N2O Exposures Research Articles

Possible impact of the COVID-19 pandemic on the recreational use of nitrous oxide in the Paris area, France

IntroductionRecreational use of nitrous oxide (N2O) is increasing in Western countries, including France. During the COVID-19 pandemic, some authors warned that recreational N2O use could increase further as the supply of illicit drugs was impacted by various containment measures. MethodsWe retrospectively analyzed N2O exposures reported to the Paris Poison Control Center (France) from 2010/01/01 to 2021/04/15. The Poison Severity Score was used to grade severity. ResultsDuring the study period, 93 cases of N2O recreational exposures were reported (male/female ratio: 1.1; median age: 20.9 years range: [14.8-49.0]). The first case was reported in 2012, 84/93 (90%) and 65/93 (70%) were reported since 2019 and March 17th 2020 (first lockdown in France) respectively. Most of the patients were symptomatic (88/93; 95%) and developed neurological symptoms (78/93; 84%). Among the fourteen patients who developed moderate to severe symptoms, eleven were reported after March 2020. ConclusionDespite a marked increase in recreational N2O exposures during the COVID-19 pandemic, the exact impact of COVID-19 on this increase remains to be determined as it was observed from 2019.

Nitrous Oxide Impairs Axon Regeneration after Nervous System Injury in Male Rats.

Nitrous oxide can induce neurotoxicity. The authors hypothesized that exposure to nitrous oxide impairs axonal regeneration and functional recovery after central nervous system injury. The consequences of single and serial in vivo nitrous oxide exposures on axon regeneration in four experimental male rat models of nervous system injury were measured: in vitro axon regeneration in cell culture after in vivo nitrous oxide administration, in vivo axon regeneration after sharp spinal cord injury, in vivo axon regeneration after sharp optic nerve injury, and in vivo functional recovery after blunt contusion spinal cord injury. In vitro axon regeneration 48 h after a single in vivo 70% N2O exposure is less than half that in the absence of nitrous oxide (mean ± SD, 478 ± 275 um; n = 48) versus 210 ± 152 um (n = 48; P < 0.0001). A single exposure to 80% N2O inhibits the beneficial effects of folic acid on in vivo axonal regeneration after sharp spinal cord injury (13.4 ± 7.1% regenerating neurons [n = 12] vs. 0.6 ± 0.7% regenerating neurons [n = 4], P = 0.004). Serial 80% N2O administration reverses the benefit of folic acid on in vivo retinal ganglion cell axon regeneration after sharp optic nerve injury (1277 ± 180 regenerating retinal ganglion cells [n = 7] vs. 895 ± 164 regenerating retinal ganglion cells [n = 7], P = 0.005). Serial 80% N2O exposures reverses the benefit of folic acid on in vivo functional recovery after blunt spinal cord contusion (estimate for fixed effects ± standard error of the estimate: folic acid 5.60 ± 0.54 [n = 9] vs. folic acid + 80% N2O 5.19 ± 0.62 [n = 7], P < 0.0001). These data indicate that nitrous oxide can impair the ability of central nervous system neurons to regenerate axons after sharp and blunt trauma.

Nitrous Oxide Induces Prominent Cell Proliferation in Adult Rat Hippocampal Dentate Gyrus.

The identification of distinct and more efficacious antidepressant treatments is highly needed. Nitrous oxide (N2O) is an N-methyl-D-aspartic acid (NMDA) antagonist that has been reported to exhibit antidepressant effects in treatment-resistant depression (TRD) patients. Yet, no studies have investigated the effects of sub-anesthetic dosages of N2O on hippocampal cell proliferation and neurogenesis in adult brain rats. In our study, adult male Sprague-Dawley rats were exposed to single or multiple exposures to mixtures of 70% N2O and 30% oxygen (O2). Sham groups were exposed to 30% O2 and the control groups to atmospheric air. Hippocampal cell proliferation was assessed by bromodeoxyuridine (BrdU) incorporation, and BrdU-positive cells were counted in the dentate gyrus (DG) using confocal microscopy. Results showed that while the rates of hippocampal cell proliferation were comparable between the N2O and sham groups at day 1, levels increased by 1.4 folds at day 7 after one session exposure to N2O. Multiple N2O exposures significantly increased the rate of hippocampal cell proliferation to two folds. Therefore, sub-anesthetic doses of N2O, similar to ketamine, increase hippocampal cell proliferation, suggesting that there will ultimately be an increase in neurogenesis. Future studies should investigate added N2O exposures and their antidepressant behavioral correlates.

Modelling levels of nitrous oxide exposure for healthcare professionals during EMONO usage.

