Systemic Ozone Therapy Research Articles

Effectiveness of enriching drug treatment with systemic ozone therapy in patients with post-COVID asthenic syndrome

Effectiveness of enriching drug treatment with systemic ozone therapy in patients with post-COVID asthenic syndrome

Systemic Ozone Therapy May Improve the Perception of Quality of Life: Ozonized Glucose Solution 5% Extends Reach to Patients Ineligible for Blood Infusion.

Ozone therapy is a complementary treatment that has gained popularity due to its safety and wide range of applications. Systemic ozone therapy involves withdrawing 100 to 200 ml of blood, treating it with an oxygen-ozone mixture, and then reinfusing it. This process requires large-caliber venous access, which can be a limitation. To overcomethis, alternative administration methods have been explored, including the use of ozonized solutions.The aim of this study is to evaluate the clinical effects of systemic ozone therapy on the perception of quality of life and to analyze the outcomes of different administration methods. Three groups of patients were treated: one group received classical systemic ozone therapy, another received ozone therapy via intravenous infusion of a 5% glucose solution, and the third group alternated between the two methods. The results showed an improvement in perceived quality of life in all groups, regardless of the method used.Thus, systemic ozone therapy showed efficacy in improving the perception of quality of life in our group. Moreover, intravenous infusion of a 5% glucose solution has made it possible to treat patients who could not be treated with the classical method, achieving similar results.

Effect of Ozone Therapy on Epidural Fibrosis in Rats

To demonstrate the effect of medical ozone therapy on the development of epidural fibrosis. A total of 25 Sprague-Dawley male rats were randomly divided into 3 groups: a control group (L3-L4 laminectomy only), a systemic ozone therapy (SOT) group (L3-L4 laminectomy only+ intraperitoneal 15 mL [30 μg/mL] ozone), and a local ozone therapy (LOT) group (L3-L4 laminectomy only+ subcutaneous 15 mL [30 μg/mL] ozone). Ozone therapy was administered 4 times on a 3-day interval during the wound-healing process, with the first dose immediately administered after surgery. The effects of ozone therapy on vascular endothelial growth factor, inflammation, and epidural fibrosis between groups were evaluated. Staining with vascular endothelial growth factor was significantly less in the group that received SOT compared with the control group (P= 0.021). When the groups were compared in terms of inflammation, it was found that inflammation was less common in the SOT and LOT groups compared with the control group (SOT vs. control: P= 0.004 and LOT vs. control: P= 0.024), whereas inflammation was found to be significantly less in the SOT group compared with the LOT group (P= 0.008). In the histopathologic evaluation of epidural fibrosis, there was no significant difference between the SOT and LOT groups but less epidural fibrosis was observed in both groups compared to the control group (LOT vs. control: P= 0.037; SOT vs. control: P= 0.018). Medical ozone therapy may be an alternative method that can be used effectively and safely in the prevention of epidural fibrosis after laminectomy.

The chemotherapy-induced peripheral neuropathy treatment with novel systemic ozone therapy method: A case report

Cancer is one of the leading causes of death in the world today. Chemotherapy is promising to overcome it, but chemotherapy accompanies with side effects. Among these side effects can be pointed to Chemotherapy Induced Peripheral Neuropathy (CIPN).

Ozone in dentistry: systemic ozone therapy and local use of ozonated water and ozonated olive oil in dentistry and dental surgery

The local application of ozonated water in dentistry, as a disinfectant, as means for detoxification. Systemically administered ozone in the low concentration range (10 to 40 ?g/ml) in the form of autohemotherapy (MAH) or rectal insufflation (RI) works synergistically inducing bioregulation.
 Chronic subclinical inflammations often have their origin in teeth and jawbone structures.Toxins, like the products of bacterial metabolism, may cause inflammations. Ozozated water has the potential to degrade toxins and to disinfect the surgical site from local infections. Additionally there must be taken mechanical cleansing efforts, to remove biofilms and toxins in all fields of dentistry. Toxin conjugation in the liver is activated by systemic ozone therapy.
 Therapy of chronic inflammatory diseases needs both, the local application of ozonated water in dentistry and systemic ozone treatments.

