Injectable Ozone-Rich Nanocomposite Hydrogel Loaded with D-Mannose for Anti-Inflammatory and Cartilage Protection in Osteoarthritis Treatment.

Osteoarthritis (OA) is a dynamic condition characterized by cartilage damage and synovial inflammation. Ozone (O3) shows potential therapeutic effects owing to its anti-inflammatory properties; however, its high reactivity and short half-life substantially limit its effectiveness in OA treatment. In this study, an ozone-rich thermosensitive nanocomposite hydrogel loaded with D-mannose is developed for OA treatment. Briefly, O3 is encapsulated in nanoparticles (NPs) composed of perfluorotributylamine and fluorinated hyaluronic acid to improve its stability. Next, D-mannose is conjugated with α-amino of the hydroxypropyl chitin (HPCH) via Schiff base to prepare MHPCH. These nanoparticles are encapsulated in MHPCH to produce O3 NPs@MHPCH. In vitro cell experiments demonstrate that the O3 NPs@MHPCH treatment significantly reduced VEGF and inflammation levels, accompanied by a decrease in inflammatory factors such as IL-1ß, IL-6, TNF-α, and iNOS. Furthermore, O3 NPs@MHPCH promotes the expression of collagen II and aggrecan and stimulates chondrocyte proliferation. Additionally, in vivo studies show that O3 NPs@MHPCH significantly alleviated OA by reducing synovial inflammation, cartilage destruction, and subchondral bone remodeling. O3 NPs@MHPCH offers a promising option for improving the efficacy of O3 therapy and reducing the risk of synovial inflammation and cartilage degeneration in OA.

Topical application of ozonated sunflower oil accelerates the healing of lesions of cutaneous leishmaniasis in mice under meglumine antimoniate treatment.

Besides being scarce, the drugs available for treating cutaneous leishmaniasis have many adverse effects. Ozone is an option to enhance the standard treatment due to the wound-healing activity reported in the literature. In this study, we evaluated the efficiency of ozonated sunflower oil as an adjuvant in treating cutaneous lesions caused by Leishmania amazonensis. BALB/c mice were infected with L. amazonensis, and after the lesions appeared, they were treated in four different schedules using the drug treatment with meglumine antimoniate (Glucantime®), with or without ozonated oil. After thirty days of treatment, the lesions' thickness and their parasitic burden, blood leukocytes, production of NO and cytokines from peritoneal macrophages and lymph node cells were analyzed. The group treated with ozonated oil plus meglumine antimoniate showed the best performance, improving the lesion significantly. The parasitic burden showed that ozonated oil enhanced the leishmanicidal activity of the treatment, eliminating the parasites in the lesion. Besides, a decrease in the TNF levels from peritoneal macrophages and blood leukocytes demonstrated an immunomodulatory action of ozone in the ozonated oil-treated animals compared to the untreated group. Thus, ozonated sunflower oil therapy has been shown as an adjuvant in treating Leishmania lesions since this treatment enhanced the leishmanicidal and wound healing effects of meglumine antimoniate.

In Vitro and In Vivo Effects of Melatonin-Containing Combinations in Human Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) has poor prognosis and high mortality rates. Therefore, it is necessary to identify new targets and therapeutic strategies to improve the prognosis of patients with PDAC. Integrative therapies are increasingly being used to boost the efficacy of the known anticancer therapeutic approaches. Hence, this study aimed to evaluate the effects of a novel combination of different potential anticancer molecules, melatonin (MLT), cannabidiol (CBD), and oxygen-ozone (O2/O3) to treat PDAC using in vitro and in vivo models of human PDAC. The effect of this combination was investigated in combination with gemcitabine (GEM), the most common chemotherapeutic drug used for PDAC treatment. The combination of MLT + CBD + O2/O3 was more effective than the individual treatments in inhibiting PDAC cell viability and proliferation, inducing cell death, and modulating the RAS pathway protein levels. Moreover, different combinations of treatments reduced tumor mass in the PDAC mouse model, thus promoting the effect of GEM. In conclusion, a mixture of MLT + CBD + O2/O3 could serve as a potential adjuvant therapeutic strategy for PDAC.

