SAUNA III - The next generation noble gas system for verification of nuclear explosions.

The SAUNA III represent the next generation of the SAUNA systems designed for detection of low levels of radioactive xenon in the atmosphere, with the main purpose of detecting underground nuclear explosions. The system automatically collects, processes and measures 40 m3 atmospheric samples every 6 h, increasing both the sensitivity and time resolution as compared the systems currently in use. The higher sensitive increases the number of detections, especially for samples were more than one isotope of xenon are detected. This improves the understanding of the background and the possibility to screen out signal from civilian sources. The increased time resolution of the new system also provides a more detailed picture of the plumes, especially important for near-by sources. The design of the system as well as data from the first two years of operation are presented.

Xenon-enhanced dual-energy tomosynthesis for functional imaging of respiratory disease-Concept and phantom study.

BACKGROUND: Xenon-enhanced dual-energy (DE) computed tomography (CT) and hyperpolarized noble-gas magnetic resonance imaging (MRI) provide maps of lung ventilation that can be used to detect chronic obstructive pulmonary disease (COPD) early in its development and predict respiratory exacerbations. However, xenon-enhanced DE-CT requires high radiation doses and hyper-polarized noble-gas MRI is expensive and only available at a handful of institutions globally. PURPOSE: To present xenon-enhanced dual-energy tomosynthesis (XeDET) for low-dose, low-cost functional imaging of respiratory disease in an experimental phantom study. METHODS: We propose using digital tomosynthesis to produce Xe-enhanced low-energy (LE) and high-energy (HE) coronal images. DE subtraction of the LE and HE images is used to suppress soft tissues. We used an imaging phantom to investigate image quality in terms of the area under the reciever operating characteristic curve (AUC) for the Non-PreWhitening model observer with an Eye filter and internal noise (NPWEi). The phantom simulated anatomic clutter due to lung parenchyma and attenuation due to soft tissue and lung tissue. Aluminum slats were used to simulate rib structures. A stepwedge consisting of an acrylic casing with sealed cylindrical air-filled cavities was used to simulate ventilation defects with step thicknesses of 0.5, 1, and 2 cm and cylindrical radii of 0.5, 0.75, and 1 cm. The phantom was ventilated with Xe and projection data were acquired using a flat-panel detector, a tube-voltage combination of 60/140 kV with 1.2  mm of copper filtration on the HE spectrum and an angular range of ± 15 ∘ $\pm 15^{\circ}$ in 1° increments. The AUC of a NPWEi observer that has access only to a single coronal slice was calculated from measurements of the three-dimensional noise power spectrum and signal template. The AUC was calculated as a function of ventilation defect thickness and radius for total patient entrance air kermas ranging from 1.42 to 2.84 mGy with and without rib-simulating Al slats. For the AUC analysis, the observer internal noise level was obtained from an ad hoc calibration to a high-dose data set. RESULTS: XeDET was able to suppress parenchyma-simulating clutter in coronal images enabling visualization of the simulated ventilation defects, but the limited angle acquisition resulted in residual clutter due to out-of-plane bone-mimmicking structures. The signal power of the defects increased linearly with defect radius and showed a ten-fold to fifteen-fold increase in signal power when the defect thickness increased from 0.5 to 2 cm. These trends agreed with theoretical predictions. Along the depth dimension, the power of the defects decreased exponentially with distance from the center of the defects with full-width half maxima that varied from 1.85 to 2.85 cm depending on the defect thickness and radius. The AUCs of the 1-cm-radius defect that was 2 cm in thickness ranged from good (0.8-0.9) to excellent (0.9-1.0) over the range of air kermas considered. CONCLUSIONS: Xenon-enhanced DE tomosynthesis has the potential to enable functional imaging of respiratory disease and should be further investigated as a low-cost alternative to MRI-based approaches and a low-dose alternative to CT-based approaches.

Calibration of methylene-referenced lipid-dissolved xenon frequency for absolute MR temperature measurements.