Effectiveness of systemic ozone therapy for the correction of endotoxin aggression in children with generalized appendicular peritonitis

The aim: to study the effectiveness of the use of systemic ozone therapy according to the method developed by us in the complex treatment of children with generalized appendicular peritonitis at the stage of postoperative treatment in relation to the correction of indicators of endotoxin aggression. Materials and methods. On the basis of the Clinic of Pediatric Surgery of the Children’s Republican Clinical Hospital (Donetsk) 60 school-age children (from 7 to 17 years old), operated on for generalized appendicular peritonitis, were examined. The group 1 consists of 30 children, who at the stage of the postoperative period in addition to comprehensive therapy received a course of systemic ozone therapy developed by us. 30 patients of the group 2 received the traditional treatment. In all children the initial level of systemic endotoxemia indicators was determined. Blood sampling from patients was carried out initially before surgery. The dynamics of the studied indicators were evaluated on the 7th and 14th days of the postoperative period. Results. In all patients with generalized appendicular peritonitis the development of endotoxin aggression was established. Against the background of a course of systemic ozone therapy by the 14th day of the postoperative period, a statistically significant (p < 0.05) decrease in the level of indicators of endotoxin aggression relative to patients of the comparison group was noted. Conclusions. The results obtained prove that the development of widespread appendicular peritonitis occurs in children with the formation of endotoxin aggression. The use of systemic ozone therapy according to our proposed method in the complex therapy of these patients at the stage of the postoperative period makes it possible to achieve a reduction in laboratory indicators of endotoxin aggression in a shorter time.

The effectiveness of the inclusion of ozone therapy in comprehensive rehabilitation programs for post-COVID syndrome

BACKGROUND: The global scale of the pandemic of a new coronavirus infection is determined by the involvement of the entire world population in the problem. Recently, the scientific and medical community has been paying increased attention to the consequences of COVID-19, including aspects of the rehabilitation of patients who have had this infection.&#x0D; AIM: to evaluate the effectiveness and safety of including ozone therapy in the rehabilitation of patients with long COVID.&#x0D; MATERIALS AND METHODS: This randomized controlled clinical trial included 51 patients aged 29 to 78 years with a confirmed diagnosis of pneumonia associated with SARS-CoV-2 (J12.8). Patients were divided into three statistically comparable groups depending on the complex of rehabilitation treatment, which they received. In the first (control) group (n=17), a 10-day course included daily breathing exercises and physiotherapy for the lungs. In the second (main) group (n=18), in addition to the complex of basic measures, daily intravenous infusions of ozonized saline with an ozone concentration of 2.0 mg/l were performed daily. Patients in the third group (comparison, n=16) received ozone therapy every other day. In order to determine the effectiveness and safety of the inclusion of systemic ozone therapy in a comprehensive program for the rehabilitation of patients after COVID-19, an analysis of blood oxygen saturation in air, laboratory parameters (D-dimer and C-reactive protein), changes in peripheral blood flow, a decrease in patients' oxygen demand to and after a 10-day course of rehabilitation treatment. The dynamics of patients' complaints and changes in the patient's quality of life during rehabilitation were assessed using the EQ5D questionnaire.&#x0D; RESULTS: All patients during rehabilitation had positive dynamics in all parameters, there were no adverse reactions during the course and 2 months after rehabilitation. An analysis of various indicators revealed a greater effectiveness in prescribing systemic ozone therapy for rehabilitation. When comparing different methods, it turned out that daily ozone therapy had a better effect on laboratory parameters than daily ozone therapy.&#x0D; CONCLUSIONS: The use of ozone therapy in the complex rehabilitation of patients after COVID-19 is safe and effective. Further study in more patients is needed to determine indications and criteria for use.

Effect of ozone therapy on the emotional state of a patient after the novel coronavirus infection

Purpose of the study. To assess the impact of systemic ozone therapy on the emotional state of patients after the novel coronavirus infection in the early recovery period. Materials and methods. A randomized controlled clinical trial, including 39 patients aged 29 to 78 years with a confirmed diagnosis of bilateral polysegmental viral pneumonia associated with SARS-CoV-2 coronavirus (J12.8), was conducted. The patients were divided into 2 statistically comparable groups. In the first group (N=19), the patients received a standard complex of rehabilitation treatment: exercise therapy, chest massage, and physiotherapy procedures (low-frequency magnetic therapy and drug electrophoresis in the projection of the lung fields), while the patients in the second group received daily intravenous infusions of ozonated saline solution with an output ozone concentration of 2.0 mg/l in addition to the basic complex rehabilitation. In order to assess the impact of systemic ozone therapy on the emotional state of the patients who underwent COVID-19, we analyzed the dynamics of complaints, changes in the quality of life of the patient based on the EQ-5D-3L questionnaire, as well as the severity of anxiety and depression according to the results of the HADS (Hospital Anxiety and Depression Scale) on the 1st and 10th days of the rehabilitation treatment. Results. In all patients, positive dynamics was noted against the background of rehabilitation measures in relation to complaints, the severity of anxiety and depression, as well as the quality of life. At the same time, the analysis of various indicators revealed greater efficiency in the prescription of a comprehensive program, including systemic ozone therapy. Conclusions. The use of ozone therapy in the complex rehabilitation of patients who have undergone COVID-19 has shown its efficiency and safety. Further study in higher number of patients is required to determine indications and criteria for its use.