Efficacy of ozone therapy for oral mucosa wound healing: a systematic review and meta-analysis.

OBJECTIVES: To conduct a systematic review and meta-analysis to assess the effectiveness of ozone therapy in oral ulcers healing when compared to placebo or active treatments. MATERIALS AND METHODS: The search was carried out using PubMed, EMBASE, Scopus, and Lilacs databases. Clinical trials involving human participants were included. The Risk Ratio (RR) and the standardized mean difference (SMD) with 95%CI (confidence interval) were calculated. The ROBINS-I (risk of bias in non-randomized studies of interventions) and RoB2 (risk of bias tool for randomized trials) assessment tool was used to detect bias. RESULTS: After the selection process, 12 studies were included. The meta-analysis showed that ozone therapy helps to reduce the size of the traumatic and autoimmune ulcers (RR=-0.44; 95% CI -0.71,-0.17; I2=0%) in comparison to placebo. Regarding pain reduction, ozone was superior to placebo (RR = 1.29, 95% CI -1.6 to -0.95); I2=0%), and equivalent to topical corticosteroid and laser photobiomodulation (RR = 0.26, 95% CI -0.27,0.78, p = 0.34). CONCLUSION: Ozone therapy is an alternative for accelerating healing and reducing pain for both traumatic and autoimmune ulcers. However, the quality of evidence is limited. CLINICAL RELEVANCE: Oral ulcerations are usually painful and impact quality of life requiring different approaches to boost wound healing and reduce symptoms. For this purpose, ozone therapy is a promising strategy.

Effect of Medical Ozone Therapy in Preventing Compromised Nasal Skin in Revision Rhinoplasty.

BACKGROUND: Ozone is often used as an additive therapy for skin conditions like infectious diseases, wound healing, diabetic foot, and pressure ulcers. The viability of the nasal skin has crucial importance in revision rhinoplasty cases. The study investigates the potential benefits of medical ozone therapy in healing the nasal skin in multiple-operated cases. METHODS: The study retrospectively examined 523 revision rhinoplasty patients operated by the first author from January 2017 to January 2024. Patients consenting to ozone therapy received 3 major autohemotherapy sessions post-surgery. Patients were divided into 2 groups: those with compromised nasal skin (infection, poor vascular supply) and those with normal healing. Age, gender, smoking, diabetes, previous surgeries, grafting materials, and techniques were considered. RESULTS: Of the 523 patients, 12 (2.3%) experienced major skin complications like infection and necrosis, while 511 (97.7%) had no or minor issues, such as discoloration. In total, 301 patients accepted and received ozone therapy. Of the patients without major complications, 299 (58.3%) received ozone therapy, while 212 (41.7%) did not. Among the 12 with major complications, two (16.7%) received ozone therapy, and the remaining 10 (83.3%) did not. Ozone therapy recipients showed statistically fewer skin problems (p<0.05). Costal cartilage as tip and septal extension graft was linked to skin issues (p<0.05). No major adverse effects from ozone therapy were noted. CONCLUSIONS: Our findings indicate that ozone therapy may be a safe and potentially effective option for patients undergoing revision rhinoplasty, especially those with compromised nasal skin. It appears to aid in skin healing and regeneration, possibly through enhancing oxygen delivery and modulation of the immune response. Ozone therapy is a promising adjunct treatment for managing skin complications in revision rhinoplasty patients. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Mitochondrial Dysfunction, Its Oxidative Stress-Induced Pathologies and Redox Bioregulation through Low-Dose Medical Ozone: A Systematic Review.