PURPOSE: Absolute MR temperature measurements are currently difficult because they require precalibration procedures specific for tissue types and conditions. Reference of the lipid-dissolved 129 Xe resonance frequency to temperature-insensitive methylene protons (rLDX) has been proposed to remove the effect of macro- and microscopic susceptibility gradients to obtain absolute temperature information. The scope of this work is to evaluate the rLDX chemical shift (CS) dependence on lipid composition to estimate the precision of absolute temperature measurements in lipids. METHODS: Neat triglycerides, vegetable oils, and samples of freshly excised human and rodent adipose tissue (AT) are prepared under 129 Xe atmosphere and studied using high-resolution NMR. The rLDX CS is measured as a function of temperature. 1 H spectra are also acquired and the consistency of methylene-referenced water proton and rLDX CS values are compared in human AT. RESULTS: Although rLDX CS shows a dependence on lipid composition, in human and rodent AT samples the rLDX shows consistent CS values with a similar temperature dependence (-0.2058 ± 0.0010) ppm/°C × T (°C) + (200.15 ± 0.03) ppm, enabling absolute temperature measurements with an accuracy of 0.3°C. Methylene-referenced water CS values present variations of up to 4°C, even under well-controlled conditions. CONCLUSIONS: The rLDX can be used to obtain accurate absolute temperature measurements in AT, opening new opportunities for hyperpolarized 129 Xe MR to measure tissue absolute temperature.

Change of Tinnitus with Xenon Phototherapy of the Stellate Ganglion.

OBJECTIVE: To develop a treatment for tinnitus called xenon phototherapy of the stellate ganglion (XPSG) and analyze its effect on tinnitus. METHODS: Patients with chronic tinnitus received XPSG. Symptoms were assessed subjectively with tinnitus handicap inventory (THI) and numerical rating scale (NRS). THI and NRS scores were analyzed in XPSG (n = 43) and sham treatment (non-XPSG) (n = 18) groups. RESULTS: THI and NRS scores improved significantly after 3 months of XPSG. Severe cases with high THI or NRS score showed greater improvement. No significant difference was observed between before and after sham treatment in non-XPSG groups. CONCLUSIONS: XPSG significantly improved THI and NRS scores with high patient satisfaction.

Methods for Defining the Neuroprotective Properties of Xenon.

Xenon has features that make it an ideal general anesthetic agent; cost and scarcity mitigate xenon's widespread use in the operating room. Discovery of xenon's cytoprotective properties resulted in its application to thwart ongoing acute neurologic injury, an unmet clinical need. The discovery that xenon's neuroprotective effect interacts synergistically with targeted temperature management (TTM) led to its investigation in clinical settings, including in the management of the postcardiac arrest syndrome, in which TTM is indicated. Following successful demonstration of xenon's efficacy in combination with TTM in a preclinical model of porcine cardiac arrest, xenon plus TTM was shown to significantly decrease an imaging biomarker of brain injury for out of hospital cardiac arrest victims that had been successfully resuscitated. With the development of an efficient delivery system the stage is now set to investigate whether xenon improves survival, with good clinical outcome, for successfully resuscitated victims of a cardiac arrest.

Improvement in Ventilation-Perfusion Mismatch after Bronchoscopic Lung Volume Reduction: Quantitative Image Analysis.

