oseph priestley, one of the three scientists credited with the discovery of oxygen, described the death of mice that were deprived of oxygen. However, he was also well aware of the toxicity of too much oxygen, stating, "For as a candle burns much faster in dephlogisticated [oxygen-enriched] than in common air, so we might live out too fast, and the animal powers be too soon exhausted in this pure kind of air. A moralist, at least, may say, that the air which nature has provided for us is as good as we deserve." 1In this review we examine the remarkable mechanisms by which different organs detect and respond to acute changes in oxygen tension. Specialized tissues that sense the local oxygen tension include glomus cells of the carotid body, neuroepithelial bodies in the lungs, chromaffin cells of the fetal adrenal medulla, and smooth-muscle cells of the resistance pulmonary arteries, fetoplacental arteries, systemic arteries, and the ductus arteriosus. Together, they constitute a specialized homeostatic oxygen-sensing system. Although all tissues are sensitive to severe hypoxia, these specialized tissues respond rapidly to moderate changes in oxygen tension within the physiologic range (roughly 40 to 100 mm Hg in an adult and 20 to 40 mm Hg in a fetus) (Fig. 1).In fetal life, the pulmonary vascular bed has a high resistance to blood flow. Consequently, oxygenated blood returning from the placenta is diverted from the unventilated lungs and across the foramen ovale and ductus arteriosus. At birth, when air breathing begins, the lungs expand and oxygen levels rise. With reversal of fetal hypoxic pulmonary vasoconstriction, the pulmonary vessels dilate and the ductus arteriosus constricts, thereby establishing the transition from the fetal to the neonatal circulation.After birth, hypoxic pulmonary vasoconstriction remains important, because it reduces perfusion of poorly ventilated areas of lung, and in so doing it decreases the shunting of desaturated, mixed venous blood to the systemic circulation. Inhibition of hypoxic pulmonary vasoconstriction reduces the systemic arterial oxygen tension, particularly in small-airway disease. 2 Moreover, as was first demonstrated in humans in 1947, 3 the intensity of hypoxic pulmonary vasoconstriction depends on the severity and duration of alveolar hypoxia. 4,5 The endothelium produces vasodilators, such as nitric oxide and prostacyclin, and vasoconstrictors, such as endothelin and thromboxane A 2 ; these molecules from endothelial cells modulate hypoxic pulmonary vasoconstriction, but the ability of small pulmonary vessels to contract in response to hypoxia resides in their smooth-muscle cells. 6 Three sites in these cells are involved in the mechanism of hypoxic pulmonary vasoconstriction: the membrane, the sarcoplasmic reticulum, and the contractile apparatus.

NF-κB is activated during acute inflammatory states as well as in other injury response disease states. Several pathologic states in squamous tissue injury response are characterized by increased squamous proliferation. This study was performed to investigate the hypothesis that Pseudomonas aeruginosa LPS is able to activate a proliferative phenotype in squamous cells via NF-κB induction and that this NF-κB-mediated response may be abrogated with the classic anti-inflammatory agent indomethacin. EMSA, luciferase reporter gene experiments, Western blots, and cellular proliferation assays were performed in normal and transformed human keratinocytes after stimulation with P. aeruginosa LPS. EMSA and luciferase reporter gene assays showed a 3- to 5-fold induction of active NF-κB in human keratinocyte cell lines after stimulation with P. aeruginosa LPS. The stimulation correlated with significantly increased cellular proliferation. As one potential mechanism for this increase in proliferation, an NF-κB-specific activation of cyclin D1 was observed. Both the NF-κB induction and proliferation response were inhibited with indomethacin and in dominant negative stable transfection clones. P. aeruginosa LPS activates proliferation of human keratinocytes, potentially through the induction of NF-κB and cyclin D1. These findings suggest that bacterial components can contribute to proliferative disease states in squamous epithelium through NF-κB activation.

Syncope is a relatively common clinical syndrome that is a subset of a broader range of conditions that cause transient loss of consciousness (TLOC). Other TLOC conditions include seizures, concussions, and intoxications. However, despite frequent confusion in the medical literature, syncope is and should be clearly distinguished from those other causes of TLOC by virtue of its pathophysiology; specifically, syncope is the result of self-terminating inadequacy of global cerebral nutrient perfusion, while the other forms of TLOC have different etiologies. Unfortunately, the diagnostic evaluation of syncope remains for the most part poorly managed and inefficient. Careful history-taking, physical examination, and judicious use of tests can not only increase the diagnostic yield of the evaluation, but also increase patient safety and reduced overall healthcare costs.

Our findings suggest that closely spaced subcutaneous electrodes identify changes in local tissue/vascular bioimpedance that correlate well with direct invasive measures of induced hypotension in a porcine model.