BackgroundComputational fluid dynamics (CFD) has been used to compute nitrous oxide (N2O) levels within a room during the administration of an equimolar mix of N2O/oxygen (EMONO) in the clinical setting. This study modelled realistic scenarios of EMONO usage in hospital or primary care, in order to estimate the potential N2O exposure of healthcare professionals (HCP) with routine EMONO use and to provide guidance for EMONO users.MethodsSixteen scenarios were defined by carrying out a survey of practitioners. CFD simulations were performed for each scenario and N2O concentrations over time were calculated. N2O exposures (time-weighted average of concentration over 8 h [TWA-8 h]) were calculated at the HCPs’ mouth to be compared with a predefined occupational exposure limit (OEL).ResultsAdministration duration and ventilation type were the main factors influencing N2O levels; ventilation type also influenced wash-out time between EMONO administrations. N2O concentration showed a plume distribution towards the ceiling and was highly heterogeneous, highlighting the importance of measurement location. Although estimated TWA-8 h varied widely, 13 of the 16 scenarios had an N2O TWA-8 h of <100 parts per million.ConclusionsData demonstrate that EMONO usage in well ventilated rooms – as recommended – helps to ensure that N2O exposure does not exceed the OEL and does not signal any major risks for HCPs when recommendations are followed. Although these data are numerical simulations and should be considered as such, they can provide guidance for EMONO users.

Persistence of a hyperthermic sign-reversal during nitrous oxide inhalation despite cue-exposure treatment with and without a drug-onset cue

We asked whether chronic tolerance and the hyperthermic sign-reversal induced by repeated 60% N2O exposures could be extinguished using a cue-exposure paradigm. Rats received 18 N2O administrations in a total calorimetry system that simultaneously measures core temperature (Tc), metabolic heat production (HP), and body heat loss (HL). Each exposure entailed a 2-h baseline period followed by a 1.5-h N2O exposure. The 18 drug exposures induced a robust intra-administration hyperthermia in which the initial hypothermic effect of N2O inverted to a significant hyperthermic sign-reversal during N2O inhalation due primarily to an acquired robust increase in HP. The rats were then randomized to one of 3 extinction procedures (n = 8/procedure) over a 20-d interval: 1) a N2O-abstinent home-cage group (HC) that received only the usual animal care; 2) a cue-exposure group (CEXP) in which the animals were placed in the calorimeter 8 times but received no N2O; and 3) a drug-onset-cue group (DOC) in which animals received a brief N2O exposure in the calorimeter that mimicked the first 3 min of an actual 60% N2O trial. Following the extinction sessions, all rats received a 60% N2O test trial and Tc, HP and HL were assessed. The hyperthermic sign-reversal remained fully intact during the test trial, with no significant differences observed among groups in any post-baseline change in any thermal outcome. These data suggest that cue exposure may not be an efficacious strategy to reduce sign-reversals that develop with chronic drug use.

Pt-coated InN nanorods for selective detection of hydrogen at room temperature

Single crystal InN nanorods were successfully grown on c-Al2O3 by hydride-metalorganic vapor phase epitaxy. The measured resistance of bare InN nanorods does not change upon exposure to hydrogen ambient. The addition of sputter-deposited clusters of Pt onto the surface of the InN nanorods, however, produced a significant change in the measured room temperature resistance. The measured resistance changed systematically by 0.5%–12% as the ambient hydrogen concentration in N2 was varied between 10 and 250 ppm after 15 min exposure time. Importantly, a relatively low power consumption of ∼0.3mW was measured under these conditions. There was no response at room temperature to O2, N2O, or NH3 exposures.

A long-term study of the development of N2O controls at a pediatric dental facility.

A review is given of National Institute for Occupational Safety and Health (NIOSH) efforts to control N2O at a pediatric dental operatory from 1978 to the present. Measurements of N2O concentrations were made on four occasions before and after installation of different controls, using an infrared analyzer. Air velocity and volumetric flow measurements also were taken, Video imaging was done in some cases simultaneously with real-time N2O measurements to correlate work practices with exposure data. An infrared imaging system was used to identify sources of N2O. Critical components of resulting recommendations for control include monitoring of N2O concentrations; use of engineering controls, such as a scavenging mask, an effective dilution ventilation system, and auxiliary exhaust; good work practices; maintenance of the equipment; and worker education. Data presented strongly supports the hypothesis that better implementation of controls leads to reduction of N2O exposures. N2O concentrations were reduced by a factor of 61 from their initial levels. The current NIOSH recommended exposure limit of 25 ppm TWA during the time of N2O administration appears to be achievable.

Effect of prenatal N2O exposure on startle reflex reactivity

The teratogenic effect of N2O is of interest because thousands of pregnant women are exposed to this gaseous anesthetic each year. The effects of repeated N2O exposures were investigated for offspring of mice exposed to air or N2O (5%, 15%, or 35%) for 4 hours per day on days 6 through 15 of pregnancy. Ten litters per exposure group were studied. Exposures did not affect reproductive indices, survival, or physical milestones of development. Body weights showed significant exposure effects that could not be isolated to specific exposure groups; however, N2O-exposed mice tended to weigh more than air-exposed animals. Brain weights measured on postnatal day (PND) 126 or 127 were not different among exposure groups or between genders. Ability to stay on a rotating rod was not affected by prenatal N2O exposure. Prenatal exposure to N2O resulted in hyporeactivity of the startle reflex in response to acoustic or tactile stimuli. On PND 95 the results were statistically significant for all N2O-exposed groups compared with the air-exposed group. On PND 60, although not statistically significant, there was a definite trend toward hyporeactivity for the N2O groups. There was a significant age-related difference in startle response; control animals were significantly more reactive at 95 than at 60 days of age. Of the N2O-exposed groups, only the 15% group showed a statistically significant increase in reactivity from 60 to 95 days of age. The risk of behavioral or functional abnormalities for humans following in utero N2O exposure is unknown and cannot be directly extrapolated from the present study.(ABSTRACT TRUNCATED AT 250 WORDS)

