Clinical Outcomes and Mortality Impact of Hyperbaric Oxygen Therapy in Patients With Carbon Monoxide Poisoning.

OBJECTIVES: Carbon monoxide poisoning affects 50,000 per year in the United States alone. Mortality is approximately 3%, and up to 40% of survivors suffer from permanent neurocognitive and affective deficits. Hyperbaric oxygen therapy has shown benefit on reducing the long-term neurologic sequelae of carbon monoxide poisoning but has not demonstrated improved survival. The objective of this study is to assess the efficacy of hyperbaric oxygen for acute and long-term mortality in carbon monoxide poisoning using a large clinical databank. DESIGN: Retrospective analysis. SETTING: University of Pittsburgh Medical Center healthcare system (Pittsburgh, PA). PATIENTS: One-thousand ninety-nine unique encounters of adult patients with carbon monoxide poisoning. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Baseline demographics, laboratory values, hospital charge transactions, discharge disposition, and clinical information from charting were obtained from the electronic medical record. In propensity-adjusted analysis, hyperbaric oxygen therapy was associated with a reduction in inpatient mortality (absolute risk reduction, 2.1% [3.7-0.9%]; p = 0.001) and a reduction in 1-year mortality (absolute risk reduction, 2.1% [3.8-0.4%]; p = 0.013). CONCLUSIONS: These data demonstrate that hyperbaric oxygen is associated with reduced acute and reduced 1-year mortality. Further studies are needed on the mortality effects of hyperbaric oxygen therapy in carbon monoxide poisoning.

A Complementary Metal Oxide Semiconductor Process-Compatible Ferroelectric Tunnel Junction.

In recent years, experimental demonstration of ferroelectric tunnel junctions (FTJ) based on perovskite tunnel barriers has been reported. However, integrating these perovskite materials into conventional silicon memory technology remains challenging due to their lack of compatibility with the complementary metal oxide semiconductor process (CMOS). This communication reports the fabrication of an FTJ based on a CMOS-compatible tunnel barrier Hf0.5Zr0.5O2 (6 unit cells thick) on an equally CMOS-compatible TiN electrode. Analysis of the FTJ by grazing angle incidence X-ray diffraction confirmed the formation of the noncentrosymmetric orthorhombic phase (Pbc21, ferroelectric phase). The FTJ characterization is followed by the reconstruction of the electrostatic potential profile in the as-grown TiN/Hf0.5Zr0.5O2/Pt heterostructure. A direct tunneling current model across a trapezoidal barrier was used to correlate the electronic and electrical properties of our FTJ devices. The good agreement between the experimental and theoretical model attests to the tunneling electroresistance effect (TER) in our FTJ device. A TER ratio of ∼15 was calculated for the present FTJ device at low read voltage (+0.2 V). This study suggests that Hf0.5Zr0.5O2 is a promising candidate for integration into conventional Si memory technology.

Nitrite reductase and nitric-oxide synthase activity of the mitochondrial molybdopterin enzymes mARC1 and mARC2.

Mitochondrial amidoxime reducing component (mARC) proteins are molybdopterin-containing enzymes of unclear physiological function. Both human isoforms mARC-1 and mARC-2 are able to catalyze the reduction of nitrite when they are in the reduced form. Moreover, our results indicate that mARC can generate nitric oxide (NO) from nitrite when forming an electron transfer chain with NADH, cytochrome b5, and NADH-dependent cytochrome b5 reductase. The rate of NO formation increases almost 3-fold when pH was lowered from 7.5 to 6.5. To determine if nitrite reduction is catalyzed by molybdenum in the active site of mARC-1, we mutated the putative active site cysteine residue (Cys-273), known to coordinate molybdenum binding. NO formation was abolished by the C273A mutation in mARC-1. Supplementation of transformed Escherichia coli with tungsten facilitated the replacement of molybdenum in recombinant mARC-1 and abolished NO formation. Therefore, we conclude that human mARC-1 and mARC-2 are capable of catalyzing reduction of nitrite to NO through reaction with its molybdenum cofactor. Finally, expression of mARC-1 in HEK cells using a lentivirus vector was used to confirm cellular nitrite reduction to NO. A comparison of NO formation profiles between mARC and xanthine oxidase reveals similar Kcat and Vmax values but more sustained NO formation from mARC, possibly because it is not vulnerable to autoinhibition via molybdenum desulfuration. The reduction of nitrite by mARC in the mitochondria may represent a new signaling pathway for NADH-dependent hypoxic NO production.

Lipase is essential for the study of in vitro release kinetics from organogels.

In vitro drug release studies remain indispensable in the development of drug delivery systems, even if correlations between in vitro and in vivo results are often imperfect. In this work, an improved in vitro analysis method for studying in situ-forming lipid-based implants was developed. More specifically, lipase was found to be an essential additive for evidencing differences in drug release kinetics from organogels of different amino acid-based organogelators, organogelator concentrations, drug loadings, and volumes. Lipases are thought to participate in the degradation of and release from amino acid-based organogel implants in vivo. Our experimental conditions allowed for the rapid and reliable screening of in vitro parameters that may be optimized to slow or accelerate drug release, once preliminary in vivo data are available.

Toxaphene, but not beryllium, induces human neutrophil chemotaxis and apoptosis via reactive oxygen species (ROS): involvement of caspases and ROS in the degradation of cytoskeletal proteins.

Chemicals of environmental concern are known to alter the immune system. Recent data indicate that some contaminants possess proinflammatory properties by activating neutrophils, an area of research that is still poorly investigated. We have previously documented that toxaphene activates human neutrophils to produce reactive oxygen species (ROS) and accelerates apoptosis by a yet unknown mechanism. In this study, we found that toxaphene induces another neutrophil function, chemotaxis. Furthermore, we found that toxaphene induces both chemotaxis and apoptosis via a ROS-dependent mechanism, since these responses were blocked by the addition of catalase to the culture. In addition, toxaphene was found to induce the degradation of the cytoskeletal proteins gelsolin, paxillin, and vimentin during apoptosis, and this was reversed by the addition of z-VAD-FMK (caspase inhibitor) or catalase, demonstrating the importance of caspases and ROS in this process. In contrast to toxaphene, we found that beryllium does not induce superoxide production, and, this correlates with its inability to induce chemotaxis and apoptosis. We conclude that toxaphene induces chemotaxis and apoptosis via ROS and that caspases and ROS are involved in the degradation of cytoskeletal proteins.