Purpose To evaluate whether bronchoscopic lung volume reduction (BLVR) increases ventilation and therefore improves ventilation-perfusion (V/Q) mismatch. Materials and Methods All patients provided written informed consent to be included in this study, which was approved by the Institutional Review Board (2013-0368) of Asan Medical Center. The physiologic changes that occurred after BLVR were measured by using xenon-enhanced ventilation and iodine-enhanced perfusion dual-energy computed tomography (CT). Patients with severe emphysema plus hyperinflation who did not respond to usual treatments were eligible. Pulmonary function tests, the 6-minute walking distance (6MWD) test, quality of life assessment, and dual-energy CT were performed at baseline and 3 months after BLVR. The effect of BLVR was assessed with repeated-measures analysis of variance. Results Twenty-one patients were enrolled in this study (median age, 68 years; mean forced expiratory volume in 1 second [FEV1], 0.75 L ± 0.29). After BLVR, FEV1 (P < .001) and 6MWD (P = .002) improved significantly. Despite the reduction in lung volume (-0.39 L ± 0.44), both ventilation per voxel (P < .001) and total ventilation (P = .01) improved after BLVR. However, neither perfusion per voxel (P = .16) nor total perfusion changed significantly (P = .49). Patients with lung volume reduction of 50% or greater had significantly better improvement in FEV1 (P = .02) and ventilation per voxel (P = .03) than patients with lung volume reduction of less than 50%. V/Q mismatch also improved after BLVR (P = .005), mainly owing to the improvement in ventilation. Conclusion The dual-energy CT analyses showed that BLVR improved ventilation and V/Q mismatch. This increased lung efficiency may be the primary mechanism of improvement after BLVR, despite the reduction in lung volume. © RSNA, 2017 Online supplemental material is available for this article.

Fluorescent incisionless cholangiography as a teaching tool for identification of Calot's triangle.

BACKGROUND: Intraoperative incisionless fluorescent cholangiogram (IOIFC) has been demonstrated to be a useful tool to increase the visualization of Calot's triangle. This study evaluates the identification of extrahepatic biliary structures with IOIFC by medical students and surgery residents. METHODS: Two pictures were taken, one with xenon light and one with near-infrared (NIR) light, at the same stage during dissection of Calot's triangle in ten different cases of laparoscopic cholecystectomy (LC). All twenty pictures were organized in a random fashion to remove any imagery bias. Twenty students and twenty residents were asked to identify the biliary anatomy. RESULTS: Medical students were able to accurately identify the cystic duct on an average 33.8 % under the xenon light versus 86 % under NIR light (p = 0.0001), the common hepatic duct (CHD) on an average 19 % under the xenon light versus 88.5 % under NIR light (p = 0.0001), and the junction on an average 24 % under xenon light versus 80.5 % under NIR light (p = 0.0001). Surgery residents were able to accurately identify the cystic duct on an average 40 % under the xenon light versus 99 % under NIR light (p = 0.0001), the CHD on an average 35 % under the xenon light versus 96 % under NIR light (p = 0.0001), and the junction on an average 24 % under the xenon light versus 95.5 % under NIR light (p = 0.0001). CONCLUSIONS: IOIFC increases the visualization of Calot's triangle structures when compared to xenon light. IOIFC may be a useful teaching tool in residency programs to teach LC.

Preclinical neuroprotective actions of xenon and possible implications for human therapeutics: a narrative review.

PURPOSE: The purpose of this report is to facilitate an understanding of the possible application of xenon for neuroprotection in critical care settings. This narrative review appraises the literature assessing the efficacy and safety of xenon in preclinical models of acute ongoing neurologic injury. SOURCE: Databases of the published literature (MEDLINE® and EMBASE™) were appraised for peer-reviewed manuscripts addressing the use of xenon in both preclinical models and disease states of acute ongoing neurologic injury. For randomized clinical trials not yet reported, the investigators' declarations in the National Institutes of Health clinical trials website were considered. PRINCIPAL FINDINGS: While not a primary focus of this review, to date, xenon cannot be distinguished as superior for surgical anesthesia over existing alternatives in adults. Nevertheless, studies in a variety of preclinical disease models from multiple laboratories have consistently shown xenon's neuroprotective properties. These properties are enhanced in settings where xenon is combined with hypothermia. Small randomized clinical trials are underway to explore xenon's efficacy and safety in clinical settings of acute neurologic injury where hypothermia is the current standard of care. CONCLUSION: According to the evidence to date, the neuroprotective efficacy of xenon in preclinical models and its safety in clinical anesthesia set the stage for the launch of randomized clinical trials to determine whether these encouraging neuroprotective findings can be translated into clinical utility.

