Ozone rectal insufflation mitigates chronic rapid eye movement sleep deprivation-induced cognitive impairment through inflammation alleviation and gut microbiota regulation in mice.

A range of sleep disorders has the potential to adversely affect cognitive function. This study was undertaken with the objective of investigating the effects of ozone rectal insufflation (O3-RI) on cognitive dysfunction induced by chronic REM sleep deprivation, as well as elucidating possible underlying mechanisms. O3-RI ameliorated cognitive dysfunction in chronic REM sleep deprived mice, improved the neuronal damage in the hippocampus region and decreased neuronal loss. Administration of O3-RI may protect against chronic REM sleep deprivation induced cognitive dysfunction by reversing the abnormal expression of Occludin and leucine-rich repeat and pyrin domain-containing protein 3 inflammasome as well as interleukin-1ß in the hippocampus and colon tissues. Moreover, the microbiota diversity and composition of sleep deprivation mice were significantly affected by O3-RI intervention, as evidenced by the reversal of the Firmicutes/Bacteroidetes abundance ratio and the relative abundance of the Bacteroides genus. In particular, the relative abundance of the Bacteroides genus demonstrated a pronounced correlation with cognitive impairment and inflammation. Our findings suggested that O3-RI can improve cognitive dysfunction in sleep deprivation mice, and its mechanisms may be related to regulating gut microbiota and alleviating inflammation and damage in the hippocampus and colon.

Computed Tomography-Guided Dorsal Root Ganglion Ozone Injection Combined With Pulsed Radiofrequency for Acute Herpes Zoster Neuralgia Treatment of Middle-aged and Elderly People: A Randomized, Double-blinded, Controlled Trial.

OBJECTIVES: To investigate the efficacy and safety of pulsed radiofrequency of the dorsal root ganglion combined with ozone injection for treating acute herpes zoster (HZ) neuralgia in middle-aged and elderly adults. METHODS: A total of 164 middle-aged and elderly patients with acute HZ were randomly assigned to 2 groups: the pulsed radiofrequency combined with ozone injection group (group A) and the pulsed radiofrequency group (group B). The therapeutic effects were evaluated using Numeric Rating Scale (NRS) scores and the average doses of gabapentin (mg/d) preoperatively and 1 day, 2 weeks, 4 weeks, 12 weeks, and 24 weeks postoperatively. The incidence of clinically significant postherpetic neuralgia (PHN) and complications in the 2 groups were recorded. RESULTS: The data showed that the NRS scores and the doses of gabapentin after treatment were significantly lower when compared with the baseline values in both groups. Compared with group B, the NRS scores and the doses of postoperative gabapentin were significantly lower in group A. The incidence of PHN was significantly lower at weeks 4, 12, and 24 in group A than in group B. No adverse reactions occurred in either of the 2 groups post-treatment. CONCLUSIONS: The results indicated that ozone injection in the dorsal root ganglion combined with pulsed radiofrequency therapy was more effective in treating acute HZ neuralgia in middle-aged and elderly adults. It provides patients with longer-lasting pain relief, decreased incidence of PHN and the doses of medication, and improved quality of life than with Pulsed Radiofrequency treatment.

Ozone therapy by rectal insufflation in dogs: safety and oxidative stress - a randomized cross-over study.

Ozone therapy acts in the body inducing controlled oxidative stress, thereby improving the antioxidant, immune and circulatory responses. However, very little is known about how this therapy affects oxidative stress indicators in dogs. We aimed to assess the clinical, hematological, biochemical and oxidative stress parameters of healthy dogs subjected to ozone therapy and oxygen therapy by rectal insufflation. Ten healthy dogs were allocated into three experimental groups in a cross-over design: control, without intervention; ozone, which received 100 µg of O3/kg through rectal insufflation; and oxygen, which received an ozone-equivalent volume of medicinal O2 through rectal insufflation. Dogs received four applications weekly and were followed up until the seventh week. Ozone therapy significantly increased the weight, mean corpuscular volume and mean platelet volume and decreased total cholesterol of treated dogs. Regarding oxidative stress, ozone therapy reduced total antioxidant capacity by ferric reduction (TAC-FRAP) in D7 compared with baseline and the control, significantly increased total antioxidant capacity by cupric reduction (TAC-CUPRAC) in D42 and D49 compared with the control group, caused an increase in uric acid compared with the oxygen group and decreased lipid peroxidation on D21 compared with the control group. In conclusion, ozone therapy through rectal insufflation causes transient oxidative stress followed by an antioxidant response and discreetly interferes with a few clinical, hematological and biochemical variables in healthy dogs, although variables still remained within the reference ranges for the species, thus proving the safety of the therapy. Furthermore, oxygen therapy causes oxidative stress without inducing a subsequent antioxidant response.

