Safety evaluation of carbon tetrafluoride as an inert hyperbaric breathing gas in Sprague-Dawley rats.

Carbon tetrafluoride (CF4) is an inert gas with higher molecular weight and lower water solubility than commonly used hyperbaric breathing gases. These inert gas properties decrease time required to decompress and avoid decompression sickness after deep dives. To assess CF4 toxicity, Sprague-Dawley rats were exposed to 8 atm absolute (ATA) air (10 males, 10 females) or 8 ATA 79% CF4/21% O2 (25 males, 25 females). Exposures were 30 min daily for 5 days. Rat behavior was normal throughout the testing period. There were no gross or microscopic pathology abnormalities following repeat dose exposure. Male body weight trends were similar between groups. Female body weight trends were 0.5 ± 0.8% day-1 for hyperbaric air exposure and - 0.2 ± 0.8% day-1 for hyperbaric CF4 exposure (P = 0.01) but remained within literature cited norms. Organ weights and hematologic indices remained within or near literature normal ranges. Clinical chemistry panels showed no signs of toxicity in renal or hepatic biomarkers. Polychromatic erythrocyte micronucleus frequency showed no chromosomal damage. Comet assay showed no DNA damage in lung tissue. Females exposed to CF4 had 2.5 times greater percent tail DNA in liver tissue than controls (P = 0.009). However this result remained within the normal range of local negative controls. A bacterial reverse mutation assay with exposure to 1 ATA 79% CF4/21% O2 for 72 h was nonmutagenic in four strains of Salmonella typhimurium and one strain of Escherichia coli. Overall, there was no evidence that CF4 caused organ toxicity or genetic toxicity.

GAT inhibition preserves cerebral blood flow and reduces oxidant damage to mitochondria in rodents exposed to extreme hyperbaric oxygen.

Oxygen breathing at elevated partial pressures (PO2's) at or more than 3 atmospheres absolute (ATA) causes a reduction in brain γ-aminobutyric acid (GABA) levels that impacts the development of central nervous system oxygen toxicity (CNS-OT). Drugs that increase brain GABA content delay the onset of CNS-OT, but it is unknown if oxidant damage is lessened because brain tissue PO2 remains elevated during hyperbaric oxygen (HBO2) exposures. Experiments were performed in rats and mice to measure brain GABA levels with or without GABA transporter inhibitors (GATs) and its influence on cerebral blood flow, oxidant damage, and aspects of mitochondrial quality control signaling (mitophagy and biogenesis). In rats pretreated with tiagabine (GAT1 inhibitor), the tachycardia, secondary rise in mean arterial blood pressure, and cerebral hyperemia were prevented during HBO2 at 5 and 6 ATA. Tiagabine and the nonselective GAT inhibitor nipecotic acid similarly extended HBO2 seizure latencies. In mice pretreated with tiagabine and exposed to HBO2 at 5 ATA, nuclear and mitochondrial DNA oxidation and astrocytosis was attenuated in the cerebellum and hippocampus. Less oxidant injury in these regions was accompanied by reduced conjugated microtubule-associated protein 1A/1B-light chain 3 (LC3-II), an index of mitophagy, and phosphorylated cAMP response element binding protein (pCREB), an initiator of mitochondrial biogenesis. We conclude that GABA prevents cerebral hyperemia and delays neuroexcitation under extreme HBO2, limiting oxidant damage in the cerebellum and hippocampus, and likely lowering mitophagy flux and initiation of pCREB-initiated mitochondrial biogenesis.

Molecular analysis of blood with micro-/nanoscale field-effect-transistor biosensors.

Rapid and accurate molecular blood analysis is essential for disease diagnosis and management. Field-effect transistor (FET) biosensors are a type of device that promise to advance blood point-of-care testing by offering desirable characteristics such as portability, high sensitivity, brief detection time, low manufacturing cost, multiplexing, and label-free detection. By controlling device parameters, desired FET biosensor performance is obtained. This review focuses on the effects of sensing environment, micro-/nanoscale device structure, operation mode, and surface functionalization on device performance and long-term stability.

Carbon Monoxide Levels in the Extravehicular Mobility Unit by Modeling and Operational Testing.

INTRODUCTION: Carbon monoxide (CO) is a toxic gas with potential for detriment to spaceflight operations. An analytical model was developed to investigate if a maximum CO contamination of 1 ppm in the oxygen (O2) supply reached dangerous levels during extravehicular activity (EVA). Occupational monitoring pre- and postsuited exposures provided supplementary data for review.METHODS: The analytical model estimated O2 and CO concentrations in the extravehicular mobility unit (EMU) based on O2 and CO flow rates into and out of the system. The model was based on 3 h of prebreathe at 15.2 psia, 8 h of EVA at 4.3 psia, and 1 h at 15.2 psia for suit doffing. The Coburn-Forster-Kane equation was used to calculate crewmember carboxyhemoglobin saturation (COHb%) as a function of time. Monitoring of hemoglobin CO saturation (Spco) with a CO-oximeter was conducted pre- and post-EVA during operations on the International Space Station and in ground-based analog environments.RESULTS: The model predicted a maximum PCO in the EMU of 0.061 mmHg and a maximum crewmember COHb% of 2.1%. Operational Spco measurements in mean ± SD during ground-based analog testing were 0.7% ± 1.8% pretest and 0.5% ± 1.5% posttest. Spco values on the ISS were 1.5% ± 0.7% pre-EVA and 1.1% ± 0.3% post-EVA.DISCUSSION: The model predicted that astronauts are not exposed to toxic levels of CO during EVA and operational measurements did not show significant differences between Spco levels between pre- and post-EVA.Makowski MS, Norcross JR, Alexander D, Sanders RW, Conkin J, Young M. Carbon monoxide levels in the extravehicular mobility unit by modeling and operational testing. Aerosp Med Hum Perform. 2019; 90(2):84-91.

Kinase detection with gallium nitride based high electron mobility transistors.

A label-free kinase detection system was fabricated by the adsorption of gold nanoparticles functionalized with kinase inhibitor onto AlGaN/GaN high electron mobility transistors (HEMTs). The HEMTs were operated near threshold voltage due to the greatest sensitivity in this operational region. The Au NP/HEMT biosensor system electrically detected 1 pM SRC kinase in ionic solutions. These results are pertinent to drug development applications associated with kinase sensing.

Erratum: "Kinase detection with gallium nitride based high electron mobility transistors" [Appl. Phys. Lett. 103, 013701 (2013)].

[This corrects the article on p. 013701 in vol. 103.].

Gallium nitride is biocompatible and non-toxic before and after functionalization with peptides.

The toxicity of semiconductor materials can significantly hinder their use for in vitro and in vivo applications. Gallium nitride (GaN) is a material with remarkable properties, including excellent chemical stability. This work demonstrated that functionalized and etched GaN surfaces were stable in aqueous environments and leached a negligible amount of Ga in solution even in the presence of hydrogen peroxide. Also, GaN surfaces in cell culture did not interfere with nearby cell growth, and etched GaN promoted the adhesion of cells compared to etched silicon surfaces. A model peptide, "IKVAV", covalently attached to GaN and silicon surfaces increased the adhesion of PC12 cells. Peptide terminated GaN promoted greater cell spreading and extension of neurites. The results suggest that peptide modified GaN is a biocompatible and non-toxic material that can be used to probe chemical and electrical stimuli associated with neural interfaces.