Moderate hypothermia within 6 h of birth plus inhaled xenon versus moderate hypothermia alone after birth asphyxia (TOBY-Xe): a proof-of-concept, open-label, randomised controlled trial.

BACKGROUND: Moderate cooling after birth asphyxia is associated with substantial reductions in death and disability, but additional therapies might provide further benefit. We assessed whether the addition of xenon gas, a promising novel therapy, after the initiation of hypothermia for birth asphyxia would result in further improvement. METHODS: Total Body hypothermia plus Xenon (TOBY-Xe) was a proof-of-concept, randomised, open-label, parallel-group trial done at four intensive-care neonatal units in the UK. Eligible infants were 36-43 weeks of gestational age, had signs of moderate to severe encephalopathy and moderately or severely abnormal background activity for at least 30 min or seizures as shown by amplitude-integrated EEG (aEEG), and had one of the following: Apgar score of 5 or less 10 min after birth, continued need for resuscitation 10 min after birth, or acidosis within 1 h of birth. Participants were allocated in a 1:1 ratio by use of a secure web-based computer-generated randomisation sequence within 12 h of birth to cooling to a rectal temperature of 33·5°C for 72 h (standard treatment) or to cooling in combination with 30% inhaled xenon for 24 h started immediately after randomisation. The primary outcomes were reduction in lactate to N-acetyl aspartate ratio in the thalamus and in preserved fractional anisotropy in the posterior limb of the internal capsule, measured with magnetic resonance spectroscopy and MRI, respectively, within 15 days of birth. The investigator assessing these outcomes was masked to allocation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00934700, and with ISRCTN, as ISRCTN08886155. FINDINGS: The study was done from Jan 31, 2012, to Sept 30, 2014. We enrolled 92 infants, 46 of whom were randomly assigned to cooling only and 46 to xenon plus cooling. 37 infants in the cooling only group and 41 in the cooling plus xenon group underwent magnetic resonance assessments and were included in the analysis of the primary outcomes. We noted no significant differences in lactate to N-acetyl aspartate ratio in the thalamus (geometric mean ratio 1·09, 95% CI 0·90 to 1·32) or fractional anisotropy (mean difference -0·01, 95% CI -0·03 to 0·02) in the posterior limb of the internal capsule between the two groups. Nine infants died in the cooling group and 11 in the xenon group. Two adverse events were reported in the xenon group: subcutaneous fat necrosis and transient desaturation during the MRI. No serious adverse events were recorded. INTERPRETATION: Administration of xenon within the delayed timeframe used in this trial is feasible and apparently safe, but is unlikely to enhance the neuroprotective effect of cooling after birth asphyxia. FUNDING: UK Medical Research Council.

Method for the assessment of effects of a range of wavelengths and intensities of red/near-infrared light therapy on oxidative stress in vitro.

Red/near-infrared light therapy (R/NIR-LT), delivered by laser or light emitting diode (LED), improves functional and morphological outcomes in a range of central nervous system injuries in vivo, possibly by reducing oxidative stress. However, effects of R/NIR-LT on oxidative stress have been shown to vary depending on wavelength or intensity of irradiation. Studies comparing treatment parameters are lacking, due to absence of commercially available devices that deliver multiple wavelengths or intensities, suitable for high through-put in vitro optimization studies. This protocol describes a technique for delivery of light at a range of wavelengths and intensities to optimize therapeutic doses required for a given injury model. We hypothesized that a method of delivering light, in which wavelength and intensity parameters could easily be altered, could facilitate determination of an optimal dose of R/NIR-LT for reducing reactive oxygen species (ROS) in vitro. Non-coherent Xenon light was filtered through narrow-band interference filters to deliver varying wavelengths (center wavelengths of 440, 550, 670 and 810 nm) and fluences (8.5x10(-3) to 3.8x10(-1) J/cm2) of light to cultured cells. Light output from the apparatus was calibrated to emit therapeutically relevant, equal quantal doses of light at each wavelength. Reactive species were detected in glutamate stressed cells treated with the light, using DCFH-DA and H2O2 sensitive fluorescent dyes. We successfully delivered light at a range of physiologically and therapeutically relevant wavelengths and intensities, to cultured cells exposed to glutamate as a model of CNS injury. While the fluences of R/NIR-LT used in the current study did not exert an effect on ROS generated by the cultured cells, the method of light delivery is applicable to other systems including isolated mitochondria or more physiologically relevant organotypic slice culture models, and could be used to assess effects on a range of outcome measures of oxidative metabolism.

