• El ozono y sus aplicaciones médicas:

Oxidative stress diagnosis in ozone therapy.
Hernández F. (Cuba)

Ozone therapy is closely related with the oxidative stress concept since one of its main properties is to produce, paradoxically, an antioxidant effect by means of transient, regulated, exogenous and repeated oxidative stress. This ozone therapy property is able to regulate the endogenous oxidative stress established in different diseases. Therefore, the diagnosis or measurement of oxidative stress level is relevant for ozone therapy because allows treatment individualization and to know therapy effectiveness. One of the main reasons limiting the approval of ozone therapy by orthodox medicine has been the lack of controls. Competent control systems to assess the benefits and risks of systemic ozone therapy are not always used and in such case the treatment is based on anecdotal reports. A real diagnosis of the oxidative stress should be used as control system in systemic ozone therapy. A system for oxidative stress diagnosis has been developed in the Ozone Research Center of Cuba, which has been successfully evaluated in different pathologic conditions before and after ozone therapy cycles of treatment. Eight blood biochemical parameters are determined and their results computerized in software, which assess a redox index giving five grades of oxidative stress. The grade zero means no oxidative stress, grade 1 indicates slight oxidative stress, grade 2 is moderate oxidative stress, grade 3 is severe oxidative stress, and grade 4 is very severe oxidative stress. The ozone therapist can estimate the ozone concentration to be applied taking into account the grade of oxidative stress the patients have. Those patients in grade 4 it is recommended to treat with antioxidants before systemic ozone treatment, or to apply ozone therapy at a very low concentration and dosage being very cautious. During the evaluation of our system for oxidative stress diagnosis we found that the majority of patients with different diseases, where oxidative stress was involved, improved their oxidative stress condition after ozone therapy treatment.

First UAE pilot study on the therapeutic potentia of the ozone-oxygen mixture.
Re L and Al Jaziri A. (Italy)

The ozone therapy represents since many years a challenge in the treatment of several pathologies of apparent different aetiology. In the last years, many interesting reports revealed the ability of ozone in reducing pain in several osteoarticular diseases and being effective in lumbar disk herniation. The lack of randomised clinical trials still induce scepticism, however the direct clinical evidence reinforced the hypothesis that oxygen-ozone mixtures could be useful in different illness and in reducing the intake of the more used drugs, such as cortisones and anti-inflammatory agents. This work is a first attempt of a wide pilot study in the aim to better characterize at clinical level the efficacy of low ozone concentrations. The pilot study was designed for the treatment of various common pathologies using ozone-oxygen (OO) therapy. A controlled protocol of rectal insufflations (60-100 mL mixture 30-50 µg/mL ozone/oxygen) joined with the minor autohaemo,local intradermic (200 mL mixture 5-12 µg/mL ozone/oxygen) and the systemic minor autohemo (10 mL mixture 30-60 µg/mL ozone/oxygen in 10 mL blood) in conjunction with the major autohemo (120 mL mixture 30-60 µg/mL ozone/oxygen in 120 mL blood) were assessed. Two hundred and seventy six patients were scheduled for the OO protocol. Among these, 12 (4.3 %) were excluded prior the study started, due to the exclusion statements (clinical evidence of hyper-thyroidism and pregnancy). During the first two months were executed 1040 treatments. The patients who completed the treatment were 65 (23.5%) while 154 (55.8%) reached the middle phase of the programmed sessions. The remaining 45 patients (16.3%) are still in progress with the indicated treatment. Lumbar and knee pain represented the main clinical sign for both the sexes, with a mean percentage of 29.7 % and 27.9 % respectively. For the patients which reached the end of treatment (8-12 sessions) was evaluated the reduction of the symptoms during the treatment (mid) and at the end of the therapy (end) according to the VAS scale by assuming the start value of 100 %. The best result was for the male sex, which reached a reduction of the clinical signs of 7 1% in comparison with a reduction of 64 % for the female sex at the end of the treatment. The medium reduction of pain for both sexes was 40 % in the mid and 67 % in the end phase of the treatment, respectively. All the OO patients group showed a rapid relief of symptoms. The haematological parameters, including ESR, transaminases and hemocromo-cytometric data, resulted in the normal range after the final OO session. We hope that in conjunction, and not in alternative, of the most common pharmacological therapies for all the pathologies that more frequently affect the human population, OO treatment could represent a valid help in the context of a more ethic and safety medical treatment.

Methods of ozone therapy in treatment of superfluous weight.
Uphimtseva L.A. (Russia)

During a year, 77 female patients with obesity (I-II stages), at the ages of 35 to 47 years, were studied. Among them 56 female patients revealed, according to U.S.I.:

• The diffuse increasing I-II stages (all women live in Irkutsk or Irkutsk region, which is the territory of goiter endemia), 15 % among these patients had treated by the iodine preparations and thyroid hormones.
• The level of TTH was low and approached to the lower figure of the standard level.
• Cholesterol figure, b-LP and atherogenic coefficient increased to 3.8.

So, the cause of the overweight of the body in this experimental group is combined: alimentary and insufficient function of the thyroid. For the treatment, the infusions O.P.S. and subcutaneous inyections 0₂/0₃ in S.Z.C. were used for 10 days. The procedures were alternated in a day.

After the treatment:

• U.S.J is without negative dynamic.
• Hormone figure achieved the normal level.
• Cholesterol figure and b-LP had a trend to decrease and the atherogenicity index was lower 3.6.

Index of the body mass decreased 7 %, as average. Anthropometric measures (breast hips, shoulders and waist) decreased 4 % - 7 %, as average. It was recommended to low the doses of the prophylactic and thyroid medication to these patients.

Ozone Therapy in bronchial asthma.
Calunga J.L., Turrent J., Menéndez S., Soler L., Hernández F. and Montenegro A. (Cuba)

Bronchial asthma is a pathological condition characterized by several reaction of the respiratory ways. Bronchial asthma is the disease that has gained interest from many countries, due mainly to its high death rate and its high hospital cost. In the other hand, when ozone is applied to human in appropriate doses and by a therapeutic way of administration, it produces a sort of biological action with beneficial results without causing adverse reactions or genotoxic damage. In our study, ozone therapy was the treatment for patients with moderate bronchial asthma Ozone was administered by different ways of applications: rectal insufflation and autohemotherapy, in 20 ozone therapy sessions. The respiratory test was assay by Peak Flow, Vital Capacity, Expiratory Volume, HLA_DR molecule expression and the serum level of IgE, at the beginning and at the end of our study. The results demonstrated that ozone therapy increases the Peak Flow and the expiratory volume at the first second and reduced HLA_DR molecule expression and serum level of IgE. These results show that ozone treatment can be a beneficial alternative therapy in inflammatory process of respiratory way. This study try to explain that ozone therapy mechanism can decrease the inflammatory reaction of respiratory way in patients with bronchial asthma and increase their quality of life.