The effect of intra-articular ozone injection combined with home-based exercise on pain and function in daily living activities of patients with mild to moderate knee osteoarthritis, a randomized double-blinded controlled clinical trial.

BACKGROUND: Knee osteoarthritis is the most common arthritis. Various treatments such as analgesics, exercise therapy, and surgery in high-grade OA have been shown to reduce pain and improve patients' function; however, determining the optimal treatment remains a challenge. Ozone therapy is one of the injection techniques used for symptom relief in these patients. Therefore, this study aimed to evaluate the effect of ozone injection in mild to moderate knee osteoarthritis. METHODS: Thirty-three patients with grade II-III knee osteoarthritis based on the Kellgren-Lawrence classification were involved in the study, by block randomisation. Totally 42 knees were included. All patients received exercise therapy, 500 mg of acetaminophen tablets (up to 2 g per day as needed), and healthy nutrition. In a double-blinded method, the intervention group received Ozone injections, but the control group received placebo injections. Functional tests, including timed-up-and-go and 6-min walk tests, were assessed at baseline and immediately after the 6-week intervention. In addition, the pain was measured by VAS score, and stiffness and activity of daily living (ADL) were evaluated by KOOS questionnaire before and after a 6-week intervention and then one and six months afterwards. FINDINGS: Improvements in pain and KOOS scores were seen in both groups in the 6th week of injections (p < 0.05), with significant differences between groups. However, the effects on pain and KOOS scores disappeared in the 1st and 6th months of follow-ups in the control group. Nevertheless, the effects persisted in the intervention group compared to the baseline and control group, which means that in the mentioned time points intervention group showed significant improvement compared to the control group (p < 0.05). In addition, functional tests showed significant differences between the two groups in the 6th week of injections (p < 0.001). INTERPRETATION: Ozone injection is a non-surgical treatment for mild to moderate knee osteoarthritis that could decrease pain and improve function and ADL of patients in the short to mid-term (3-6 months), so it seems that adding Ozone injection to the routine exercise therapy in management of patients with knee OA could improve outcomes.

Efficacy of Medical Ozone for Treatment of Chronic Musculoskeletal Pain with Abnormal Mitochondrial Redox State: Prospective Randomized Clinical Trial.

BACKGROUND: Chronic primary musculoskeletal pain is multifaceted and 20% of the adult population lives with severe chronic pain and experience symptoms such as intense pain, depression, weakness, sleep problems, decreased quality of life and decreased emotional well-being. OBJECTIVES: This paper studies the efficacy of trigger point injections with ozone compared to standard steroid injection or combination therapy for the treatment of chronic musculoskeletal pain in patients with abnormal mitochondrial redox state. STUDY DESIGN: This is a prospective randomized clinical study conducted with 51 patients experiencing chronic musculoskeletal pain. SETTING: Medical Research Institute Hospital, Alexandria University. METHODS: By computer-generated random numbers the 51 patients were divided into 3 groups. Group A (17 patients) received ozone injection, group B (17 patients) received betamethasone injection and group C (17 patients) received combined ozone and betamethasone injections. The groups were compared based on the intensity of pain and correction of mitochondrial redox state of the patients. RESULTS: Three days after intervention, the visual analog scale (VAS) scores reported by patients were lower in group A compared to group B (with a mean difference 1.27, 95% confidence interval (CI) of 0.15-2.39 (P < 0.02). One and 3 weeks after intervention, VAS scores of patients were lower in groups A and C compared to group B. At one week the mean difference between A and B was 1.2, with a 95% CI of 0.15-2.25 (P < 0.02) and the mean difference between C and B was 1.73 with a 95% CI of 0.69-2.78 (P < 0.001). At 3 weeks the mean difference between A and B was 1.5 with a 95% CI of 0.2-2.87 (P < 0.01) and the mean difference between C and B was 2.27 with a 95% CI of 0.93-3.60 (P < 0.0001). The reduced/oxidized glutathione ratio after intervention was higher in groups A and C compared to group B (P > 0.008). The mitochondrial copy number was higher in group A compared to group B (P < 0.002). LIMITATION: This study didn't allow for the comparison of the experimental groups with a placebo or control group for musculoskeletal pain conditions in orderto establish the role of an abnormal mitochondrial redox state on the pathogenesis of patients from an ethical view. CONCLUSIONS: Ozone therapy or combined ozone and betamethasone treatment are  effective techniques for management of pain since it produced a significant reduction of muscle pain and increase of the pain free interval experienced by patients. Ozone therapy causes pain improvement which increases with time and it improves muscle oxygenation and mitochondrial function. TRIAL REGISTRATION: This study was approved by the Ethics Committee of Medical Research Institute (IORH: IOR 00088812) and was registered at the Pan African Clinical Trial Registry (www.pactr.org) under the identification number PACTR201908620943471. The registration this experiment started on 07/08/2019. This study's protocol followed the CONSORT guidelines and was performed under the relevant guidelines.

