Ozone Therapy Research Articles

Is the increased ozone dosage key factor for its anti-inflammatory effect in an experimental model of mesenteric ischemia?

Ischemia/reperfusion injury of the intestines is a severe surgical condition. This study aimed to reveal ozone therapy effects with relatively increased ozone dosage in a created ischemia/reperfusion injury model. In this study, 24 albino Wistar rats were examined in three groups. Rats in the control group (CG, n=8) underwent only a laparotomy. In the sham group (SG, n=8) and ozone group (OG, n=8), the superior mesenteric artery (SMA) of the rats was occluded for 1 h. After de-occluding the SMA, the abdomen was closed, physiological saline was infused intraperitoneally in the SG, and an increased ozone/oxygen mixture dose (from 0.7 mg/kg to 1 mg/kg) was infused intraperitoneally in the OG. Small intestine samples were obtained at the 24th h for histopathological examination of intestinal mucosal injury and evaluated according to the Chiu score. In addition, Malondialdehyde and Myeloperoxidase levels were evaluated for oxidant levels, whereas, Glutathione (GSH) enzyme activity was measured to evaluate the tissue antioxidant system. Histopathologically, the Chiu score was the lowest in the CG. It was lower in the OG compared to the SG showing the ameliorating effect of ozone on the intestinal mucosa. Chiu score in the OG was higher compared to that in the CG, but not statisti-cally significant. A significantly higher GSH level was observed in the OG compared to the SG, proving antioxidant activity. In this experimental model of ischemia/reperfusion in rats, treatment with an increased ozone level decreased the inflammatory process through antioxidant mechanisms and reduced intestinal mucosal damage. However, the effectiveness of ozone therapy depends on its dosages.

Comparison of ıntracanal ozone and low-level laser therapy on postoperative pain in vital teeth with symptomatic apical periodontitis:placebo-controlled randomize trial.

The aim of this study was to compare the effect of ozone and low-level-laser therapy (LLLT) on postoperative pain after root canal treatment in symptomatic apical periodontitis on vital teeth. Eighty patients were divided into four groups using a web program as follows: LLLT placebo (mock laser therapy), LLLT, Ozone placebo (mock ozonated water irrigation), and Ozone. Postoperative pain levels for 7 days after treatment and percussion pain levels at the 7th day were recorded on the visual analog scale. A regression analysis, Cochran's Q test, Chi-square test, Kruskal-Wallis tests were performed to analyze the data (P=.05). A regression analysis demonstrated that the most effective variables are "group" and "jaw" (P=0.01). Pain in the lower jaw is higher than the upper jaw. There was difference between the groups on postoperative pain at the days 1, 2, and 3; however, there was no significant difference on other days. LLLT and ozone groups had less postoperative pain and pain on percussion. Low-level laser and ozone therapy are useful methods on postoperative-pain in vital symptomatic teeth ,but they don't have superiority to each other.

Use of Ozone Therapy in Diabetic Foot Ulcers.

ozone therapy is a therapy composed of ozone. This gas is in the atmosphere with various general effects: direct disinfectant and trophic effects and a systemic antibacterial and antiviral effect. This gas also improves blood circulation, makes glucose metabolism more effective, improves erythrocyte metabolism, and improves fatty acid metabolism. Provide evidence of the effectiveness of ozone therapy in wounds of patients with diabetic foot. Analyze the effectiveness of ozone therapy compared to other treatments to achieve good wound healing in patients with diabetic foot. To study the benefits of the use of ozone therapy in ulcers of patients. Analyze the management of ozone therapy and other treatments to achieve healing of ulcers in patients. A bibliographic review focused on articles published between November 2014 and June 2023 was carried out. The following databases were consulted: Pubmed (Medline), Dialnet, Google Scholar, Web of Science (WOS), Scielo, and Scopus. After applying the article selection criteria and evaluating the quality of the methodology, a total of 17 articles were obtained. The results affirm ozone therapy as promising for the treatment of wounds in patients with diabetic foot. the evidence has been able to determine that ozone therapy is adequate for the treatment of diabetic foot ulcers. In addition, the therapy has been shown to be effective, safe, and beneficial, with few adverse effects for the treatment of diabetic foot ulcers.