Oxygen-ozone therapy in the sport: a case report.
Re L, Giovagnoli L., Belegni R., Francesca R. and Re F. (Italy)

The employment of the oxygen-ozone therapy in the muscular and articular lesions has been neglected in the past both for the presence of consolidated principles by the pharmacological point of view like FANS, corticosteroids, etc, and for the presence of instrumental and rehabilitative techniques endowed with a certain and sure action. The observations of recovery in the sport traumatism, so as rapid as more precocious it is the treatment from the moment of the traumatic event, the disappearance of muscular lesions and the full restitutio ad integrum of the athletes submitted to the ozone treatment has conducted us to propose this case report both for the excellent result and for the completeness of the anamnesis, the instrumental and the therapeutic data available. The report describes the effect obtained in a subject of masculine sex, age 18, belonging to the National Athletic Italian League for the specialties 100 and 200 meters. The patient showed a history of trauma to the right leg during a competition the preceding year with diagnosis of femoral two-headed stretching after a complete RMN examination. Due to the chronic persistence of the diagnostic elements after the most common therapeutic treatments and the presence of pain symptoms, which makes still precarious the normal athletic preparation activity, the athlete was submitted to our evaluation for a possible therapy through oxygen-ozone. After careful anamnesis evaluation it is decided to intervene with biweekly sessions through intra-muscular administration of oxygen-ozone (8-12 µg/mL), during 4 weeks. Every session, performed with circadian personalized protocol, it foresaw the administration to divide of 60 cc of mixture to the concentration of which above in the nearness of the zone interested from the lesion and of 30 cc in the same muscular area of the symmetric limb. The resumption of the trainings has already happened progressively before the end of the cycle. The athlete has continued to gradually train himself underlining the absence of any painful or contractile phenomenon. The complete absence of symptoms has also been confirmed by the control RMN performed at the end of the treatment where "any alterations of the right semi-membranous muscle could be appreciated, neither alterations of the vascular structures were present. To the light of the results of which above, thanks also to the acquired documentation executed in different clinics and accomplishedly documented, ozone therapy is set as matter of scientific discussion in relationship to its potential employment in the sport trauma. Our casuistry in the last year of reference is appraisable in around 60 athletes divided for various disciplines. In the almost totality of the athletes (85 %) a resumption of the competitive activity is occurred within the first week by the ozone treatment with a limitation to the employment of medicines, usually not deprived from serious collateral effects mainly after their chronic assumption.

Lymphotrophic introduction of medical ozone in case of inflammatory diseases of female reproductive system.
Alechina S. and Belskaja A. (Russia)

Among the gynecological diseases of women in reproductive age, the incidence of inflammatory processes in uterus and uterine appendages is in the third position. Appropriate methods of treatment prevent the development of partial recurrences and menstrual, reproductive and sexual dysfunctions. The main treatment of chronic salpingo-oopforitis is antibacterial therapy. Evident abnormalities in blood circulation and in the structure of tissues in the affected organ are observed. Nonspecific anti-inflammatory therapy, remedies improving microcirculation in the focus of pathology preventing formation of microtromboses and development of micronecroses and those activating cellular and humoral immunity are used. Taking into account the properties of medical ozone, that influences in all the components of the pathogenesis of the given nosology, a new method of ozone and antibiotic therapy lymphotrophically was developed in the clinic of Medical Technologies at NNMA. Twenty six women have been treated for chronic salpingo-oophoritis and 7, for subacute inflammatory processes in the organs of pelvis minor. The ages were between 19-36 years old. Antibiotic as gentamicin was administered to all patients intranodularly through inguinal lymph nodes (nodi lymphatici inguinales). It has been observed that the first endolymphatic introduction of antibiotic caused in 9 patients a spike in temperature, 0.7 - 1.0 ^oC increase of temperature being caused by ousting toxins into blood. The increase of temperature diminishes with subsequent introductions. Simultaneously during 10 days, rectal insufflations of 900 mL/kg of ozone-oxygen mixture and introduction of medical ozone (100 mL/kg) into round ligament (ligamentum teres uteri) of uterus projection were applied. No side effects were observed. On the third-fourth day of treatment discomfort and heaviness in the lower part of the abdomen disappeared, stool and urination came to normal in comparison with the check patient population. By the fifth-sixth days abdominal pains had disappeared and in 6 cases normalization of menstrual cycle had been observed (after 2-6 months retention menstrual - like reaction appeared), there had also been observed general improvement of health condition, sleep and appetite. Gynecological examination and swab analysis revealed positive dynamics - disappearance of abdominal wall tenderness, normalization of ovary size, disappearance, in the majority of cases, of cystic changes, abatement of band of fibrous tissue and induration of uterine tubes, loosening and softening of adhesions, which was confirmed by ultrasound. As the result of treatment, the number of lipid peroxidation products, characteristic of chronic inflammation decreases and the antioxidant enzymes considerably increase in the blood of patients. Thus, lymphatrophic therapy plus ozone therapy decrease the local inflammatory process and improve the general health of patients suffering from gynecological diseases.

Ozone Therapy in Diabetes Mellitus.
Menéndez S., León O.S., Al-Dalien S.M., Martínez G., Candelario E.J. and Fernádez-Montequín J.I. (Cuba)

It is well recognized the presence of oxidative stress in Diabetes Mellitus. Ozone can exert its protective effects by means of an oxidative preconditioning, stimulating and/or preserving the endogenous antioxidant systems. The aim of this paper is to evaluate the ozone effects in the oxidative stress associated to diabetes, in a preclinical and clinical studies. Preclinical study - Rats were divided in: 1- negative control group; 2- positive control group, using streptozotocin (STZ) as a diabetes inductor; 3- ozone, 10 treatments (1 mg/kg), after STZ-induced diabetes and 4- oxygen (26 mg/kg), as group 3 but using oxygen. There was a correspondence between the decrease of hyperglycemia, the reduction of oxidative stress and the histopathological results. Ozone treatment was able to protect b -cells against STZ damage demonstrating how its antioxidant properties preserved b -cells function and reduced hyperglycemia induced by STZ. Clinical study - 101 Patients with neuroinfectious diabetic foot were divided in 2 groups: ozone, 52 patients (using 20 sessions of rectal and local ozone) and antibiotic, 49 patients (using systemic and local antibiotics). The efficacy of the treatments was evaluated comparing the glycemic figures, the area and perimeter of the lesion and the biochemical parameters involved in oxidative stress and endothelial damage, between both groups. Ozone treatment improved glycemic control by decreasing hyperglycemia, increased insulin sensitivity, prevented oxidative stress associated to Diabetes Mellitus and its complications, standardized organic peroxides figures and activated superoxide dismutase in comparison with antibiotic therapy. The pharmacodynamic effect of ozone, in the treatment of patients with neuroinfectious diabetic foot, can be ascribed to the possibility of being a superoxide scavenger. Clinically, patients treated with ozone therapy had a better (also with a less number of amputations) and faster recovery of their lesions in comparison with the patients treated with antibiotic therapy (26 days vs 34 days). Any side effect was found. These results demonstrated that medical ozone treatment could be a future alternative therapy of diabetes and its complications.

Intravenous ozone therapy applications for the treatment of sensorineural deafness with various genesis.
Barkhotkina T. (Russia)

The purpose of the present work is to study the influence of parenteral applications of ozonized physiological solution to the auditory function status of patients with sensorineural deafness. This includes its postinfectious, vascular, toxic and posttraumatic genesis. The criteria, of the treatment clinical efficiency, are the threshold pure tone audiometry and a number of other standard audiological tests, such as the subjective noise presence (SN), the dynamics of whispered (WS) and conversational speech (CS) appreciation and the change of mean hearing loss (MHL) during the inpatient treatment. The positive results of therapy are evidence of the appreciable amelioration of an auditory analyzer function, resulting from the intravenous ozonized physiological solution introductions. The WS increment averaged is 2.26 m, CS - 2.1 m, MHL reduction - up to 19 dB . The clinical efficiency is confirmed with the optimization of lipid peroxidation-antioxidant system (LP-AOS) state, energy metabolism and immune status with this category of patients. The state of peripheral blood erythrocytes has also been researched by a method of holographic interference microscopy. Today, the live fringes holographic interferometry is only one method of determining the phase microobjects, in particular erythrocytes in their native forms at real time. It is recognized, that all the sensorineural hard of hearing patients, regardless of etiology and prescription of disease, have erythrocytes as flat disks. There are slugged erythrocytes and blood microclots. As a result of parenteral ozone therapy the one-type qualitative changes of the erythrocytes forms are to be observed. They acquire the biconcave disocyte form corresponding to physiological pattern and have a wholesome influence on the state of the organism. Analyzing the data, it is possible to establish the high efficiency of ozone therapy in the treatment of acoustic analyzer pathology based on correcting the main parts of the disease pathogenesis.