Impact of Hyperpolarization-activated, Cyclic Nucleotide-gated Cation Channel Type 2 for the Xenon-mediated Anesthetic Effect: Evidence from In Vitro and In Vivo Experiments.

BACKGROUND: The thalamus is thought to be crucially involved in the anesthetic state. Here, we investigated the effect of the inhaled anesthetic xenon on stimulus-evoked thalamocortical network activity and on excitability of thalamocortical neurons. Because hyperpolarization-activated, cyclic nucleotide-gated cation (HCN) channels are key regulators of neuronal excitability in the thalamus, the effect of xenon on HCN channels was examined. METHODS: The effects of xenon on thalamocortical network activity were investigated in acutely prepared brain slices from adult wild-type and HCN2 knockout mice by means of voltage-sensitive dye imaging. The influence of xenon on single-cell excitability in brain slices was investigated using the whole-cell patch-clamp technique. Effects of xenon on HCN channels were verified in human embryonic kidney cells expressing HCN2 channels. RESULTS: Xenon concentration-dependently diminished thalamocortical signal propagation. In neurons, xenon reduced HCN channel-mediated Ih current amplitude by 33.4 ± 12.2% (at -133 mV; n = 7; P = 0.041) and caused a left-shift in the voltage of half-maximum activation (V1/2) from -98.8 ± 1.6 to -108.0 ± 4.2 mV (n = 8; P = 0.035). Similar effects were seen in human embryonic kidney cells. The impairment of HCN channel function was negligible when intracellular cyclic adenosine monophosphate level was increased. Using HCN2 mice, we could demonstrate that xenon did neither attenuate in vitro thalamocortical signal propagation nor did it show sedating effects in vivo. CONCLUSIONS: Here, we clearly showed that xenon impairs HCN2 channel function, and this impairment is dependent on intracellular cyclic adenosine monophosphate levels. We provide evidence that this effect reduces thalamocortical signal propagation and probably contributes to the hypnotic properties of xenon.

Early treatment with xenon protects against the cold ischemia associated with chronic allograft nephropathy in rats.

Chronic allograft nephropathy (CAN) is a common finding in kidney grafts with functional impairment. Prolonged hypothermic storage-induced ischemia-reperfusion injury is associated with the early onset of CAN. As the noble gas xenon is clinically used as an anesthetic and has renoprotective properties in a rodent model of ischemia-reperfusion injury, we studied whether early treatment with xenon could attenuate CAN associated with prolonged hypothermic storage. Exposure to xenon enhanced the expression of insulin growth factor-1 (IGF-1) and its receptor in human proximal tubular (HK-2) cells, which, in turn, increased cell proliferation. Xenon treatment before or after hypothermia-hypoxia decreased cell apoptosis and cell inflammation after reoxygenation. The xenon-induced HK-2 cell proliferation was abolished by blocking the IGF-1 receptor, mTOR, and HIF-1α individually. In the Fischer-to-Lewis rat allogeneic renal transplantation model, xenon exposure of donors before graft retrieval or recipients after engraftment enhanced tubular cell proliferation and decreased tubular cell death and cell inflammation associated with ischemia-reperfusion injury. Compared with control allografts, xenon treatment significantly suppressed T-cell infiltration and fibrosis, prevented the development of CAN, and improved renal function. Thus, xenon treatment promoted recovery from ischemia-reperfusion injury and reduced susceptibility to the subsequent development of CAN in allografts.