Short Term Toxicity of Nitrous Oxide on the Immune, Hemopoietic, and Endocrine Systems in CD-1 Mice

Occupational exposures to subanesthetic levels of N2O have been documented to result in suppressed proliferative cell activities. Male CD-1 mice were exposed to 0, 50, 500, and 5000 ppm of N2O for 6 hr/day, 5 days/week for 2 or 13 weeks. Tritiated-thymidine ([3H]-TdR) uptake was measured in CD-1 splenic lymphocytes cultured with and without mitogens and in a mixed lymphocyte culture (MLC). Antibody-mediated immunocompetency was determined for sheep red blood cell (SRBC)-sensitized animals by plaque forming cell (PFC) assay and serum anti-SRBC antibody (Ab) titer. Deoxyuridine suppression tests (dUrdST) were performed on bone marrow cells. There was significantly decreased splenic lymphocyte uptake of [3H]-TdR by cells cultured with mitogenic substances and in MLC following 2-week exposures to 5000 ppm. After 13-week exposures the animals' splenic lymphocytes showed increased [3H]-TdR uptake following high N2O dosing in both the mitogen-induced blastogenesis and MLC assays. Compared to control animals, the 5000 ppm exposure group had significantly depressed PFC activity and circulating anti-SRBC Ab levels following the 13-week N2O exposures, and all 13-week exposure groups demonstrated decreased liver weights and leukopenia. Bone marrow activity at these dosing levels was depressed in a dose-dependent fashion following 13-week gas exposures.

Nitrous Oxide Decreases Substance P Receptor Binding in The Rat Spinal Cord

Synaptic transmission of substance P (SP) in the spinal cord during nitrous oxide (N2O) exposure was examined in rats. In the analgesia study, 75% N2O significantly increased tail-flick latency by 57% during the first 2-h N2O exposure and by 19% after a second 2-h N2O exposure, suggesting development of acute tolerance. In the SP content study, SP in the dorsal part of the spinal cord significantly increased by 120% at the end of first N2O exposure, but returned to the control level by the end of second N2O exposure. In the receptor binding study, N2O significantly decreased the [I]Bolton-Hunter-SP ([I]BH-SP) binding (SP-P) in laminae I-II of the dorsal horn by 19, 18, and 18% at the end of first N2O exposure, at the end of the second N2O exposure, and at 4 h after the second N2O exposure, respectively, as compared to the control. This decrease in the [I]BH-SP binding became statistically insignificant by 12 h after the second N2O exposure. In contrast, [I]Bolton-Hunter-eledoisin binding (SP-E) remained unchanged. In the equilibrium binding study, the number of SP-P receptor (Bmax) in laminae I-II of the dorsal horn significantly decreased by 24, 38, and 30% at the end of the first and at the end of the second N2O exposure, and at 4 h after the second N2O exposure, respectively, without significant changes in the affinity (Ka). The present study demonstrated that tolerance to N2O analgesia occurred during the two repeated N2O exposures. SP receptor binding decreased and remained decreased 4 h after discontinuation of N2O. This evidence is the first demonstration of the functional changes caused by N2O in SP synaptic transmission of the spinal cord.

Comparison of Low Intensity Laser Enhancement of Oxygen Chemisorption on GaAs Using O2 and N2O

AbstractThe sticking coefficient for molecular oxygen on GaAs(110) up to about one-halft monolayer coverage can be enhanced by two or three orders of magnitude when the semiconductor surface is illuminated by an argon ion laser with intensities of 5 W/cm2 or less. Previous work has shown that this effect is nonthermal and roughly independent of wavelength for above-bandgap radiation, implying that photogenerated electrons and/or holes are responsible in some way. In this paper we present recent work which shows that transfer of energy from the GaAs to oxygen molecules physisorbed on the surface causes the breakup of the oxygen and so enhances the reaction. This conclusion comes from comparison of our photoemission results for O2 and N2O exposures made under the same conditions, N2O being chosen since only 1.7 eV is needed to remove the oxygen atom as opposed to the 5.1eV required to break an O-O bond. Nitrous oxide, in contrast to O2, shows only slight photoenhancement and has a much lower activation energy for the dissociative sticking coefficient, demonstrating that removal of the dissociation of O2 as a reaction step also removes the major part of the activation energy barrier to oxygen chemisorption. Since N20 and photoenhanced O2 have similar kinetics, we conclude that the breakup of O2 is the reaction step accelerated by illumination. Another clue to the nature of the photoenhancement comes from our finding that both n- and p-type GaAs display similar O2 laser enhancement ratios. An estimate of the carrier concentrations at the surface predicts that electrons and holes are present in equal amounts at the surfaces of both doping types, however, so this result does not distinguish between single-carrier and recombination-related enhancement mechanisms.