Sudden deafness and its treatment using ozone therapy and laser puncture.
Turrent J., Machin V., Palmón M.T., Menéndez S. and González L. (Cuba)

Sudden deafness is a severe hearing loss, usually in only one ear, that develops over a period of a few hours or less. It produces a sensorineural hearing loss, that requires an appropriate care. Considering the ozone biological effects (improvement of the antioxidant defense system, modulation of the immunological system, enhancement of blood rheological properties, increase of tissue oxygenation) and the therapeutic effects of low power laser (2 mW), we decided to use ozone therapy in combination with laser puncture in patients suffering of sudden deafness. Twenty patients (16 having sudden deafness in one ear and 4 in both ears), between 35 and 58 years old, were included in the study. In all cases it was their first episode of the disease. The lapse between the beginning of the symptoms and the application of the treatment varied since 4 hours to one month. To all patients, an initial and final audiometry (one month after the end of the treatment) were performed. In the initial stage, all patients presented a sensorineural hearing loss, either in all the frequencies registered (125 to 8000 Hz) or in one or more frequencies. The range of the hearing loss intensity fluctuated between 30 and 80 decibels. Hemogram, glycemia, cholesterol, triglycerides and creatinine had normal figures. CAT scan was performed in 10 patients and it was normal. Ozone therapy was applied, daily, by autohemotherapy (mixing 200 mL of ozone in 200 mL of blood with an ozone concentration of 40 mg/L) for a total of 15 sessions. Laser puncture was applied also daily, 15 sessions, and was stimulated the macrosystem points in relation with the ear and the microsystem points in relation with the external part of the ear. Radiation was made towards the ear canal, perpendicular to the eardrum. The results demonstrated that the patients treated had a total, partial and no recovery in 17 (88 %), 2 (9 %) and 1 patients (3 %), respectively. The ozone positive effect in the oxygen transport to tissue, in the blood rheological properties and its immune modulatory capacity, as well as the stimulation of the microcirculation and the improvement of cell biology produced by the laser and the stimulation of points of acupuncture had a decisive role in the therapeutic results achieved in this study.

Intratonsilar ozone therapy.
Silva L. (Cuba)

The present study summarizes the evolution of 2 300 patients with diagnosis of tonsillitis, treated by the method of ozone therapy intratonsillar, during the last eight years. The ozone concentration used was 50 mg/L and a volume of 5 mL, in each tonsil. The main number of ozone applications was four. To these patients, an exam of its pharynx, as well as microbiological pharyngeal studies were performed, at the beginning and at the end of the treatment and along a year after the treatment. A system for oxidative stress diagnosis, measuring different antioxidants and pro-oxidants biomarkers, was performed in 10 patients. The oxidative stress results demonstrated that these patients were in no stress condition after the ozone treatment. Outstanding results were obtained in 97 % of patients. No relapse was presented along the year of evaluation. Also, the economic advantages in comparison with the traditional surgical method (amigdalotomy) were pointed out.

Ozone in radiology.
Ugarte J.C., Guerra J.A., García J. and Cruz Y. (Cuba)

In 1989, we began to use the ozone as a contrast media in Digital Subtraction Angiography (DSA). It gives us: a good image quality, some advantages in high risk patients, decrease of side effects, decrease of the cost and have some therapeutic actions. Other advantages, as contrast medium in DSA, are the possible use in patients with: renal failure, hepatic failure, heart insufficiency and myeloma. Ozone was used as a contrast media in: 277 aorto-iliac arteries, 340 right femoral arteries, 237 left femoral arteries, 489 renal arteries, and in 5 mesenteric arteries. Also, a protocol for ozone thrombolytic evaluation had been developed and the basic criteria measured were: plasminogen determination, platelet clot, fibrinogen determination, fibrin degradation products. The thromboelastometry determination, as well as all the final results showed that ozone has thrombolytic properties. We have used ozone, as a thrombolytic agent in Percutaneos Transluminal Angioplasty (PTA), in 621 examinations, being done 153 in high risk patients, with intolerance to iodinated contrast media, diabetic or with renal failure. All the procedures were performed by Seldinger’s technique catheterization of the femoral arteries or by the way of the axilar arteries. Arteriography was restricted only to the infradiaphragmatic arteries and it s branches. Any side effect was observed.

Application of ozone in liver cirrhosis.
Hernández J, Llanio R. and Ávila L. (Cuba)

This paper presents the results of 5 years of ozone treatment in patients with liver cirrhosis of different etiologies, using intra-rectal and intramuscular ways of ozone administration. The Cuban ozone generator OZOMED’s equipment was used. A group of 42 patients with liver cirrhosis post alcoholic, autoimmune, cardiac and post virus B and C was taken into account. The gas was applied in cycles of 30 applications three times per year, during the first and second years; two times in the next two years and only one in the fifth-last year. The ozone concentration was 40 mg/L. The results showed the normalization of more than 85 % of the clinical symptoms and signs, haemochemical parameters plus others, since the six months of treatment. Some patients eliminated the virus B or C. Patients increased their health quality. No adverse effects were observed in any patient.

Ozone therapy in AIDS. A case report.
Méndez N.I., Menéndez S. and Rivero J. (Cuba)

The widespread use of ozone therapy is due to the biological effects of ozone, such as: oxidative stress, metabolic and immune system regulator, as well as its germicidal power. In the Acquired Immune Deficiency Syndrome (AIDS), the target of the virus that causes the disease are the cells having the CD4 molecule on their surface, where the main cells of the immune systems are located. The virus destroys those cells and causes the unbalance of the organism, while the disease is developing. The use of ozone in AIDS, as a powerful immune modulator and antioxidant is applicable as complementary therapy. A IIIc AIDS patient suffering from fatigue, cachexia, diarrhea, dehydration, anemia, high levels of glucose, creatinine and protombine time, a 0.37 % CD4/CD8 index and a viral load in 2 400 000/mL, who was taking a retroviral cocktail was treated with an ozone cycle by rectal route, with a 5 mg dose with interferon, transfer factor and erythropoietin. After finishing the ozone treatment, a final assessment was performed. We found then that the fatigue, diarrhea, dehydration and anemia had disappeared, the patient had gained 8 kg in weight and the glucose, creatinine and protombine time levels were normal. Moreover, three months after the ozone treatment was finished and without interrupting the administration of interferons and a pentatherapy, the CD4/CD8 index increased 0.71 % and the viral load decreased to 1 700/mL. In our report, we assess the effect of ozone as an immune modulator, an antimicrobial and antioxidant in AIDS/HIV patients.

Application of ozone therapy in patients with psoriasis.
Recio E., Rodríguez M., Harrys C., Cuesta, I. Mapolón Y. and Rodríguez J.L. (Cuba)

Psoriasis is a common, genetically-determined dermatitis consisting of discrete pink lesions surmounted by characteristic silvery scaling. Lesions are usually chronic. General and nonspecific measures are utilized to give comfort to the patient, as well as to help control the disease. Taking into account the positive biological effects of ozone, a prospective study about the effectiveness of ozone therapy in patients with psoriasis was carried out in the "Orfilio Peláez Molina" Provincial Center of Retinitis Pigmentosa, of Camagüey Province. The sample was constituted by 130 adult patients, of both sexes, who accepted to participate in this study. Ozone was applied by rectal administration, at a concentration of 48 mg/L and 200 mL, for a cycle of 20 sessions. It was taking into account the symptoms and signs refered, as well as the classification of the psoriasis. Weekly evolutions were carried out during the treatment. The principal results were achieved in the female group, with 65 % of recovery. Signs and symptoms dissapeared, mainly pruritus and eritema. In general, all patients had a satisfactory behaviour, with savings of 1870 pesos, in comparison with conventional therapy.

