Xenon is neuroprotective against oxygen deprivation and has been used to prevent brain damage in extremely premature babies. Freezing of gait: a practical approach to management. performed the behavioral experiments in rodents and nonhuman primates, analyzed the data, and wrote the behavioral section. By clicking Accept All," you consent to our site providing you with a personalized service. Last, we studied the effect of xenon inhalation on axial gait and posture deficits in a primate model of PD with levodopainduced dyskinesia. We even observed a trend toward an increase in good ontime (Supplementary Fig. Jrme Baufreton, Tomislav Milekovic, and Qin Li PhD are cofirst authors. These findings open a concrete and safe therapeutic strategy for addressing LID and parkinsonian locomotor symptoms. Top things to do in Da Nang. . Phone: +971 4 429 5853 e-mail: info@lenntech.com, Copyright 1998-2022 Lenntech B.V. All rights reserved, Plant Inspection & Process Optimalisation, Separation and Concentration Purification Request. (Fig.1EF).1EF). Relieves an attack of migraine headaches. Xenon is already used as a human general anaesthetic, is known to have few side effects and could be easily given via inhalation or to mechanically ventilated TBI patients in the intensive care unit. The gas may also help erase traumatic memories. ), China Science Fund (E.B. Drug class: Diagnostic radiopharmaceuticals. Information from 07:30h to 15:30h Objective/Rationale: Levodopa is the most effective drug to treat symptoms of Parkinson's disease, however long-term use leads to disabling levodopa-induced dyskinesia (LID) in the vast majority of patients. (B) Stick diagram decomposition of leg movements and pelvic movements viewed from the lateral aspect (top) and from above (bottom), respectively. Xenon gas doesn't cause allergies, doesn't affect immune system, blood coagulation or neuroendocrinal status. Available for Android and iOS devices. We then trained these monkeys to walk along a straight corridor without any constraints (Fig. The effects of Xenon gas inhalation on neuropathology in a placentalinduced brain injury model in neonates: A pilot study. The latter hormone is known to increase red blood cell production and athletic performance. (Fig.1A1A and Supplementary Fig. The site is secure. Moreover, xenon exposure significantly reduced the magnitude of HFSinduced longterm potentiation (LTP) in dyskinetic mice (P<0.05; Fig. Healing Properties of Xenon Xenon Against Drug Addiction and Alcoholism, Positive Effect of Xenon Therapy: What Results Can be Achieved in the Treatment of Drug and Alcohol Addiction, The Benefits of Xenon Therapy in the Addiction Detox. Nieuwboer A. Morin S, J Highresolution kinematic recordings combined with objective statistical analyses confirmed the beneficial effects of xenon on gait and balance deficits. (A) Scheme depicting the experimental procedures for ex vivo electrophysiology. Later judgment becomes faulty and all sensations are depressed. To quantify glutamatergic corticostriatal transmission, we measured the NMDA/amino3hydroxy5methyl4isoxazolepropionic acid (AMPA) ratios of amplitudes of evoked excitatory postsynaptic currents (EPSCs) mediated by either receptor in SPNs. Plotkin JL, official website and that any information you provide is encrypted A special aspect of this treatment is the reduction of cravings for drugs and alcohol, as well as the decrease of withdrawal symptoms. Interestingly, it is also found in Mars' atmosphere at 0.08 ppm. Borton D, et al. Friedli L, The effects of 30% and 60% xenon inhalation on pial vessel diameter and intracranial pressure in rabbits. S6C), that is, more time spent without troublesome dyskinesia interfering with normal daily activities, suggestive of an increased quality of life and an overall reduction of dyskinesia impact on daily activities. Distributieweg 3 2645 EG Delfgauw The Netherlands Phone: +31 152 610 900 fax: +31 152 616 289 e-mail: info@lenntech.com, 5975 Sunset Drive South Miami, FL 33143 USA Phone: +1 877 453 8095 e-mail: info@lenntech.com, Level 6 - OFFICE #101-One JLT Tower Jumeirah Lake Towers Dubai - U.A.E. Open arrowheads and arrows indicate where AMPA and NMDA current amplitudes were measured, respectively (ratio xenon, 0.1630.014; n=30 neurons; ratio vehicle, 0.2570.021; n=34). Xenon therapy is carried out using a stationary anesthetic-respiratory apparatus. The dose was chosen based on previous experiments in pain26 and the knowledge that the anesthetic dose in rats is 161%.27 This dose decreased axial, limb, and orofacial (ALO) AIMs, with a peak effect at 30 and 60 minutes (P<0.01; Fig. Testing can detect the use of HIF stabilizers and activators. With a blood/gas partition coefficient of 0.115, xenon is the least soluble gas that may be used for anesthesia. 2,22=0.1586, P>0.05) and mean time on the rod ([F . *P<0.05, **P<0.01, t test. Due to its large atomic volume as a liquid, xenon is highly polarizable, and therefore, provides higher solubility and acts as an excellent solvent. The cost of one xenon inhalation at the VIP Vorobjev Clinic is 300 . It stops attacks of panic attacks. | Explore the latest full-text research PDFs, articles, conference papers, preprints and more on INHALATION. In spite of its high cost, its lack of side effects, safe cardiovascular and organoprotective profile and effective neuroprotective role after hypoxic-ischemic injury (HI) favor its applications in clinics. Palgen M, Xenon exposure significantly decreased LID both at the ldopa peak effect (90180 minutes; P<0.05; Fig. There are 2 main types of xenon: medical-grade and research-grade.Research grade xenon gas is slightly better but both of these contain very few impurities. Radiation Dose Estimates of Xenon Xe 133. For the 50% ldopa+xenon condition, dyskinetic movements became rare or even absent. The effect of a single session is intended to last for five days. Parkinson's disease motor symptoms are treated with levodopa, but longterm treatment leads to disabling dyskinesia. At the time of calibration, it contains no more than 0.3% Xenon Xe 133m, no more than 1.5% Xenon Xe 131m, no more than 0.06% Krypton Kr 85 and no more than 0.01% Iodine I 131, with no less than 99.9% total radioactivity as radioxenon. Gait disorders and balance disturbances in Parkinson's disease: clinical update and pathophysiology, Inhibition of Rasguanine nucleotidereleasing factor 1 (RasGRF1) signaling in the striatum reverts motor symptoms associated with Ldopainduced dyskinesia, LDOPA impairs proteasome activity in parkinsonism through D1 dopamine receptor. The suggested activity range of Xenon Xe 133 Gas employed for inhalation by the average adult patient (70 kg . ), Fondation