Immune changes at the injured sites in oxazolone-induced ulcerous colitis: Influence of ozone therapy

Impaired immunoregulation and development of autoimmune response to antigens of own intestinal microbiota and inflammation-altered antigens of colonic cells represent the key links in pathogenesis of inflammatory bowel diseases. Multimodal biological effects of ozone presunme the usage of local and systemic ozone therapy in complex treatment of many inflammatory diseases of the gastrointestinal tract. The aim of our work was to study effects of intraperitoneal and rectal ozone therapy upon immune parameters of the lesion focus in oxazolone-induced ulcerative colitis in the course of time. The study was carried out on 64 adult male inbred Wistar rats weighing 240±20 g. Experimental ulcerative colitis was produced by oxazolone treatment (4-ethoxymethylene-2-phenyl-2-oxazolin-5-one) (SigmaAldrich, USA). The ozone-oxygen mixture was injected intraperitoneally or rectally at a concentration of 1.0-1.2 mg/l, once a day, in a volume of 10 ml, at the 6-day course. The results of experiments were recorded on the days +2, +4 and +6. The concentrations of IL-17 and IL-23 was determined in a homogenate of intestinal tissues (Bender Medsystems, Austria) using a Personal LAB analyzer; expression of CD4 and FoxP3 on intestinal lymphocytes was determined by immunohistochemistry technique (ElisaKit, China). The observed tissue damage of large intestine showed an increase from day 2 to day 6 of oxazolone-induced ulcerative colitis. The total number of lymphocytes significantly increased upon development of experimental colitis, with parallel decrease in the number of CD4+ lymphocytes and FoxP3-positive T lymphocytes. IL-17 and IL-23 concentrations in the tissues increased with the severity of inflammatory changes in the lesion focus. Intraperitoneal ozone administration was associated with significant reduction of lymphocyte contents in the damaged tissues on the 6th day, whereas the numbers of CD4+ and FoxP3 positive T lymphocytes normalized by the 6th day. The levels of IL-17 and IL-23 increased from day 2 to day 6, with a lower IL-23 values on day 6 as compared with non-treated animals. Rectal administration of ACS led to the normalization of FoxP3 cells on the 6th day to the values of intact animals. The levels of proinflammatory cytokines (IL-17 and IL-23) significantly decreased on the 6th day as compared to the group of animals without treatment, which could be due to anti-inflammatory properties of ozone.

The role of systemic ozone therapy in the rehabilitation of patients after COVID-19

To evaluate the effectiveness and safety of ozone therapy in rehabilitation of patients with previous COVID-19. A randomized controlled clinical trial included 51 patients aged 29 - 78 years with SARS-CoV-2 pneumonia (J12.8). Patients were divided into 3 comparable groups depending on the complex of rehabilitation. In the first (control) group (n=17), a 10-day course included daily breathing exercises and physiotherapy for the lungs (drug electrophoresis and low-frequency magnetotherapy). In the second (main) group (n=18), rehabilitation was combined with daily intravenous infusions of ozonized saline with ozone concentration of 2.0 mg/l within 5 days with subsequent standard rehabilitation. In the third group (n=16), patients received 5 ozone therapy procedures every other day. To determine the effectiveness and safety of systemic ozone therapy in rehabilitation of patients with previous COVID-19, we analyzed oxygen saturation, laboratory data (D-dimer and C-reactive protein), need for oxygen support before and after rehabilitation course. Complaints and quality of life throughout the rehabilitation program were assessed using the EQ-5D questionnaire. All patients had positive changes of all parameters. There were no adverse reactions throughout the rehabilitation program and 2 months later. We observed higher effectiveness of rehabilitation with systemic ozone therapy. Moreover, daily ozone therapy had a better effect on laboratory parameters compared to ozone therapy every other day. Ozone therapy is safe and effective in complex rehabilitation of patients with previous COVID-19. Further studies of large samples are needed to determine indications and appropriate criteria for this rehabilitation program.

