Noninvasive ventilation in trauma.

Trauma patients are a diverse population with heterogeneous needs for ventilatory support. This requirement depends mainly on the severity of their ventilatory dysfunction, degree of deterioration in gaseous exchange, any associated injuries, and the individual feasibility of potentially using a noninvasive ventilation approach. Noninvasive ventilation may reduce the need to intubate patients with trauma-related hypoxemia. It is well-known that these patients are at increased risk to develop hypoxemic respiratory failure which may or may not be associated with hypercapnia. Hypoxemia in these patients is due to ventilation perfusion mismatching and right to left shunt because of lung contusion, atelectasis, an inability to clear secretions as well as pneumothorax and/or hemothorax, all of which are common in trauma patients. Noninvasive ventilation has been tried in these patients in order to avoid the complications related to endotracheal intubation, mainly ventilator-associated pneumonia. The potential usefulness of noninvasive ventilation in the ventilatory management of trauma patients, though reported in various studies, has not been sufficiently investigated on a large scale. According to the British Thoracic Society guidelines, the indications and efficacy of noninvasive ventilation treatment in respiratory distress induced by trauma have thus far been inconsistent and merely received a low grade recommendation. In this review paper, we analyse and compare the results of various studies in which noninvasive ventilation was applied and discuss the role and efficacy of this ventilator modality in trauma.

Role of p90(RSK) in regulating the Crabtree effect: implications for cancer.

High glucose inhibits mitochondrial respiration, known as the 'Crabtree effect', in cancer cells and possibly other cell types. The upstream pathways regulating this phenomenon are poorly understood. In diabetes, where glucose levels are elevated, the p90(RSK) (p90 ribosomal S6 kinase) has received much attention as a potential upstream mediator of the effects of high glucose. Evidence is also emerging that p90(RSK) may play a role in cancer cell signalling, although the role of p90(RSK) in regulating cancer cell metabolism is unclear. In the present paper, we provide an overview of the Crabtree effect and its relationship to mitochondrial metabolism. Furthermore, preliminary data are presented suggesting a role for p90(RSK) and its upstream components, the ERK (extracellular-signal-regulated kinase) family of MAPKs (mitogen-activated protein kinases), in the Crabtree effect.

A novel mitochondrial K(ATP) channel assay.

RATIONALE: The mitochondrial ATP sensitive potassium channel (mK(ATP)) is implicated in cardioprotection by ischemic preconditioning (IPC), but the molecular identity of the channel remains controversial. The validity of current methods to assay mK(ATP) activity is disputed. OBJECTIVE: We sought to develop novel methods to assay mK(ATP) activity and its regulation. METHODS AND RESULTS: Using a thallium (Tl(+))-sensitive fluorophore, we developed a novel Tl(+) flux based assay for mK(ATP) activity, and used this assay probe several aspects of mK(ATP) function. The following key observations were made. (1) Time-dependent run down of mK(ATP) activity was reversed by phosphatidylinositol-4,5-bisphosphate (PIP(2)). (2) Dose responses of mK(ATP) to nucleotides revealed a UDP EC(50) of approximately 20 micromol/L and an ATP IC(50) of approximately 5 micromol/L. (3) The antidepressant fluoxetine (Prozac) inhibited mK(ATP) (IC(50)=2.4 micromol/L). Fluoxetine also blocked cardioprotection triggered by IPC, but did not block protection triggered by a mK(ATP)-independent stimulus. The related antidepressant zimelidine was without effect on either mK(ATP) or IPC. CONCLUSIONS: The Tl(+) flux mK(ATP) assay was validated by correlation with a classical mK(ATP) channel osmotic swelling assay (R(2)=0.855). The pharmacological profile of mK(ATP) (response to ATP, UDP, PIP(2), and fluoxetine) is consistent with that of an inward rectifying K(+) channel (K(IR)) and is somewhat closer to that of the K(IR)6.2 than the K(IR)6.1 isoform. The effect of fluoxetine on mK(ATP)-dependent cardioprotection has implications for the growing use of antidepressants in patients who may benefit from preconditioning.