by member of RAS Valery LUNIN, Head of the Department of Physical Chemistry, Chemical Faculty, M. Lomonosov Moscow State University,

Pavel MOROZOV, Dr. Sc. (Medicine), Head of the Clinical Center of the Moscow Medical Academy,

Irina KOSHELEVA, Cand. Sc. (Medicine), Head of the Oxygen Therapy Unit, Clinic of Skin and Venereal Diseases, Moscow Medical Academy

Ozone therapeutic device UOTA-60 - 01 MEDOZONE.

Thin atmospheric layer protecting all that is alive from the harmful exposure of short-wave ultraviolet solar radiation... Fresh odor in the air after storm... These are the most frequent associations linked with ozone. But for the hundreds of thousands of patients in Russia and foreign countries, who experienced the favorable effects of a new therapeutic method-oxygen-ozone therapy (OOT), this word is associated with relief from suffering.

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Ozonometer for ozone concentration measuring in water solutions.

Local application of oxygen-ozone mixture.

Ozone is one of allotropic form of oxygen. Its molecule, in contrast to common O2, consists of three atoms, due to which it acquires specific physico-chemical characteristics, responsible for unique biological effects*. During the interactions with living tissues, this highly reactive gas-oxidizer reacts mainly at the site of double carbon bonds (-C=C-) in unsaturated fatty acids and sulfohydryl groups (-SH-) in aromatic amino acids and peptides. It immediately reacts with bio-organic substrates. By contrast, "common" oxygen in such a situation needs assistants, or biocatalyzers, such as enzymes, trace elements.

Attempts to apply ozone in medicine were made as long ago as in the mid-19th century; this was due to its oxidative effects, which were obvious. However, ozone therapeutic application became possible only in the second half of the 20th century after the comprehensive studies of O3 were held and its role as a regulator of biological processes at molecular and cellular levels became obvious. Of course, before clinical trials, the new method was thoroughly studied on laboratory animals. A cycle of studies was carried out, for example, at the Department of Experimental and Clinical Pathology, Research Center of Central Institute for Post-Graduate Medical Education (Moscow). Experimental rats with artificially induced acute diffuse peritonitis at different stages of the disease were intravenously and intraperitoneally injected with ozonized saline with ozone concentration in the solution 10 mg/l. This therapy had a favorable influence on the acute inflammatory process, reducing the death rate, improving the function of the antioxidant system by activating its enzymatic components, and stimulating cellular and humoral immunity. So, systemic treatment with ozone resulted in a multi-component metabolic effect: improvement of energy provision for tissues stimulation of hepatic and pancreatic functions, normalization of oxygen supply. A pronounced antistress effect was observed; external treatment with ozone had a disinfecting effect. Experimental studies pathogenetically proved the efficacy of therapeutic use of O3; indications for this therapy and contraindications were formulated.

The first experience of OOT in Russia dates back to the 1980s. However, technological imperfection of medical ozone generators (special devices intended to "produce" ozone-oxygen mixture with the preset concentration of ozone) prevented wide use of the method. This problem was solved by scientists from the Laboratory of Catalysis and Gas Electrochemistry, Chemical Faculty of M. Lomonosov Moscow State University. Physico-chemical bases of synthesis and methods for measurements of ozone concentrations in gaseous and water phases, research of the polymers resistant to ozone are the main scientific directions for the laboratory during several decades. Due to the findings, the recommendations of physicians were transformed into real constructions and, in cooperation with Medozone Ltd. (Moscow), an effective device was created.

In industrial devices ozone is synthesized in the barrier discharge plasma during oxygen flux through a gas discharge cell. The discharge is called "barrier" because it flows between two electrodes separated by a dielectric. Real discharge processes take place in the microdischarge fine channels. They are really quite small: their duration and the duration of current in them is just several tens of nanoseconds, the value of the transferred charge is approximately several nanocoulombs. Ozone is formed in these channels. The nonequilibrium condi-

* See: V. Roshchina, "Ozone and Live Organisms", Science in Russia, No. 2, 2005. -Ed.

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Scheme of gas flows in UOTA-60-01 device: 1 - pressure reducer; 2 - unit for oxygen flux regulation and measurement; 3 - ozone generator; 4 - unit for ozone concentration photometry; 5 - ozone generator feeding unit; 6 - unit for ozone concentration photometry in water solutions; 7 - central processor; 8 - liquid crystal information monitor.

tions, when electron energy is by several orders of magnitude higher than the mean gas temperature, rather easily form in such a discharge. That is why dissociation of molecular oxygen with subsequent synthesis of O3 is very effective in such a discharge.