Potential therapeutic effect of oxygen-ozone in controlling of COVID-19 disease.

Atmospheric ozone is produced when nitrogen oxides react with volatile organic compounds. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome contains a unique N-terminal fragment in the Spike protein, which allows it to bind to air pollutants in the environment. ‘Our approach in this review is to study ozone and its effect on the SARS-CoV-2 virus and patients with coronavirus disease 2019 (COVID-19). Article data were collected from PubMed, Scopus, and Google Scholar databases. Ozone therapy has antiviral properties, improves blood flow, facilitates the transfer of oxygen in hypoxemic tissues, and reduces blood coagulation phenomena in COVID-19 patients. Ozone has immunomodulatory effects by modulating cytokines (reduction of interleukin-1, interleukin-6, tumor necrosis factor-α, and interleukin-10), induction of interferon-γ, anti-inflammatory properties by modulating NOD-, LRR- and pyrin domain-containing protein 3, inhibition of cytokine storm (blocking nuclear factor-κB and stimulating nuclear factor erythroid 2-related factor 2 pathway), stimulates cellular/humoral immunity/phagocytic function and blocks angiotensin-converting enzyme 2. In direct oxygen-ozone injection, oxygen reacts with several biological molecules such as thiol groups in albumin to form ozonoids. Intravenous injection of ozonated saline significantly increases the length of time a person can remain hypoxic. The rectal ozone protocol is rectal ozone insufflation, resulting in clinical improvement in oxygen saturation and biochemical improvement (fibrinogen, D-dimer, urea, ferritin, LDH, interleukin-6, and C-reactive protein). In general, many studies have shown the positive effect of ozone therapy as a complementary therapy in the recovery of COVID-19 patients. All the findings indicate that systemic ozone therapy is nontoxic and has no side effects in these patients.

Combination ozone therapy as an effective method of radiomodification in chemoradiation treatment of patients with cervical cancer.

e17515 Background: The purpose of the study was to evaluate advantages of combination ozone therapy as an effective factor of radiomodification and radioprotection in the treatment of patients with cervical cancer. Methods: The study included 20 patients with stage IIIb cervical cancer T3бNхM0, the mean age 52 years. Controls (n = 10) received standard chemoradiation therapy; the main group (n = 10) received combination ozone therapy in addition to chemoradiation therapy. Systemic ozone therapy involved intravenous administration of 250 ml ozonized solution of 0.9% sodium chloride, 15 sessions during external beam radiotherapy. Local ozone therapy involved 15-minute instillations into the vagina during brachytherapy. All patients received standard chemoradiation therapy, total irradiation dose to the primary focus 80 Gy, plus weekly cisplatin 40 mg/m2. Results: In the main group, pain and discomfort in the lower abdomen were managed in 20% patients by the 5th session of ozone therapy; 30% - on the 10th day; in 50% - on the 14th day. In the control group, such symptoms in 40% of patients were reduced after 20 days. The main group showed a more rapid regression of tumor infiltration, disappearance of purulent discharge, relief of intoxication syndrome. Manifestations of gastrointestinal toxicity were observed in 10% of the main group and in 100% controls; leukopenia developed in 7 patients in the control group and was not registered in the main group. MRI showed complete clinical regression in 90% in the main group and in 65% in the control group. The treatment was completed within 7 weeks in the main group and 8.5 weeks in the control group. Conclusions: Combination ozone therapy causes a more pronounced antitumor effect, and its radioprotective effects significantly reduce the severity of chemotherapy-induced disorders. It does not aggravate concomitant pathology and shortens the treatment period.