Vaginal Ozone Insufflation in Management of Vaginal Candidiasis

The vagina of a woman is a sophisticated microecology system. Typically, the H2O2-producing Lactobacillus dominates the vaginal microbiota of healthy women. This bacterium converts glycogen in vaginal epithelial cells into lactic acid, sustaining the vagina's natural acidic environment. Understanding the substantial correlation between the vaginal and upper genital tract microbiota and vaginal and genital tract infections has led to an interest in these areas. However, the spectrum of microbial types consistent with a functioning genital tract and the variables influencing the flora remains perplexing. The most prevalent gynecological condition seen in primary care, vaginitis caused by Candida albicans, is a significant public health concern due to its high frequency. Candidal vulvovaginitis, also known as vaginal thrush and vaginal yeast infection, is an overgrowth of yeast in the vagina that irritates. Ozone treatment has made its way into German medical practice, where it is successfully applied to treat several disorders. Medical ozone's qualities, such as its bactericidal, virucidal, fungicidal, analgesic, and other effects, have been utilized in therapy, surgery, obstetrics and gynecology, dermatology, stomatology, and the treatment of infectious and venereal illnesses. During ozone treatment or therapy, a catheter was used to insufflate an ozone/oxygen gas mixture into the female reproductive system. They were completed continuously by attaching a catheter to the ozone output hose and allowing the ozone/oxygen gas mix to flow for the allotted time. Based on clinical and microbiological evidence, the effectiveness standards Complete clinical and microbiological recovery observable clinical symptoms that are objective. The vaginal mucous membrane was free of inflammatory disorders following treatment, and vaginal cultures were negative.

Elucidating the molecular mechanisms of ozone therapy for neuropathic pain management by integrated transcriptomic and metabolomic approach.

Introduction: Neuropathic pain remains a prevalent and challenging condition to treat, with current therapies often providing inadequate relief. Ozone therapy has emerged as a promising treatment option; however, its mechanisms of action in neuropathic pain remain poorly understood. Methods: In this study, we investigated the effects of ozone treatment on gene expression and metabolite levels in the brainstem and hypothalamus of a rat model, using a combined transcriptomic and metabolomic approach. Results: Our findings revealed significant alterations in key genes, including DCST1 and AIF1L, and metabolites such as Aconitic acid, L-Glutamic acid, UDP-glucose, and Tyrosine. These changes suggest a complex interplay of molecular pathways and region-specific mechanisms underlying the analgesic effects of ozone therapy. Discussion: Our study provides insights into the molecular targets of ozone treatment for neuropathic pain, laying the groundwork for future research on validating these targets and developing novel therapeutic strategies.

Current affairs in the use of medical ozone. Biological effects. Mechanisms of action