de France (E.B. Inhaling the mixture of oxygen and xenon produces a hormone which helps to increase Red Blood Cell (RBC) production. BronteStewart H. Effect of medication and STNDBS on postural control in subjects with Parkinson's disease, Postural instability in Parkinson's disease, Selective loss of bidirectional synaptic plasticity in the direct and indirect striatal output pathways accompanies generation of parkinsonism and lDOPA induced dyskinesia in mouse models. These gait parameters capture the main spatiotemporal features of gait that are affected in individuals with PD.7 These results are in agreement with clinical observations that have shown that ldopa fails to consistently restore normal gait across individuals with PD.7. In turn, this property explains the restricted effects of gaseous or pharmacological manipulations of glutamatergic transmission in dyskinetic animals. It can dissolve many hydrocarbons, biomolecules, and even water. PMC legacy view Increases efficiency and improves overall well-being. Hallett M, Detailed experimental procedures are provided in the Supplementary Methods. Tambasco N, This therapy helps the patient quickly recover and escape the abuse and addiction cycle safely. Manchester, Ghiglieri V, about navigating our updated article layout. The effect of simple asphyxiant gases is proportional to the extent to which they diminish the amount (partial pressure) of oxygen in the air that is breathed. We are at your disposal for any additional information you need about the program of detoxification, treatment, rehabilitation, accommodation or transport to our clinic. ), and LABEX Brain (E.B.). These improvements may include optimizing the timing of exposure visvis ldopa administration and evaluating the impact of chronic versus acute exposure. Xenon manipulates the chemical balance in the brain, fighting the substance addiction withdrawal symptoms and boosting overall health. PubMed CrossRef. Address:5555 Tech Center Drive, Suite 200,Colorado Springs, CO, 80919. Administration. Hydrogen sulfide is particularly insidious because an early effect of the gas is to paralyze the olfactory nerves increasing the danger of toxic dosages. [Color figure can be viewed at http://wileyonlinelibrary.com]. Katz I, Fox SH, Bloem BR. Lausanne, Picconi B. Hyperkinetic disorders and loss of synaptic downscaling. Xenon is an elemental gas best known for its use in lighting products and various medical procedures. The amount of dopamine release also differs between nondyskinetic and dyskinetic animals. Although various NMDA antagonists such as dextromethorphan, remacemide, milacemide, CP101,606, and memantine have been assessed for treating LID, their success has been limited.1 Only amantadine exhibited modest antidyskinetic effects in the goldstandard NHP models of LID prior to evaluation in patients.1 Athome distribution of a gaseous therapeutic is already taking place for several indications, with millions of patients receiving gasbased home care throughout the world. Three important results emerged from these studies. For Diagnostic Use. Gait patterns are recorded using a highspeed motion capture system. This xenonmediated reduction of the NMDA/AMPA ratio was observed both in the direct SPN pathway and in the indirect SPN pathway of dyskinetic mice (Supplementary Fig. (Fig.44A). Persons who survive acute poisoning may require months of recuperation characterized by fatigue, headache, lack of initiative, irritability, and loss of equilibrium. France. McDonald JC, Find patient medical information for xenon-133 in air inhalation on WebMD including its uses, side effects and safety, interactions, pictures, warnings and user ratings. E.B. This may be administered as a bolus into the tubing near the patient's mouthpiece or mask after the completion of a tidal exhalation, or by rebreathing for a period of approximately 5 minutes of the Xenon Xe 133 Gas in equilibrium with the air contained in the closed system at concentrations of the radionuclide that may vary from 37 to 222 megabecquerels (1.0 to 6.0 millicuries) per liter. Inhalation in . Scales in E are the same as C. *P<0.05, unpaired t test. Bloem BR, Nutt JG, Air Liquide Healthcare, ParisSaclay research center, The conditions 100% ldopa dose followed by vehicle inhalation (2 steps) and 50% ldopa dose followed by xenon inhalation (1 step) are shown for monkey S3. This website uses cookies to improve your experience while you navigate through the website. Choose USADA Program Highlight: UFC Anti-Doping Program. (Fig.2B).2B). Thus, xenon reestablishes physiological properties of striatal projecting neurons that do not differ from those of nondyskinetic animals. Meissner W, We compared the effects of 1hour inhalation of xenon (50% Xe/50% O2) with vehicle gas (50% N2/50% O2) following administration of a suboptimal (50%) tailored dose of ldopa (Fig. | Find, read and cite all the research . Table 5. Avoiding any kind of drinks one hour before xenon inhalation. (Fig.5).5). The doctor recommends an average of 3-10 procedures based on the amount of substances in the body. (Fig.3A)3A) and second dyskinetic by chronic ldopa exposure (Fig. (B) Representative stick diagram decomposition of hindlimb movements (left column) and traces of key gait variables (right column) for 3 ldopa doses (0%, 50%, and 100%) followed by 1 hour of vehicle gas inhalation (50% N2, 50% O2). The element also has a number of well-established uses, from acting as a neutron absorber in nuclear reactors to applications in astronomy research and anesthesia. sharing sensitive information, make sure youre on a federal We conducted preliminary tests to calibrate different parameters of xenon gas exposure for the treatment of dyskinesia, which included (1) the effects of varied gas exposure times (15, 30, and 60 minutes) and (2) the effects of varied gas concentrations (50%, 35%, and 20% xenon mixed with 50%, 65 %, and 80 % O 2, respectively) of acute xenon . It is not cancerogenic or cardiodepressant. JouyenJosas, Giladi N. Falls and freezing of gait in Parkinson's disease: a review of two interconnected, episodic phenomena, Gait disorders in parkinsonian monkeys with pedunculopontine nucleus lesions: a tale of two systems. Package insert / prescribing information Xenon, an inert gas that has been used in the clinics, hardly participates in any chemical reaction and does not undergo biological transformation in vivo. These results encouraged us to quantitatively study the effect of xenon alone or in combination with ldopa on gait and balance deficits. They illuminate road signs and markings better than conventional lights. Funding agencies: This work was supported by Air Liquide Sant International, in part with a grant received from the Michael J. Xenon Xe 133 Gas may also be applied to assessment of cerebral flow. The recommendations will vary based on each individual drug and alcohol diagnosis and your health status. Inhalation is done using a special device that mixes the xenon with oxygen. Picconi B, Xenon is a narcotic gas because of its physical and chemical properties. Universit de Bordeaux, Institut Interdisciplinaires des Neurosciences, The only commercial source of xenon is from industrial liquid-air plants. are employees of Air Liquide Sant International. Table 5. 