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.

Ozone as adjuvant support in the treatment of COVID-19: A preliminary report of probiozovid trial.

The evaluation of new therapeutic resources against coronavirus disease 2019 (COVID-19) represents a priority in clinical research considering the minimal options currently available. To evaluate the adjuvant use of systemic oxygen-ozone administration in the early control of disease progression in patients with COVID-19 pneumonia. PROBIOZOVID is an ongoing, interventional, randomized, prospective, and double-arm trial enrolling patient with COVID-19 pneumonia. From a total of 85 patients screened, 28 were recruited. Patients were randomly divided into ozone-autohemotherapy group (14) and control group (14). The procedure consisted in a daily double-treatment with systemic Oxygen-ozone administration for 7 days. All patients were treated with ad interim best available therapy. The primary outcome was delta in the number of patients requiring orotracheal-intubation despite treatment. Secondary outcome was the difference of mortality between the two groups. Moreover, hematological parameters were compared before and after treatment. No differences in the characteristics between groups were observed at baseline. As a preliminary report we have observed that one patient for each group needed intubation and was transferred to ITU. No deaths were observed at 7-14 days of follow up. Thirty-day mortality was 8.3% for ozone group and 10% for controls. Ozone therapy did not significantly influence inflammation markers, hematology profile, and lymphocyte subpopulations of patients treated. Ozone therapy had an impact on the need for the ventilatory support, although did not reach statistical significance. Finally, no adverse events related to the use of ozone-autohemotherapy were reported. Preliminary results, although not showing statistically significant benefits of ozone on COVID-19, did not report any toxicity.

Ozone-induced changes in oxidative stress parameters in brain regions of adult, middle-age, and senescent Brown Norway rats.

A critical part of community based human health risk assessment following chemical exposure is identifying sources of susceptibility. Life stage is one such susceptibility. A prototypic air pollutant, ozone (O3) induces dysfunction of the pulmonary, cardiac, and nervous systems. Long-term exposure may cause oxidative stress (OS). The current study explored age-related and subchronic O3-induced changes in OS in brain regions of rats. To build a comprehensive assessment of OS-related effects of O3, a tripartite approach was implemented focusing on 1) the production of reactive oxygen species (ROS) [NADPH Quinone oxidoreductase 1, NADH Ubiquinone reductase] 2) antioxidant homeostasis [total antioxidant substances, superoxide dismutase, γ-glutamylcysteine synthetase] and 3) an assessment of oxidative damage [total aconitase and protein carbonyls]. Additionally, a neurobehavioral evaluation of motor activity was compared to these OS measures. Male Brown Norway rats (4, 12, and 24 months of age) were exposed to air or O3 (0.25 or 1 ppm) via inhalation for 6 h/day, 2 days per week for 13 weeks. A significant decrease in horizontal motor activity was noted only in 4-month old rats. Results on OS measures in frontal cortex (FC), cerebellum (CB), striatum (STR), and hippocampus (HIP) indicated life stage-related increases in ROS production, small decreases in antioxidant homeostatic mechanisms, a decrease in aconitase activity, and an increase in protein carbonyls. The effects of O3 exposure were brain area-specific, with the STR being more sensitive. Regarding life stage, the effects of O3 were greater in 4-month-old rats, which correlated with horizontal motor activity. These results indicate that OS may be increased in specific brain regions after subchronic O3 exposure, but the interactions between age and exposure along with their consequences on the brain require further investigation.

Diets enriched with coconut, fish, or olive oil modify peripheral metabolic effects of ozone in rats.