Introduction. Oxygen-ozone therapy stands as a medically endorsed practice confirmed by numerous international clinical studies. Various authors have illustrated the beneficial clinical outcomes of ozone therapy in terms of its capacity to regulate redox balance, cellular inflammatory responses, and adaptation to ischemia/reperfusion processes. Ozone therapy extends to encompass a range of viral infections, inflammatory disorders, and degenerative ailments, used as both monotherapy and as an adjunct to unified conventional therapies. Material and methods. Narrative literature review study. Bibliographic search was conducted using the PubMed, Hinari, and SpringerLink databases, as well as the National Center of Biotechnology Information and Medline. Articles published between 1990 and 2022 were selected using various combinations of keywords, including “ozone”, “ozone therapy”, “mechanisms of ozone action”, “biological effects of ozone”, “antioxidant effect”, “anti-inflammatory effect” and “immunomodulatory effect.” Information regarding ozone’s mechanisms of action was identified and processed. Following the database information processing and search criteria, a total of 475 full-text articles were found. The final bibliography consists of 52 relevant sources that were deemed representative of the materials published on the topic of this synthesis article. Results. The effects of ozone on oxygen metabolism are explained by changes in the rheological properties of blood, including inhibition of erythrocyte aggregation and stimulation of 2,3-diphosphoglycerate in erythrocytes, favoring the transport and delivery of oxygen to tissues while facilitating the substantial elimination of nitric oxide and increasing blood flow. Intracellular triatomic oxygen enhances the oxidative carboxylation of pyruvate, stimulating ATP production, which also contributes to reducing peripheral vascular resistance. Conclusions. Ozone generates a moderate oxidative stress. Yet, it can set off several beneficial biochemical mechanisms that reactivate both the intra- and extracellular antioxidant systems and reverse chronic oxidative stress in various inflammatory and degenerative processes. Ozone induces a mild activation of the immune system by triggering neutrophil activation and stimulating the synthesis of certain cytokines (IL-2, TNF-α, IL-6, and IFN-γ), thereby initiating a complete cascade of immune responses. Ozone therapy yields the following biological reactions: optimization of blood circulation and oxygen delivery to ischemic tissue, regulation of cellular antioxidant enzymes, initiation of a slight immune system activation, and enhancing the release of growth factors.

Clinical and Radiographic Evaluation of Ozone Therapy in Odontectomy of Impacted Mandibular Third Molar

Clinical and Radiographic Evaluation of Ozone Therapy in Odontectomy of Impacted Mandibular Third Molar

Combination Therapy of Major Autohemotherapy and Ozonated Bagging in a Case Diagnosed with Buerger's Disease (Thromboangiitis Obliterans)

It is well known that ozone therapy provides positive results as a complementary method in peripheral obstructive arterial diseases alongside medical treatment. This article presents a case diagnosed with Buerger's disease, where rapid improvement was observed after a combination of major autohemotherapy (AHT) and ozonated bagging.

Long non-coding RNA Snhg16 Lessens Ozone Curative Effect on Chronic Constriction Injury mice via microRNA-719/SCN1A axis.

We investigated the function and molecular mechanism of long non-coding RNA (lncRNA) small nucleolar RNA host gene 16 (Snhg16) in modifying ozone treatment for neuropathic pain (NP) in a mouse model of chronic constriction injury (CCI). Pain-related behavioral responses were evaluated using paw withdrawal threshold (PWT), paw lifting number (PLN), and paw withdrawal latency (PWL) tests. Interleukin (IL)-1β, IL-10, IL-6, and tumor necrosis factor-alpha (TNF-α) were measured by ELISA and qRT-PCR to evaluate neuroinflammation. qRT-PCR was performed to detect expressions of Snhg16, microRNA (miR)-719, sodium voltage-gated channel alpha subunit 1 (SCN1A), and inflammatory factors. Bioinformatics, dual-luciferase reporter assay, and RNA pull-down verified the underlying molecular mechanisms. Snhg16 expression increased in CCI mice. Snhg16 overexpression retarded the curative effect of ozone and induced NP. miR-719 was sponged by Snhg16. SCN1A was a target of miR-719. Inhibition of miR-719 markedly reversed the effects of Snhg16 on pain-related behavioral responses and neuroinflammation. Upregulation of SCN1A partly abrogated the effects of elevated miR-719 levels on the occurrence of NP. The findings demonstrate that lncRNA Snhg16 promotes NP progression in CCI mice by binding to miR-719 to increase SCN1A expression. The Snhg16/miR-719/SCN1A axis may influence the curative effects of ozone therapy in treating NP.

