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Medical gases, differences and similarities in therapeutic

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The presentation outlines the concept of hormoligos as a new approach to understanding the mechanism of action of medical gases using hydrogen, ozone and xenon as an example.

The presentation outlines the concept of hormoligos as a new approach to understanding the mechanism of action of medical gases using hydrogen, ozone and xenon as an example.

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Medical gases, differences and similarities in therapeutic

  1. 1. Hormoligos as a new approach to understanding the mechanism of action of medical gases using hydrogen, ozone, and xenon as an example. E.I.Nazarov Asian-European Union of ozone therapists In the last decade, a new direction has arisen and is actively developing - the study of medical gases as a separate group of pharmacological substances. Since 2011, the multidisciplinary journal Medical Gas Research has been published devoted to the use of medical gases in therapy.
  2. 2. The gases that are called “medical gasses” are Oxygen, Ozone, Hydrogen, Monoxide and Carbon Dioxide, Hydrogen Sulfide, Carbon Disulfide, Nitrous Oxide, Helium, Argon, Krypton, Xenon and Radon. In this presentation, we consider three gases - an ozone as oxidizing agent, a hydrogen as reducing agent, and an inert gas xenon. Surprisingly, these gases have an almost identical spectrum of pharmacological activity. This is contrary to the basic principles of pharmacology, in which the chemical properties of a substance determine the pharmacological effect. Let's try to figure it out and start with hydrogen.
  3. 3. CHART 2 HYDROGEN THERAPY
  4. 4. METHODS OF HYDROGEN THERAPY inhalation of 2-4% hydrogen-air mixture. Drinking saturated (1.6 ppm) and superaturated (5-6 ppm) water intravenous infusion of a Saline saturated with hydrogen (1.6 ppm) AHT-H2 autohemotherapy major with hydrogen 4
  5. 5. The pharmacological activity of the molecular hydrogen in animal models of pathological conditions of the body. 5
  6. 6. Drinking hydrogen water reduces liver obesity in the diabetic mouse line and even reduces their size. Molecular hydrogen improves obesity and diabetes by inducing hepatic fibroblast growth factor 21 and stimulating energy metabolism in db/db mice. Kamimura, N., Nishimaki, K., Ohsawa, I.,et al (2011). Obesity, 19(7), 1396-1403
  7. 7. Molecular hydrogen is protective against 6-hydroxydopamine-induced nigrostriatal degeneration in a rat model of Parkinson's disease. Fu, Y., Ito, M., Fujita, Y., Ito, M., Ichihara, M., Masuda, A., ... & Ohsawa, I. (2009). Neuroscience Letters, 453(2), 81-85 methamphetamine- induced rotation test in mice 6-hydroxydopamine-induced nigrostriatal degeneration in a rat model of Parkinson's disease is largely prevented by drinking hydrogen water. This is seen on gistological slices of the Substance Nigra. Another model of Parkinson's disease estimated on methamphetamine-induced, rotation movement of mice is also prevented by hydrogen water. 7
  8. 8. Control Alcohol H2-Alcohol Alcohol+free access to H2Water Alcohol treated with hydrogen under conditions of reproduction of a model of chronic alcohol intoxication causes a significant limitation of pathological metabolic changes in laboratory rats.