Ozone Therapy for a Soccer Player With Osteitis Pubis: A Case Report.

CONTEXT: Osteitis pubis (OP), which occurs as a result of excessive use of the symphysis pubis and parasymphysis bones, is more common in long-distance runners and kicking athletes, especially football players. Due to the poor results of commonly used treatments for OP, there is a need for investigation of more effective treatments, such as ozone therapy. Ozone therapy is used to treat a variety of diseases, including musculoskeletal conditions. CASE PRESENTATION: A 30-year-old amateur soccer player diagnosed with OP received conservative treatment with traditional physiotherapy and analgesic medications. After 6 months and no resolution of symptoms, the patient presented to the sports medicine outpatient clinic seeking alternative therapy options. MANAGEMENT AND OUTCOMES: The patient received ozone injections in 3 sessions administered at 10-day intervals. At 1, 3, 6 and 12 months after the treatment, the patient's complaints and pain levels were re-evaluated and examined. The patient was able to return to competition at the same level after the first injection. No recurrence was revealed at a minimum of 12 months of follow-up. CONCLUSION: In this article, we present a case in which OP was successfully treated with ozone injection.

Efficacy of ozone injections for reducing musculoskeletal pain in comparison with corticosteroid injections: A systematic review and meta-analysis.

BACKGROUND: Corticosteroid injections are frequently used in the short-term treatment of musculoskeletal pain, but their use is controversial as repeated exposures to corticosteroids can lead to deleterious effects on musculoskeletal tissue. Ozone injections have been proposed as a possible treatment for musculoskeletal pain; however, their effectiveness has not been compared with corticosteroids. OBJECTIVE: To evaluate the effectiveness of ozone injections for reducing pain in individuals with musculoskeletal pain in comparison with corticosteroid injections through a meta-analysis. METHODS: An online systematic search was performed using electronic databases up to September 2023. We searched for studies that compared corticosteroid injections with ozone injections in the treatment of musculoskeletal pain of diverse origins. RESULTS: Eleven studies were included comprising a total of 534 individuals. In the overall pooled analysis, a pain reduction in favor of corticosteroid injections was found in the short term (d= 0.31, 95% CI 0.01 to 0.60, p (z) 0.04, I2 = 32%). In the medium term, no significant differences were found in reducing pain between groups (d=-0.17, 95% CI -0.42 to 0.07, p (z) 0.15, I2 = 0%). CONCLUSIONS: Our results suggest that corticosteroids injections are more effective in reducing musculoskeletal pain in the short term, but equally effective in the medium term when compared with ozone injections. Nonetheless, better-quality clinical trials are necessary to corroborate these results.

US/CT fusion imaging and virtual navigation to guide lumbar intradiscal oxygen-ozone therapy: a pilot study.

