powerful tool to describe the relationships between MMF doses and the MPA exposures and also to identify potential predictive patients’ demographic and clinical characteristics for dose tailoring during the post-transplant immunosuppresive treatment.

Effect of temperature and carpel size during pre-anthesis on potential grain weight in wheat

The effect of environmental conditions immediately before anthesis on potential grain weight was investigated in wheat at the experimental field of the Faculty of Agronomy (University of Buenos Aires, Argentina) during 1995 and 1996. Plants of two cultivars of wheat were grown in two environments (two contrasting sowing dates) to provide different background temperature conditions. In these environments, transparent boxes were installed covering the spikes in order to increase spike temperature for a short period (c. 6 days) immediately before anthesis, i.e. between ear emergence and anthesis. In both environments, transparent boxes increased mean temperatures by at least 3n8 mC. These increases were almost entirely due to the changes in maximum temperatures because minimum temperatures were little affected. Final grain weight was significantly reduced by higher temperature during the ear emergence–anthesis period. It is possible that this reduction could be mediated by the effect of the heat treatment on carpel weight at anthesis because a curvilinear association between final grain weight and carpel weight at anthesis was found. This curvilinear association may also indicate a threshold carpel weight for maximizing grain weight.

Identification of metabolites and thermal transformation products of quinolones in raw cow milk by liquid chromatography coupled to high resolution mass spectrometry.

The presence of residues of antibiotics, metabolites, and thermal transformation products (TPs), produced during thermal treatment to eliminate pathogenic microorganisms in milk, could represent a risk for people. Cow"s milk samples spiked with enrofloxacin (ENR), ciprofloxacin (CIP), difloxacin (DIF), and sarafloxacin (SAR) and milk samples from cows medicated with ENR were submitted to several thermal treatments. The milk samples were analyzed by liquid chromatography-mass spectrometry (LC-MS) to find and identify TPs and metabolites. In this work, 27 TPs of 4 quinolones and 24 metabolites of ENR were found. Some of these compounds had been reported previously, but others were characterized for the first time, including lactose-conjugated CIP, the formamidation reaction for CIP and SAR, and hydroxylation or ketone formation to produce three different isomers for all quinolones studied.