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. Vascular reactivity and endothelial NOS activity in rat thoracic aorta during and after hyperbaric oxygen exposure. Am J Physiol Heart Circ Physiol 291: H1988 -H1998, 2006. First published April 28, 2006 doi:10.1152/ajpheart.00145.2006.-Accumulating evidence suggests that hyperbaric oxygen (HBO) stimulates neuronal nitric oxide (NO) synthase (NOS) activity, but the influence on endothelial NOS (eNOS) activity and vascular NO bioavailability remains unclear. We used a bioassay employing rat aortic rings to evaluate vascular NO bioavailability. HBO exposure to 2.8 atm absolute (ATA) in vitro decreased ACh relaxation. This effect remained unchanged, despite treatment with SOD-polyethylene glycol and catalase-polyethylene glycol, suggesting that the reduction in endothelium-derived NO bioavailability was independent of superoxide production. In vitro HBO induced contraction of resting aortic rings with and without endothelium, and these contractions were reduced by the NOS inhibitor N -nitro-L-arginine. In addition, in vitro HBO attenuated the vascular contraction produced by norepinephrine, and this effect was reversed by N -nitro-L-arginine, but not by endothelial denudation. These findings indicate stimulation of extraendothelial NO production during HBO exposure. A radiochemical assay was used to assess NOS activity in rat aortic endothelial cells. Catalytic activity of eNOS in cell homogenates was not decreased by HBO, and in vivo HBO exposure to 2.8 ATA was without effect on eNOS activity and/or vascular NO bioavailability in vitro. We conclude that HBO reduces endothelium-derived NO bioavailability independent of superoxide production, and this effect seems to be unrelated to a decrease in eNOS catalytic activity. In addition, HBO increases the resting tone of rat aortic rings and attenuates the contractile response to norepinephrine by endothelium-independent mechanisms that involve extraendothelial NO production. nitric oxide synthase; acetylcholine relaxation; autooxidation HYPERBARIC OXYGEN (HBO) is used in clinical medicine in the management of different diseases and conditions, because it mediates some useful actions, such as stimulation of angiogenesis and inhibition of leukocyte adhesion. However, the underlying biochemical mechanisms have not been fully elucidated.Nitric oxide (NO) bioavailability in rat and mouse cerebral cortex, measured by NO-specific microelectrodes, is increased early during HBO exposure and paralleled by an increase in regional blood flow (40). Thom et al. (40) reported that cerebral NO production was increased much more in knockout mice lacking genes for endothelial NO synthase (eNOS) than in those lacking genes for neuronal NO synthase (nNOS), suggesting that changes in eNOS activity during HBO exposure are minimal compared with changes in nNOS activity. However, because of the predominance of nNOS in the central nervous system (20), this might not be the case in the systemic circulation. Increased nNOS-but not eNOS-derived NO was also observed at the abluminal side of th...

Antibiotic treatments have detrimental effects on the microbiome and lead to antibiotic resistance. To develop a phage therapy against a diverse range of clinically relevant Escherichia coli, we screened a library of 162 wild-type (WT) phages, identifying eight phages with broad coverage of E. coli, complementary binding to bacterial surface receptors, and the capability to stably carry inserted cargo. Selected phages were engineered with tail fibers and CRISPR–Cas machinery to specifically target E. coli. We show that engineered phages target bacteria in biofilms, reduce the emergence of phage-tolerant E. coli and out-compete their ancestral WT phages in coculture experiments. A combination of the four most complementary bacteriophages, called SNIPR001, is well tolerated in both mouse models and minipigs and reduces E. coli load in the mouse gut better than its constituent components separately. SNIPR001 is in clinical development to selectively kill E. coli, which may cause fatal infections in hematological cancer patients.

Divers have worked at 500 m depth in the sea and have reached 700 m in simulated chamber dives. A prerequisite for this has been extensive physiological studies of the body's reactions to pressure and pressure changes. This paper reviews such physiological and pathophysiological studies with emphasis on recent developments.