Our hypothesis that controlled ozone applications interfere with the redox balance of a biological organism (first published in 1998 with a preclinical trial on protecting the liver from CCl4 intoxication) has been verified over the past two decades in reactive oxygen species (ROS)-induced mitochondrial pathologies, such as rheumatoid arthritis, osteoarthritis, aging processes and type 2 diabetes, and in the prevention of intoxications. Low-dose ozone acts as a redox bioregulator: the restoration of the disturbed redox balance is comprehensible in a number of preclinical and clinical studies by a remarkable increase in the antioxidant repair markers, here mainly shown as a glutathione increase and a reduction in oxidative stress markers, mainly malondialdehyde. The mechanism of action is shown, and relevant data are displayed, evaluated and comprehensively discussed: the repair side of the equilibrium increases by 21% up to 140% compared to the non-ozone-treated groups and depending on the indication, the stress markers are simultaneously reduced, and the redox system regains its balance.

[Prospects for the use of ozone therapy and low-intensity laser therapy in the treatment of atrophic pharyngitis]. / Perspektivy primeneniya ozonoterapii i nizkointensivnoi lazeroterapii pri lechenii atroficheskogo faringita.

Chronic pharyngitis (CP) is one of the most common diseases of the oropharynx. The number of referrals from patients with CP reaches 70% of the total number of referrals to an otorhinolaryngologist. The development of this disease is facilitated by the neuro-reflex factor and a violation of trophic and metabolic processes. It should be noted that of all forms of CP, the greatest impact on the quality of life is noted precisely in atrophic pharyngitis (AP), due to the presence of pronounced subjective sensations from the oropharynx. Many of the modern methods of treatment do not provide a lasting effect due only to the application, superficial local effect on the altered mucous membrane of the posterior pharyngeal wall, without taking into account the changes caused by a violation of trophic processes in the tissue. A promising direction in the treatment of atrophic pharyngitis is the use of a combined technique - ozone therapy and low-intensity laser therapy. The article presents the results of the application of fine-drip irrigation of the mucous membrane of the posterior pharyngeal wall with Ozonide oil in combination with low-intensity laser radiation on the projection of vessels supplying blood to the middle parts of the oropharynx. OBJECTIVE: Improving the effectiveness of treatment of patients with atrophic pharyngitis through the use of ozone therapy and low-intensity laser therapy. MATERIAL AND METHODS: A single-center experimental controlled randomized open-label study of 90 patients with AP aged 18 and over was conducted. All patients were randomly divided into three groups depending on the treatment performed: group I - traditional treatment method (rinsing the oropharynx with antiseptic solutions, the use of tablets for resorption), group II - treatment with ozone therapy (fine drip irrigation of the mucous membrane of the posterior pharyngeal wall with Ozonide oil), group III - treatment with ozone therapy and laser therapy. During the examination of patients, anamnesis collection, examination of ENT organs, cytological and microbiological examination of the mucous membrane of the posterior pharyngeal wall, contact endoscopy of the mucous membrane of the posterior pharyngeal wall were performed. 5-point visual analogue scales (VAS) were used to assess complaints and pharyngoscopic signs. RESULTS: Our results showed a statistically significant improvement in the quality of life of patients with AP (p=0.012), an improvement in the pharyngoscopic picture (p=0.003). The results obtained by us indicate an improvement in microcirculation under the influence of ozone therapy and low-intensity laser radiation. The technique using ozone therapy and low-intensity laser therapy is characterized by a bactericidal and fungicidal effect. There is a decrease in the total contamination of the posterior wall of the oropharynx with pathogenic and saprophytic microflora (there is a decrease in the contamination of the posterior wall of the pharynx with saprophytic and pathogenic microflora (p≤0.05), the differences are statistically significant). The technique using ozone therapy and low-intensity laser therapy has a pronounced anti-inflammatory effect, which was expressed in a decrease in the severity of dyskeratosis and hyperkeratosis. Thus, the use of ozone therapy in combination with laser therapy opens up new prospects for pathogenetically sound and effective treatment of AP.

Ozone therapy restores immune dysfunction in refractory idiopathic granulomatous mastitis as a novel potential therapeutic approach.