[Xenon light therapy].

The xenon light, generated by high-intensity electrical stimulation of xenon gas, is used to sterilize wounds, aid tissue repair, and relieve pain as a low-level light therapy. The light produced consists of non-coherent beams of multiple wavelengths in the ultraviolet to infrared spectrum. This broad-band light can be emitted in a continuous wave or pulsed mode, with the wave band chosen and the energy distribution controlled for the purpose. Specifically, wavelengths in the 500-700 nm range are suitable for treating superficial tissue, and wavelengths between 800 and 1,000 nm are suitable for deeper-seated tissues, due to longer optical penetration distances through tissue. One of the most common benefits in the xenon light therapy is considered to be the wide and deep irradiation of optimal rays to living tissue. Research into the use of xenon light for tissue repair and pain reduction is restricted within open-label studies and case reports. The present review expounded the effects of xenon light therapy on the basis of the available evidence in vitro and in vivo studies using a laser beam of single wavelength.

[Concept of mechanisms of anesthetic and therapeutic properties of xenon].

The molecular theory of L. Poling is a genius example of scientific prediction, made in the middle of 20th century, when the studies about clathrates and methods of roentgen structured analysis were doing their first steps. The views expressed in this message are some additions on the structure of xenon clathrates, function-free xenon water associates and the use of cameras in the liberated associates of the water molecules, for the process of supramolecular detoxification and attempts to develop this theory more widely, to better understand the mechanisms of xenon anesthesia and treatment for further justification of its therapeutic features as well as for the use of other inert gases (Ar, Kr) in modern medicine.

Effective thermal penetration depth in photo-irradiated ex vivo human tissues.

OBJECTIVE: In this work, a model of bioheat distribution is discussed for ex vivo human tissue samples, and the thermal penetration depth measurements performed on several tissues are presented. BACKGROUND DATA: Optical radiation is widely applied in the treatment and diagnosis of different pathologies. A power density of incident light at 100 mW/cm(2) is sufficiently high enough to induce a temperature increase of >5°C in irradiated human tissue. In this case, knowledge of the thermal properties of the tissue is needed to achieve a better understanding of the therapeutic effects. METHOD: The application of the diffusion approximation of the radiative transfer equation for the distribution of optical radiation, the experimental setup, and the results thereof are presented and discussed. RESULTS: The effective thermal penetration depth in the studied tissues has been determined to be in the range of 4.3-7.0 mm. CONCLUSIONS: The effective thermal penetration depth has been defined, and this could be useful for developing models to describe the thermal effects with a separate analysis of the tissue itself and the blood that irrigates it.

Hypoperfusion in the acute phase of subarachnoid hemorrhage.

PURPOSE: Acute disruption of cerebral perfusion and metabolism is a well-established hallmark of the immediate phase after subarachnoid hemorrhage (SAH). It is thought to contribute significantly to acute brain injury, but despite its prognostic importance, the exact mechanism and time course is largely unknown and remains to be characterized. METHODS: We investigated changes in cerebral perfusion after SAH in both an experimental and clinical setting. Using an animal model of massive, experimental SAH (n=91), we employed Laser-Doppler flowmetry (LDF), parenchymal microdialysis (MD; n=61), Diffusion-weighted imaging (DWI) and MR spectroscopy (MRS; n=30) to characterize the first hours after SAH in greater detail. The effect of prophylactic treatment with hypothermia (HT; 32°C) and an endothelin-A (ET-A) receptor antagonist (Clazosentan) was also studied. In a group of patients presenting with acute SAH (n=17) we were able to determine cerebral blood flow (CBF) via Xenon-enhanced computed tomography (XeCT) within 12 h after the ictus. RESULTS: The acute phase after SAH is characterized both experimentally and clinically by profound and prolonged hypoperfusion independent from current intracranial pressure (ICP), indicating acute vasospasm. Experimentally, when treated with hypothermia or a ET-A receptor antagonist prophylactically, acute hypoperfusion improved rapidly. DWI showed a generalized, significant decline of the apparent diffusion coefficient (ADC) after SAH, indicating cytotoxic edema which was not present under hypothermia. SAH causes a highly significant reduction in glucose, as well as accumulation of lactate, glutmate and aspartate (MD and MRS). HT significantly ameliorated these metabolic disturbances. CONCLUSION: Acute vasospasm, cytotoxic edema and a general metabolic stress response occur immediately after experimental SAH. Prophylactic treatment with hypothermia or ET-A antagonists can correct these disturbances in the experimental setting. Clinically, prolonged and ICP-independent hypoperfusion was also confirmed. As the initial phase is of particular importance regarding the neurological outcome and is amenable to beneficial intervention, the acute stage after SAH demands further investigation and warrants the exploration of measures to improve the immediate management of SAH patients.