  9. 9. On the left is the appearance of rats after a month of alcohol intoxication. In the center - also when intoxicated with alcohol saturated with hydrogen, on the right - also with free access to drinking water saturated with hydrogen. Назаров Е.И., Дерюгина А.В., Иващенко М.Н.., Влияние молекулярного водорода на активность печеночных маркеров, Естесственные и технические науки. № 9 (135) 2019 г., стр. 87
  10. 10. The dynamics of the life span of rats under conditions when the only source of water was tap water (blue curve), water with a O2(red curve), water with H2(green curve). The data are borrowed from [. Pavel D. Kolesnichenko et al. Natality and Mortality with Reduced RED-OX Potential Drinking Water, Journal of International Pharmaceutical Research, v 45, p 450-453]. H2 water O2 water Tap water
  11. 11. Some clinical data on the therapeutic activity of hydrogen 11
  12. 12. 12 A IV infusion of saline, saturated with hydrogen, reduces the area, of infarction zone, of a brain stem stroke. Practically, in ten days with hydrogen therapy , the specified parameter decreases to a normal value. Improved brain MRI indices, in the acute brain stem infarct sites, treated with hydroxyl radical scavengers, Edaravone and hydrogen, as compared to Edaravone alone. Ono, H., Nishijima, Y., Adachi, N et al., 2011 Medical gas research. – 2011. Т. 1. №. 1. С. 1
  13. 13. Hydrogen inhalation, prevents the deterioration ,of the NIHSS index, which is used, to assess the neurological outcome, and the degree of recovery, in patients with stroke (level of consciousness, sensory function, language, etc.). The Barthel Index, (BI) - index of independent living, also becomes more stable, with hydrogen inhalations. There is another study that, investigated the comparative activity of Edvarone and hydrogen. The study, was conducted, on a group of 25 patients, who received inhalation, of 3% H2, for one hour, within 7 days. . 13 Hydrogen Gas Inhalation Treatment in Acute Cerebral Infarction: A Randomized Controlled Clinical Study on Safety and Neuroprotection. H. Ono, Y. Nishijima at al. Journal of Stroke and Cerebrovascular Diseases, Vol. 26, No. 11 (November), 2017: pp 2587–2594
  14. 14. Total Unified Parkinson’s Disease Rating Scale (UPDRS) scores in the H2-water group (n=9) improved (median, -1.0; mean +- standard deviation, -5.7+-8.4), whereas UPDRS scores in the placebo group (n=8) worsened (median, +4.5; mean+-standard deviation, 4.1+-9.2) Drinking hydrogen water, in the amount of two liters per day, for one year, causes the reverse development, of symptoms of Parkinson's disease. 14 Pilot study of H2 therapy in Parkinson's disease: A randomized double‐blind placebo‐controlled trial. Yoritaka A. et al. Movement Disorders. – 2013. – Т. 28. – №. 6. – С. 836- 839.
  15. 15. Drinking water, saturated with hydrogen is useful, in the prevention of diabetes mellitus (T2DM) or impaired glucose tolerance (IGT). Patients consumed 900 ml hydrogen water a day, or 900 ml of simple water, (placebo) for 8 weeks. It can be seen from the slide, drinking hydrogen water, shifts the average glucose level, for a group, below the upper level of norm. Supplementation of hydrogen-rich water, improves lipid and glucose metabolism, in patients with type 2 diabetes, or impaired glucose tolerance. Kajiyama S. et al. Nutrition Research. – 2008. – Т. 28. – №. 3. – С. 137-143.
  16. 16. Hydrogen baths, and intravenous infusions, of hydrogen-saturated saline, are effective, in treating skin diseases. Two-months treatment, with hydrogen baths, causes a 75%, decrease in the psoriasis severity index. On the right, the result of the use of hydrogen droppers (400 ml, 1.6 ppm H2) in the treatment of acute herpetic inflammation, of the skin, is shown. Positive effects of hydrogen-water bathing in patients of psoriasis and parapsoriasis en plaques . Zhu Q. et al. Scientific reports. – 2018. – Т. 8. – №. 1. – С. 8051. Ono H, Nishijima Y, Adachi N, et al (2012): Hydrogen (H2) treatment for acute erythymatous skin disease. A report of 4 patients with safety data and a non-controlled feasibility study with H2 concentration measurement on two volunteers. Med Gas Res, 2: 14. 16
  17. 17. First approach - Hydrogen is a selective scavenger of radicals 17 We have seen above that molecular hydrogen is a very effective therapeutic agent that surpasses the currently available traditional medicine. However, what is the mechanism of this activity? There are two approaches to explaining the therapeutic effect of molecular hydrogen. The first is well known to ozone therapists. This approach explains all the therapeutic effects of hydrogen with the antioxidant effect of the latter.
  18. 18. 18 At body temperature, hydrogen is a kinetically inert gas, and practically does not participate, in the vast majority, of biochemical reactions. The reason for this inertness is that, in order for hydrogen to react, for example, with oxygen, you need to raise the temperature, to 550 degrees of Celsius. Therefore, earlier, molecular hydrogen, was considered, as a biologically inert gas. The situation changed, since 2007, after the pioneering work of Oshawa, and his coauthors. They revealed that, hydrogen can react with hydroxyl and peroxynitrite radicals, at body temperature. As a result, these dangerous radicals, are inactivated.