Динамика изменений показателей свободно-радикального окисления при изолированном переломе бедренной кости в условиях системной озонотерапии

Введение. Изолированные переломы бедренной кости (ИПБК) составляют более 10% от числа всех дорожных травм. Реакция организма в ответ на травму сопровождается нарушением гомеостаза, активацией процессов свободно-радикального окисления. Одним из перспективных направлений коррекции метаболических нарушений при хирургической патологии является озонотерапия. Цель исследования - оценка в динамике показателей свободно-радикального окисления в плазме крови у пациентов с изолированным переломом бедренной кости в условиях применения системной озонотерапии. Методика. Исследование выполнено на 36 пациентах с ИПБК и 20 условно здоровых лицах. Содержание изопропанол- и гептан-растворимых первичных, вторичных и конечных продуктов перекисного окисления липидов (ПОЛ) в плазме оценивали на 5-7-е сут после травмы до начала хирургического лечения, а также на 18-е сут после травмы, хирургического лечения и стандартного курса терапии, в том числе дополненного курсом малой аутогемотерапии (МАГТ), - 7-9 инъекций с озонированием крови (концентрация озона 20 мг/л). Результаты. Ранний посттравматический период у пациентов с ИПБК до оперативного лечения сопровождается накоплением первичных (диеновые конъюгаты), вторичных (ацилгидроперекиси, кетодиены и сопряженные триены) и конечных (основания Шиффа) продуктов ПОЛ в гептановой фазе липидного экстракта плазмы, а также вторичных и конечных продуктов ПОЛ в изопропанольной фазе липидного экстракта плазмы. У пациентов с ИПБК после оперативного лечения на фоне стандартной консервативной терапии сохраняется высокий уровень продуктов ПОЛ в гептановой и изопропанольной фазах липидного экстракта плазмы, что свидетельствует об эскалации окислительного стресса. Применение процедуры МАГТ с озонированием крови приводит к снижению и полному восстановлению уровня продуктов ПОЛ в изопропанольной фазе, снижению и частичному восстановлению продуктов ПОЛ в гептановой фазе липидного экстракта плазмы. Заключение. Применение МАГТ с озонированием крови оптимизирует состояние про- и антиоксидантных систем крови и ограничевает эскалацию окислительного стресса. Introduction. Isolated femoral fractures (IFF) account for more than 10% of all road injuries. The body responds to trauma with homeostatic disorders and activation of free radical oxidation. The ozone therapy is one of promising directions for correction of metabolic disorders in surgical pathology due to the pleiotropic effects of reactive oxygen species. The aim of the study was to evaluate changes in indexes of free radical oxidation in plasma of patients with isolated femoral fracture during the systemic ozone therapy. Methods. The study included 36 patients with IFF and 20 healthy individuals. Plasma concentrations of isopropanol and heptane-soluble primary, secondary, and end products of lipid peroxidation (LPO) were measured at 5-7 days after the injury, prior to the surgical treatment, and at 18 days after the injury following the surgical treatment and a standard therapy, including a course of minor autohemotherapy (7-9 injections of ozonated blood with ozone concentration of 20 mg/l). Results. The early post-traumatic period preceding the surgical treatment was associated with accumulation of LPO primary (conjugated dienes), secondary (ketodienes, and conjugated trienes) and end (Schiff bases) products in the heptane phase of plasma lipid extract, as well as LPO secondary and end products in the isopropanol phase of plasma lipid extract. In patients with IFF after the surgical treatment in combination with a standard, conservative therapy, high levels of LPO products remained in the heptane and isopropanol phases of plasma lipid extract, which indicated escalation of oxidative stress. The use of minor autohemotherapy with blood ozonation resulted in a decrease and complete restoration of the level of LPO products in the isopropanol phase and a decrease and partial return to the normal level of LPO products in the heptane phase of plasma lipid extract. Conclusions. The use of minor autohemotherapy with blood ozonation improved the condition of pro- and antioxidant blood systems and restricted the escalation of oxidative stress.

Theoretical Basements for a Clinical Trial on COVID-19 Patients with Systemic Ozone Therapy

Theoretical Basements for a Clinical Trial on COVID-19 Patients with Systemic Ozone Therapy

Bone turnover markers in patients with isolated femoral shaft fracture undergoing systemic ozone therapy