Competitive inhibition at the glycine site of the N-methyl-D-aspartate receptor mediates xenon neuroprotection against hypoxia-ischemia.

BACKGROUND: The general anesthetic gas xenon is neuroprotective and is undergoing clinical trials as a treatment for ischemic brain injury. A small number of molecular targets for xenon have been identified, the N-methyl-D-aspartate (NMDA) receptor, the two-pore-domain potassium channel TREK-1, and the adenosine triphosphate-sensitive potassium channel (KATP). However, which of these targets are relevant to acute xenon neuroprotection is not known. Xenon inhibits NMDA receptors by competing with glycine at the glycine-binding site. We test the hypothesis that inhibition of the NMDA receptor at the glycine site underlies xenon neuroprotection against hypoxia-ischemia. METHODS: We use an in vitro model of hypoxia-ischemia to investigate the mechanism of xenon neuroprotection. Organotypic hippocampal brain slices from mice are subjected to oxygen-glucose deprivation, and injury is quantified by propidium iodide fluorescence. RESULTS: We show that 50% atm xenon is neuroprotective against hypoxia-ischemia when applied immediately after injury or after a delay of 3 h after injury. To validate our method, we show that neuroprotection by gavestinel is abolished when glycine is added, confirming that NMDA receptor glycine site antagonism underlies gavestinel neuroprotection. We then show that adding glycine abolishes the neuroprotective effect of xenon, consistent with competitive inhibition at the NMDA receptor glycine site mediating xenon neuroprotection. CONCLUSIONS: We show that xenon neuroprotection against hypoxia- ischemia can be reversed by increasing the glycine concentration. This is consistent with competitive inhibition by xenon at the NMDA receptor glycine site, playing a significant role in xenon neuroprotection. This finding may have important implications for xenon's clinical use as an anesthetic and neuroprotectant.

Assessing the depth of hypnosis of xenon anaesthesia with the EEG.

Xenon was approved as an inhaled anaesthetic in Germany in 2005 and in other countries of the European Union in 2007. Owing to its low blood/gas partition coefficient, xenons effects on the central nervous system show a fast onset and offset and, even after long xenon anaesthetics, the wake-up times are very short. The aim of this study was to examine which electroencephalogram (EEG) stages are reached during xenon application and whether these stages can be identified by an automatic EEG classification. Therefore, EEG recordings were performed during xenon anaesthetics (EEG monitor: Narcotrend®). A total of 300 EEG epochs were assessed visually with regard to the EEG stages. These epochs were also classified automatically by the EEG monitor Narcotrend® using multivariate algorithms. There was a high correlation between visual and automatic classification (Spearman's rank correlation coefficient r=0.957, prediction probability Pk=0.949). Furthermore, it was observed that very deep stages of hypnosis were reached which are characterised by EEG activity in the low frequency range (delta waves). The burst suppression pattern was not seen. In deep hypnosis, in contrast to the xenon EEG, the propofol EEG was characterised by a marked superimposed higher frequency activity. To ensure an optimised dosage for the single patient, anaesthetic machines for xenon should be combined with EEG monitoring. To date, only a few anaesthetic machines for xenon are available. Because of the high price of xenon, new and further developments of machines focus on optimizing xenon consumption.