USE OF OZONIOTHERAPY FOR SUBMENTONAL FAT REDUCTION

USE OF OZONIOTHERAPY FOR SUBMENTONAL FAT REDUCTION

Effects of Different Ozone Doses Added to the Antibiotic Treatment on Cytokine Levels in Experimental Sepsis Model

We aimed to examine the changes caused by ozone therapy added to the antibiotic treatment on proinflammatory and anti-inflammatory cytokine levels in an experimental sepsis model formed with E. coli endotoxin. Rats were divided into 6 groups of 10 rats. Sepsis was formed by dosing 5 groups of rats with intraperitoneal E. coli endotoxin injection. For the first 3 groups, 0.6 mg/kg, 0.9 mg/kg, and 1.1 mg/kg doses of ozone therapy were added to the antibiotic treatment and group-4 only received antibiotic treatment. Group-5 was not treated. Group-6 received intraperitoneal serum physiologic injection simultaneously with the other groups. All treatments were sustained for 5 days. IL-1, IL-10, and TNF-alpha levels were detected in blood serum taken from rats sacrificed on day 6. It was seen that IL-1, TNF-alpha levels are significantly lower than the levels in other groups that received ozone therapy. In the comparisons amongst the groups receiving ozone therapy, it was observed that IL-1 levels do not have a significant difference and TNF-alpha levels are significantly lower in the two groups receiving lower doses than the group receiving a higher dose. There were no significant differences detected between groups at serum levels of IL-10 which is an anti-inflammatory cytokine. It was concluded that ozone added to the antibiotic treatment in sepsis could have a positive effect on survival rates by suppressing inflammatory process.

What Do We Know About Some Popular Methods of Complementary and Alternative Medicine: An Overview of Cochrane Systematic Reviews

Objective: This study aims to investigate the level of evidence on the effectiveness and safety of 14 complementary and alternative medicine (CAM) methods legalized in Turkey.
 
 Methods: A systematic literature search was conducted in the Cochrane Systematic Review Database for acupuncture, apitherapy, hypnotherapy, leech therapy, homeopathy, cupping therapy, chiropractic, prolotherapy, osteopathy, maggot therapy, mesotherapy, music therapy, reflexology, ozone therapy. After screening, 287 studies were included in the qualitative synthesis. Evidence quality was classified as ‘high/moderate/low’. AMSTAR-2 was used to evaluate the quality of systematic reviews. This study was registered to PROSPERO (CRD42019127509).
 
 Results: There are 16 low (LQE) and four moderate-quality evidence (MQE) of effectivity for various conditions were found for acupuncture, while it has no effectivity on 13 conditions. There are six LQE and one MQE on its safety. One study found high-quality evidence of the effectivity of apitherapy concluded that honey accelerates the healing of burn wounds. Three LQE and two MQE quality evidence found for some conditions, and five studies have shown no effectivity. Thirteen LQE and three MQE showed the effectiveness of music therapy, while one study reported it as ineffective. Four studies found LQE showing hypnotherapy might be effective in some conditions, and one study found it was ineffective. Regarding osteopathy, one study found MQE, and one study found LQE. One study reported LQE for the effectiveness of chiropractic. The only evidence for the effectivity of homeopathy is of low quality and four studies have shown that it is not effective. There is a LQE on its safety. 
 
 Conclusions: Since there is insufficient evidence, 14 CAM methods legalised in Turkey shoud not be used in daily practice. Future researches aiming to produce high-quality evidence are needed to be able to make benefit-risk assessments scientifically.

Ozone Therapy in Medicine and Dentistry: A Review of the Literature.

Ozone has been successfully used in medicine for over 100 years due to its microbiological qualities. Its powerful oxidation impact, which results in the production of free radicals, and its ability to cause the direct death of nearly all microorganisms is the basis for its bactericide, virucide, and fungicide properties. Ozone also has a medicinal impact that speeds up blood flow and aids wound healing. Ozone may be applied as a gas or dissolved in water for medical purposes. Despite the benefits of using ozone therapeutically, concerns about its use in dentistry still exist. We aimed to provide a summary of the current uses of ozone in medicine and dentistry. An electronic search was performed for all English scientific papers published between 2012 and 2023 using PubMed, Cochrane, and Google Scholar search engines. Ozone, clinical applications, medicine, and dentistry were the search terms used. Seventy full-text articles describing the use of ozone therapy in medicine and dentistry were included in the present review. Ozone has shown several beneficial effects in the medical field. However, despite the encouraging in vitro evidence, the clinical use of ozone in dentistry has not yet been demonstrated as highly effective.