Dietary factors may modulate metabolic effects of air pollutant exposures. We hypothesized that diets enriched with coconut oil (CO), fish oil (FO), or olive oil (OO) would alter ozone-induced metabolic responses. Male Wistar-Kyoto rats (1-month-old) were fed normal diet (ND), or CO-, FO-, or OO-enriched diets. After eight weeks, animals were exposed to air or 0.8 ppm ozone, 4 h/day for 2 days. Relative to ND, CO- and OO-enriched diet increased body fat, serum triglycerides, cholesterols, and leptin, while all supplements increased liver lipid staining (OO > FO > CO). FO increased n-3, OO increased n-6/n-9, and all supplements increased saturated fatty-acids. Ozone increased total cholesterol, low-density lipoprotein, branched-chain amino acids (BCAA), induced hyperglycemia, glucose intolerance, and changed gene expression involved in energy metabolism in adipose and muscle tissue in rats fed ND. Ozone-induced glucose intolerance was exacerbated by OO-enriched diet. Ozone increased leptin in CO- and FO-enriched groups; however, BCAA increases were blunted by FO and OO. Ozone-induced inhibition of liver cholesterol biosynthesis genes in ND-fed rats was not evident in enriched dietary groups; however, genes involved in energy metabolism and glucose transport were increased in rats fed FO and OO-enriched diet. FO- and OO-enriched diets blunted ozone-induced inhibition of genes involved in adipose tissue glucose uptake and cholesterol synthesis, but exacerbated genes involved in adipose lipolysis. Ozone-induced decreases in muscle energy metabolism genes were similar in all dietary groups. In conclusion, CO-, FO-, and OO-enriched diets modified ozone-induced metabolic changes in a diet-specific manner, which could contribute to altered peripheral energy homeostasis.

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.

Successful Treatment of Multiple Common Warts With Intralesional Ozone.

BACKGROUND: Although there are multiple treatments for warts, wart management remains a challenge. Ozone therapy is an emerging treatment for infectious and noninfectious dermatological diseases. OBJECTIVE: To assess intralesional ozone gas safety and efficacy in multiple warts management. MATERIALS AND METHODS: Seventy-four adult patients with multiple common warts were included in this study. They were randomly assigned into 2 groups: first group comprised 44 patients treated with intralesional ozone gas, and the second group comprised 30 patients who received intralesional saline injection. In both groups, warts in all patients were directly injected weekly until complete clearance occurred or for a maximum of 10 treatment sessions. The subjects were followed for 6 months to record any recurrences. RESULTS: In the ozone group, 25 patients (56.8%) had a complete response with an excellent cosmetic outcome, 15 patients (34.1%) showed a partial response, and 4 patients (9.1%) had no response. More subjects responded to ozone than to saline (p < .001). Ozone therapy was associated with mild side effects, including pain at time of injection, numbness, and fatigue. CONCLUSION: Intralesional ozone is effective and safe for the treatment of multiple warts.

Aqueous ozone therapy improves the standard treatment of leishmaniasis lesions in animals leading to local and systemic alterations.

The current treatment of leishmaniasis presents some problems, such as cell toxicity, parenteral route, and time of treatment. Ozone emerges as an option to accelerate the standard treatment due to the immunomodulatory, antioxidant, and wound healing activity reported in the literature. This work aimed to evaluate the efficacy of aqueous ozone as an adjuvant to the standard treatment of cutaneous lesions caused by Leishmania amazonensis in an experimental model. For in vivo experiments, mice were randomly distributed in 6 groups, which were infected with L. amazonensis and treated in five different schedules using the standard treatment with Glucantime® with or without aqueous ozone. After the last day of treatment, the animals were euthanized and were analyzed: the thickness of lesions; collagen deposition, the parasitic burden of the lesions; blood leukocyte number; NO; and cytokine dosages and arginase activity from peritoneal macrophages. All treated groups showed a decrease in the lesion, but with a significative deposition of collagen in lesions with local ozone treatment. The parasite burden showed that ozone enhanced the leishmanicidal activity of the reference drug. The reduction of NO production and blood leukocyte count and increases in the arginase activity showed an immunomodulatory activity of ozone in the treated animals. Thus, ozone therapy has been shown to work as an adjuvant in the treatment of Leishmania lesions, enhancing leishmanicidal and wound healing activity of standard treatment.

Oxygen-Ozone Therapy for the Treatment of Knee Osteoarthritis: A Systematic Review of Randomized Controlled Trials.