Ozone therapy and acupuncture in degenerative osteoarthritis. An alternative treatment.
Milanés J.R., Pérez A., Corengia C., Menéndez S., Daniel O. and Prieto E. (Cuba)

In order to study the efficacy in pain treatment, as well as other signs and unpleasant symptoms in the degenerative osteoarthritis, two alternative therapeutic methods: ozone therapy and acupuncture were applied. A sample of 200 patients were divided at random, into two groups of 100 cases for each treatment (ozone and acupuncture). It was used an OZOMED equipment (Cuba) for the production of ozone. Ozone group: patients with generalized arthritis were treated daily, by rectal application, with an ozone concentration of 50 mg/L and a volume of 200 mL. In patients with knee pains, ozone was injected in the antero-external part of the knee, using an ozone concentration of 35 mg/L and a volume of 20 mL, twice per week. In patients with shoulder pains, an ozone concentration of 35 mg/L with a volume of 10 mL was applied in the superior region of the shoulder, near the acromion, twice per week. Acupuncture group: acupuncture was applied, in the pain area, three times per week, taking into account the theory of points and meridians, described by the Asiatic school. The needle was maintained during 20 min, with a manual stimulation each 5 min. In both treatments, the number of sessions were in relation with the pain disappearance and the improvement in the objective and subjective symptoms referred by the patients. Ozone therapy and acupuncture achieved improvements of 59 % and 53 %, respectively, without significant differences between both groups. It was eliminated or diminished the number of medicines given to the patients, as well as those already described undesirable effects of the AINES, already mentioned in the world bibliography. A significant economic saving is also reported in comparison with the traditional methods (analgesics, anti-inflammatory drugs). The employment of these methods allowed the patients to increase the independence in its daily works. Adverse effects were not presented during and after these therapies. It was only need a scarce number of applications (between 3 and 7) in order to obtain an improvement, as well as the decrease or disappearance of the pains and of other symptoms and signs presented in this pathology. An increase in the quality of life of these patients was achieved.

Adverse reactions in ozone therapy.
Pérez L.J., Román C. and García. (Cuba)

he aim of this paper is to describe the presence or not of adverse reactions during and after the applications of ozone therapy in patients with Retinitis Pigmentosa in the last ten years. A retrospective study was done with 2486 Retinitis Pigmentosa patients in the "Camilo Cienfuegos" International Retinitis Pigmentosa Center, from January 1993 to January 2003. Major autohemotherapy, 15 applications, (with an ozone concentration of 40 mg/mL and 50 mL of volume) or rectal insufflations (with the same number of ozone applications and ozone concentration, with a volume of 100 mL) were applied to these patients. The results demonstrated that 8 patients referred some kind of adverse reactions: 2 with nauseas, other 2 with stomach depletion, euphoria in 2, unusual fatigue in 1 and metal taste in 1; 5 of them receiving rectal insufflations. This represents the 0.001 % of the total of patients treated. No ophthalmic side effects were observed in this group. Conclusion: In our institution the ozone therapy has been found to be an extremely safe medical therapy, free from side effects.

Ozone therapy in chronic arterial insuffiency.
Sayoux C., Eleías-Calles B. and Rivas N. (Cuba)

Chronic arterial insufficiency is a group of clinical events related to a partial and progressive reduction of arterial blood flux in arms and legs. A surgical treatment can be employed but the evolution of patients is variable.Taking into account the ozone therapy effects on oxygenation and blood rheological properties, a study was performed on 46 patients from the Angiology and Vascular Surgery Service of the hospital during 2001 - 2002. Most of the patients were male and aged from 61 to 80 years old.Two groups (with and without surgical operation) were treated with daily rectal insufflation or intra-muscular injection, in cycles of 20 sessions. The treatment was repeated after a three months period. Local ozone was also used for the treatment of sores. Clinical symptoms as claudication and skin colour, before and after treatment, were evaluated. Health improvements in 61 % and 78 % of patients were observed at the end of the first and second cycles of ozone treatment, respectively.

Ozone therapy in sickle cell anemia.
Rivas N., Durán B. and Eleías-Calles B. (Cuba)

Drepanocitic or sickle cell anemia is a chronic haemolytic anemia due to congenital troubles of red blood cells haemoglobin. This illness is frequent in Cuba , mainly in black people.The study was performed on 12 patients attended in the Haematology Service of the Hospital. Most of them were male (36 - 45 years old). Each patient was treated with daily intra-rectal ozone insufflation for 15 days in 3 cycles per year. Complementary analysis before and after treatment showed an increase of the oxygen partial pressure in blood and light modification of haematic variables. A decrease of vaso occlusive crisis and a good clinical evolution was observed in 79 % of the treated patients after a year of evolution. Also, the use of ozonized sunflower oil OLEOZON^® showed a great efficacy in the treatment of maleolar ulcers present in these patients

Application of ozone therapy in ulcerative colitis.
Hernández J., Llanio R. and Ávila L. (Cuba)

We report the preliminary results in the treatment of Ulcerative Idiopathic Colitis and Crohn Disease using ozone by intramuscular and intra-rectal ways of administration. The main objective was to describe the ozone action in those pathologies. An OZOMED equipment made in the Ozone Research Center (Cuba) was used. A group of 10 patients of ulcerative idiopathic colitis and 10 patients with Crohn disease were studied during two years. The gas was applied in cycles of 30 applications, twice per year and at ozone concentrations between 30 - 40 mg/L. Important signs and symptoms, like diarrhea with mucus and blood, intestinal pain, articular inflammation, disappeared in the first year of treatment, in both pathology, in more than 75 % of patients treated. The patients gained body weight and had a higher health quality.

Behavior of adverse reactions in patients treated with ozone therapy.
Rodríguez M., Betancourt Y., Mapolón Y., Recio E., Palma M. and Harrys C. (Cuba)

The aim of this study is to evaluate the presence or not of side effects, as well as the grade of satisfaction, in 100 patients treated with ozone therapy in the "Orfilio Peláez Molina" Provincial Center of Retinitis Pigmentosa, in Camagüey Province. The ozone was applied by rectal administration, at a concentration of 41 mg/L and 200 mL, for a total of 20 sessions. The majority of cases were in the age group of 25 - 35 years and of male sex. The more common patology were optalmological diseases and giardiasis. None of the patients treated showed any sign of adverse reactions or undesirable effects due to the therapy applied. This study is in agreement with the literature, because when ozone therapy is applied in an appropriate way (concentration, doses, ways of application) any deletereous effect is present. Also, a good and fast recovery of the patients was achieved, improving their quality of life, with less cost in medicine and considerable savings from the social security point of view.

Ozone and acupuncture in the treatment of patients with incomplete cochleo-vesticular syndrome.
Borroto V. and Menéndez S. (Cuba)

The aim of this study is to evaluate the Doppler effect of the basilar trunk, in patients suffering fr om an incomplete cochleo vestibular syndrome with dizzy predominance, treated with ozone, acupuncture and medications. Sixty patients were divided, at random, into four groups of 15 patients each: 1-ozone, 2-acupuncture, 3-ozone plus acupuncture and 4-medications. A vascular examination with Doppler, of the basilar vertebra trunk, was made to each patient at the beginning, at the end of the different treatments and after 6 and 12 months. Ozone treatment was applied, daily, by rectal insufflation (50 mg/L and 200 mL) for a total of 15 sessions. Patients treated with acupuncture received 10 sessions (2 per week) in the regular meridians and auriculotherapy. The medication used in group 4 was meclizine or cinarize (1 tablet every 8 h, during 3 weeks). The Doppler results demonstrated a significant improvement (90 %) in those patients treated with ozone and ozone plus acupuncture in comparison with group 2 and 4. This improvement persisted during the whole year of evaluation. No significant differences, between groups 1 and 3, were obtained. It is concluded that ozone therapy can be an appropriate treatment for this disease.

Ozone therapy is proper for tympanic perforations?
Gómez M., Iglesias O. and Lorenzo T. (Cuba)

It is known that ozone has an antifungal and antibacterial role, as well as modulates the immunological system. Authors studied a group of 48 patients (up to 14 years old) presenting tympanic perforation since 2 years (both, mesotympanic or epitympanic), considering that these patients could have anatomical and immunological alterations, and constitutional factor. Ozone was applied, daily, by rectal insufflation, 30 sessions, in doses depending on the age. Otorrhea, disappearance of hypoacusia, enhancement of the general status, as well as the nutritional disorder were taking as evolution criteria. The results demonstrated that 94 % of patients cured, according to the evolution criteria. No side effects were presented (e.g. vertiginous status, mastoiditis or meningeal symptoms).