PURPOSE: To test the feasibility of US/CT fusion imaging to guide lumbar intradiscal O2/O3 therapy to treat discogenic degenerative low back pain due to lumbar disc herniation (LDH). METHODS: We retrospectively included consecutive patients affected by low back pain and/or sciatica due to LDH resistant to conservative therapies, who underwent to lumbar intradiscal O2/O3 injection under CT/US fusion imaging guidance (Fusion Group) and standard CT guidance (Control Group). For each procedure, we collected procedure operative time, room utilization time, number of CT passes, complications, and O2/O3 intradiscal diffusion adequacy. Technical success was defined as the ability to complete the procedure as initially planned to reach the disc. Technical efficacy was based on O2/O3 intradiscal diffusion adequacy, as demonstrated by the last CT scan. RESULTS: Six patients (4 males; mean age: 68 ± 15 years) were included in the Fusion group, six (4 males; mean age: 66 ± 12 years) in Control group. No complications were observed in both groups. In Fusion group we found significantly lower room utilization time (30 ± 6 min vs. 46 ± 10 min, p = 0.008), procedure operative time (14 ± 3 min vs. 24 ± 6 min, p = 0.008), and number of CT passes (2 [2,2] vs. 3 [3,3], p = 0.006) than in Control Group, respectively. Technical success and efficacy were 100% in both Groups. CONCLUSION: CT/US fusion imaging seems to be a feasible and safe guidance for intradiscal O2/O3 injections, allowing decrease of procedure time and number of CT passes.

Ozonation of Brazil nuts (Bertholletia excelsa H.B.K. ): effect of column height on the saturation process and changes in quality / Ozonização de castanha-do-Brasil (Bertholletia excelsa H.B.K. ): efeito da altura da coluna no processo de saturação e alterações na qualidade

The objective of this study is to examine the saturation process in a column containing Brazil nuts and possible changes in the quality of the product. Brazil nut samples were initially placed in a cylindrical PVC column 15 cm in diameter and 110 cm in height. The ozone gas concentrations of 2.5, 4.5, 9.0, and 14.0 mg L-1 and a flow rate of 3.0 L min-1 were applied at a temperature of 25 ºC. Ozone gas was injected at the base of the cylindrical column, and the seed column height values adopted were 0.25, 0.50, and 0.75 m. Saturation concentration and time were determined. To measure possible changes in the quality of ozonized Brazil nuts, moisture and color, as well as qualitative variables of the crude oil were evaluated at the exposure times of 0, 3, 6, 9, and 12 h. To evaluate the quality of the crude oil extracted from ozonized nuts, the free fatty acid content, peroxide value, and iodine value were analyzed. Increasing ozonation times increased ozone concentration at all inlet gas concentrations. Saturation time decreased as the inlet gas concentration was increased, at the different product column heights. There was no change in product moisture in response to ozonation. Ozonation did not induce significant changes in color or in the crude oil, due to the triple interaction between column height, ozone concentration, and exposure time. In conclusion, the height of the product's column influences saturation time and concentration during the ozonation process. Considering the color of the product and characteristics of its crude oil, the use of ozone under the conditions adopted in the present study does not affect the quality of Brazil nuts to the point of rendering them unmarketable.

O objetivo do presente trabalho é estudar o processo de saturação em coluna contendo castanha-do-Brasil e possíveis alterações na qualidade do produto. Inicialmente as amostras de castanha-do-Brasil foram acondicionadas em coluna cilíndrica de PVC de 15 cm de diâmetro e 110 cm de altura. Foram adotadas as concentrações do gás ozônio de 2,5, 4,5, 9,0 e 14,0 mg L-1 e vazão de 3,0 L min-1, na temperatura de 25 ºC. O gás ozônio foi injetado na base da coluna cilíndrica e os valores adotados de altura da coluna de grãos foram de 0,25, 0,50, e 0,75 m. Determinaram-se o tempo e a concentração de saturação. Na avaliação de possíveis alterações na qualidade de castanhas-do-Brasil ozonizadas foram determinados a umidade, coloração e variáveis qualitativas do óleo bruto, com tempos de exposição de 0, 3, 6, 9 e 12 h. Para avaliação da qualidade do óleo bruto extraído de castanhas ozonizadas foram analisadas o teor de ácidos graxos livres, o índice de peróxido e o índice de iodo. A elevação do período de ozonização promoveu aumento da concentração do ozônio para todas as concentrações de entrada do gás. No que se refere aos valores de tempo de saturação, à medida que se elevou a concentração de entrada do gás, houve redução do tempo de saturação, nas diferentes alturas de coluna do produto. Não houve variação da umidade do produto em decorrência da ozonização. A ozonização não provocou alterações significativas na cor e no óleo bruto, em decorrência da interação tripla entre altura da coluna do produto, concentração do ozônio e tempo de exposição. É possível concluir que a altura da coluna do produto influencia o tempo e a concentração de saturação, durante o processo de ozonização. O uso do ozônio nas condições adotadas no presente estudo não afeta a qualidade da castanhado-Brasil, considerando-se a cor do produto e características do óleo bruto, de tal forma a inviabilizar a comercialização.