As accurate dosage is a very important aspect of OOT (ozone concentration varies from 1 to 100 mg per liter of mixture, with an accuracy of up to 1 mg), creation of a device with such characteristics was an intricate technological problem and it was solved in the 1990s. Combination of a wide range of generated ozone concentrations and precise metrology of its content (the measurements are carried out with the help of an optical device by UV photometry) is an advantage of this device in comparison with available analogs. The possibility of measuring ozone in water solutions is unique and has no analogs in Russia and abroad. Operations with the ozone generator under clinical conditions should be as simple as possible. Creating the UOTA-60 - 01 Med-ozone device, the authors paid special attention to "saturation" of electron blocks by microprocessors. To trigger this or that program the operator has only to press the button.

By the beginning of wide clinical application of OOT in Russia, the German specialists were the principal practitioners in this sphere of medicine; they considered parenteral (intravenous) injection of gaseous ozone as the main method for ozone saturation of the blood. However, this mode of treatment posed high requirements to the staff qualification and conditions of this procedure, and hence, another variant was sought for. An alternative method consists in intravenous injection of the ozonated saline (saline, saturated with ozone by means of transmission of the gaseous mixture through it, saline functioning as a neutral carrier in this situation). Injection of ozonated saline is a standard and simple manipulation for medical staff.

Today OOT is successfully used at several departments of Moscow Medical Academy. For example, OOT is introduced into everyday clinical practice at the departments of obstetrics and gynecology, skin and venereal diseases; extensive data on the use of this therapy is accumulated. As was mentioned above, the volume of ozone in "cocktail" with pure medical oxygen varies depending on the disease and therapeutic method.

When is ozone therapy effective? Let us first of all speak about the diseases important for pregnant women and, eventually, the health of the future generation.

Chronic placental insufficiency and intrauterine hypoxia lead to the fetal growth delay and appearance of small-for-date babies, poorly adapted to life, often suffering from cerebral disorders. Microscopic examination of the placentas from these mothers showed signs of previous infarctions, scleroses, and stenosed vessels, paralleled by attenuation of compensatory processes. Intravenous injections of the ozonated saline led to positive shifts. Ultrasonic examinations showed a selective effect of ozone on the placental vessels and stimulation of villous* differentiation-one of the main parameters characterizing the activity of fetoplacental transport (the metabolic processes between maternal and fetal blood are particularly active in the villi). Active growth of the villi was observed, the number and length of plethoric dilated vessels increased. Initially high levels of molecular products of lipid peroxidation decreased, previously low activity of antioxidant enzymes (superoxide dismutase and erythrocyte catalase) increased. Hence, the changes developing under the effect of ozone lead to normalization of microcirculation and oxygenation and are essential for the prevention and treatment of fetoplacental insufficiency. Clinical laboratory analysis of the newborns whose mothers received OOT indicated better weights and body lengths of these babies and their more rapid adaptation.

It was found that the new therapy effectively suppressed bacterial and viral infections in pregnant women (chlamydiasis, herpes simplex, cytomegaloviral infection, etc.) without antibiotics. Ozone played an important role, reducing the drug loading, primarily due to

* Villi arc processes on the chorionic membrane surface, by means of which the embryo is connected to the uterine wall; the placenta forms from villi. Nutrients pass from the mother to the embryo through villous walls. -Ed.

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Scleroderma: a - before and b - after the ozone treatment.

minimization of antibiotic doses, thus promoting normal gestation and appearance of healthy progeny.

In order to validate combined use of ozone and antibacterial therapy, an experiment was carried out to evaluate their separate and combined effects. The effects of serial dilutions of antibiotics and ozonated saline with ozone concentrations from 1.0 to 3.5 mg/l were studied on a culture of unicellular organisms. The results were evaluated by visual response of the cells to the treatment (presence of movements and their type, reversibility/ irreversibility of movement arrest, changes in the shape and degradation of cells).

Treatment of cell culture by the studied antibiotics (10-fold dilution) resulted in just an irreversible arrest of microorganism movements without alteration of their shape, which was interpreted as a decrease in the drug cytotoxic effect. Treatment with ozonized saline with ozone concentration of 1.0 - 1.5 mg/l saline caused a deceleration of movement, ozone concentration of 2.0 mg/l arrested movements, while the concentration of 2.5 - 3.0 mg/l led to the delayed destruction of bacterial cells.

