Extended time-of-flight measurements down to 100 keV at the AMANDE facility with a stilbene scintillator.

The time-of-flight (ToF) method with scintillators is routinely used for determining neutron energy. However, a technical difficulty related to the loss of scintillator efficiency below 1 MeV makes this technique difficult to implement for the energy decade [100 keV-1 MeV]. New crystal production techniques provide stilbene scintillators efficient in this low neutron energy region, making it possible to extend the ToF technique below 1 MeV. In this manner, measurements of secondary reactions (d,n) on carbon or oxygen nuclei in this range become feasible, which should lead to improved reference calibration conditions in neutron fields produced by a deuterium ion beam.

Modulation of CYP3a expression and activity in mice models of type 1 and type 2 diabetes.

CYP3A4, the most abundant cytochrome P450 enzyme in the human liver and small intestine, is responsible for the metabolism of about 50% of all marketed drugs. Numerous pathophysiological factors, such as diabetes and obesity, were shown to affect CYP3A activity. Evidences suggest that drug disposition is altered in type 1 (T1D) and type 2 diabetes (T2D). The objective was to evaluate the effect of T1D and T2D on hepatic and intestinal CYP3a drug-metabolizing activity/expression in mice. Hepatic and intestinal microsomes were prepared from streptozotocin-induced T1D, db/db T2D and control mice. Domperidone was selected as a probe substrate for CYP3a and formation of five of its metabolites was evaluated using high performance liquid chromatography. Hepatic CYP3a protein and mRNA expression were assessed by Western blot and reverse-transcription quantitative polymerase chain reaction respectively. Hepatic microsomal CYP3a activity was significantly increased in both T1D and T2D groups versus control group. Intestinal CYP3a activity was also significantly increased in both T1D and T2D groups. Moreover, significant increases of both hepatic CYP3a mRNAs and protein expression were observed in both T1D and T2D groups versus control group. Additional experiments with testosterone further validated the increased activity of CYP3a under the effect of both T1D and T2D. Although differences exist in the pathophysiological insults associated with T1D and T2D, our results suggest that these two distinct diseases may have the same modulating effect on the regulation of CYP3a, ultimately leading to variability in drug response, ranging from lack of effect to life-threatening toxicity.