Immunological dysfunction has been suggested to play a major role in the pathogenesis of idiopathic granulomatous mastitis (IGM). We recently showed that ozone therapy was effective in patients with steroid-resistant IGM. This study assessed alterations in intracellular cytokine expression patterns in different T-lymphocyte subsets after ozone therapy in refractory IGM. Peripheral blood T lymphocyte subsets (CD8+ , CD4+ , CD4+ CD25+ CD127- ) were analyzed via flow-cytometry for intracellular cytokine expressions IFN-γ, TNF-α, IL-10, and TGF-ß before and after completion of 4-month systemic ozone therapy. Ozone therapy significantly increased the CD4+ IFN-γ+ (p = 0.032), CD4+ TNF-α+ (p = 0.028), and the CD8+ TNF-α+ (p = 0.012) T cells. In contrast, significant decreases in CD4+ IL-10+ (p = 0.047) and CD8+ IL-10+ T cells (p = 0.022) and CD4+ CD25+ CD127-//low Treg cells secreting TGF-ß (p = 0.005) were found after ozone therapy. When patients were analyzed according to the response to ozone therapy, patients with a complete remission were more likely to have increased CD3- CD16+ CD56+ natural killer cells (p = 0.0027) and decreased CD19+ B lymphocytes (p = 0.046) following ozone therapy. Our results suggest that ozone therapy stimulated a T-helper-1 response associated with IFN-γ production and downregulation of TGF-ß expression in CD4+ CD25+ CD127- Treg cells. These alterations in the immune system following ozone therapy can improve wound healing and restore immune dysfunction in patients with refractory IGM.

Effectiveness of intravesical ozone in interstitial cystitis by the O'Leary-Sant symptom index.

INTRODUCTION AND HYPOTHESIS: A prospective clinical, preliminary study was performed in patients with interstitial cystitis/bladder pain syndrome (IC/BPS) who were nonresponders to conventional treatment and received intravesical ozone as a therapeutic alternative. METHODS: Sixteen patients received six applications of intravesical ozone at a concentration of 41 µg/mL. We evaluated therapeutic efficacy by the percentage reduction of Interstitial Cystitis Symptom and Problem Index scores (ICSI/ICPI-the O'Leary-Sant symptom index), recurrence rate, nonresponse, and side effects in scores collected on admission (pre-treatment), at the end of the therapeutic protocol (post-treatment), and 180 days (follow-up) after the last ozone application. RESULTS: The mean age of women was 52.9 years (SD: 15.5), and the duration of symptoms was 5.7 years (SD: 7.1). The median ICSI on admission was 17 (IQR: 14.25-19.5) and at follow-up was 0.5 (IQR: 0-2), with a reduction of 97.5% (CI: 85.7-100). The median ICSI/ICPI on admission was 31.5 (IQR: 29-35.2) and at follow-up was 2.0 (IQR: 0-3.75), with a reduction of 92.3% (CI: 88.8-100). The recurrence rate was only 6.25%, and no patients were nonresponders to the treatment. CONCLUSIONS: The application of intravesical ozone was effective in the treatment of patients with IC/BPS who were nonresponders to conventional therapy, showing a progressive and safe effect, at least in the short term.

Ozonized gels vs chlorhexidine in non-surgical periodontal treatment: A randomized clinical trial.

OBJECTIVE: To evaluate the efficacy of newly introduced ozonated gels compared with conventional chlorhexidine gel in the home management of periodontal patients. MATERIALS AND METHODS: 30 patients with bilateral periodontal disease (severity I, complexity II) were enrolled (split-mouth study design). After nonsurgical mechanical periodontal debridement, the teeth were randomly divided into two groups: teeth in the Control group were treated with a chlorhexidine-based gel to aid oral hygiene maneuvers for 2 weeks after the first visit, while teeth in the Test group were treated in the same way with ozone-based gels. After the baseline assessment, the follow-up included assessments at 1, 2, and 6 months. The variables evaluated were clinical attachment loss (CAL), probing pocket depth (PPD), bleeding on probing (BoP), plaque control record (PCR), recession (R), and tooth mobility (TM). RESULTS: For CAL, PPD, BoP, and PCR, significant intragroup differences were found for both groups (p < 0.05), in contrast to intergroup differences (p > 0.05). No significant differences were found for R and TM. CONCLUSION: Nonsurgical mechanical periodontal debridement with adjunctive use of ozone and chlorhexidine was found to be effective in periodontal treatment. Ozone could be suggested as an alternative to chlorhexidine.