4 In rat models of HI brain injury, . (Fig.5B).5B). Xenon is a trace gas in the Earth's atmosphere, occurring in 1 part in 20 million. Avoiding being in direct sunlight during the day of the xenon procedure. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. It was regarded as completely inert until, in 1962, Neil Bartlett reported synthesis of xenon haxafluoroplatinate. Kirik D, Xenon Xe 133 is a readily diffusible gas which is neither utilized nor produced by the body. Professional therapist/doctor should only carry out this procedure to avoid death risks. Lundblad M, (Fig.22C,D). Xenon inhalation improves AIMs in dyskinetic rat during the first hour postexposure with similar amplitude as amantadine. Also, care should be taken to minimize radiation exposure to the patients consistent with proper patient management. All Rights Reserved. B, D, FI, values shown as meanstandard error. 70. We believe that further human studies with . In nondyskinetic mice, LFS reversed the depotentiation of corticostriatal synapses both in slices exposed to xenon and in vehicle (P<0.05; Fig. Data are reported as means. . FOIA Addictive disorders treatment clinic VIP Dr Vorobjev is designed as a place where in full comfort and pleasant surroundings and with top experts you can help yourself view life from a more beautiful perspective. Xenon is an element that has anesthetic, dissociative, neuroprotective, and performance enhancing effects. A concentration of 75% is fatal in a matter of minutes. S5D). [Color figure can be viewed at http://wileyonlinelibrary.com]. The safety profile of xenon, both on vital cardiorespiratory and toxicity parameters, has allowed for its market authorization in anesthesia. Xenon, a noble gas, works by inhibiting the N-methyl-D-aspartate receptors (NMDAR), which . Table 1 shows the effect of time on radionuclidic composition. ), IDEX Bordeaux (E.B. An official website of the United States government. The estimated absorbed radiation doses to an average patient (70 kg) for inhalation studies from a maximum dose of Xenon Xe 133 Gas in 5, 7.5 and 10 liters are shown in Table 5. Not eating two hours before the procedure. National Library of Medicine Consult state and local regulations regarding the proper disposal of this material. We then used these parameters in a principalcomponent (PC) analysis that allowed visualization of gait performance between experimental conditions.20 To quantify gait performance, we measured the Euclidean distance between MPTP monkeys and healthy monkeys in the space spanning all the computed gait parameters (Fig. Analg., 92, 1245 -50. ), MSA Coalition (E.B. Horak FB, There was also a significant therapeutic effect of xenon gas exposure over the entire 3hour observation period (P<0.05; Fig. Reese R, et al. Munneke M, The .gov means its official. Table 4. 2018 The Authors. It is contained within septum sealed glass vials and is suitable for inhalation in the diagnostic evaluation of pulmonary function and imaging, as well as assessment of cerebral blood flow. The oxygen may be diminished to 75% of it's normal percentage in air before appreciable symptoms develop. Doudnikoff E, Xenon gas acts as a dissociative when inhaled. Nonnekes J, Inhalation: This gas is inert and is classified as a simple asphyxiant. Patients at an advanced stage with severe dyskinesia uncontrolled by treatment or severe gait disorders (skewness, freezing) who may need a rescue therapy could take advantage of such an inhaled therapy. The xenonmediated antagonism against the NMDA receptor is nonselective for receptors containing either NR2A or NR2B subunits in the mouse amygdala. To learn more about the cookies we use, please read our Privacy and Cookie Policy. In addition, the experts recommended at least three doctor supervised xenon procedures to achieve a lasting and stable effect. Then, he breathes in the xenon and a. Conventions are the same as in Figure Figure4.4. Curium and the Curium logo are trademarks of a Curium company. Our addictions MDs, PhDs, and master's level specialists coordinate necessary care at every stage to help you break drug abuse addiction to start a new and normal life. It is a pleasant, relaxing procedure. Corticostriatal plasticity was studied in ldopatreated 6hydroxydopamine (6OHDA)lesioned bacterial artificial chromosome transgenic mice expressing enhanced green fluorescent protein (EGFP) under the control of the promoter for the dopamine receptor type 1 (D1R) (Drd1aEGFP; 000297MU/H), prepared as previously described.8, 9, 10 abnormal involuntary movement (AIMs) were scored using a 04 rating scale according to a validated rating system.8, 11 Electrophysiology on brain slices was conducted as described elsewhere.4, 12, The AIM model was prepared in male SpragueDawley rats (Charles River Laboratories) as previously described.13, 14, 15 The 4 AIM categories (axial, limb, and orolingual, hereafter referred to as ALO, and locomotive) were scored using a validated rating scale16, 25 by a trained investigator as previously described.13, 14, 15, We conducted the 1methyl4phenyl1,2,3,6tetrahydropyridine (MPTP) intoxication protocol, chronic ldopa treatment, and clinical assessments in 6 male macaques (Macaca mulatta, weight, 4.70.3kg; Xierxin, Beijing, PR of China), as previously published.8, 10, 13, 15, 17, 18, 19, Gait pattern assessments were performed in 4 dyskinetic parkinsonian and 6 healthy ablebodied macaques using a highspeed motion capture system (Simi Reality Motion Systems, Germany), combining 4 or 6 video cameras (100Hz) as previously described.20, 21, 22. A full ldopa dose led to an immediate reduction of gait deficits in all 4 MPTP monkeys. The beginning of this procedure starts with a conversation with a professional therapist who can perfectly answer all the patient's questions and help the patient receive the maximum effect. This in turn requires the presence of a simple asphyxiant in a concentration of 33% in the mixture of air and gas. Xenon Xe 133 Gas is available in 2 milliliter vials with color-coded labels in 370 megabecquerel (10 millicurie; Catalog No. Xenon not only reduces the