Efficiency of topical ozone gel as an adjunct to antibiotics and analgesics on sequelae after extraction of impacted mandibular third molar / Eficiencia del gel de ozono tópico como complemento de antibióticos y analgésicos en las secuelas tras la extracción del tercer molar mandibular impactado

Introduction: Extraction of the impacted mandibular third molar is a common procedure in dentistry. Many complications may arise after this operation, the most common being pain, trismus, and swelling. Systemic medications have been used in an attempt to manage these problems, but because of their side effects, the need for non-medication treatment arises to treat these complications without side effects, such as cryotherapy, ice packs, low-level laser therapy, and ozone. Ozone is one of the most effective antimicrobials used in the dentistry field, and it also has a positive effect on soft tissue healing, activates cellular metabolism, and can react with blood components; for these reasons ozone is used to manage trismus, swelling, and pain after removal of the mandibular third molar. Aim: The purpose of the study was to assess the effects of topical ozone gel on complications from the extraction of the impacted mandibular third molar. Materials and Methods: Thirty patients were enrolled in the current study and were randomly divided into two equal groups. Preoperatively clinical examination included measurement of facial swelling measurements and maximum mouth opening. The position and configuration of the impacted lower third molar, the surrounding bone, the mandibular canal, and the neighboring tooth were all assessed using a panoramic X-ray. On days 2 and 7, after surgery, the facial swelling dimensions and maximum mouth opening were again assessed. Statistics were used to analyze results. Results: Findings indicate statistical significance for pain, but not for swelling or mouth opening. Conclusions: After lower third molar surgery, topical ozone gel helps reduce postoperative pain.

Introducción: La extracción del tercer molar mandibular retenido es un procedimiento común en odontología. Pueden surgir muchas complicaciones después de esta operación, siendo las más comunes dolor, trismo y edema. Se han utilizado medicamentos sistémicos en un intento de controlar estos problemas, pero debido a sus efectos secundarios, surge la necesidad de tratamientos sin medicamentos para tratar estas complicaciones sin efectos secundarios, como crioterapia, bolsas de hielo, terapia con láser de baja intensidad y ozono. El ozono es uno de los antimicrobianos más eficaces utilizados en el campo de la odontología, además tiene un efecto positivo en la cicatrización de los tejidos blandos, activa el metabolismo celular y puede reaccionar con los componentes sanguíneos; Por estas razones, el ozono se utiliza para controlar el trismo, la hinchazón y el dolor después de la extracción del tercer molar mandibular. Objetivo: El propósito del estudio fue evaluar los efectos del gel de ozono tópico sobre las complicaciones de la extracción del tercer molar mandibular impactado. Materiales y Métodos: Se inscribieron treinta pacientes en el estudio actual y se dividieron aleatoriamente en dos grupos iguales. El examen clínico preoperatorio incluyó la medición de la hinchazón facial y la apertura máxima de la boca. La posición y configuración del tercer molar inferior impactado, el hueso circundante, el canal mandibular y el diente vecino se evaluaron mediante una radiografía panorámica. Los días 2 y 7, después de la cirugía, se evaluaron nuevamente las dimensiones de la hinchazón facial y la apertura máxima de la boca. Se utilizaron estadísticas para analizar los resultados. Resultados: Los hallazgos indican significación estadística para el dolor, pero no para la hinchazón o la apertura de la boca.Conclusión: Después de la cirugía del tercer molar inferior, el gel de ozono tópico ayuda a reducir el dolor postoperatorio.

Ozone ultrafine bubble water inhibits the early formation of Candida albicans biofilms.