Efficacy of ultrasound guided caudal epidural steroid injection with or without ozone in patients with lumbosacral canal stenosis; a randomized clinical controlled trial.

BACKGROUND: Lumbosacral canal stenosis is known as the most common cause of back surgery with several complications. Selecting a minimally invasive treatment with high efficacy in such patients is necessary. This study was designed to evaluate the effectiveness of ozone therapy in combination with caudal epidural steroid in patients with lumbar spinal stenosis. METHODS: A double-blind randomized clinical trial was conducted on 50 patients with lumbar spinal stenosis allocated into two study groups. Under ultrasound guidance, the first group received 80 mg of triamcinolone hexavalent with 4 mL of Marcaine 0.5% and 6 mL of distilled water to the caudal epidural space. The second group received an injection similar to the first group, combined with 10 mL of ozone (O2-O3) gas at a concentration of 10 µg/cc. The patients were followed at baseline, one, and six months after injection with clinical outcomes measures using Visual Analog Scale (VAS), Walking Distance (WD) and Oswestry Disability Index (ODI). RESULTS: The mean age of subjects, 30 males (60%) and 20 females (40%), was reported as 64.51 ± 7.19 years old. Reduction of pain intensity based on VAS score was statistically significant in both groups at follow-up periods (P < 0.001). The VAS changes in the first month and sixth months showed no significant difference between the two groups (P = 0.28 and P = 0.33, respectively). The improvement in disability index (ODI) in both types of treatment during follow-up was significant (P < 0.0001), and there was no difference between the two treatment groups in one month and six months (P = 0.48 and P = 0.88, respectively). As for walking distance, the improvement process with both types of treatment during follow-up periods was significant (P < 0.001). However, after one and six months of treatment, the rate of improvement in patients' walking distance in the caudal epidural steroid injection plus ozone group was significantly higher than in the epidural steroid group (p = 0.026 and p = 0.017, respectively). CONCLUSIONS: In this study, the results of VAS and ODI outcomes showed that caudal epidural steroid injection combined with ozone has no advantage over caudal epidural steroid injection alone. Interestingly, our results demonstrated that the group receiving caudal epidural steroid injection plus ozone scored significantly higher on the walking distance index than the group receiving caudal epidural steroid alone. TRIAL REGISTRATION: IRCT IRCT20090704002117N2 (registration date: 07/08/2019).

Cost-utility analysis and net monetary benefit of Platelet Rich Plasma (PRP), intra-articular injections in compared to Plasma Rich in Growth Factors (PRGF), Hyaluronic Acid (HA) and ozone in knee osteoarthritis in Iran.

PURPOSE: To evaluate the cost-effectiveness of Platelet Rich Plasma (PRP), Plasma Rich in Growth Factors (PRGF), Hyaluronic Acid (HA) and ozone as effective treatment approaches in knee osteoarthritis management from Iran Health care perspective. METHODS: A decision tree model was conducted to assess the cost-effectiveness of four common intra-articular treatment approaches in patients with mild and moderate knee osteoarthritis. The data on clinical effectiveness was obtained from a randomized controlled trial (RCT) conducted in Iran and used to estimate utility values. The direct medical costs were estimated according to tariffs for public medical centers and hospitals, approved by the Iran Ministry of Health and Medical Education in 2021. The incremental cost-effectiveness ratio (ICER) and the net monetary benefit (NMB) were used to evaluate the cost-utility analysis. Deterministic and probabilistic sensitivity analyses are performed to investigate the robustness of the results and account for the different sources of uncertainty. RESULTS: In this study, HA intra-articular injection-related costs ($581.67/patient) were defined as the highest cost, followed by PRGF ($328.10/patient), PRP (318.58/patient), and Ozone (103.20/patient). According to the utility value, PRP and PRGF (0.68) have the same and the most utility among Intra-articular injections in knee osteoarthritis management. However, the PRP injection method was identified as the most cost-effective intervention due to its high NMB and ICER estimates. Based on the Monte Carlo Simulation, PR intervention, compared to other ones, was introduced as the dominant strategy regarding knee OA management, with a WTP of $10,000 for 100% of cases. CONCLUSION: The study result demonstrated that intra-articular injection of PRP, compare to other injections, is a cost-effective treatment option for patients with mild and moderate knee osteoarthritis. In addition, intra-articular injection of PRP was identified as the best injection, with the highest level of net monetary benefit, for knee OA management.