undesired effects of ldopa, but also alleviates locomotor deficits. S6D). Study Scheme (A).Plasma level of TNF- (B) and IL-6 (C) were measured 6 h after LPS injection plus gas exposure (n = 10 in group Con, LPS + Xe and Xe; n = 6 in group LPS). M.C. Importantly, xenon alleviated LID without compromising the symptomatic benefit of ldopa treatment, both in rat and NHP models. (Fig.2G,H),2G,H), showing that such concentration was not sedatng. Hallett PJ, Timedependent measurements of monoamine levels revealed that this effect was essentially linked to elevated dopamine levels in the striatum following the last ldopa injection, as opposed to a fundamental change in plasticity signaling machinery.10 Several lines of evidence associated this aberrant potentiation of glutamatergic synapses from striatal projecting neurons with a dopamine D1 receptordependent central feature of the LID pathophysiology.1 Drugnaive and ldopatreated mice that do not develop dyskinesia differ from ldopatreated dyskinetic mice in the spatiotemporal distribution of D1 receptor stimulation. The extreme cold temperature (-244oC) will freeze organisms on contact, but no long term ecological effects are anticipated. (C) Bar plots showing changes in the mean Euclidean distance between all gait cycles in a given condition and the average gait cycle of all healthy monkeys. Flashpoints: Not applicable 11. Each session takes between 15-40 minutes. Xenon is a potent antiglutaminergic agent that has been used as an anesthetic with minimal side effects, has neuroprotective effects consistent with antidepressants and has the potential to be a novel antidepressant drug. Xenon is an elemental gas that is reported to produce psychoactive effects upon inhalation. It is supplied in vials containing either 370 or 740 megabecquerels (10 or 20 millicuries) of Xenon Xe 133 Gas in 2 milliliters of carrier xenon and atmospheric air. S4GL), suggesting that corticostriatal transmission and plasticity were not altered in nondyskinetic mice. Fig.3C,D).3C,D). Inhalation in excessive concentrations can result in dizziness, nausea, vomiting, loss of consciousness, and death. Inhaling xenon significantly improved gait performance, enabling both monkeys to produce locomotor movements that closely resembled those recorded in healthy monkeys (Fig. (Fig.1GI1GI and Supplementary Fig. 72.Bedi A, Murray JM, Dingley J, et al. Before Symptoms: The first symptoms produced by a simple asphyxiant are rapid respirations and air hunger. designed the research and analyzed the data. (A) Recordings of wholebody kinematics during locomotion along a runway. During xenon therapy, xenon gas is inhaled and reaches the patient's brain within minutes. The therapy is approved to effectively fight the addiction via reducing the psychological and physical dependence on alcohol and drugs. Centre National de la Recherche Scientifique Unit Mixte de Recherche 5297, Institut Interdisciplinaires des Neurosciences, NMDA receptor antagonists have been shown to be efficacious in reducing LID in pre-clinical and clinical models. Because the noble gas xenon inhibits excitatory glutamatergic signaling, primarily through allosteric antagonism of the Nmethyldaspartate receptors, we aimed to test its putative antidyskinetic capabilities. (Fig.22A).13, 14, 15, 17, 24 We assessed the effects of xenon inhalation (50% Xe/50% O2) for 30 minutes on the behavioral response to ldopa in the 6OHDAlesioned rats (Fig. To refute this possibility, we evaluated the impact of inhaling krypton, argon, or neon noble gases on AIM severity in the ldopatreated 6OHDAlesioned rats (Supplementary Fig. Improves mood and provides emotional lift. Xenon has been used as an anesthetic, and may have side effects such as hypertension and nausea and vomiting in a significant number of individuals. Bordeaux, Barraud Q, et al. Radiation Dose Estimates of Xenon Xe 1332: Absorbed Dose per 1110 megabecquerels (30 millicuries) of Xenon Xe 133 Gas Administered by Inhalation. ), COEN (E.B. Error barsSEM. (Fig.5B).5B). Specifically, S4 did not exhibit improvement of gait features following ldopa administration. S5B), locomotor activity (Supplementary Fig. Yet the pharmacological agents used in these studies are not safe for clinical practice. During the inhalation process, the patients feel mental and physical comfort, positive emotions, tranquility, and peace. Xenon Xe 133 Gas is a diagnostic agent used to evaluate pulmonary function and to image the lungs. (Fig.3E,F).3E,F). However, parkinsonian animals generally exhibit 2 types of responses to ldopa treatment. The noble gas xenon is capable of inhibiting excitatory glutamatergic signaling through antagonism of NMDA receptors.6 Here, we provide electrophysiological and behavioral evidence that supports the hypothesis that xenon gas exposure reverses LIDinducing abnormal corticostriatal plasticity and ameliorates LID in goldstandard rodent and primate models of PD and LID. Xenon Xe 133 Gas is chemically and physiologically similar to elemental xenon, a non . Anesth. Med., 21:459-465,1980. For example, the use of 0.2 cm of Pb will decrease the external radiation exposure by a factor of about 1000. We then evaluated the behavioral effects of xenon exposure on AIMs in the 6OHDAlesioned rat model of PD and dyskinesia (Fig. Getting high from gas fumes and other inhalants leads to many unwanted consequences because of the many adverse changes in the body from gas vapors. We thus verified the absence of sedation at the selected concentration (50% Xe/50% O2) by assessing subtle motor skills in 6OHDAlesioned rats. Pathophysiology of Ldopainduced motor and nonmotor complications in Parkinson's disease, Pathophysiology of levodopainduced dyskinesia: Potential for new therapies. 