This study aimed to investigate the effect of ozone ultrafine bubble water (OUFBW) on the formation and growth of Candida albicans (C. albicans) biofilms and surface properties of denture base resins. OUFBWs were prepared under concentrations of 6 (OUFBW6), 9 (OUFBW9), and 11 ppm (OUFBW11). Phosphate buffered saline and ozone-free electrolyte aqueous solutions (OFEAS) were used as controls. Acrylic resin discs were made according to manufacturer instructions, and C. albicans was initially cultured on the discs for 1.5 h. A colony forming unit (CFU) assay was performed by soaking the discs in OUFBW for 5 min after forming a 24-h C. albicans biofilm. The discs after initial attachment for 1.5 h were immersed in OUFBW and then cultured for 0, 3, and 5 h. CFUs were subsequently evaluated at each time point. Moreover, a viability assay, scanning electron microscopy (SEM), Alamar Blue assay, and quantitative real-time polymerase chain reaction (qRT-PCR) test were performed. To investigate the long-term effects of OUFBW on acrylic resin surface properties, Vickers hardness (VH) and surface roughness (Ra) were measured. We found that OUFBW9 and OUFBW11 significantly degraded the formed 24-h biofilm. The time point CFU assay showed that C. albicans biofilm formation was significantly inhibited due to OUFBW11 exposure. Interestingly, fluorescence microscopy revealed that almost living cells were observed in all groups. In SEM images, the OUFBW group had lesser number of fungi and the amount of non-three-dimensional biofilm than the control group. In the Alamar Blue assay, OUFBW11 was found to suppress Candida metabolic function. The qRT-PCR test showed that OUFBW down-regulated ALS1 and ALS3 expression regarding cell-cell, cell-material adhesion, and biofilm formation. Additionally, VH and Ra were not significantly different between the two groups. Overall, our data suggest that OUFBW suppressed C. albicans growth and biofilm formation on polymethyl methacrylate without impairing surface properties.

Fatigue in post-acute sequelae of SARS-CoV2 (PASC) treated with oxygen-ozone autohemotherapy - preliminary results on 100 patients.

OBJECTIVE: Post-acute sequelae of SARS-CoV2 infection (PASC) are a novel terminology used to describe post-COVID persistent symptoms, mimicking somehow the previously described chronic fatigue syndrome (CFS). In this manuscript, we evaluated a therapeutical approach to address PASC-derived fatigue in a cohort of past-COVID-19 positive patients. PATIENTS AND METHODS: A number of 100 patients, previously diagnosed as COVID-19 positive subjects and meeting our eligibility criteria, was diagnosed having PASC-related fatigue. They were recruited in the study and treated with oxygen-ozone autohemotherapy (O2-O3-AHT), according to the SIOOT protocol. Patients' response to O2-O3-AHT and changes in fatigue were measured with the 7-scoring Fatigue Severity Scale (FSS), according to previously published protocols. RESULTS: Statistics assessed that the effects of O2-O3-AHT on fatigue reduced PASC symptoms by 67%, as a mean, in all the investigated cohort of patients (H = 148.4786 p < 0.0001) (Figure 1). Patients following O2-O3-AHT therapy, quite completely recovered for PASC-associated fatigue, a quote amounting to about two fifths (around 40%) of the whole cohort undergoing ozone treatment and despite most of patients were female subjects, the effect was not influenced by sex distribution (H = 0.7353, p = 0.39117). CONCLUSIONS: Ozone therapy is able to recover normal functionality and to relief pain and discomfort in the form of PASC-associated fatigue in at least 67% of patients suffering from post-COVID sequelae, aside from sex and age distribution.

Oxygen-ozone therapy for the treatment of low back pain: a systematic review of randomized controlled trials.