Cytokine profiles in COVID-19 patients undergoing adjunct ozone therapy: some comments.

A comment to: Ghaleh HEG, Izadi M, Javanbakht M, Ghanei M, Einollahi B, Jafari NJ, Alishiri G, Aslani J, Abolghasemi H, Simonetti V, Khafaei M, Zhao S, Saadat SH, Ahmadi M, Parvin S, Vazifedoust S, Alvanagh AG. Cytokine profile and antioxidants status in the moderate and severe COVID-19 patients: a trial of ozone therapy impact as a medicinal supplement. Inflammopharmacology. 2023 Jul 12. https://doi.org/10.1007/s10787 -023-01288-9.

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

BACKGROUND: 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, and antiparasitic properties. 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. METHODS: The statistical sample of this study included two hundred patients with COVID-19. One hundred COVID-19 patients (treatment group) received 240 ml of the patient's blood and an equal volume of O2/O3 gas at a concentration of 35-50 µg/ml daily, which gradually increased in concentration, and were kept for 5-10 days and one hundred patients (control group) received standard treatment. The secretion levels of IL-6, TNF-α, IL-1ß, IL-10 cytokines, SOD, CAT and GPx were compared between control patients (standard treatment) and standard treatment plus intervention (ozone) before and after treatment. RESULTS: The findings indicated a significant decrease in the level of IL-6, TNF-α, IL-1ß 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. CONCLUSIONS: 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.

Direct Pulp Capping with Advanced Platelet-Rich Fibrin: A Report of Two Cases.

This article aims to prove dentin bridge formation in two cases after direct pulp capping in reversible pulpitis using the platelet concentrate A-PRF+ and preservation of the vitality of the dental pulp. The hemostasis process for the pulp wound and cavity disinfection with gaseous ozone was performed under anesthesia. A large A-PRF+ membrane was prepared from blood plasma and applied to the pulp wound. After placing an MTA, the cavity was closed using glass-ionomer cement. Clinical and cone beam computed tomography findings demonstrated the formation of a dentin bridge in both cases. After the definitive restoration was conducted during the sixth month, the teeth from both patients were asymptomatic and had normal electric pulp testing values. Conclusions: Via clinical and CBCT examinations, we observed the dentin bridge formation after placing the platelet concentrate A-PRF+ in both cases. The vitality of the dental pulp was preserved. Further research is needed to refine the clinical protocol, recommended period for control examination, clarification of the precise indications of platelet concentrates, etc.

Quality of Life in Patients with Venous Leg Ulcers Treated by Means of Local Hyperbaric Oxygen Therapy or Local Ozone Therapy-A Single Center Study.