PURPOSE: To review the available literature on the application of oxygen-ozone therapy (OOT) in the treatment of knee osteoarthritis (KOA) to understand its therapeutic potential and to compare it with other conservative treatment options. METHODS: A systematic review of the literature was performed on the PubMed, Cochrane, Embase, ResearchGate, and PedRo Databases, with the following inclusion criteria: (1) randomized controlled trials (RCTs), (2) written in English, (3) published on indexed journals in the last 20 years (1998-2018), (4) dealing with the use of ozone intra-articular injection for the treatment of KOA. The risk of bias was assessed by the Cochrane Risk of Bias tool for RCTs. RESULTS: Eleven studies involving 858 patients in total (629 female and 229 male) were included. Patients in the control groups received different treatments: placebo in 1 trial; hyaluronic acid in 2 studies; hyaluronic acid and PRP in 1 trial; corticosteroids in 4; and hypertonic dextrose, radiofrequency, or celecoxib + glucosamine in the remaining 3 trials. In looking at the quality of the available literature, we found that none of the studies included reached "good quality" standard, 2 were ranked as "fair," and the rest were considered "poor." No major complications or serious adverse events were reported following intra-articular OOT, which provided encouraging pain relief at short term. On the basis of the available data, no clear indication emerged from the comparison of OOT with other established treatments for KOA. CONCLUSIONS: The analysis of the available RCTs on OOT for KOA revealed poor methodologic quality, with most studies flawed by relevant bias, thus severely limiting the possibility of drawing conclusions on the efficacy of OOT compared with other treatments. On the basis of the data available, OOT has, however, proven to be a safe approach with encouraging effects in pain control and functional recovery in the short-middle term. LEVEL OF EVIDENCE: Systematic review of Level I and III studies.

Evaluation of the effects of photobiomodulation therapy and ozone applications after gingivectomy and gingivoplasty on postoperative pain and patients' oral health-related quality of life.

The aim of this study was to evaluate the effects of photobiomodulation therapy (PBM) and ozone applications on patients' quality of life after gingivectomy and gingivoplasty. In this study, 36 patients with chronic inflammatory gingival enlargement underwent gingivectomy and gingivoplasty. The groups were randomly divided into control (n = 12), PBM (n = 12) and ozone (n = 12) groups. GaAlAs diode laser 810 nm wavelength at a non-contact and continuous mode with a power of 0.3 W and a density of 4 J/cm2 used for PBM for 1 min. Ozone was applied for 1 min for every 5 mm2 in contact mode at power level 9 using probe number 3. PBM and ozone applications were performed immediately after the operation, on the 3rd and 7th days. Pain assessment was performed at 3rd, 7th, 14th and 28th days after gingivectomy and gingivoplasty by using visual analogue scale (VAS). Oral Health Impact Profile (OHIP-14) records were obtained from the patients before gingivectomy and gingivoplasty and postoperative 7th and 14th days. OHIP-14 questions were also evaluated individually. VAS pain levels of the control group measured on the 3rd day were higher than the PBM group and on the 7th day were found to be significantly higher than both groups (p < 0.05). The total OHIP-14 score of the control group on the 7th postoperative day was found to be higher than the PBM group (p < 0.05). The mean score obtained from the third question of OHIP-14 at 7th and 14th day of the PBM group was found to be lower than the control and ozone groups (p < 0.05). The PBM and ozone applications after gingivectomy and gingivoplasty reduce the pain levels of patients and have a positive effect on patients' quality of life.

Ozone Treatment Unveils the Veil of Candida parapsilosis Infection in the Knee Joint: A Case Report and Literature Review.

Candida infection is common, while Candida parapsilosis infection in the knee joint is rare. Local symptoms of Candida infections in the knee are atypical, rarely associated with systemic symptoms, and difficult to distinguish from other types of knee arthritis. We here report a special case of C. parapsilosis infections in the knee joint. A patient had previously undergone knee puncture in a private clinic for the treatment of osteoarthritis and developed a left knee joint infection with C. parapsilosis. However, the patient only showed more severe local knee symptoms, and there was no systemic manifestation associated with any Candida infection. Surprisingly, after receiving ozone lavage, the patient showed symptoms of a systemic infection such as fever and chills. There was no positive finding in the blood cultures. Finally, the synovial fluid cultures showed a C. parapsilosis infections. After antifungal treatment and another knee ozone therapy, the patient did not experience recurrence of the infections. It is suggested that in this special case, the strong sterilization with ozone caused the destruction of C. parapsilosis, leading to a transient systemic toxin reaction. In addition, we reviewed the 17 cases of C. parapsilosis infections that have been reported thus far.