Correction of hypoxia disorders of blood during extra corporeal processing with ozone and antihypoxia medicine.
Peretyagin S.P., Kostina O.V., Vilkov S.A. and Peretyagina N.S. (Russia)

We have studied on a dog model if the blood hypoxia disorders may be corrected with ozone and gutimin (guanilurea) after a hemorrhagic shock. Heparinized blood (52 mL) with a preliminary added antihypoxia medication was subjected in vitro to the ozone processing in an oxygenator. The ozone dose was 250 µg. Hypoxia alterations were defined by increase in blood glucose and incompletely oxygenated products (lactate, pyruvate), statistically significant pH change (acidosis), hypercapnia, growing buffered base lack, decreased antioxidant activity, increasing the primary products of lipid peroxide oxidation, growing the chemiluminescence and erythrocytes aggregation. Blood ozonization caused pH shift into alkaline side, gaining pO₂ and soluble oxygen amount more than 2 times and an increase of chemiluminescence by 24 %. This ozone-intensified peroxidation simultaneously induced a blood own antioxidant system activity growth (its fermental part), aerobic glycolysis growth (carbohydrate conversion products decreased more than 30 %), disrupted the free radical oxidation chain at the primary products, and also decreased significantly erythrocytes aggregation, apparently due to an increase of fluidity of their membranes and oxidation fibrinogen modification. Combined use of gutimin and ozone, increased significantly the blood antioxidant capability, improved acid-alkaline condition and aggregation characteristics to optimum values. Gutimin as a substrate of antioxidant protection served as a target to be bombed by active oxygen. Repairing oxidation blood metabolism (lactate and pyruvate levels decreased) and detoxication ozone effect without hyperoxia appearance were abserved.

Possibilities of ozonized oil (O’TRI) in the treatment of burnts.
Peretyagin S.P., Sokolov S.A., Pylaeva S.I., Struchkov A.L., Kuvakina N.A. and Babushkin V.V. (Russia)

It was analyzed the medical behavior of enamel ozonized olive oil "O’TRI" prepared on base of "Olive Oil Refined Pharma DAB-10" for the treatment of burnt patients. It has a wide spectrum of chemical characteristics: the main components are glycerins of oleic and linolenic acid. The method of preparation was using 2 different ways: poorly ozonized olive oil and strongly ozonized olive oil. Chemically it contains:

Index	Poorly ozonized olive oil	Strongly ozonized olive oil
- O - O -	2.40 %	4.06 %
superoxide number	240	406
acid number	11.4	15.4
average molecular mass	4.920	3.643

Its bactericidal action was proved in 7 germ cultures obtained from festering-surgical patients: Proteus, Staphylococcus aureus, Pseudomonas, Streptococcus, Neisseria. After 24 hours of incubation, using ozonized oil, all the samples turned out to be sterile. Clinical use of ozonized olive oil, in the first 3 - 4 days after burn, for the local treatment of thermal injury with bacterial association (Staphylococcus aureus and Pseudomonas) decreases the microbial load in 3 - 4 levels. Also, the use of ozonized oil promote a more fast growing of granulation tissue and healing, normalizes the blood bactericidal activity, increases the level of lysozyme, phagocytic activity, reaction blastic transformation of lymphocytes and the production of antibodies (normalizing content of circulatory antibodies components). The healing time for the burn area was between 7 - 10 days.

Ozone effect on proteolytic activity in brunt patients.
Kontorschikova K.N., Peretyagin S.P., Efremenko Y.R. and Kostina O.V. (Russia)

Proteolysis has been emphasized for the last years due to its participation in physiological function, regulation and development of many pathological conditions. The aim of this study is to evaluate the proteolytic system in burnt patients after ozone therapy. A control group included 30 patients with burns over 20 % total body surface area that received the standard treatment procedures. Eight patients combined the conventional treatment with major autohaemotherapy with an ozone dose of 2.5 mg. The ozone therapy duration was 10 procedures. Investigations were made on the 3 - 5 days and 13 - 15 days after sustaining the thermal trauma. The investigations showed that the patients had trypsin and elastase activity increased 2.6 and 10 times the normal figures, respectively (p < 0.001), on the 3 - 5 days after the injury. Inhibitor protein activity of a 1 -antitrypsin was decreased 4 times (p < 0.001). On the 13-15 days there are reducing the trypsin and elastase activity as much as 1.5 times (p < 0.001) in the control group and increasing the a 1 -antitrypsin activity as much as 1.5 times. It has been found the thermal trauma leads to increasing lipid peroxidation activity appearing in a chemiluminescence increase and total antioxidant activity decrease in blood plasma. The major autohaemotherapy resulted in more considerable reduction of proteinase activity: trypsin - as much as 2 times, elastase - as much as 2.3 times (p < 0.001). The a 1 -antitrypsin activity was strengthened 5 times that was 1.5 times as high as the normal values. Lipid peroxidation intensity was kept about the same level. There was a statistically significant increase of the total antioxidant activity by 54 %. Thus, the major autohaemotherapy with ozone in complex burn disease treatment causes an adaptive system activation observed by rising the a 1 -antitrypsin activity and, therefore, bringing the proteolytic process down as well as by the positive effect on the pro- and antioxidant balance.

Kallikrein-kinin system in condition of oxidative influence.
Yefremenko J.R and Kontorschikova C.N. (Russia)

Kallikrein-kinin system is the proteolytic system, which regulates the activity of basic physiologic system: fibrinolysis, hemostasis, complement system and renin-aldosteron-angiotensin system. Kallikrein are known to perform the role of allergic and inflammatory mediators and to participate in regulation of microcirculation and arterial pressure. The aim of this work was to investigate the effect of oxygen and ozonated saline solution on the kallikrein-kinin system activity. The proteolytic activity of kallikrein and kinin-destroying enzymes was studied by Erlanger method with the help of peptic substrate in plasma and in homogenates of the pancreas and of the small intestine. Injection of oxygen saline solution led to increase the activity of kallikrein and kinase during 48 hours in plasma and pancreas (p < 0.001). Injection of ozonated saline solution was characterized with dose-dependent response of proteolytic system. The low doses of ozone did not cause activation of kallikrein-kinin system. The high doses of ozone induce free radicals processes, increase of proteolytic activity of kallikrein and decrease of kinin-destroying enzymes. Thus, estimation of proteolytic enzymes can be used as a sensitive criterion to control efficacy and safety of ozone therapy.

Free-radical condition estimating during ozone therapy treatment.
Kuzima E., Kubysheva N., Kontorschikova C.N. and Kostina O. (Russia)

We used the hardware - methodical complex for "activity of peroxide oxidation of lipids" (POL activity) determination and the "antioxidant activity" (AOA) estimation. The complex uses automatic analysis of the chemiluminescent kinetic curve, inducted by modeling system - hydrogen peroxide + Fe²⁺ ions. Determination of POL and AOA was carried out in plasma of human blood, urine and saliva. Besides, conditions of "peroxide resistance of erythrocytes" (PRE) and "phagocyte activity" were determined. Patients with pneumonia, bronchial asthma and burns were studied. Antioxidant therapy and ozone therapy were used in these patients. Antioxidants for each patient were individually selected, according to the degree of antioxidant influence on PRE in a modeling system. There was noted the correlation of POL activity, AOA changes with a degree of patient condition. At a high degree of intoxication, confirmed with traditional methods, POL activity was reduced on 25 - 40 %, comparing to the normal level. AOA was also below the normal level. Inflammation diseases increased POL activity without lowering AOA. Ozone therapy was conducted with a permanent control of POL - AOA system state. The greatest clinical effect was noted at AOA growth and AOA normalization. In case of POL activity growth and AOA lowering, treatment was made with the help of individually picked-up antioxidants. This treatment leads to POL activity and AOA normalization and improves the condition of erythrocytes. Ozone therapy produces an immune status normalization, which can be estimated using data about the phagocytes activity.