OBJECTIVE: The aim of the study was to review the available literature on the application of oxygen-ozone therapy (OOT) in the treatment of low back pain (LBP), to understand its therapeutic potential and compare it with other available treatment options. MATERIALS AND METHODS: A systematic review was performed on the PubMed and Scopus databases, with the following inclusion criteria: (1) randomized controlled trials (RCTs), (2) published in the last 20 years, (3) dealing with OOT in patients with LBP and herniated disc, (4) comparing the results of OOT with those of other treatments. The risk of bias was assessed by the Cochrane Risk of Bias tool. RESULTS: Fifteen studies involving 2597 patients in total were included. Patients in the control groups received different treatments, from oral drugs to other injections, instrumental therapy and even surgery: corticosteroids were used in 5 studies, analgesic therapy in 2 studies; placebo, microdiscectomy, laser-therapy, TENS and postural rehabilitation, percutaneous radiofrequency intradiscal thermocoagulation and psoas compartmental block were tested in the other trials. Looking at the quality of the literature, none of the studies included reached "good quality" standard, 3 were ranked as "fair" and the rest were considered "poor". Comparison of OOT results with other approaches showed that, in the majority of studies, OOT was superior to the control treatment, and also when compared to microdiscectomy, ozone showed non inferiority in terms of clinical outcomes. CONCLUSIONS: The analysis of literature revealed overall poor methodologic quality, with most studies flawed by relevant bias. However, OOT has proven to be a safe treatment with beneficial effects in pain control and functional recovery at short to medium term follow-up.

Ozone in Medicine. The Low-Dose Ozone Concept and Its Basic Biochemical Mechanisms of Action in Chronic Inflammatory Diseases.

Low-dose ozone acts as a bioregulator in chronic inflammatory diseases, biochemically characterized by high oxidative stress and a blocked regulation. During systemic applications, "Ozone peroxides" are able to replace H2O2 in its specific function of regulation, restore redox signaling, and improve the antioxidant capacity. Two different mechanisms have to be understood. Firstly, there is the direct mechanism, used in topical treatments, mostly via radical reactions. In systemic treatments, the indirect, ionic mechanism is to be discussed: "ozone peroxide" will be directly reduced by the glutathione system, informing the nuclear factors to start the regulation. The GSH/GSSG balance outlines the ozone dose and concentration limiting factor. Antioxidants are regulated, and in the case of inflammatory diseases up-regulated; cytokines are modulated, here downregulated. Rheumatoid arthritis RA as a model for chronic inflammation: RA, in preclinical and clinical trials, reflects the pharmacology of ozone in a typical manner: SOD (superoxide dismutase), CAT (catalase) and finally GSH (reduced glutathione) increase, followed by a significant reduction of oxidative stress. Inflammatory cytokines are downregulated. Accordingly, the clinical status improves. The pharmacological background investigated in a remarkable number of cell experiments, preclinical and clinical trials is well documented and published in internationally peer reviewed journals. This should encourage clinicians to set up clinical trials with chronic inflammatory diseases integrating medical ozone as a complement.

Ozone inactivation of airborne influenza and lack of resistance of respiratory syncytial virus to aerosolization and sampling processes.

Influenza and RSV are human viruses responsible for outbreaks in hospitals, long-term care facilities and nursing homes. The present study assessed an air treatment using ozone at two relative humidity conditions (RHs) in order to reduce the infectivity of airborne influenza. Bovine pulmonary surfactant (BPS) and synthetic tracheal mucus (STM) were used as aerosols protectants to better reflect the human aerosol composition. Residual ozone concentration inside the aerosol chamber was also measured. RSV's sensitivity resulted in testing its resistance to aerosolization and sampling processes instead of ozone exposure. The results showed that without supplement and with STM, a reduction in influenza A infectivity of four orders of magnitude was obtained with an exposure to 1.70 ± 0.19 ppm of ozone at 76% RH for 80 min. Consequently, ozone could be considered as a virucidal disinfectant for airborne influenza A. RSV did not withstand the aerosolization and sampling processes required for the use of the experimental setup. Therefore, ozone exposure could not be performed for this virus. Nonetheless, this study provides great insight for the efficacy of ozone as an air treatment for the control of nosocomial influenza A outbreaks.

A meta-analysis of ozone effect on tooth bleaching.

This systematic review assessed the effectiveness of ozone (O3) in the color change of in-office tooth bleaching in vital teeth (TB) and the sensitivity control. Only randomized controlled clinical trials were included. Seven databases were used as primary search sources, and three additional sources were searched to capture the "grey literature" partially. The JBI tool was used to assess the risk of bias. TB was assessed using the ΔELab color change metric comparing tooth color pre- and post-bleaching. We meta-analyzed the ΔELab estimates per method and calculated the absolute standardized mean difference using random-effect models. The GRADE approach assessed the certainty of the evidence. The ΔELab estimates ranged from 1.28 when the O3 was used alone to 6.93 when combined with hydrogen peroxide (HP). Two studies compared O3 and HP alone, but their TB was similar (SMD = - 0.02; 95%CI: - 0.54; 0.49). The bleaching effectiveness for the combination of O3 + HP compared to HP was similar (SMD = 0.38; 95%CI: - 0.04; 0.81). Thus, based on the available literature, our findings suggest that O3 is not superior to the conventional technique using HP on the change of tooth color. The O3 did not present sensitivity when used alone. When O3 was used in combination with HP, patients reported hypersensitivity only when O3 was applied before HP, i.e., no sensitivity was perceived when O3 was applied after HP.

