Frequency distribution of cytochrome P450 3A4 gene polymorphism in ethnic populations and in transplant recipients.

CYP 3A4 plays a vital role in the metabolism of many drugs including immunosuppressants. An association between a transition of A --> G at position -290 of the 5'-regulatory region of the CYP 3A4 gene and an effect on the level of transcription has been reported. The CYP 3A4-G variant frequency varies substantially in different populations.

Molecular analysis of inflammatory markers in trauma patients at risk of postinjury complications.

Background: Genetic differences associated with individual's immune responses appear to be a major contributing factor to the development of trauma- induced sepsis. Thus, effective treatment of sepsis requires the identification of the patients who are at increased risk for sepsis.

Methods: Sixty-eight patients, of which the majority had an injury severity score >15, and 118 controls from the same geographic region were genotyped.

Neurotrophin and GDNF family ligands promote survival and alter excitotoxic vulnerability of neurons derived from murine embryonic stem cells.

Embryonic stem (ES) cells are genetically manipulable pluripotential cells that can be differentiated in vitro into neurons, oligodendrocytes, and astrocytes. Given their potential utility as a source of replacement cells for the injured nervous system and the likelihood that transplantation interventions might include co-application of growth factors, we examined the effects of neurotrophin and GDNF family ligands on the survival and excitotoxic vulnerability of ES cell-derived neurons (ES neurons) grown in vitro. ES cells were differentiated down a neural lineage in vitro using the 4-/4+ protocol (Bain et al.

A proteasomal stress response: pre-treatment with proteasome inhibitors increases proteasome activity and reduces neuronal vulnerability to oxidative injury.

We report here that exposure to low concentrations of proteasome inhibitors (e.g. 10-100 nm MG-132, 0.

NMDA antagonists exacerbate neuronal death caused by proteasome inhibition in cultured cortical and striatal neurons.

The proteasome is involved in multiple cellular processes including control of the cell cycle, apoptosis and intracellular signalling; loss of proteasome function has been postulated to participate in the pathogenesis of triplet repeat diseases. We examined the vulnerability of central neurons to proteasome inhibition and tested the ability of anti-excitotoxic and anti-apoptotic treatments to attenuate proteasome inhibition-induced neuronal death. Exposure of murine neocortical cultures to proteasome inhibitors (0.