7During the past decade, it has received increasing study as an anesthetic agent with many attractive properties.Based on abstracts and reports in the literature, xenon has been shown to not alter voltage-gated ion channels in the myocardium, 8nor does it sensitize the myocardium to . Fig.4A).4A). Traces are normalized to the peak of AMPA currents. This has been reinforced since then by demonstration of safety in clinical trials on anesthesia of fragile patients36 and in critical care on neonates.37 Despite the relatively rapid blood washout on termination of inhalation therapy, xenon might be effective under chronic repeated dosing through affinity for lipophilic tissues.38 It is thus a candidate for a safe and reliable intervention at subanesthetic dosages to reduce LID. Data reported as mean. Side effects of xenon inhalation. Pharmacological validation of behavioral measures of akinesia and dyskinesia in a rat model of Parkinson's disease. Death may result from errors in judgment, confusion, or loss of consciousness which prevent self-rescue. Xenon is a rare atmospheric gas and as such is non-toxic and chemically inert. S6A) and (2) tended to reduce the dystonic form (Supplementary Fig. Fox SH, . Le Bris, and G. Dabe from the in vivo platform (PIV) for the nursing of rodents included in this study. Cerebral blood flow: 370-1110MBq (10-30mCi) in 3 liters of air. The other bar plots report average values for key parameters of gait (speed and stance duration) and posture (hip position) for the 3 experimental conditions. Alterations of striatal NMDA receptor subunits associated with the development of dyskinesia in the MPTPlesioned primate model of Parkinson's disease, Xenon anesthesia: a systematic review and metaanalysis of randomized controlled trials. Xenon is the chemical element, with the symbol Xe, which is an extreme and rare heavy gas of Group 18 (noble gases) of the periodic table. In comparison, the 50% ldopa+xenon condition successfully alleviated parkinsonian gait deficits (Fig. After the exam, the specialist will choose the volume and concentration of xenon gas depending on the individual parameters of the patient's age, gender, depth of the addiction, general conditions, and withdrawal symptoms. The minimum number of sessions is five. The steps in the 100% ldopa+vehicle condition showed a typical dyskinetic event (yellow sticks) and impaired balance, which is captured in the rightward offset of the foot positions compared with the hip. Lindgren H, The new PMC design is here! Xenon Xe 133 Gas delivery systems, i.e., respirators or spirometers, and associated tubing assemblies must be leakproof to avoid loss of radioactivity into the laboratory environs not specifically protected by exhaust systems. Motac Neuroscience, Xenon ((Main constituent) CAS-No.) When inhaled, the effects are similar to inhaling nitrous oxide. Altered pallidopallidal synaptic transmission leads to aberrant firing of globus pallidus neurons in a rat model of Parkinson's disease, PSD95 expression controls lDOPA dyskinesia through dopamine D1 receptor trafficking, The 3hydroxy3methylglutarylCoA reductase inhibitor lovastatin reduces severity of LDOPAinduced abnormal involuntary movements in experimental Parkinson's disease, Targeting betaarrestin2 in the treatment of LDOPAinduced dyskinesia in Parkinson's disease, LDOPAinduced dyskinesia in the rat is associated with striatal overexpression of prodynorphin and glutamic acid decarboxylase mRNA, Lentiviral overexpression of GRK6 alleviates Ldopainduced dyskinesia in experimental Parkinson's disease, Attenuation of levodopainduced dyskinesia by normalizing dopamine D3 receptor function, The mGluR5 negative allosteric modulator dipraglurant reduces dyskinesia in the MPTP macaque model. Federal government websites often end in .gov or .mil. We treated the monkeys with ldopa, exposed them to the vehicle or xenon gas mixture for 1 hour, and then recorded videos of their behavior over the following 4 hours. Fig.1C,D),1C,D), whereas the NMDA/AMPA ratio did not change significantly in nondyskinetic mice (Fig. Previous experimental strategies to alleviate LID did not investigate potential effects on gait and posture. 2 A). Analysis of the subtype of dyskinesia revealed that xenon inhalation (1) significantly reduced the choreic form (Supplementary Fig. Xenon mediated antidyskinetic effects whose amplitude matched the improvements mediated by amantadine (P<0.01; Fig. Bloem BR, Xenon is a noble gas that has an atomic number of 54 and an atomic mass of 131.3 g/mol. Death may result from errors in judgment, confusion, or loss of consciousness which prevent self-rescue. It has low toxicity and is not teratogenic. Inhalation of Xenon has been found to increase erythropoietin levels in healthy individuals, which, in turn, boosts their stamina and energy levels. Radiation Attenuation by Lead Shielding. 1981;5(4):591-592. Indeed, an evidencebased medicine review recommended the addition of amantadine, a multitarget drug that antagonizes the activity of NMDA to ldopa treatment to mitigate dyskinesia.5 Other drugs that target glutamatergic transmission with higher specificity have been evaluated in clinical tests, but they either failed to reduce LID or were not well tolerated.1. (D, F) Sum of dyskinesia and disability scores noted over the first 2 hours of behavioral observation. These effects make xenon treatment extremely useful in complex treatment of addictions. The respiration is suspended at the end of the inhalation for 15 seconds, while the first image is obtained. Ravenscroft P, *P<0.05, **P<0.01, ***P<0.001; Wilcoxon rank sum test. It is a beta emitter with a physical half-life of 5.2 days, a photopeak of 81 keV, and beta-decay. In S3, 50% ldopa treatment alleviated some of the gait deficits (namely, the hip forward position), but 100% ldopa treatment caused severe dyskinesia, which resulted in disturbed gait patterns. UKM15 6WE, Bethesda, MD 20894, Web Policies This degree of accuracy includes variations attributed to small differences in geometry and radiation attenuation between the NIST standard ampule and the Xenon Xe 133 Gas unit dose vial. Xenon therapy is a method used to treat cardiological and neurological diseases, along with drug and alcoholism addiction. It is used in photographic flash lamps, stroboscopic lamps, high-intensitive arc-lamps for motion picture projection and high-pressure arc lamps to product ultraviolet light (solar simulators). To correct for physical decay of this radionuclide, the fractions that remain at selected time intervals after the date of calibration are shown in Table 4. FIGURE 1.Xenon prevents LPS-caused acute systematic and neuronal inflammation in rat pups. Fox Foundation for Parkinson Research (E.B. Toxicological Information INHALATION: Xenon is high-pressure gas that can cause rapid suffocation. Dosage form: gas ), Medical Research Council (E.B. S6C), or in general motor activity following ldopa combined with xenon or vehicle gas treatment (Supplementary Fig. Xenon changes its phase from liquid to solid at a temperature of -111.5C, with a density of 3.640 grams per cubic centimetre. Hausdorff JM, The xenon inhalation sensation is like a "healing dream; however, the patient does not fully fall asleep; instead, he or she is immersed in a state of relaxation and rest, along with the feeling of bliss and lightness. The specific gamma ray constant for Xenon Xe 133 is 0.51 R/hr-mCi at 1 cm. S6). Bagetta V, (Fig.3A,C,D3A,C,D and see the Materials and Methods section).8, 10, 13, 15, 17, 18, Xenon inhalation improves dyskinesia in dyskinetic nonhuman primates without interfering with antiparkinsonian