Ozone therapy in the treatment of hypertension.
Maslennikov O. and Gribkova I. (Russia)

According to the membrane theory of hypertonic disease, the increase of arterial pressure is caused by the dysfunctions of regulatory mechanisms in circulation system, due to energy deficiency on the cellular level. The decrease of cellular energy is connected with genetic changes of membrane regulation (overload) of intracellular calcium. Mitochondria are known to be responsible for energy supply with oxygen playing the leading role. It is in mitochondria with participation of oxygen that oxidation of fatty acids and glucose takes place. The released energy (in a form of ATP) is then used to meet energetic needs of the body. The most significant manifestation of membrane defect in calcium regulation is observed in decrease of ATP synthesis and consequently the reduction of free energy delivered to membrane pumps. It makes cellular membrane system function on a lower energetic level. Hypertension is considered to be a compensatory response of the circulation system to the reduction of cellular energy by activating sympathetic nervous system, endocrine system and other integration systems. Thus, the increased ATP is a natural circulation condition that corresponds to the decreased level of cellular energy. In ozone therapy, increase of cellular oxygen supply activates proton ATP-ase, that connects the processes of respiration and oxidative phosphorilation in mitochondria, improving ATP synthesis. It normalizes the activity of K, Na, Ca ATP-ase transport pumps responsible for maintenance of cation concentration gradient and, thus, increases cellular energetic potential. It is also stipulated by activation of glycolytic and pentose ways of glucose oxidation. It becomes evident from the fact that ozone therapy, as independent hypotensive remedy, proved to be effective in 70 % of cases in initial labial hypertension. In patients with steady hypertension-II, when it became irreversible due to structural changes in the heart and vessels, kidneys, adrenal glands and systems, ozone therapy was used in combination with hypotensive medications, reducing their dosage.

Perspectives of using ozone in the case of fetus hypoxia in obstetric practice.
Grischenko V.I., Zinchenko V.D., Lypoyad K.V., Golota V.I., Sykchomlin E.A. and Lypoyad V.S. (Ukraine)

Ozone therapy was used as a component in the complex treatment of intrauterus fetus hypoxia (IFH). Pregnant women with IFH were intravenous injected with ozonized physiological solution, 200 mL per day, during 5 days. The concentration of ozone in the solution was 1 - 3 mg/L. For the production of ozone, a new type of ozonizer was used, in which ozone is synthesized by the means of barrierless glow discharge of high pressure. Working on pure oxygen such ozonizer allows to produce ozone concentrations from 0.1 to 80 mg/L. The analysis of clinical histories of the new-born children showed that in the group, where pregnant women with IFH received intravenous injections of ozonized physiological solution, the average indicators of the parameters of physical development of the new-born children were higher than that in control group: mass 3300 ± 58 g and length 53 ± 0.5 cm versus 2920 ± 80 g and 48.4 ± 0.4 cm. The clinical results can be explained by the improvement of oxygen-transport function of erythrocyte after the impact of therapeutic doses of ozone.

Effects of ozonated saline solution on apoptosis.
Alyasova A., Kontorschikova C. and Novikov V. (Russia)

The aim of the present investigation is to evaluate the effect of the ozonated saline solution on apoptosis of immunocompetent cells. Ninety six patients with breast cancer have been studied. Fifty women received polychemotherapy, 46 patients were complementarily introduced ozonated saline solution. Concentration of the soluble form of CD95 and the content of the cells carrying membrane CD95 antigen before and after treatment in both groups have been estimated. In patients receiving only polychemotherapy after the course of treatment the number of cells carrying membrane CD95 antigen had increased, and concentration of the soluble form of FAS- antigen was elevated. In the group infused with ozonated saline solution statistically significant decrease of the soluble form of FAS-antigen (p < 0.05) has been noted, and the number of CD95 + cells has reduced by 16 % (p < 0.05). Evidently, the observed effects of ozonated saline solution are connected with membrane- stabilizing, immunomodulating, and fibrinolytic effects of ozone.

Effect of ozone therapy on the level of biomines in patients with rheumatic arthritis.
Kontorschikova C.N., Artemyeva E.G. and Zhuravlyeva N.V. (Russia)

The purpose of this article is to study the efficiency of ozone therapy in patients with rheumatic arthritis (RA), and first of all its effect on the dynamics of histamine, serotonin and catecholamine levels. Clinical observations in 140 patients with RA, at the age of 18 - 56 have been carried out. In 70 patients (control group) were administered intravenous infusions of ozonated saline solution (0,9 % NaCl), at an ozone concentration of 2 mg/L in conjunction with the conventional therapy. The other 70 patients (the comparative group) did not receive ozone therapy. Before and after the treatment, smears were taken from all the patients - imprints of periferal blood. To reveal catecholamines, serotonin and histamines fluorescence, histochemical technique with cytofluorometry in a fluorescence microscope, was used. Intensity of luminescence was measured in conditional units. Original blood tests of the RA patients showed elevated figures of histamine, serotonin, and catecholamines in erythrocytes, polymorphonuclear leucocytes, lymphocytes, thrombocytes, and plasma. In patients of the control group general condition after ozone therapy has improved, positive dynamics of the main parameters of rheumatoid process activity has been noted: ESR (erythrocyte sedimentation rate), levels of C-reactive protein, a2 - globulins, seromucoid, fibrinogen, hydroxiproline (p = 0.01), as well as albumine globulin index (p = 0.01). The reduction in the medication dosage for the patients of this group started from the 5 - 6^th day. Dosages of nonsteroid preparations were cut on the average by 30 - 40 %. In half of the patients taking glucocorticoids, medications were withdrawn, in the others the intake reduced by 30 - 40 %. During ozone therapy more rapid regression of systemic manifestations has been observed (vasculitis, peripheral lymphodenopathy). The most significant changes of biogenic amine levels have been noted in polymorphonuclear leukocytes and lymphocytes. The reduction of all biogenic amines during ozone therapy was significantly more marked in the control group compared to the patients undergoing conventional therapy. Thus, positive effect of ozone on one of the pathological link of rheumatic arthritis has been clearly demonstrated.

Complex use of ozone for an anaerobic infection control in the burnt patients.
Struchkov A.A., Peretyagin S.P., Corotkova N.L., Vilkov S.A., Pylaeva S.L. and Kuvakina N.A. (Russia)

The presence of anaerobic infection in patients with large areas of thermal lesion influences significantly against the burn disease evolution, as well as increases lethality, achieving 56 % in clostridium infection and 48 - 60 % in non clostridium form. Eight patients have been treated in the Russian Burn Center for the last 5 years, in which a trauma was complicated with an anaerobic infection with the expressed clinical manifestations and a critical intoxication. In 6 patients a sepsis was diagnosed, supported by the laboratory investigations, in two cases a non clostridium infection was revealed in a blood test. Ozone was used for the control of the anaerobic infection. Major autohemotherapy (10 sessions) with an ozone dose of 500 - 1000 µg was applied under a blood chemoluminescence control. The damaged extremities were irrigated with ozone-oxygen mixture, using plastic bags, with an ozone concentration of 10 mg/L and a 60 min exposure locally after a surgical treatment. Besides, the injured surface was irrigated with ozonized physiologic saline solution at an ozone concentration of 3 mg/L. A sanction of premises by ozone with a concentration, exceeding an admissible concentration limit, was concluded twice a day by 45 min in the individual isolated ward for the hospital infection control. A patient’s respiration during a session of sanation was provided through an oxygen mask. The general state of these patients was improved after 2-3 days of treatments, also the concentrations of creatinine, urea, myoglobin titer in blood were decreased, the tissue edema was significantly decreased, the wound bacterial dissemination was 2 - 4 times decreased. The sensibility of microflora to antibiotics was 3 - 5 times increased.