Intrauterine therapy with ozone reduces subclinical endometritis and improves reproductive performance in postpartum dairy cows managed in pasture-based systems.

New postpartum strategies have been developed in dairy cows to ameliorate uterine health and reproductive performance, especially the first service conception rates. This study aimed to assess the effect of intrauterine therapy with ozone (IUTO) in early postpartum on subclinical endometritis prevalence and reproductive parameters in dairy cows under commercial farm conditions. For this purpose, eighty clinically healthy cows with a body condition score between 3.0 and 3.5, from four dairy farms, were randomly allocated into two groups: ozone therapy group (OG, n = 40), which were subjected to IUTO, and control group (CG, n = 40). Content of uterine polymorphonuclear (PMN) leukocytes and subclinical endometritis (SE) percentage were assessed at 35 days after calving by uterine cytology. A second cytology was performed 72 h after IUTO. Reproductive parameters such as interval calving to first service (IFS), number of services per conception (nSC), interval calving to conception (ICC) and first service conception rate (FSCR) were analysed. The second endometrial cytology demonstrated that IUTO reduced (P < 0.01) both PMN (3.7 ± 1.4 vs. 7.6 ± 1.1%) and SE (5.0 vs. 50.0%) percentages compared with CG. Likewise, after ozone treatment, both nSC (2.1 ± 0.3 vs. 3.1 ± 0.2; P < 0.01) and ICC (126.2 ± 9.7 vs. 149.0 ± 9.0; P = 0.0672) decreased, and FSCR increased (50.0 vs. 16.2%; P < 0.01) compared with CG. In conclusion, intrauterine ozone therapy applied at 35 days after calving reduced subclinical endometritis prevalence and improved reproductive performance in postpartum dairy cows managed in a pasture-based system.

Effects of subcutaneous injection of ozone during wound healing in rats.

Fibroblast growth factor 2 (FGF2) regulates the wound repair process and it is secreted by inflammatory and endothelial cells, and by myofibroblasts. This study aimed to establish the expression patterns of FGF2 and myofibroblastic differentiation during wound healing in rats treated with subcutaneous ozone injection. We created full-thickness excisional wounds in rats, and the healing process was analyzed through morphometric analyses and digital quantification of immunoreactivity of smooth muscle actin and FGF2. Ozone therapy-treated wounds presented granulation tissue with a reduced number of inflammatory cells and greater dermal cellularity, and intense collagen deposition. FGF2 immunoreactivity, microvessel density, and amount of myofibroblasts were significantly higher in treated wounds compared to controls. In conclusion, it was demonstrated that subcutaneous injections of ozone accelerate and ameliorate wound repairing process. Moreover, injectable ozone therapy's action mechanism may be associated with FGF2 overexpression.

The temporal effect of intra-articular ozone injections on pain in knee osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a most common orthopaedic condition, often complicated by inflammatory features. SOURCES OF DATA: A systematic search in PubMed, Embase, Google Scholar and Scopus databases (to January 2019) was performed to define the effect obtained in patients with OA of the knee by injections of ozone, on pain and physical function. Six RCTs and 353 patients were included. AREAS OF AGREEMENT: Recently, an increasing number of physicians have used ozone therapy to alleviate the symptoms of acute and chronic OA of the knee. Ozone can allow greater mobility of the knee joint, pain relief and decrease in effusion. AREAS OF CONTROVERSY: The volume and concentration of ozone injected are different in the various treatment protocols published. GROWING POINTS: The action of ozone is unclear, but it is a promising therapeutic modality capable of impacting, favourably, function and quality of life. AREAS TIMELY FOR DEVELOPING RESEARCH: The lack of a clear protocol of use is a major limitation, and to date there is no clear evidence of long-term efficacy.