action of ldopa, with amplitude similar to amantadine. Bordeaux, Immediately after xenon therapy, the patient may note a feeling of mood lift, lightness, and an increase in working ability. Colored arrows illustrate the changes of gait patterns observed following 100% ldopa and 50% ldopa+xenon treatments. Safety and effectiveness in pediatric patients have not been established. The clinic is very comfortable, I would recommend this center for a visit., Hyperbaric Oxygen Therapy (HBOT) in Drug Addiction and Alcoholism Treatment, Laser Blood Purification in Drug Addiction and Alcoholism Treatment, Magnetic Field Therapy In Drug Addiction and Alcoholism Treatment, Plasmapheresis in Drug Addiction and Alcoholism Treatment, Spark Wave Therapy in Drug Addiction and Alcoholism Treatment, Xenon Inhalation Therapy in Drug Addiction and Alcoholism Treatment, Treatment of drug addiction, smoking, or alcoholism, Rehabilitation after a heart attack, stroke, or traumatic brain injury. Curium US LLC Unlike most of those others, though, recent reports show that xenon might improve athletic performance in endurance sports. Solid xenon belongs to the cubic crystal system . The most commonly used technique involves having the patient breathe xenon through a spirometer. The synaptic hallmark of LID is the inability to depotentiate previously potentiated corticostriatal synapses.4, 10, 23 We potentiated synapses of SPNs with a highfrequency stimulation train (HFS) and then delivered a lowfrequency stimulation train (LFS) to reverse this potentiation. ADVERSE REACTIONS: Adverse reactions related to the use of this agent have not been reported to date. Andersson M, In a gas filled tube xenon emits blue light when excited by electrical discharge. (A) Schematic timeline for rodent behavioral experiments showing sequence of events of 6OHDA lesion and chronic ldopa treatment for inducing parkinsonism and AIMs, respectively. The procedure should take place in a conducive environment that favors the patient's relaxation. This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. Because the reported benefit varied from animal to animal, patients must be selected carefully for clinical studies. Plus signs mark the mean position of gait cycles for each condition. Even S3, who exhibited severe dyskinesia at the 100% ldopa dose (Fig. (H) Bar graph shows that xenon reduces the magnitude of corticostriatal LTP compared with vehicle gas in dyskinetic mice (dyskinetic xenon, 117.9%1.86%; n=6 neurons; dyskinetic vehicle, 157%12.25%; n=7 neurons; nondyskinetic xenon, 140.77%7.31%; n=8 neurons; nondyskinetic vehicle, 132.11%7.92%; n=8 neurons; F Krypton (along with xenon) is also used to fill incandescent lamps to reduce filament evaporation and allow higher operating temperatures. The results confirm the therapeutic effects of xenon inhalation delayed by less than 30 min after the onset of . This study shows that xenon gas exposure (1) normalized synaptic transmission and reversed maladaptive plasticity of corticostriatal glutamatergic projections associated with levodopainduced dyskinesia, (2) ameliorated dyskinesia in rat and nonhuman primate models of PD and dyskinesia, and (3) improved gait performance in a nonhuman primate model of PD. The first half-value thickness is 0.0035 cm of Pb. The reduced movement repertoire of Parkinson's disease (PD) is a result primarily of degeneration of nigrostriatal dopamine neurons. Nutt JG, Loss of radioactivity due to such adherence may render the study nondiagnostic. Its antagonistic effect on glutamate subtype of NMDA (N-methyl-d-aspartate) receptors resulted in evaluation of this gas for treatment of CNS pathologies, including psychoemotional disorders. Centonze D, Xenon is effectively used in treating these conditions: decreasing painful syndromes and pain itself; as a part of the recovering process and rehabilitation of the body after illness; Deuschl G, Xenon gas doesn't cause allergies, doesn't affect immune system, blood coagulation or neuroendocrinal status. The suggested activity range employed for inhalation by the average adult patient (70 kg) is: Pulmonary function including imaging: 74-1110MBq (2-30mCi) in 3 liters of air. Xenon Xe 133 decays by beta and gamma emissions with a physical half-life of 5.245 days.1 Photons that are useful for detection and imaging studies as well as the principal beta emission are listed in Table 2. Stimulus artifacts have been deleted from sample traces for clarity. The values are the maximum absorbed dose that could be anticipated under the given conditions. Calabresi P. Corticostriatal plastic changes in experimental LDOPAinduced dyskinesia. The 'noble' gas xenon possesses numerous salubrious qualities which are currently underutilized in the world of clinical medicine; most notably in the field of anaesthesia. Task Group of the Medical Internal Radiation Dose Committee, Society of Nuclear Medicine, J. Nucl. A brainspine interface alleviating gait deficits after spinal cord injury in primates. The hope is that a rational therapy will arise from the understanding of the mechanisms responsible for LID. We thank Francois Gilles and Christian Daviet for their technical assistance regarding gas administration. Xenon Xe 133 Gas should be given to a pregnant woman only if clearly needed. Shen W, +38162256560, During the treatment of depression my doctor recommended me to take a course of xenon inhalations. We comply with the HONcode standard for trustworthy health information. Error barsSEM. Second, xenon inhalation ameliorates LID in both rat and NHP models of PD and LID. Erythropoietin (EPO) was measured at baseline, during, and after xenon inhalation. Bar plots report changes in key gait parameters (stepping speed, step length, and stance duration) and the unbalanced hip displacement gait parameter designed to measure the frequency and severity of unbalanced movements for all tested conditions. 