The efficiency of ozone therapy in complex treatment of patients with oncogynecological diseases.
Kontorschikova E., Kontorschikova C., Novikov V., Kryzhanova M., Kachalina T. and Grechkanev G. (Russia)

This work presents the ozone therapy results in patients with ovary and uterus cancer (with dissemination), after nonradical surgical intervention. All the patients were undergoing chemotherapy according to individual programme. Besides clinical examination, to all the patients were measured: lipid peroxidation in blood serum according to the chemiluminescence index, primary (dien conjugates), secondary (trien conjugates) and final (Shiff bases) products and general antioxidant activity. To assess the immune status the mononuclear cell of peripheral blood were immunophenotyped regarding the quantity of CD4, CD8, CD16, CD22, CD25, CD71, CD38, CD95, HLA 1, HLA DR. Also, the activity of cellular and humoral immunity, cells capacity for adhesion and apoptosis were determined. All the patients showed a depression in lipid peroxidation processes, antioxidant activity and immune status index. Taking into consideration the capacity of low ozone concentration to improve the immunity and lipid peroxidation, ozone was used in these patients. Ozone therapy was applied, daily, by rectal insufflations, with an ozone concentration of 2000 µg/L of gas mixture, cycle of treatment of 5 - 7 days, with a break for a day of chemotherapy. The clinical effect could be seen in the improvement of appetite, better sleep, reduction of nausea and weakness. Initial laboratory results demonstrated the increase in total antioxidant blood activity. The lipid peroxidation and immune status indexes changed according to the individual treatment of chemotherapy and initial conditions of the patients. Preliminary conclusions can be done on the expediency of ozone therapy in the treatment of chemotherapy complications in patients with oncogynecologycal pathology.

The use of ozone in the treatment of inflammatory diseases of uterus and appendages.

Peretiagina N.S., Kachalina T.S. and Grechkanyov G.O. (Russia)

Acute inflammatory processes of female genital organs cause, in a great number of cases, serious problems in menstrual, sexual and reproductive functions and are marked by long and current relapses. They are accompanied by the following clinical features: increase of microflora resistance to antibiotics, appearance of medical intolerance, that essentially reduces the efficiency of standard methods of treatment. It results in high frequency (up to 76.6 %) of chronic non-specific inflammatory processes in internal genital organs. There were 37 patients with uterus and appendages inflammatory diseases, under control, who along with traditional therapy were treated with 8 to 10 infusions of 0.9 % ozonized physiological solution with an ozone concentration of 3000 µg/L. At the same time, in the control group 15 patients received only traditional antibacterial, sedative, desensibilizing therapy and vitamins. It was shown that, at the given category of patients, infusions of ozonized solution plus the traditional treatment, positively influenced the biochemical and cytological parameters of blood, albumin and lipid exchange, endogen intoxication and coagulation ability of blood. On the background of local inflammatory process subsiding the patients had the increase of curtailing time and bleeding, decrease in activity of plasma procoagulants, protrombin index and fibrinogen. Some parameters of endogen intoxication were simultaneously reduced: the level of lipid peroxidation, malonic dialdehyde, the level of middle peptides, bilirubin, creatinin. Positive influence of ozone therapy on the albumin synthesis of liver function is revealed. Application of ozone in the complex therapy of inflammatory diseases of female genital organs allows to improve the treatment results, to diminished the frequency of complications and to reduce the time of treatment.

Correction by ozonized physiologic salt solution of the alterations of microcirculation and rheologic properties of blood in patients with neurocirculatory dystonia.
Shikhragimov V.A. and Struchkov A.A. (Russia)

The meaningful pathogenetic factors of a neurocirculatory dystonia (NCD) are the disturbances of microcirculation and rheologic properties of blood. The different stress agents favour a NSD progression and its transition to hypertension, atherosclerosis. We have earlier established that a parenteral use of one of the active forms of an oxygen - ozone at the background of a stress state (a postresuscitation period) significantly improves microcirculation and the micro- and macrorheologic properties of blood. The aim of the present work is to study the efficacy of the ozonized physiologic salt solution (OPS) on peripheric circulation in patients with a NCD. Treatment included 8 - 10 intravenous infusions of the OPS, 200 mL with an ozone content of 60 µg. The state of microcirculation (by a biomicroscopy of conjunctiva, a capillaroscopy of a nail matrix), peripheric circulation (by the radioactive "Xe 133") and the blood rheologic properties (on a rotational viscosimeter) were investigated. Seventy two patients were examined, 52 of them were with a NCD. The microcirculatory disturbances (spasticoatonic state of micreovessels, their initial microscopic alterations, the perivascular edema, appearance of the erythrocyte intravascular aggregation) and the appearance of the rheologic deviations (a blood viscosity increase) were presented in these patients. A treatment of the microcirculatory disturbances has been conducted in 32 patients with NCD. An intravenous infusion of the OPS was included in a standard scheme of therapy (the low-molecular dextrans, antiaggregants, beta-blockers, anticoagulants). The analysis of the results permitted to reveal a trustworthy decrease of total microcirculatory index, the decrease in arteriole constriction, the improvement of "Xe 133" clearance, the decrease of blood viscosity, the improvement of the erythrocyte deformity and a decrease in venous partial pressure. This study sustain the ozone preparation inclusion in a complex therapy of NCD in order to obtain a more effective correction of the microcirculatory disturbances.

Homeostasis state at a use of ozone in the wounded and having been burnt in a postshock period.
Peretyagin S.P., Miroshin S.I., Startsev Y.P., Struchkovm A.A., Vilkov S.A. and Shikhragimov V.A. (Russia)

A modern trauma is characterised by the expressed disturbances of homeostasis. A traumatic and a burn shock, frequently accompanying the similar lesions, presupposes a development of dangerous for life complications and requires a use of highly effective, pathogenetically methods of treatment. Thus, we’ll explain the interest to elaborations of the oxidative therapy means. A possibility of a systemic ozone therapy use in the wounded and having been burnt in a state of shock and an early postshock period is investigated in this work. The intravenous infusions of 400 mL of a physiologic salt solution, saturated by ozone, as well as reinfusions and hemotransfusions of blood treated by ozone were included in a program of an antishock therapy after an adequate compensation of the lost volumes of blood and stabilization of the hemodynamic values. Twenty eight patients were studied. The ozone concentration in a gaseous phase at saturation of NaCl solution by it, was 2.5 - 3 mg/L. A 4 mg/L ozone concentration was used for treatment of reinfusing and conserved donor blood (with the dates of storage, exceeded 3 days). In a group of patients, in which ozone was used for getting them out of a shock state, an earlier increase of arterial pressure up to a stable level (compared to a control group where ozone was not used), a tachycardia decrease and a "shock" index correspondingly, an increase in blood hemoglobin and erythrocyte level, a decrease of rectocutaneous gradient of temperature and an hour diuresis reduction were observed. We have used a new approach to correction of the hemodynamic deviations (the microcirculation, hemorheology, hemoconcentration disturbance) - an exfusion of an erythrocyte mass and substitution of that volume by the oxygenated perftorane. A substantial increase of oxygen tension in arterial and venous link of a vascular bed and a stability of the hemodynamic parameters are observed clinically in burnt patients. Thus, the use of oxygen-containing means, in a complex antishock therapy composition, demonstrates their perspectiveness.

Prevention and regulation of endogenous intoxication in burnt patients in complex treatment with ozone.
Peretyagin S.P., Struchkov A.L., Vilkov S.A., Kostina O.V., Voroviev A.V., Lebedev M.Y., Borisevich A.L. and Kuvakina N.A. (Russia)

Intoxication is considered one of the most severe appearance of early burn disease and it is the result from restoring the postshock circulation, absorbing the incompletely oxygenated metabolites and products of protein and cell degradation from microcirculation and the wound surface. Efferent detoxication methods quite often lead to complications and have no persuasive efficacy in burnt patients, especially in timeless application. That’s why we have used local and systemic ozone therapy in an early period of the burn disease for the last years (1998 - 2004) side by side with an active surgical interference and complex therapy including infusion-transfusion therapy, medicines and efferent methods. The ozone therapy is aimed at the substituting oxidation detoxication within blood vessels and in tissues, activation and sustaining the oxygenous homeostasis links, at immunomodulation and optimization of all detoxication systems. Ozone therapy contributes to optimize the treatment by decreasing the wound contamination with microbes. A number of microbic strains decreases as much as nearly 2 times. A Gram-negative microflora reduction amounts to 12 - 23 % (for the first week and the beginning of the third week). Burn wound dissemination decrease, intensifying the reparative process and active epithelization of burn IIIA wounds, with the formation of the mature granulation capable to covered the lesion. Besides the microbial contamination decrease there is lessening biochemical and immunological manifestations of endogenous intoxication and autoagression. Particularly, decrease of blood leucocytes amount is associated with the increase of lymphocytosis, with a statistically significant increase of T-helpers subpopulation and a decrease of T-suppressors. The ozone effect produces a normalization of the intoxication leukocyte index, the midmolecular level and circulating immune complexes level. There is less expressive growth of urea, creatinine and products of lipid peroxidation. Thus, ozone therapy in a complex treatment of burn disease in an early stage establishes favorable conditions to perform an early autodermoplasty and to obtain an optimum autograft survival.