CORonavirus-19 mild to moderate pneumonia Management with blood Ozonization in patients with Respiratory failure (CORMOR) multicentric prospective randomized clinical trial.

BACKGROUND: Following positive experience on the use of blood ozonation in SARS-CoV-2, the CORMOR randomized trial was designed to evaluate the adjuvant role of oxygen/ozone therapy in mild to moderate SARS-CoV-2 pneumonia. METHODS: The trial (ClinicalTrial.gov NCT04388514) was conducted in four different Italian centers (April-October 2020). Patients were treated according to best available standard of care (SoC) therapy, with or without O3-autohemotherapy (O3-AHT). RESULTS: A total of 92 patients were enrolled: SoC + O3-AHT (48 patients) were compared to the SoC treatment (44 patients). The two groups differed in steroids therapy administration (72.7% in SoC arm vs. 50.0% in O3-AHT arm; p = 0.044). Steroid therapy was routinely started when it was subsequently deemed as effective for the treatment of COVID-19 disease. No significant differences in mortality rates, length of hospital stay, mechanical ventilation requirement and ICU admission were observed. Clinical improvement in patients with pneumonia was assessed according to a specifically designed score (decrease in SIMEU class, improvement in radiology imaging, improvement in PaO2/FiO2, reduction in LDH and requirement of oxygen therapy ≤ 5 days). Score assessment was performed on day-3 (T3) and day-7 (TEnd) of O3-AHT treatment. A significant increase in the score was reported at TEnd, in the O3-AHT treatment arm (0 [0-1] in the SoC arm vs. 2 [1-3] the O3-AHT arm; p = 0.018). No adverse events related O3-AHT treatment was observed. CONCLUSION: In mild-to-moderate pneumonia due to SARS-CoV-2, adjuvant oxygen/ozone therapy did not show any effect on mortality, or mechanical intubation but show a clinical improvement a day 7 from randomization in a composite clinical endpoint. Larger Randomized prospective studies alone or in combination with steroids are needed to confirm our results.

The possibilities of using the effects of ozone therapy in neurology.

OBJECTIVES: The beneficial effects of ozone therapy consist mainly of the promotion of blood circulation: peripheral and central ischemia, immunomodulatory effect, energy boost, regenerative and reparative properties, and correction of chronic oxidative stress. Ozone therapy increases interest in new neuroprotective strategies that may represent therapeutic targets for minimizing the effects of oxidative stress. METHODS: The overview examines the latest literature in neurological pathologies treated with ozone therapy as well as our own experience with ozone therapy. The effectiveness of treatments is connected to the ability of ozone therapy to reactivate the antioxidant system to address oxidative stress for chronic neurodegenerative diseases, strokes, and other pathologies. Application options include large and small autohemotherapy, intramuscular application, intra-articular, intradiscal, paravertebral and epidural, non-invasive rectal, transdermal, mucosal, or ozonated oils and ointments. The combination of different types of ozone therapy stimulates the benefits of the effects of ozone. RESULTS: Clinical studies on O2-O3 therapy have been shown to be efficient in the treatment of neurological degenerative disorders, multiple sclerosis, cardiovascular, peripheral vascular, orthopedic, gastrointestinal and genitourinary pathologies, fibromyalgia, skin diseases/wound healing, diabetes/ulcers, infectious diseases, and lung diseases, including the pandemic disease caused by the COVID-19 coronavirus. CONCLUSION: Ozone therapy is a relatively fast administration of ozone gas. When the correct dose is administered, no side effects occur. Further clinical and experimental studies will be needed to determine the optimal administration schedule and to evaluate the combination of ozone therapy with other therapies to increase the effectiveness of treatment.