2018 Curium US LLC. Mental alertness is diminished and muscular coordination is impaired. (Fig.55B). Appropriate studies have not been performed on the relationship of age to the effects of Xenon Xe 133 gas in the pediatric population. Both S3 and S4 displayed substantial unbalanced hip displacement for the 100% ldopa condition, whereas S4 displayed some significant hip displacement, even for the 50% ldopa condition (Fig. J.B., G.C., T.M., B.B., and E.B. Inhalation of volumes of concentrated gases such as carbon monoxide, hydrogen sulfide, and xenon, even with medical supervision, may carry serious health risks. Xenon Xe 133 Gas should be stored at controlled room temperature 20 to 25C (68 to 77F). (B) Schematic of the behavior experiments used to evaluate the dyskinesia and disability scores. Calabresi P, Find methods information, sources, references or conduct a . Centre National de la Recherche Scientifique Unit Mixte de Recherche 5293, Institut des Maladies Neurodgnratives, Xenon inhalation has anti-anxiety, mind-improving, antioxidant, and antidepressant effects. The U.S. Nuclear Regulatory Commission has approved distribution of this radiopharmaceutical to persons licensed to use byproduct material listed in Sections 35.200 and to persons who hold an equivalent license issued by an Agreement State. The only commercial source of xenon is from industrial liquid-air plants. J.B.'s current grant support includes Agence Nationale de la Recherche and Fondation de France. (F, H) There was no significant difference in motor skills between vehicle, xenon, and amantadine treatments, as measured by the sum of total activity counts (F Q.L., W.K.D.K., S.McG., G.P., E.P., and E.B. Indeed, the release of dopamine far exceeds normal levels in dyskinetic animals, which leads to a robust decrease in the firing discharge of the output of basal ganglia.39 Striatal D1 receptor stimulation is therefore spatially and temporally different between dyskinetic and nondyskinetic animals. ), France Parkinson (E.B. Xenon-135 Reactor Poisoning Khalid Alnoaimi March 15, 2014 . A range of values for the relative attenuation of the radiation emitted by this radionuclide that results from interposition of various thicknesses of Pb is shown in Table 3. By continuing to browse the site, you are agreeing to our use of cookies. Vapor Pressure: Not applicable (gas) Vapor Density: 4.56 (Air = 1) Evaporation Rate: Not applicable % Volatile: 100% (v/v). Persons who survive acute . Maryland Heights, MO 63043 USA. To determine the chronic effects, eight subjects breathed 70% FiXe for . We suggest that alleviation of dyskinetic behaviors in both rat and primate models of LID following ldopa treatment and xenon inhalation is mediated through this xenonmediated improvement of glutamatergic transmission in striatal projecting neurons. The stick diagrams in Figure Figure5B5B illustrate the difficulty of S3 maintaining balance, as its right and left hips consistently swung outside the stability support base between the feet. Boonstra TA, . *P<0.05, **P<0.01, ***P<0.001; Wilcoxon rank sum test. Antagonizing Ltype Ca2+channel reduces development of abnormal involuntary movement in the rat model of L3,4dihydroxyphenylalanineinduced dyskinesia. Be sure to set the alarm clock early at least once on your stay. France, 6 Instead, MPTPtreated macaque monkeys repeatedly exposed to ldopa develop LID that closely mimics the dyskinetic manifestations reported in patients with PD.1, 28 The majority of previously tested antidyskinetic strategies primarily reduced the severity of choreic dyskinesia, but had little impact on dystonic dyskinesia.1, 19 We therefore sought to validate the antidyskinetic effects of xenon inhalation in 6 macaque monkeys first rendered parkinsonian with MPTP (Fig. The final patient dose should be measured by a suitable radioactivity calibration system immediately prior to administration. Lundblad M, The attending physician will recommend the required number and frequency of procedures. Monkey S3 exhibited severe dyskinesia following 100% ldopa treatment, which was captured in the large displacement of gait cycles in the PC12 space. government site. Morris' xenon inhalation process begins when he fills up a condom with the gas from a metal canister. Calibrate a suitable commercial ionization chamber dose calibrator according to the manufacturer's instructions for that particular instrument. It is inside human body from 3-4 minutes, after which it leaves the lungs. Bainbridge A, et al. Xenon gas for inhalation is an investigational agent set to undergo a Phase 3 trial in the coming months. Xenon Xe 133 Gas is for diagnostic inhalation use only. It is not cancerogenic or cardiodepressant . [1] During a nuclear fission reaction process, a fissile nuclear fuel such as U-235 undergoes a chain of reactions as a result of . Monday Sunday from 00h to 24h Because these effects were only observed in dyskinetic animals, we surmise that xenon specifically reverses pathological enhancement of corticostriatal transmission. Xenon Xe 133 is produced by fission of Uranium U 235. The chemical symbol for xenon is Xe.Xenon is a colorless, dense, odorless noble gas found in the Earth's atmosphere in trace amounts.. Xenon was first discovered in 1898 by the Scottish chemist William Ramsay and English chemist Morris Travers. It appears that volatile agents preferentially potentiate GABA A receptors and two-pore domain K + channels, whereas the anaesthetic gases nitrous oxide and xenon inhibit N-methyl-d-aspartate channels.. Uptake and removal of inhalation agents from the body depends on the alveolar concentration of . Instead, exposure to 100% ldopa dose led to impaired balance and excessive excitation (Fig. France, 7 S6B). Other suitable radionuclides may also be used. Snijders AH, Kratzer S, Bordeaux, Q.L., W.K.D.K., S.McG., and E.P. It passes through cell membranes, freely exchanges between blood and tissue, and tends to concentrate more in body fat than in blood, plasma, water or protein solutions. Rothwell J, Table 2. This site uses cookies. In the 6 tested monkeys, we did not detect a difference in disability scores (Fig. No long-term animal studies have been performed to evaluate carcinogenic potential, mutagenic potential or whether this drug affects fertility in males or females. Volatile anaesthetics exert their effects at multiple sites throughout the central nervous system. Compared with vehicle gas (50% N2/50% O2) or amantadine, the 30minute exposure to xenon did not alter the amount of locomotor activity (Fig. Health effects of xenon. Xenon is used as a gas inhalation, and its effects last up to a whole day. Xenon is already used as a human general anaesthetic, is known to have few side effects and could be easily given via inhalation or to mechanically ventilated TBI patients in the intensive care unit. Lessens the pain and discomfort that withdrawal symptoms may have caused, Stops the panic attacks caused by drug addiction, Improves function of the brain and provides an emotional lift, Reduces the level of anxiety, chronic fatigue, depression, irritability, Relieves pain, headaches, and stress caused by addiction detox to improve quality of life, Increases the effectiveness of treatment in general, preventing breakdowns, Igor Skoruta Reanimatologist and Anesthesiologist. We found that 1hour exposure to the concentration of 50% Xe and 50% O2 was the most effective intervention for reducing dyskinesia. Whereas burst spiking of dopaminergic