Efferent physical therapy holds promise as an adjunct to the combination treatment of femoral fractures in young, working-age individuals. The aim of the study was to investigate the dynamics of bone turnover markers at different stages of femoral fracture consolidation in patients undergoing ozone therapy. The study enrolled 20 men (group 2, 47.8 ± 3.5 years) with a femoral shaft fracture (AO/ASIF 32А, 32В). The control group (group 1, 46.8 ± 3.7 years) comprised 10 healthy males. Subgroup 2a (n = 10) was assigned to receive standard therapy; subgroup 2b (n = 10) was assigned to receive standard therapy complemented by minor autohemotherapy (MAHT) at 20 mg/L ozone concentrations. On days 7, 30 and 90, fracture consolidation was assessed on the RUST scale and blood levels of С-terminal telopeptides of type I collagen (bCTx, pg/ml) and procollagen type I carboxy-terminal propeptide (PICP, ng/ml) were measured. On day 7, the total RUST score in subgroups 2a and 2b was 4 points; on day 30, it was 6.5 and 8.7 points, respectively, and on day 90, it reached 10 and 11.5 points, respectively. Bone mineral density was as high as 90% in the MAHT subgroup vs. 78% in subgroup 2а, indicating faster bone healing. On day 30, bCTx levels in subgroup 2b were higher than in subgroup 2a (2289.4 [2145.3; 2365.4] vs. 1894.6 [1745.3; 2098.2], respectively. On day 7, PICP was significantly elevated in subgroup 2b in comparison with subgroup 2a; its levels peaked on days 30 and 90 (day 30: 268.3 [231.2; 286.3] vs. 183.2 [174.6; 195.6]; day 90: 584.6 [512.3; 589.3] vs. 351.2 [312.3; 369.4]. Thus, MAHT produces a positive effect on the quality and intensity of bone healing in men with isolated closed femoral shaft fractures.

Effect of systemic ozone therapy as a biomodulator of tissue regeneration and inflammatory response in rats

Abstract Introduction Among the therapeutic effects of ozone therapy, improvement in cell metabolism and peripheral tissue oxygenation have been highlighted. Objective to evaluate the systemic effect of bio-oxidative therapy with ozone gas on wound healing. Material and method Tissue lesions with a circumference of 1.0 cm were induced in the skin on the back of 24 male Wistar rats. The animals were randomly divided into two groups: 1) Group C (control; n=12): with simulation of the application of ozone gas via the rectum and, 2) Group O3 (test; n=12): with application of ozone gas by means of rectal insufflation at a concentration of 50 µg/mL. The animals were euthanized at seven and 15 days, and samples were removed, fixed in formalin, and submitted to macroscopic, histological, and histometric analyses. Result The animals in the O3 group presented mixed inflammation at seven days, which translated into an absence of inflammation at 15 days. The C group exhibited acute inflammation on the 7th day, translating to chronic inflammation, which significantly increased from the 7th to the 15th day. The findings showed that the O3 group presented greater wound contraction (P&lt;0.05) and a greater degree of neovascularization on the 7th day (P&lt;0.05) when compared to group C. On the 15th day, both groups (O3 and C) showed complete re-epithelialization, however, the O3 group demonstrated complete muscle regeneration. Conclusion The systemic ozone therapy had a biomodulatory effect, reducing the characteristics of acute inflammation and increasing tissue repair and regeneration in rat skin.

Homeostatic and endocrine responses as the basis for systemic therapy with medical gases: ozone, xenon and molecular hydrogen.

Among medical gases, including gases used therapeutically, this review discusses the comparative physiological activity of three gases – ozone (O3), xenon (Xe) and molecular hydrogen (H2), which together form representatives of three types of substances – typical oxidizing, inert, and typical reducing agents. Upon analysis of published and proprietary data, we concluded that these three medical gases can manipulate the neuroendocrine system, by modulating the production or release of hormones via the hypothalamic-pituitary-adrenal, hypothalamic-pituitary-thyroid, hypothalamic-pituitary-gonadal axes, or the gastrointestinal pathway. With repeated administration of the gases over time, these modulations become a predictable consequence of conditioned homeostatic reflexes, resulting in regulation of physiological activity. For example, the regular activation of the unconditioned defense reflex in response to repeated intoxication by ozone leads to the formation of an anticipatory stable conditioned response, which counteracts the toxic action of O3. The concept of a Pavlovian conditioned reflex (or hormoligosis) is a brief metaphor for the understanding the therapeutic effect of systemic ozone therapy.

Using Ozone Therapy as an Option for Treatment of COVID-19 Patients: A Scoping Review.