Effects of ozone therapy on anxiety and depression in patients with refractory symptoms of severe diseases: a pilot study.

Patients with refractory symptoms of severe diseases frequently experience anxiety, depression, and an altered health-related quality of life (HRQOL). Some publications have described the beneficial effect of ozone therapy on several symptoms of this kind of patient. The aim of this study was to preliminarily evaluate, in patients treated because of refractory symptoms of cancer treatment and advanced nononcologic diseases, if ozone therapy has an additional impact on self-reported anxiety and depression. Before and after ozone treatment, we assessed (i) anxiety and depression according to the Hospital Anxiety and Depression Scale (HADS); (ii) the HRQOL (according to the EQ-5D-5L questionnaire), which includes a dimension on anxiety and depression and a visual analog scale (VAS) measuring self-perceived general health. Before ozone therapy, 56% of patients were on anxiolytic and/or antidepressant treatment. Before and after ozone therapy, the anxiety and depression HADS subscales (i) significantly correlated with the anxiety/depression dimension of the EQ-5D-5L questionnaire and (ii) inversely correlated with the health status as measured by the VAS. After ozone therapy, we found a significant improvement in anxiety and depression measured by both the (i) HADS subscales and (ii) EQ-5D-5L questionnaire. The addition of ozone therapy for patients with refractory symptoms of cancer treatment and advanced chronic nononcologic diseases can decrease anxiety and depression severity levels. Additional, more focused studies are ongoing to provide the needed explanatory information for this finding.

Clinical application of ozone therapy, ultrasound and cryotherapy in the treatment of infected and purulent wounds on the background of chronic venous insufficiency

Research objective: To think up and estimate efficiency of the combined ozonoterapiya at treatment it is long not healing and purulent wounds which have developed against the background of chronic venous insufficiency. Materials and methods: Clinical trial has included 134 patients with chronic venous insufficiency with are long not healing purulent wounds. In a zavisismost from the chosen treatment method patients are divided into three groups. Groups were comparable on a sex, age and weight of defeat of soft fabrics. Assessment of efficiency of treatment was carried out by results of planimetry of wounds, an acid-base condition of a wound and speed of a blood-groove on border of healthy fabric and a wound. Results: On the basis of the conducted researches have proved efficiency of the combined treatment with use of a system and local ozonoterapiya, cryogenic stimulation and ultrasound. The developed algorithm of maintaining patients with chronic venous insufficiency with it is long nekhazhivayushchy wounds, reduces a painful interval to (3,1 0,6) days, accelerates filling of wounds with granulations and emergence of a regional epitalization which appeared to (6,2 1,1) days. The developed technique of a complex ozonoterapiya normalizes blood-groove speed on border of healthy fabric and a wound and restores acid-base balance. Use of a new medical complex reduces stay of patients in a hospital by 17,4 % and reduces disability terms by 12,8 %. Conclusion: At patients with the chronic venous insufficiency complicated it is long not healing infected wounds, use of the new technologies including a local and system ozonoterapiya, cryotherapy and ultrasound is expedient.