Background and Objectives: Venous leg ulcers pose a significant medical problem worldwide. The complexity of the problem determines the need for further interdisciplinary activities that will improve the quality of life for treated patients. This study compared the quality of life of patients with venous leg ulcers who received local hyperbaric oxygen therapy or local ozone therapy procedures as part of comprehensive treatment. Materials and Methods: The study included 129 patients (62 men and 57 women) with venous leg ulcers. Group I underwent local hyperbaric oxygen therapy (HBOT), and Group II underwent local ozone therapy (OZONE). In both groups, the patients' quality of life was assessed before the start of the treatment cycle, as well as 10 weeks and 6 months after the completion of the treatment, by means of the EQ-5D-5L questionnaire and the Polish shortened version of the SF-36 scale. Results: After completing the respective therapeutic cycle, both groups showed statistically significant (p < 0.001) improvement in quality of life, according to the EQ-5D-5L questionnaire and the SF-36 scale. Differences were noted between the 1st examination (before treatment) and the 2nd examination (10 weeks after treatment), as well as the 3rd examination (6 months after treatment). In the EQ-5D-5L assessment of anxiety and depression, self-care, and activities of daily living 6 months after the end of treatment, better results were found in the group of patients treated with local hyperbaric oxygen therapy (p < 0.001). In this group, 6 months after the end of the treatment, a statistically significantly higher result on the EQ-VAS scale was also obtained (73.09 ± 19.8 points vs. 68.03 ± 17.37 points, p = 0.043). However, in the SF-36 assessment performed 6 months after the end of treatment, better results-a statistically significantly lower value of the quality of life index-were recorded in the group of patients treated with local ozone therapy (103.13 ± 15.76 points vs. 109.89 ± 15.42 points, p < 0.015). Conclusions: Hyperbaric oxygen therapy and local ozone therapy procedures have a beneficial effect on improving the quality of life of patients with venous leg ulcers.

Ozonated triglyceride protects against septic lethality via preventing the activation of NLRP3 inflammasome. / é ¸åŒ–è„‚è‚ªé ¸é ¯é€šè¿‡æŠ‘åˆ¶NLRP3炎症小体活化减少脓毒症致死（英文）.

OBJECTIVES: Sepsis is a critical dysregulated host response with high mortality and current treatment is difficult to achieve optimal efficacy. Ozone therapy has been revealed to protect infection and inflammation-related diseases due to its role in antibiotic and immunoregulatory effect. Ozonated triglyceride is a key component of ozonated oil that is one of ozone therapy dosage form. However, the potential role of ozonated triglyceride in sepsis remains unclear. This study aims to explore the effect of ozonated triglyceride on septic mouse model and the molecular mechanism. METHODS: Intraperitoneal injection of lipopolysaccharide (LPS), cecal ligation and puncture (CLP) were applied to construct septic mouse model. The mouse serum was obtained for detection of cytokines, and lung tissues were collected for hematoxylin and eosin (HE) staining to evaluate the extent of lung injury in septic mouse with ozonated triglyceride treatment at different time and doses. The survival of septic mice was observed for 96 h and Kaplan-Meier analysis was used to analyze the survival rates. In addition, primary peritoneal macrophages and human acute monocytic-leukemia cell line (THP-1) were treated with inflammasome activators with or without ozonated triglyceride. The level of cytokines was detected by enzyme-linked immunosorbent assay (ELISA). The cleavage of caspase-1 and gasdermin-D (GSDMD) was detected by Western blotting. RESULTS: Ozonated triglyceride at different time and doses reduced the release of inflammasome-related cytokines [interleukin (IL)-1ß and IL-18] (all P<0.05) but not pro-inflammatory cytokines such as IL-6 and tumor necrosis factor-α (TNF-α) in septic mice (all P>0.05). Ozonated triglyceride significantly improved the survival rate of septic mice and reduced sepsis-induced lung injury (all P<0.05). Ozonated triglyceride significantly suppressed the canonical and non-canonical activation of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome (all P<0.05) but not affected absent in melanoma 2 (AIM2) and NLR family CARD domain-containing protein 4 (NLRC4) inflammasomes in vitro (all P>0.05). Ozonated triglyceride reduced the cleavage of caspase-1 and the downstream GSDMD. CONCLUSIONS: Ozonated triglyceride presents a protect effect on sepsis lethality via reducing cytokines release and sepsis-related organ injury. The mechanism is that ozonated triglyceride specifically suppresses the activation of NLRP3 inflammasome. Ozonated triglyceride is a promising candidate for sepsis treatment.