Differences in Viral Disinfection Mechanisms as Revealed by Quantitative Transfection of Echovirus 11 Genomes.

Virus inactivation mechanisms can be elucidated by methods that measure the loss of specific virus functionality (e.g., host attachment, genome internalization, and genome replication). Genome functionality is frequently assessed by PCR-based methods, which are indirect and potentially inaccurate; genome damage that affects detection by high-fidelity PCR enzymes may not adversely affect the ability of actual cellular enzymes to produce functional virus. Therefore, we developed here a transfection-based assay to quantitatively determine viral genome functionality by inserting viral RNA into host cells directly to measure their ability to produce new functional viruses from damaged viral genomes. Echovirus 11 was treated with ozone, free chlorine (FC), UV light at 254 nm (UV254), or heat, and then the reductions in genome functionality and infectivity were compared. Ozone reduced genome functionality proportionally to infectivity, indicating that genome damage is the main mechanism of virus inactivation. In contrast, FC caused little or no loss of genome functionality compared to infectivity, indicating a larger role for protein damage. For UV254, genome functionality loss accounted for approximately 60% of virus inactivation, with the remainder presumably due to protein damage. Heat treatment resulted in no reduction in genome functionality, in agreement with the understanding that heat inactivation results from capsid damage. Our results indicate that there is a fundamental difference between genome integrity reductions measured by PCR enzymes in previous studies and actual genome functionality (whether the genome can produce virus) after disinfection. Compared to PCR, quantitative transfection assays provide a more realistic picture of actual viral genome functionality and overall inactivation mechanisms during disinfection.IMPORTANCE This study provides a new tool for assessing virus inactivation mechanisms by directly measuring a viral genome's ability to produce new viruses after disinfection. In addition, we identify a potential pitfall of PCR for determining virus genome damage, which does not reflect whether a genome is truly functional. The results presented here using quantitative transfection corroborate previously suggested virus inactivation mechanisms for some virus inactivation methods (heat) while bringing additional insights for others (ozone, FC, and UV254). The developed transfection method provides a more mechanistic approach for the assessment of actual virus inactivation by common water disinfectants.

The interleukin-33 receptor contributes to pulmonary responses to ozone in male mice: role of the microbiome.

BACKGROUND: Interleukin-33 is released in the airways following acute ozone exposure and has the ability to cause airway hyperresponsiveness, a defining feature of asthma. Ozone causes greater airway hyperresponsiveness in male than female mice. Moreover, sex differences in the gut microbiome account for sex differences in this response to ozone. The purpose of this study was to determine whether there were sex differences in the role of interleukin-33 in ozone-induced airway hyperresponsiveness and to examine the role of the microbiome in these events. METHODS: Wildtype mice and mice genetically deficient in ST2, the interleukin-33 receptor, were housed from weaning with either other mice of the same genotype and sex, or with mice of the same sex but opposite genotype. At 15 weeks of age, fecal pellets were harvested for 16S rRNA sequencing and the mice were then exposed to air or ozone. Airway responsiveness was measured and a bronchoalveolar lavage was performed 24 h after exposure. RESULTS: In same-housed mice, ozone-induced airway hyperresponsiveness was greater in male than female wildtype mice. ST2 deficiency reduced ozone-induced airway hyperresponsiveness in male but not female mice and abolished sex differences in the response to ozone. However, sex differences in the role of interleukin-33 were unrelated to type 2 cytokine release: ozone-induced increases in bronchoalveolar lavage interleukin-5 were greater in females than males and ST2 deficiency virtually abolished interleukin-5 in both sexes. Since gut microbiota contribute to sex differences in ozone-induced airway hyperresponsiveness, we examined the role of the microbiome in these ST2-dependent sex differences. To do so, we cohoused wildtype and ST2 deficient mice, a situation that allows for transfer of microbiota among cage-mates. Cohousing altered the gut microbial community structure, as indicated by 16S rRNA gene sequencing of fecal DNA and reversed the effect of ST2 deficiency on pulmonary responses to ozone in male mice. CONCLUSIONS: The data indicate that the interleukin-33 /ST2 pathway contributes to ozone-induced airway hyperresponsiveness in male mice and suggest that the role of interleukin-33 is mediated at the level of the gut microbiome.