Recent investigations are seeking a novel treatment to control the new pandemic of coronavirus 19 (COVID-19). The aim of this systematic review was to study the effect of ozone therapy on COVID-19 patients and the available supporting evidence. Electronic databases including MEDLINE (via PubMed), EMBASE, Cochrane Library (CENTRAL), and TRIP, clinical trial registries, and preprint sources were searched for published evidence-based articles. In addition, manual searching was conducted for articles published up to April 6, 2020, using MeSH and free text keywords with no language limitation. Articles were screened, categorized, and extracted for relative data. Data were reported in a descriptive manner. Among 234 articles, 9 were selected for review of the inclusion criteria. No published original articles were found regarding the efficacy of ozone therapy on COVID-19. Five review studies were found in which the potential role of systemic ozone therapy was concluded to be effective in controlling COVID-19 because of its antiviral, oxygenation, anti-inflammatory, oxidation balancing, and immunomodulation effects. Three ongoing clinical trials were registered in China. A preliminary report of an ongoing study in Italy on 46 patients (11 intubated and 35 non-intubated) showed that in 39 (84%) of the patients, an improvement was seen. In spite of the promising background data, as well as the expert opinions and a preliminary report indicating the effectiveness of ozone, there is still not enough evidence to confirm this as a viable treatment option for COVID-19.

Dynamics of the level of cytokines in the isolated femoral fracture under conditions of system ozone therapy

A close link between processes of immune-based and osteogenesis, influence of immune system on reparative processes after a traumatic femur fracture, as well as state of increased afferent signals emitted by intraosseous receptors and hyperstimulation of immune cells during trauma accounts for feasibility of using efferent multimodal therapy interventions, which may be accomplished by medical ozone. The aim of the study was to assess dynamic changes in pain syndrome and level of pro- and anti-inflammatory cytokines in isolated femur fracture treated with systemic ozone therapy. The study group coprised 32 male patients with isolated femur fracture, average age 44.2±2.4 years. Starting from day 2 after surgical treatment, all patients received standard anticoagulant treatment and antibiotic therapy, 16 patients additionally received ozone therapy applied as small autohemotherapy (MAGT) at ozone therapeutic unit by using ozone destructor UOTA-60-01 “Medozon” manufactured by Medozon LLC, Moscow. Ozone concentration in ozone-oxygen mixture was 20 mg/l, per 10 ml-volume, applied as 7-9 injections course every other day. Patient-provided assessment of pain level in all groups was investigated by using a visual analogue pain scale. Concentrations of IL-6 and IL-4 cytokines were measured by using standard test systems (pruchased from Vector-Best JSC, Novosibirsk). Statistical data processing was carried out by using software package Statistica 10.0. The subjective pain level prior to the onset of the course ozone therapy and 2 days after surgical treatment was higher than average level after the end of MAGT course, pain level decreased to low level and significantly differed from that one before surgery, which indicates developed analgesic effect after systemic ozone therapy, likely associated with oxidative modification of inflammatory mediators. The level of pro-inflammatory cytokine IL-6 in patients with IPPK during systemic ozone therapy significantly decreased, which indicates some normalizing effect induced by ozone therapy on parameters of immunocyte secretory activity and prevents ovgert effects triggered by “cytokine storm”. Concentration of IL-4 vs after traumatic femur damage did not significantly differ among patient groups, except for differences with control group. Spearman correlation analysis revealed high degree of dependence between pain intensity and level of pro-inflammatory cytokines, whereas ozone therapy led to decreased pain intensity in lesion site and directly correlated with decreased IL-6 concentration. Thus, use of ozone at therapeutic concentrations limits excessive reactions of innate immunity that can lead to massive tissue damage in early stages of the posttraumatic process.

Potential Cytoprotective Activity of Ozone Therapy in SARS-CoV-2/COVID-19.

(1) Background: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) in China at the end of 2019 has caused a large global outbreak. Systemic ozone therapy (OT) could be potentially useful in the clinical management of several complications secondary to SARS-CoV-2. The rationale and mechanism of action has already been proven clinically in other viral infections and has been shown in research studies to be highly effective at decreasing organ damage mediated by inflammation and oxidative stress. This review summarizes the OT studies that illustrate the possible cytoprotective mechanism of action of ozone and its physiological by-products in target organs affected by SARS-CoV-2. (2) Methods: This review encompasses a total of 74 peer-reviewed original articles. It is mainly focused on ozone as a modulator of the NF-κB/Nrf2 pathways and IL-6/IL-1β expression. (3) Results: In experimental models and the few existent clinical studies, homeostasis of the free radical and antioxidant balance by OT was associated with a modulation of NF-κB/Nrf2 balance and IL-6 and IL-1β expression. These molecular mechanisms support the cytoprotective effects of OT against tissue damage present in many inflammatory diseases, including viral infections. (4) Conclusions: The potential cytoprotective role of OT in the management of organ damage induced by COVID-19 merits further research. Controlled clinical trials are needed.