Ozone therapy of a duodenum ulcerous disease.
Kulyoshina N.V., Kiseloyova S.V., Fatichov R.R., Peretyagin S.P., Kostina O.V., Kuleshin V.N. and Struchkov A.A. (Russia)

The modern treatment schemes for the ulcerous disease permit to achieve an ulcer healing in not more than 70 - 89 % of patients in a period of 25 - 45 days and with a recurrence frequency in 50 - 60 % of patients. The different antibacterial medications (in high doses) are used for the eradication of Helicobacter pylori. Different side effects have been reported with the used of these treatment schemes, besides the resistance of Helicobacter pylori to certain antibiotics. We have treated 44 patients, with duodenum ulcerous disease, using ozone therapy, under the pro- and antioxidant system control by a method of chemoluminiscense. The evolution time of the disease was from 7 to 11 years. Pains were observed in 76 % of cases, heartburn in 33 %, constipations in 31 %, sleep disturbances in 60 % before ozone therapy. According to the ulcer fibrogastroduodenoscopy data, the duodenal bulbs were predominantly localized on the anterior wall in 39 % of patients. In 72 % of patients the ulcerous disease was associated with Helicobacter pylori. The scheme of treatment included to drink ozonized mineral water, two times per day, in an empty stomach, using a volume of 400 - 500 mL, at an ozone concentration of 2 mg/L, when an expressed painful syndrome existed, and further on with an ozone concentration of 0.5 mg/L After taking the ozonized water, patients drank 25 - 30 mL of ozonized olive oil. Besides, all the patients have been intravenously infused with 200 mL of an ozonized physiological saline solution, 3 times a week with an ozone dose of 100 - 120 µg during 3 weeks. The used of this ozone therapy treatment permitted to achieve an ulcer epithelisation in 8 - 10^th days. The ulcers were healing without the coarse cicatrix forming and were not accompanied by an expressed deformation of the duodenal bulb. Helicobacter pylori eradication took place in 82 % of clinical observations. No deviations of the organism antioxidant systems were observed.

Ozone therapy in breast cancer.
Kontorschikova C.N. and Alaysova A.V. (Russia)

The aim of this study is to assess the potentials of ozone therapy, as adjuvant and neoadjuvant treatments, of patients with breast cancer. The sample was constituted by 180 patients, age ranging from 35 to 65 years, with histologically confirmed breast cancer. Thirty four patients were using ozone therapy plus neoadjuvant polychemotherapy, 52 patients received ozone therapy with adjuvant treatment, 46 patients received placebo and cytostatics and 48 patients were on polychemotherapy. Ozone therapy was applied by intravenous saline infusions. The treatment results were assessed by clinical control data, lipid peroxidate and antioxidant activity (AOA) levels and immunogramme readings. The use of ozone therapy made it possible to improve the patients’ quality of life and to increase the efficiency of treatment. The women that were on neoadjuvant ozone therapy revealed its potential effect on the part of cytostatics. According to the mode ozone therapy was administered, at the end of the treatment, a reduction of Shiff bases (54 %), Dien conjugates (52 %) compared with the initial levels were observed. At the same time AOA increased.

Ozone effect on the structure and function of erythrocytes in patients with hypoxia.
Kontorschikova C.N. and Barkhotkina T.M. (Russia)

This work presents the results of erythrocytes estimation in patients with hypoxia of different origin before and after the application of 5 - 6 sessions of intravenous infusions of ozonated saline (0.9% NaCl), at an ozone concentration of 1 mg/L. The erythrocytes morphology and function, before and after intravenous ozone therapy, was assessed in blood samples by the method of interferation holographic microscopy. The method allows todepict alive erythrocytes in real time scale and by phase profile to restore its form. All the examined patients with hypoxia of different origin were found to have microthrombus and slathered erythrocytes. Erythrocytes were of flat shape and it revealed the decrease of their functional capacities. When they are treated with ozonated saline solution, with an ozone concentration of 1 mg/L, the number of pathologically destructive forms and aggregated cells diminished and erythrocytes resumed distinct biconcave shape. This effect was more pronounced in originally maximal pathological deviations in the form of erythrocytes. Healthy people did not reveal any change in the shape of erythrocytes after been treated with ozonated saline. The assessment of erythrocytes membrane viscosity was done by measuring the exemerisation of fluorescent probe. This hydrophobic probe can be installed between the chains of fatty acids and phospholipids of membranes bilayer. Fluorescent spectrum with wavelength of 370 - 390 and 460 - 470 nm is registered with a spectrofluorimeter. Therapeutic ozone concentrations did not change the h -index, responsible for viscosity of lipid bilayer. There were no changes in membrane resistance model, which was defined by the method of aspiration, but isotropic tension (T) of membrane rupture had 20 % decrease. Acid resistance of erythrocytes due to therapeutic ozone concentrations has 10 % increase. The erythrocytes were found to assume the characteristic features of increased antioxidant activity and decreased levels of peroxidation products. Thus, the effect of ozone therapy is distinctly reflected on structure and function of erythrocytes and can be modified by different methods.

Biochemical properties of ozone therapy.
Kontorschikova C.N. and Yefremenko J.R. (Russia)

The use of ozone in medicine is based on the ozone properties and are expected to be used according to its concentration. Highly concentrated ozonated solutions responsible for the bactericidal effect against a wide range of microorganisms are used externally. These ozone properties are caused by its oxidative capacity, that in high concentrations may cause activation of free radical reactions. Parenteral ozone has been proved to be effective in different diseases, when major and minor autochaemotherapy, intravenous and intraarterial ozonation are indicated. In Russia, it is the intravenous injection of ozonated physiological solution that is widely used in medical practice. In these cases the role of ozone becomes important due to the activation of oxygen dependent reactions of metabolism and Crebs cycle with formation of a large amount of protons necessary to restore the buffer capacity of antioxidant defend system against free radical and peroxidates. Ozone is capable to mantain the dynamic balance of prooxidant and antioxidant systems responsible for membrane structure and metabolism. To prevent negative effect of ozone on cell membranes in the lipid peroxidation (LP) activation processes, it is necessary to define the exact concentrations and methods. Screening method of LP estimation within 30 - 60 seconds is intensity of induced chemiluminescence. Intraperitoneal injection of ozonated saline can act trigger- like launching the main regulatory mechanisms:

• Activate H⁺ -ATP -ase, to provide ATP important energy - dependent processes.
• Bring K⁺ - Na⁺ and Ca²⁺ - ATP-ase to normal range and to regulate distribution processes in inter - and intracellular space.
• Correction of secondary messengers (cAMP and cGMP contents) in liver and tumour tissue of sarcoma - 45 inoculated animals. Levels of cAMP and c GMP can indirectly show the tendency and activity of cells physiological processes in extreme conditions cAMP contents in the cells of different organs increase in response to activation of hypathalamo-hypophis-adrenal system. In liver cells the cyclic nucleotide acts as an agent to mobilize internal potential of cells in order to provide active reactions of synthesis and energy generation.
• Dose-dependent response of proteolytic system, inhibitory antiproteolytic plasma potential. Estimation of proteolytic enzymes (trypsin-like and chymotr y psin - like proteinase, elastase, kallikrein, kininase and leucinaminopeptidase) can be used as a sensitive criterium to control efficacy and safety of ozonated saline solution.