Ozone pretreatment alleviates ischemia[sbnd]reperfusion injury-induced myocardial ferroptosis by activating the Nrf2/Slc7a11/Gpx4 axis

Myocardial ischemiareperfusion injury (MIRI) is defined as the additional damage that occurs during the process of restoring blood flow to the heart tissue after ischemia-induced damage. Ozone is a powerful oxidizer, but low concentrations of ozone can protect various organs from oxidative stress. Some studies have demonstrated a link between ozone and myocardioprotection, but the mechanism remains unclear. To establish an in vivo animal model of ischemiareperfusion injury (I/R), this study utilized C57 mice, while an in vitro model of hypoxia-reoxygenation (H/R) injury was developed using H9c2 cardiomyocytes to simulate ischemiareperfusion injury. Ozone pretreatment was used in in vitro and in vivo experiments. Through this research, we found that ozone therapy can reduce myocardial injury, and further studies found that ozone regulates the expression levels of these ferroptosis-related proteins and transcription factors in the H/R model, which were screened by bioinformatics. In particular, nuclear translocation of Nrf2 was enhanced by pretreatment with ozone, inhibited ferroptosis and ameliorated oxidative stress by initiating the expression of Slc7a11 and Gpx4. Significantly, Nrf2 gene silencing reverses the protective effects of ozone in the H/R model. In summary, our results suggest that ozone protects the myocardium from I/R damage through the Nrf2/Slc7a11/Gpx4 signaling pathway, highlighting the potential of ozone as a new coronary artery disease therapy.

Metabolic Effects of Electromagnetiс EHF Radiation and Ozone Therapy in the Engraftment of the Skin Flap

The aim of this study was to evaluate the effect of ROS on the intensity of oxidative and energy metabolism in the blood of rats with an operational model of ischemia of the dorsal skin flap in vivo. Our studies have allowed us to establish that the modeling of an extensive skin defect is accompanied by pronounced shifts in oxidative metabolism in the blood plasma of animals. At the same time, in the absence of pathogenetic treatment, signs of oxidative stress are formed, including the intensification of free radical processes and the inhibition of general antioxidant activity in combination with the accumulation of an increased amount of lipoperoxidation products (in particular, malondialdehyde). Conducting experimental therapy with the introduction of ozone or treatment with electromagnetic radiation of the EHF band allows partially compensating for these metabolic disorders, however, the most optimal option is a combination of these factors within a single scheme. It should be noted that the results obtained are of great applied importance for the creation of innovative technologies for the complex medical rehabilitation of orthopedic-traumatological patients as a tool for influencing reparative processes in the lesion to restore and maintain tissue structures.

Cytokine profile and antioxidants status in the moderate and severe COVID-19 patients: a trial of ozone therapy impact as a medicinal supplement.

Complementary ozone therapy has been identified as a revolutionary medical technique for a number of goals and ailments. At the present, it has been shown that ozone has medicinal qualities, such as antibacterial,antifungal, andantiparasiticproperties. Coronavirus (SARS-CoV-2) is quickly spread over the globe. Cytokine storms and oxidative stress seem to play a substantial role in the most of acute attacks of the disease. The aim of this research was to assess the therapeutic advantages of complementary ozone therapy on the cytokine profile and antioxidant status in COVID-19 patients. The statistical sample of this study included two hundred patients with COVID-19. One hundred COVID-19 patients (treatment group) received 240ml of the patient's blood and an equal volume of O2/O3 gas at a concentration of 35-50μg/ml daily, which gradually increased in concentration, and were kept for 5-10days and one hundred patients (control group) received standard treatment. The secretion levels of IL-6, TNF-α, IL-1β, IL-10 cytokines, SOD, CAT and GPx were compared between control patients (standard treatment) and standard treatment plus intervention (ozone) before and after treatment. The findings indicated a significant decrease in the level of IL-6, TNF-α, IL-1β in group receiving complementary ozone therapy in compared with control group. Furthermore, a significant increase was found in the level of IL-10 cytokine. Moreover, SOD, CAT and GPx levels revealed a significant increase in complementary ozone therapy group compared to control group. Our results revealed that complementary ozone therapy can be used as a medicinal complementary therapy to reduce and control inflammatory cytokines and oxidative stress status in patients with COVID-19 as revealed its antioxidant and anti-inflammatory effects.

Ozone therapy as a novel complementary therapeutic approach in refractory idiopathic granulomatous mastitis.