  19. 19. Molecular hydrogen, is a unique natural antioxidant. It is unique, because hydrogen molecules, selectively intercept only dangerous hydroxyl, and peroxynitrite radicals, practically, not suppressing the activity of “useful” reactive oxygen forms (hydrogen peroxide, anion of superoxide radical, NO radical, etc.). It is natural, because molecular hydrogen, is synthesized, by intestinal microflora, in macrovolumes. Molecular hydrogen has, the property of super-permeability, and it is rapidly distributed, by the blood in the body, when administered orally, and rectally. Compositi on of intestinal gases 19
  20. 20. It is known that, the imbalance of oxidation and antioxidant reactions, is the cause of most diseases. It is believed that, low doses of ozone, activate the antioxidant system. It is also believed that, hydrogen therapy, reduces the overall intensity, of oxidative processes. The final result is, to restore the balance of oxidative-antioxidant reactions and, consequently, improve the condition of the body, or health. This approach, familiar to us from the theory of ozone therapy, emerged in 2007 and is used as a theoretical basis for hydrogen therapy to this day. However, there is an increasing accumulation of facts that this simplified method of interpretation is not as good as it seems.
  21. 21. For example, the neuroprotective effect of drinking hydrogen water in a mouse model of Parkinson's disease persists for at least three days after end of drinking of water. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) - nerve poison kills dopaminergic neurons. Pictures is borrowed from Noda, et al., Multiple Effects of Molecular Hydrogen and its Distinct MechanismJ Neurol Disord 2014, 2:6
  22. 22. Hydrogen water releases the hormone ghrelin from the walls of the stomach. The hormone ghrelin secretes the growth factors of dopaminergic neurons in the Substance of Nigra and thus has an antiparkinsonian effect. The protective effect of hydrogen water is removed by an ɓ1-adrenergic blocker, atenolol, which blocks the increase in ghrelin concentration. The pictures is borrowed from Noda, M., Ohsawa, I., Ito, M., & Ohno, K. (2014). Beneficial effects of hydrogen in the CNS and a new brain-stomach interaction. Eur J Neurodegener Dis, 3, 25-34
  23. 23. The proposed scheme is the stomach-brain interaction mediating the neuroprotective effect of hydrogen-saturated water. The circuit is borrowed from Noda, M., Uemura, Y., Yoshii, Y., Horita, et al. (2019). Circulating messenger for neuroprotection induced by molecular hydrogen. Canadian journal of physiology and pharmacology, 97(10), 909-915. This diagram illustrates the essence of the Second approach - mediation of the effects of hydrogen by the endocrine system. What is the appeal of this approach? The attractiveness lies in the assumption that molecular hydrogen activate the neuro humoral system that underlies the homeostasis system. Since the disease in the most general sense is a violation of homeostasis, the restoration of homeostasis logically means the treatment of the disease, regardless of the etiology. Thus, a wide spectrum of pharmacological activity of hydrogen can be explained. However, does this hypothesis relate to other gases, for example for Xenon?
  24. 24. Chart 2 Xenon therapy. 1
  25. 25. Pioneer of xenon in medicine. Nikolai Vasilievich Lazarev, Russia (1895-1974)
  26. 26. Therapeutic properties of xenon analgesic, antispasmodic, cardiotonic, neuroprotective antistress, antihypoxic, immunostimulating, anti-inflammatory, anabolic, neurohumoral, vasoplegic
  27. 27. Cell apoptosis. Immunofluorescence cortex M.Maize,2004 Xenon, even at very high anesthetic concentrations, does not cause apoptosis of cortical neurons like ketamine or nitrous oxide, but even protects neurons from non-toxic poisons.
  28. 28. Neuroprotective mechanism of xenon action is currently associated with the inhibition of receptors of Glutamate (NDMA-receptors)
  29. 29. 0 10 20 30 40 50 60 70 80 90 100 0 5 10 45 100 450 1000 percentageofmaximumcurrent throughthemembrane Concentration of NMDA + Xenon Control CONTR OL + XENON NMD A NMDA 10 S 500pA Franks et al. Nature, 396:324, 1998 This is proved in a direct experiment on measuring the ion currents of a neuron membrane upon excitation of glutamate receptors.
  30. 30. Dynamics of biochemical and hormonal parameters during xenon inhalation In addition, it was found that xenon inhalations cause a change in the hormonal status of organism. This is evident from the sharp dynamics of growth hormone, cortisol, and tereotropic hormones. Thus, the neurohumoral effect of xenon can be considered proven.