Collision-induced dissociation of II-VI semiconductor nanocrystal precursors, Cd2+ and Zn2+ complexes with trioctylphosphine oxide, sulfide, and selenide.

The metal (M = Cd2+ and Zn2+) complexes with trioctylphosphine chalcogenide (TOPE, E = O, S, and Se) are prepared by electrospray ionization, and their relative stabilities and intramolecular reactions are studied by collision-induced dissociation (CID) with Xe under single collision conditions. These metal-TOPE complexes are considered as molecular precursors for the colloidal synthesis of II-VI compound semiconductor nanocrystals employing TOPO as a metal-coordinating solvent and TOPS or TOPSe as a chalcogen precursor. Of the various [M + nTOPE]2+ (n = 2-7) ions generated by ESI, the n = 2-4 complexes are characterized by CID as a function of collision energy. The collision energy at 50% dissociation (E50%) is determined from the cracking curve and the relative stabilities of the complexes are established. Between the two metal ions, the zinc-TOPE complexes are more stable than the cadmium-TOPE complexes when n = 2-3, whereas their stabilities are reversed when n = 4. Of the TOPE, TOPO binds most strongly to the metal ion, while TOPSe does most weakly. Upon CID, loss of TOPE occurs exclusively from the tetra-TOPE complexes, while extensive fragmentation of TOPE takes place from the di-TOPE complexes, showing the signature of the metal chacogenide formation. The nucleation of nanocrystals appears to begin with cracking of [M + 2TOPE]2+ (E = S and Se).

Xenon preconditioning: the role of prosurvival signaling, mitochondrial permeability transition and bioenergetics in rats.

BACKGROUND: Similar to volatile anesthetics, the anesthetic noble gas xenon protects the heart from ischemia/reperfusion injury, but the mechanisms responsible for this phenomenon are not fully understood. We tested the hypothesis that xenon-induced cardioprotection is mediated by prosurvival signaling kinases that target mitochondria. METHODS: Male Wistar rats instrumented for hemodynamic measurements were subjected to a 30 min left anterior descending coronary artery occlusion and 2 h reperfusion. Rats were randomly assigned to receive 70% nitrogen/30% oxygen (control) or three 5-min cycles of 70% xenon/30% oxygen interspersed with the oxygen/nitrogen mixture administered for 5 min followed by a 15 min memory period. Myocardial infarct size was measured using triphenyltetrazolium staining. Additional hearts from control and xenon-pretreated rats were excised for Western blotting of Akt and glycogen synthase kinase 3 beta (GSK-3beta) phosphorylation and isolation of mitochondria. Mitochondrial oxygen consumption before and after hypoxia/reoxygenation and mitochondrial permeability transition pore opening were determined. RESULTS: Xenon significantly (P < 0.05) reduced myocardial infarct size compared with control (32 +/- 4 and 59% +/- 4% of the left ventricular area at risk; mean +/- sd) and enhanced phosphorylation of Akt and GSK-3beta. Xenon pretreatment preserved state 3 respiration of isolated mitochondria compared with the results obtained in the absence of the gas. The Ca(2+) concentration required to induce mitochondrial membrane depolarization was larger in the presence compared with the absence of xenon pretreatment (78 +/- 17 and 56 +/- 17 microM, respectively). The phosphoinositol-3-kinase-kinase inhibitor wortmannin blocked the effect of xenon on infarct size and respiration. CONCLUSIONS: These results indicate that xenon preconditioning reduces myocardial infarct size, phosphorylates Akt, and GSK-3beta, preserves mitochondrial function, and inhibits Ca(2+)-induced mitochondrial permeability transition pore opening. These data suggest that xenon-induced cardioprotection occurs because of activation of prosurvival signaling that targets mitochondria and renders them less vulnerable to ischemia-reperfusion injury.