Combined treatment by antibiotics and ozonated saline with ozone concentration of 1.0 - 1.5 mg/l led to alteration of the cells, and their delayed degradation, the concentration of 2.0 mg/l led to shape modification with immediate degradation. The cytotoxic effect of the same drugs was particularly demonstrative at ozone concentrations of 2.5 - 3.5 mg/l: target cells were destroyed immediately. Hence, it was shown that ozonated saline stimulated the bactericidal activity of therapy.

Skin diseases (dermatoses) remain a great problem of modern medicine. Ozone therapy is also useful in this sphere. Eczema is one of the most prevalent stubborn allergic dermatoses, responsible for up to 40 percent of all cases of skin diseases. It is characterized by various eruptions, annoying itch, risk of secondary bacterial infection, and high level of sensitizing to environmental factors. High-dose drug therapy is inadvisable for these patients, non-pharmacological treatment being preferable.

A group of patients with eczema received intravenous infusions of ozonated saline and external treatment of skin lesions (exposure to a flow of oxygen- ozone gaseous mixture). Almost all patients noted reducing of itching, healing of painful fissures in the lesions, and separation of the crusts after one-two procedures. 86 percent of patients with eczema exhibited more than 50 percent activation of the antioxidant system parameters after OOT in comparison with the initial levels.

Study of microhemodynamics by the so-called laser Doppler flowmetry in the skin lesions within the normal skin of patients with eczema showed an almost 4-fold increase (vs. the norm) in the parameters associated with inflammation and reduction of the microcirculation efficacy. The microcirculation efficacy index was significantly reduced almost similarly within the lesion and in intact skin, indicating a systemic disease. Ozone had a favorable effect on microcirculation; inflammatory symptoms decreased. High efficiency of OOT was confirmed by rapid regression of pathological manifestations.

Without discussing the details of the treatment, let us note that the new method is promising in treatment of the inflammatory vascular diseases, such as skin angiitis, scleroderma, lichen planus, herpes, etc.

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Three-dimensional picture of the facial skin: a - before and b - after the ozone treatment.

Ultrasonic "picture" of the edematous fibrosclerotic panniculopathy ("cellulitis"): a - before and b - after the ozone treatment.

OOT can be particularly effective in dermatocosmetology, due to the unique biological effects of O3, variety of the therapeutic methods, safety and harmlessness of OOT in comparison with other methods currently used.

Methods of nonsurgical rejuvenation of facial skin attract special attention now. On the one hand, this is explained by the fact that, considering modern standards of beauty, loss of attractiveness essentially deteriorates the psychoemotional status of middle-aged females, while on the other hand, a woman feels a certain psychological barrier at a surgical intervention, this giving certain advantages to the "therapeutic" technologies.

Considering the modern concepts of the pathogenesis of skin aging, it is most likely that methods for correction of involutive changes in the skin will be used. These treatments will modify oxygen metabolism, stimulate antioxidant activity, and normalize microcirculation. Ozone therapy is quite justified from this viewpoint.

A group of 20 women aged from 30 to 50 years received subcutaneous injections of oxygen and ozone mixture (ozone concentration 1 - 2 mg/l) once a week to correct age-specific changes in the skin of the face and neck. After 4 - 5 injections the clinical effect was noted both by the doctor and the patients: the facial contour "tightened", skin color became more even, skin dryness and desquamation decreased, the number of visible wrinkles reduced. Positive effects were stable during 4 - 6 months, and then next course of treatment was suggested. Instrumental evaluation of skin status after OOT revealed a 26 percent increase in the epidermis humidity and a 20 percent reduction of transepidermal loss of water, indicating improvement of the barrier characteristics of the skin. Studies of the skin biochemical characteristics showed improvement of its elasticity.

In conclusion, we should like to say that the method, which seemed to be quite exotic recently, now proved to be effective. About 700 UOTA-60-01 Medozone installations were produced, and hundreds of thousands of patients received courses of ozone therapy. Physicians can now more rapidly return the patients to active life, simultaneously improving the quality of treatment and reducing its duration and cost.

In 2005 the authors were awarded the prize of the Government of the Russian Federation in Science and Technology for the cycle of studies of physico-chemical bases of ozone synthesis, development and practical application of principally new therapeutic technologies.

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