  31. 31. Chart 3. OZONE THERAPY
  32. 32. Does ozone therapy, affect the hormonal status of patients? Yes, and it influences very strongly, and very peculiarly. On slide the normalized level of Cortisol, in the blood of six patients (41-64 years old) in control, during the course of AHT-O3 procedures (dose 27μg/kg, every other day) and within one months after completion of the course. 7 In slide, we see, that after the start of the course of autohemotherapy with ozone, the oscillatory dynamics, of cortisol level starts. After the completion of the course of procedures, the level of cortisol stabilizes, at the reached level, for at least one month.
  33. 33. norm Cortisol This is a typical pattern, of cortisol level dynamics, during the real course of ozone therapy treatment (AHT-O3,dose of ozone - 2 mg). We see , that the initially inflated level of cortisol, unpredictably changes, during the course of the procedures. Before the fifth procedure, cortisol levels return to initially inflated level. It is important, that the patient's well-being, improves after the first procedure, and then, worsens again before the fifth procedure. Thus, cortisol levels correlate with patient well-being
  34. 34. nor m aldosterone Mineral corticoid levels, of this patient, vary even more. As a result, cortisol and aldosterone are, in the upper half of norm. This, and the previous graph, shows very clearly, the hormone modulating effect of ozone. Indeed, if under the action of a pharmacological factor, the concentration of a hormone, changes 10 times, then why look for some other reasons for the therapeutic effect of this factor?
  35. 35. Ozone are: anti-inflammatory - immune modulating, anti-microbial, anti-viral and anti-hypoxic - vasodilatory cardio-protectors ....... detoxifying agent substance, with a therapeutic index of more than 350 times, and half-life of 60 days. Adaptogens (examples - alkaloids of Rhodiola Rosea, Aloe Vera, Ginseng Rauwolfia, etc. ) are: anti-inflammatory - immune modulating, anti-microbial, anti-viral and anti-hypoxic - vasodilatory cardio-protectors ....... detoxifying agent substance with a therapeutic index of more than 350 times, and half-life of 60 days What about classification of ozone as a pharmacological agent? This is odd, but there is no pharmacological classification of ozone. We can only say that: Does pharmacology know substances, with such a wide range of therapeutic activity? Yes, these are adaptogens belonging to the group of plant alkaloids.
  36. 36. Coincidence of the pharmacological characteristics, of plant alkaloids and ozone, seems to us to be not accidental, especially since ozone, and alkaloids are potent poisons. In this regard, we propose to use the concept of hormoligos, instead of the practically empty concept of hormesis. The concept of hormoligosis , from the Greek hormo - excitation, oligo - small quantities, was offered by T. Luckey at 1975 in article Hormology with inorganic compounds / T. D. Luckey, Environ. Qual. Saf. Suppl. - 1975. —N 1. - P. 81 - 103, 115 - 118. In this concept, the action of toxicants in small doses, is associated with hormone-like or hormone modulating action of them.
  37. 37. A new approach to the therapeutic effect of systemic ozone therapy or what gives us the replacement of the concept of hormesis to the concept of hormoligosis. So, we have considered the problems, that occur, in the modern theory and practice, of systemic ozone therapy. We believe, that they can be solved by taking as a basis the hormoligosis, instead of LP of membranes, in combination with hormesis. Let me remind you, that the main thing in the concept of hormoligosis, is that poisons in low concentrations, cause hormonal shifts in the patient's organism.
  38. 38. Synthesis scheme of prostaglandins, prostacyclins, thromboxanes and leukotrienes, from arachidonic acid. As a result of the synthesis of these aicosanoids , hydroperoxides and malonic dialdehyde, which are usually considered to be products of LP of membranes, are formed.
  39. 39. A new approach to the therapeutic effect of systemic ozone therapy or what gives us the replacement of the concept of hormesis to the concept of hormoligosis. So, we have considered the problems, that occur, in the modern theory and practice, of systemic ozone therapy. We believe, that they can be solved by taking as a basis the hormoligosis, instead of LP of membranes, in combination with hormesis.
  40. 40. Understanding that the systemic effect of medical gases relies on changes in the hormonal balance allows the doctor to develop an individual approach to the duration and intensity of the course of ozone therapy based on data on the cardio intervalogram (see ozoneprotocols.org) , as well as apply combined methods of treatment with medical gases, for example, ozone-hydrogen therapy. At present Econika Engeneering, produce equipment for ozone, ozone-hydrogen and xenon therapy. Traditional ozone generators The world's first ozone-hydrogen Xenon machine Bozon- family UV-photometric generator to receive ozone tools and hydrogen from water
  41. 41. 4 2 4747 33 Thanks for your attention 23 47

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