[Enteral protection in patients with diffuse peritonitis]. / Enteroprotektsiya v povyshenii effektivnosti lecheniya patsientov s rasprostranennym peritonitom.

OBJECTIVE: To improve treatment outcomes in patients with diffuse peritonitis via enteral protection using intestinal lavage with ozonized solution through an original tube. MATERIAL AND METHODS: We analyzed 78 patients with advanced peritonitis. The control group included 39 patients who underwent standard measures after surgery for peritonitis. The main group consisted of 39 patients who underwent early postoperative intestinal lavage with ozonized solutions through original tube for 3 days. RESULTS: Clinical and laboratory parameters, as well as ultrasound data indicated better correction of enteral insufficiency in the main group. Morbidity in the main group was lower by 33.3%, length of hospital-stay - by 3.5 days. CONCLUSION: Early postoperative intestinal lavage with ozonized solutions through original tube accelerates recovery intestinal function and improves treatment outcomes in patients with widespread peritonitis.

[Chronic pharyngitis. Modern approaches to diagnosis and treatment]. / Khronicheskii faringit. Sovremennye podkhody k diagnostike i lecheniyu.

The relevance of the problem of chronic inflammatory diseases of the pharynx is due to the significant prevalence of this pathology. Among all forms of chronic pharyngitis, the most adverse effect on the quality of life is observed in chronic athrophic pharyngitis. According to the literature, in this category of patients there are no clear criteria for assessing the functional state and morphological picture of the mucous membrane of the posterior pharyngeal wall. Most of the described signs of atrophic pharyngitis are insufficienyly informative, which necessitates further improvement of existing and possible search for new diagnostic methods. Many of the modern methods of treatment do not provide a lasting effect due to the presence of only a local effect on the altered mucous membrane of the posterior pharyngeal wall, without taking into account the changes that are caused by a violation of trophic processes in the tissue, which necessitates the search for new effective methods of treating this disease.The review article outlines modern ideas about the methods of diagnosis and treatment of chronic pharyngitis, presents promising areas in the treatment of patients with atrophic pharyngitis. In foreign countries, the term «chronic tonsillopharyngitis¼ is most often used. Due to the existing difference in terminology, the predominant part of the material on the problem of chronic pharyngitis is presented by domestic literature sources.

COVID-19 and low back pain: previous infections lengthen recovery time after intradiscal ozone therapy in patients with herniated lumbar disc.

PURPOSE: To assess and compare the clinical effectiveness of percutaneous intradiscal ozone therapy in patients affected by lumbar disc herniation, with and without history of COVID-19 infection. MATERIALS AND METHODS: After the rising of COVID-19 pandemics in Italy, 47 consecutive percutaneous intradiscal ozone therapies were performed on patients with low back pain and/or sciatic pain due to lumbar disc herniation. Among these, 19 had suffered from COVID-19 and successively recovered with no residual symptoms, while the remaining 28 had not previously been affected by COVID-19 and were not convalescent. Oswestry Disability Index (ODI) was administered before the treatment and at 1-month and 3-month follow-up in order to assess the clinical outcome. RESULTS: The two groups were similar in terms of patient age (p-value 0.54), treated levels (p-value 0.26) and pre-procedure ODI (p-value 0.33). Technical success was achieved in all cases. In patients previously affected by COVID-19, mean ODI decrease was 11.58 ± 9.51 (35.72%) at 1-month follow-up and 20.63 ± 9.87 (63.63%) at 3-month follow-up. In patients never affected by COVID-19, mean ODI decrease was 20.93 ± 10.53 (58.73%) at 1-month follow-up and 22.07 ± 11.36 (61.92%) at 3-month follow-up. Eventually, clinical success was registered in 84.21% (16/19) of patients with history of COVID-19 infection and in 85.71% (24/28) of patients with no history of COVID-19 infection. No major complication was registered. CONCLUSIONS: In case of lumbar disc herniation treated with percutaneous intradiscal ozone therapy, patients previously affected by COVID-19 showed a significantly longer recovery time.