Autoimmunity may play a major role in the pathogenesis of idiopathic granulomatous mastitis (IGM). The therapeutic potential of ozone therapy has recently been shown in rheumatological diseases, and this study aimed to assess the clinical efficacy of ozone therapy (OT) in refractory IGM. Patients with biopsy-verified IGM and incomplete response after steroid therapy (n = 47) between 2018 and 2021 were enrolled. Of these, 23 cases in cohort A had standard treatment with further steroid therapy (ST), and 24 were treated with systemic OT via autohemotherapy (AHT) in addition to steroid therapy (cohort B). The median age was 33 years (range, 24-45). Patients in cohort B had a higher complete response rate after completion of a four-month ozone therapy than those in the ST-group (OT-group, 37.5% vs. ST-group, 0%; p = 0.002). At a median follow-up of 12 months (range, 12-35), the patients treated with OT had a lower one-year recurrence in the affected breast than cases in cohort A treated with ST (OT-group, 21% vs. ST-group, 70%; p = 0.001). No significant side effects were observed in patients in cohort B related to AHT. Furthermore, OT significantly decreased the total steroid treatment duration (median week of steroid use; 26 weeks in cohort A vs. 12 weeks in cohort B; p = 0.001). Systemic OT increases the complete response rate and decreases the duration of steroid treatment in patients with refractory IGM. Therefore, ozone therapy is an effective, well-tolerated, and safe novel complementary therapeutic modality.

Gestation outcomes in various options of help for pregnant women with Rh-immunization

BACKGROUND: To date, several options for helping pregnant women with rhesus immunization are known: (a) active tactics in carrying out methods of efferent therapy in the form of basic operations (plasmapheresis, hemosorption) in combination with adjuvant methods (immunoglobulin, blood photomodification with ultraviolet, laser beams, ozone therapy) to pregnant women; (b) wait-and-see active tactics with observation of the pregnant woman, followed by intrauterine intravascular transfusions of washed donor red blood cells; (c) mixed active tactics with a sequential combination, alternation of these methods. In Russia, only option 2 with fetal transfusions of washed donor red blood cells is accepted as the basis and paid for. The objective of the study is to conduct a comparative analysis of pregnancy outcomes in women with rhesus immunization using different management options.
 MATERIALS AND METHODS: A total of 392 women were followed up at seven different institutions in Russia and at the Donetsk Center for Maternal and Child Health (DNR), of whom 345 pregnant women (Group 1) received efferent therapy, 33 women (Group 2) had fetuses intrauterine bypass surgery, and 14 pregnant women (Group 3) had mixed efferent therapy and fetal PEEP bypass surgery.
 RESULTS: The analysis showed that the most favorable results for the main clinical indicators (premature, operative delivery, fetal hypoxia at birth, etc.) were in Group 1 and 3 women, in which the perinatal mortality was 14.5/1000 and 0/1000, respectively, which was significantly lower than in Group 2 (176.5/1000). It was also found that in Groups 2 and 3 women, the mean intervals between repeated transfusions of washed donor red blood cells were 8.8 0.2 and 21.4 3.8 days (p 0.01), which may be explained by the detoxifying effect of efferent therapy methods, preservation of fetal red blood cells and transfused donor red blood cells to the fetus with prolonged gestation and obtaining healthier and more viable progeny.
 CONCLUSIONS: 1. Severe Rh conflict is a manifestation of a syndrome of systemic effects of aggressive metabolites of specific and nonspecific nature. 2. The etiopathogenetic measure in the prevention and treatment of HDF/HDN in rhesus conflict is efferent therapy methods for the mother, and transfusion of washed donor rhesus-negative red blood cells to the fetus is effective, but a temporary, palliative measure, as is the case in multiple organ failure. 3. In the treatment protocols, efferent therapy methods must be present to prevent fetal red cell destruction and, equally importantly, to prevent destruction of Rh-negative donor red cells transfused to the fetus.