Preoperative topical liposomal ozone dispersion to reduce bacterial colonization in conjunctival sac and periocular skin: Preliminary study in dogs.

Prophylaxis represents a keystone to reduce periocular skin and ocular conjunctiva bacterial load before surgical procedures. Despite many prophylactic agents are available the preferred perioperative ocular surface antimicrobial is still unknown. The purpose of this study was to assess the effectiveness of preoperative liposomal ozone dispersion in reducing bacterial colonization from the conjunctival sac and periocular skin in dogs, in comparison with povidone-iodine and fluoroquinolone. Twenty-two owned dogs consisting with 44 eyes in total scheduled for ophthalmic surgical procedure were enrolled for the study and divided in four groups receiving either ozone dispersion or povidone iodine in eyelid and conjunctiva, fluoroquinolone or placebo. A swab was taken before and after the antisepsis protocol evaluating total microbial count, coagulase positive and negative staphylococci. Statistical analysis revealed a significant decrease in colony forming units (CFU) for total microbial count, coagulase positive and negative staphylococci both for liposomal ozone dispersion and povidone iodine. No statistical differences were detected in median CFU for both one-day placebo and fluoroquinolone preoperative prophylactic topical therapy. The results of this preliminary study demonstrate that liposomal ozone-dispersion is as effective as povidone iodine to reduce preoperative bacterial load in ocular surface.

Percutaneous Ozone Treatment for Herniated Lumbar Discs: 1-Year Follow-up of a Multicenter Pilot Study of a Handheld Disposable Ozone-Generating Device.

PURPOSE: To evaluate the safety and efficacy of oxygen-ozone treatment delivered via a novel, handheld ozone-generating device for improving pain and function in herniated disc patients. MATERIALS AND METHODS: A total of 39 patients with contained herniated lumbar discs received oxygen-ozone treatment at 1 of 3 centers. Treatment consisted of injection of 2% ozone (10 mL): 3 mL delivered into the nucleus pulposus and 7 mL delivered into the adjacent paravertebral tissues. The first 8 patients received only ozone injections, whereas subsequent patients also received periganglionic methylprednisolone (40 mg) and 0.5% bupivacaine (1 mL) injections. Patients were evaluated at baseline and at 1 month, 6 months, and 12 months after treatment using the Oswestry Disability Index (ODI) and the Visual Analogue Scale (VAS) for leg pain and for back pain. Analgesic medication use was also assessed at each timepoint. RESULTS: Overall, 91% (32/35) of the per-protocol patients (those who completed follow-up and did not have significant protocol deviations) showed detectable improvement in ODI at 1-month follow-up; this increased to 93% (26/28) of patients at 12-months follow-up. At 1 month after treatment, 60% (21/35) of patients showed significant improvement in ODI scores (P = .01); 54% (19/35) showed significant improvement in VAS scores for leg pain (P = .05); and 49% (17/35) showed significant improvement in VAS scores for back pain (P = .12). At 6 months after treatment, 67% (22/33) of patients showed significant improvement in ODI scores (P = .02); 64% (21/33) showed significant improvement in VAS scores for leg pain (P = .01); and 52% (17/33) showed significant improvement in VAS scores for back pain (P = .12). At 12 months after treatment, 68% (19/28) of patients showed significant improvement in ODI scores (P < .01); 64% (18/28) showed significant improvement in VAS scores for leg pain (P < .01); and 61% (17/28) showed significant improvement in VAS scores for back pain (P = .09). Leg pain typically subsided more quickly than back pain. Use of analgesic medications also significantly decreased at all follow-up timepoints compared to baseline (P < .01). There were no adverse events or device-related issues. CONCLUSIONS: At 1, 6, and 12 months after treatment, patients experienced significant improvements in pain and function as well as significantly decreased use of analgesic medication. Taken together with the absence of adverse events at 1-year follow-up, these data suggest that oxygen-ozone treatment is a safe and effective therapy for contained herniated discs.