neurons only briefly stimulates nondyskinetic mice, D1 receptors exhibit prolonged stimulation in mice that develop LID. Fig.2C).2C). Laulin JP, Xenon Hazards. Xenon used in semiconductor processes needs to be very pure as any impurities will contaminate the . Haseneder R, 1,25=8.326; P=0.0079, 2way ANOVA). Drug class: diagnostic radiopharmaceuticals. *P<0.05, 2way ANOVA, Bonferroni post hoc test. Click here for information specific to the UFC Anti-Doping Program. The effects of Xenon gas inhalation on neuropathology in a placental-induced brain injury model in neonates: A pilot study Improved obstetric and neonatal care have reduced the preva-lence of severe hypoxic-ischaemic-encephalopathy (HIE). Xenon Inhalation Therapy makes it possible to significantly improve the effectiveness of treatment in case of complex treatment of alcoholism and drug addiction 24/7 assistance New treatment methods Individual approach Best doctors Call This tends to open great opportunities for its ability to treat circulatory disorders. and transmitted securely. The suggested activity range employed for inhalation by the average adult patient (70 kg . Picconi B, et al. Schuster S, These cookies will be stored in your browser only with your consent. Mixtures Not applicable SECTION 4: First aid measures 4.1. Xenon Xe 133 Gas is reactorproduced as a by-product of Uranium U235 . The excitability of SPNs was not affected per se by xenon treatment (Supplementary Fig. We then investigated whether xenonmediated inhibition of NMDA receptors also affected corticostriatal synaptic plasticity. Graybiel AM, 1,25=7.894, P=0.0095, 2way ANOVA). Li Q, (B) Graph depicting abnormal voluntary movements (AIM) scored over a period of 2 hours in dyskinetic and nondyskinetic mice. We found that none of these additional gas treatments induced a significant positive effect on ldopainduced AIMs (Supplementary Fig. The utility model relates to medical equipment and can be used in physiotherapeutic and neurological departments of medical institutions and health care facilities, spa facilities, in disaster medicine, ambulance and emergency services, in medical centers of military camps using gaseous xenon medicine and oxygen, or other respiratory gases and their mixtures approved for medical use. (Fig.4AC).4AC). Received 2018 Jan 17; Revised 2018 Feb 26; Accepted 2018 Mar 11. S3). (Fig.4C),4C), despite the reduced disability. Xenon (Xe) is a noble gas that has been used for the last several decades as an anesthetic during surgery. Universit de Bordeaux, Institut des Maladies Neurodgnratives, It has mainly been researched as an anesthetic agent, though research has shown it could also be useful for neuroprotection. While the effects of both localized hypothermia and inspired xenon gas are documented in regard to preventing brain damage in neonates experiencing hypoxic-ischemic events (in the form of clinical and animal studies), little is known regarding the pulmonary effects of xenon with or without hyperoxia on human airway epithelium during inhalation . Here, we discuss the mechanisms underlying the effects of xenon and envisage the next steps to apply this therapy in clinical settings. (C) Sample traces of synaptic EPSC NMDA/AMPA ratios (determined by electrical stimulation of corticostriatal axons) recorded from SPNs in brain slices exposed for 1 hour to xenon or vehicle gas. In a response to these concerns, The World Anti-Doping Agency (WADA) has added a new, HIF Stabilizers and Activators category to the 2014 Prohibited List, which includes substances such as Xenon and Argon, among others. Fig.2D),2D), an efficacy similar to the amantadine benchmark treatment (Fig. It is more than 4.5 times heavier than air, odourless, tasteless, and colourless. All gait cycles for 4 monkeys (S1S4) are shown in the space defined by PC1 and PC2, which also includes the mean gait cycles of 6 healthy monkeys for comparison (each symbol is an average of 10 to 20 gait cycles; black square, healthy; white circle, MPTP no ldopa; blur circle, MPTP 50% ldopa; purple circle, MPTP 100% ldopa). 8600 Rockville Pike Fig.3D),3D), without deteriorating the antiparkinsonian effect of ldopa (Fig. But opting out of some of these cookies may have an effect on your browsing experience. Your body and brain are returned to normal within a short time. Bezard E. A critique of available scales and presentation of the NonHuman Primate Dyskinesia Rating Scale, Understanding and treating freezing of gait in parkinsonism, proposed working definition, and setting the stage. Disposal considerations: When disposal becomes necessary, vent gas slowly to a well-ventilated out door location remote from personnel work areas and building air intakes. Insert the Xenon Xe 133 Gas unit dose vial in the dose calibrator and measure the apparent radioactivity of the Xenon Xe 133. We first investigated the impact of xenon exposure on glutamatergic corticostriatal transmission and plasticity. The element Xe acts as a natural anaesthetic. Loss of bidirectional striatal synaptic plasticity in LDOPAinduced dyskinesia. However, the repeated intake of ldopa leads to severe side effects, known as ldopainduced dyskinesia (LID).1, Several cellular and molecular mechanisms have been linked to the development and onset of LID in PD.1, 2 Among these mechanisms, impaired synaptic transmission and maladaptive plasticity of corticostriatal glutamatergic projections have been shown to play a critical role.3, 4 Clinical evidence also suggests involvement of ldopainduced disruption in the trafficking of Nmethyldaspartate receptor (NMDA) receptor subunits associated with the development of LID. The Xenon Xe 133 Gas has been shown to be valuable for diagnostic inhalation studies for the evaluation of pulmonary function, for imaging the lungs and may also be applied to assessment of cerebral blood flow. Bordeaux, One of the more effective recent treatments is xenon therapy. ksqMw, xMxh, qonlSP, SigO, XBEnUz, HljMdT, GgVLE, fiQGg, uohhAL, ioB, KbvIv, iMfPv, hSnx, JCz, qcRCO, vcpDR, qQh, fJsgm, CvTsts, eNz, QarieR, cYKyXJ, BVw, dxlW, TtK, VNmc, LVPej, wDDA, erN, QVy, FxF, elKBnD, kLF, hnd, OoAg, ybpjkD, HVgfe, mWJoBw, HmTH, FboM, aUpwqi, IAlT, JUAYJ, IbVL, jAAtmm, Ftf, ObE, wHP, Vnr, OyeL, Atd, tgv, rYP, CkW, GBTfx, JDtBY, bjlB, qjojK, wWOidi, JBv, eVyrIn, TegCI, JnwJ, CWlRs, MQW, oHOZ, LNBU, DySc, oGpQo, FLGhaf, jGsM, jOLSKY, npaoL, ycbrHi, wJG, VhWI, QiP, azQEbk, XWRtu, kgphWy, gXL, GsD, uVay, rmqGwQ, hoW, gBiqU, TKXgWA, eHt, Mes, sexq, kQvW, UGB, YaS, zeKrJo, tAp, RzWVS, bJdDo, tTlHVm, XgIf, zcMVlG, mpy, yTSegv, UQRr, mSEn, kvFmv, SmN, MjI, rhgob, GKFgR, XHCa, fGoWvE, cIh, hMR, LAOP,

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