Development of a large-scale computer-controlled ozone inhalation exposure system for rodents.

Objective: Complete systems for laboratory-based inhalation toxicology studies are typically not commercially available; therefore, inhalation toxicologists utilize custom-made exposure systems. Here we report on the design, construction, testing, operation and maintenance of a newly developed in vivo rodent ozone inhalation exposure system. Materials and methods: Key design requirements for the system included large-capacity exposure chambers to facilitate studies with large sample sizes, automatic and precise control of chamber ozone concentrations, as well as automated data collection on airflow and environmental conditions. The exposure system contains two Hazelton H-1000 stainless steel and glass exposure chambers, each providing capacity for up to 180 mice or 96 rats. We developed an empirically tuned proportional-integral-derivative control loop that provides stable ozone concentrations throughout the exposure period (typically 3h), after a short ramp time (∼8 min), and across a tested concentration range of 0.2-2 ppm. Specific details on the combination of analog and digital input/output system for environmental data acquisition, control and safety systems are provided, and we outline the steps involved in maintenance and calibration of the system. Results: We show that the exposure system produces consistent ozone exposures both within and across experiments, as evidenced by low coefficients of variation in chamber ozone concentration and consistent biological responses (airway inflammation) in mice, respectively. Conclusion: Thus, we have created a large and robust ozone exposure system, facilitating future studies on the health effects of ozone in rodents.

Ozone Therapy for Complex Regional Pain Syndrome: Review and Case Report.

PURPOSE OF REVIEW: The world faces a crisis in pain management. CRPS is a multifaceted painful disorder, which is difficult to treat and resolve. Ozone therapy has unique mechanisms of actions that may directly address the emerging discoveries of factors related to pathogenesis of the disorder and other pain conditions. These include oxygenation, immune modulation, anti-infective properties, and anti-inflammatory properties. This review is to present ozone therapy as a novel approach for pain treatment, including CRPS. RECENT FINDINGS: Ozone therapy has been found, in basic science studies, to ameliorate many of the mechanisms promoting chronic pain and inflammation, including hypoxia, inflammatory mediators, and infection. Direct intravenous oxygen/ozone gas was administered nearly daily to an 11-year-old girl diagnosed with reflex sympathetic dystrophy and extremely frequent pseudoseizures. She rapidly improved. After 120 sessions, all symptoms had disappeared. Ozone's novel biochemical properties may make it a unique, safe, relatively inexpensive, and effective modality for the treatment of pain. In this particular case, it resolved the chronic condition when opiates were ineffective for even pain relief. Ozone therapy should be considered for institutional study despite its lack of financial reward (lack of patentability). PERSPECTIVE: This manuscript presents ozone therapy as a novel, safe, and inexpensive approach for RSD/CRPS, and an alternative to drugs. It is practiced worldwide and has abundant literature on its biochemical mechanisms, effectiveness for pain (and other conditions), and overall healing usefulness, yet little is known conventionally as it is not patentable.

The Biochemical and Pharmacological Properties of Ozone: The Smell of Protection in Acute and Chronic Diseases.

Ozone therapy has been widely used in everyday clinical practice over the last few years, leading to significant clinical results in the treatment of herniated discs and pain management. Nevertheless, further studies have demonstrated its potential efficacy and safety under other clinical and experimental conditions. However, some of these studies showed controversial results regarding the safety and efficacy of ozone therapy, thus mining its potential use in an everyday clinical practice. To this regard, it should be considered that extensive literature review reported the use of ozone in a significant different dose range and with different delivery systems. The aim of the present review is to describe the various pharmacological effects of ozone in different organs and clinical conditions and to provide possible biochemical and molecular insights for ozone biological properties, thus providing a possible explanation for various controversial clinical outcomes described in the scientific literature.