Abstract Title: Therapeutic relevance of ozone therapy in degenerative diseases: Focus on diabetes and spinal pain. Abstract Source: J Cell Physiol. 2018 Apr ;233(4):2705-2714. Epub 2017 Jul 11. PMID: 28594115 Abstract Author(s): Nady Braidy, Morteza Izadi, Antoni Sureda, Nematollah Jonaidi-Jafari, Abdolali Banki, Seyed F Nabavi, Seyed M Nabavi Article Affiliation: Nady Braidy Abstract: Ozone, one of the most important air pollutants, is a triatomic molecule containing three atoms of oxygen that results in an unstable form due to its mesomeric structure. It has been well-known that ozone has potent ability to oxidize organic compounds and can induce respiratory irritation. Although ozone has deleterious effects, many therapeutic effects have also been suggested. Since last few decades, the therapeutic potential of ozone has gained much attention through its strong capacity to induce controlled and moderated oxidative stress when administered in precise therapeutic doses. A plethora of scientific evidence showed that the activation of hypoxia inducible factor-1α (HIF-1a), nuclear factor of activated T-cells (NFAT), nuclear factor-erythroid 2-related factor 2-antioxidant response element (Nrf2-ARE), and activated protein-1 (AP-1) pathways are the main molecular mechanisms underlying the therapeutic effects of ozone therapy. Activation of these molecular pathways leads to up-regulation of endogenous antioxidant systems, activation of immune functions as well as suppression of inflammatory processes, which is important for correcting oxidative stress in diabetes and spinal pain. The present study intended to review critically the available scientificevidence concerning the beneficial properties of ozone therapy for treatment of diabetic complications and spinal pain. It finds benefit for integrating the therapy with ozone into pharmacological procedures, instead of a substitutive or additional option to therapy. Article Published Date : Mar 31, 2018

Abstract Title: Ozone therapy for the treatment of chronic wounds: A systematic review. Abstract Source: Int Wound J. 2018 Mar 13. Epub 2018 Mar 13. PMID: 29536625 Abstract Author(s): Erin Fitzpatrick, Olivia J Holland, Jessica J Vanderlelie Article Affiliation: Erin Fitzpatrick Abstract: Chronic wounds present a significant burden to the health care system and the patient. Ozone therapy has been proposed as a treatment for chronic wounds, potentially acting by eliciting mild oxidative stress or disinfection. The purpose of this systematic review is to evaluate the potential benefits and harms of ozone therapy as an advanced care intervention for chronic wounds. Studies were extracted from Google Scholar, PubMed, the Cochrane Library, and reference lists. General inclusion criteria included English-language randomised human trials reporting the use of ozone therapy in the topical treatment of chronic wounds. Primary outcome data included the extent of chronic wound healing, and secondary outcomes included adverse effects. Studies were assessed for level of bias and data quality. Nine studies (n = 453 patients) matched the inclusion criteria and underwent meta-analysis. Overall, there was a significant improvement in wound closure with ozone therapy. Results consistently favour the application of ozone as a treatment for chronic wounds; however, there is no conclusive evidence of ozonetherapy as superior compared with standard treatments. Compared with standard care, ozone therapy as an advanced wound care treatment may improve the proportion of chronic wounds healed in a shorter amount of time, but further research is required. Article Published Date : Mar 12, 2018

Abstract Title: The effects of ozone application on genotoxic damage and wound healing in bisphosphonate-applied human gingival fibroblast cells. Abstract Source: Clin Oral Investig. 2018 Mar ;22(2):867-873. Epub 2017 Jul 11. PMID: 28699091 Abstract Author(s): Sıdıka Sinem Akdeniz, E Beyler, Y Korkmaz, E Yurtcu, U Ates, K Araz, F I Sahin, O Y Torun Article Affiliation: Sıdıka Sinem Akdeniz Abstract: OBJECTIVES: Medication-related osteonecrosis of the jaws (MRONJ) is an extremely therapy-resistant disease involving the jaws especially following bisphosphonate treatment. Bisphosphonates accumulate in bone in concentrations sufficient to be directly toxic to the oral epithelium. Current therapeutic options are inadequate for the prevention and treatment of MRONJ. The aim of this study was to investigate effects of ozone gas plasma therapy on wound healing in bisphosphonate-applied human fibroblasts. MATERIAL AND METHODS: Human primary gingival fibroblasts were cultured. Cytotoxic concentrations (IC50) of bisphosphonates (pamidronate (PAM), alendronate (ALN), and zoledronate (ZOL)) were determined by MTT test. A 60 μg/μl for 30 s of ozone gas plasma application was performed to all experimental culture flasks after drug treatment at 24-h intervals as 3 s/cm. Genotoxic damages were evaluated by comet assay and wound healing was determined by in vitro scratch assay. RESULTS: PAM, ALN, and ZOL applications caused genotoxic damage on primary human gingival fibroblast DNA. Ozone gas plasma therapy significantly decreased the genotoxic damage (p < 0.05), and this application provided 25, 29, and 27% less genotoxic damage in order of ALN, PAM, and ZOL groups. Ozone gas plasma therapy significantly increased wound healing rates both in postsurgical 24th and 48th hours for all doses of experimental drug groups (p < 0.05). CONCLUSION: The ozone gas plasma application decreased genotoxic damage effect of bisphosphonate usage while improved the wound closure rate on human gingival fibroblasts. CLINICAL RELEVANCE: Ozone gas plasma therapy may be helpful in prevention of gingival healing delay in MRONJ pathogenesis especially when applied simultaneously with surgical intervention. Article Published Date : Feb 28, 2018

Abstract Title: [Topical ozone application: An innovative therapy for infantile atopic dermatitis]. Abstract Source: Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2018 Feb 28 ;43(2):163-167. PMID: 29559600 Abstract Author(s): Guizhi Qin, Jinhua Huang, Yizhi Pan, Yaping Xiang, Chunxiang Ou, Jian Huang, Lihua Gao, Jianyun Lu Article Affiliation: Guizhi Qin Abstract: To evaluate the clinical efficacy and safety of the innovative topical ozone therapy for infantile atopic dermatitis.
 Methods: Sixty children with atopic dermatitis were divided into a treatment group and a control group. The treatment group was showered with ozonated water (3-5 times a week) and smeared with ozonated oil (twice a day), while the control group was washed with warm running water and smeared withbase oil, adding moisturizer if necessary. The treatment course was 2 weeks. Efficacy and side effect were evaluated.
 Results: The skin exudation was reduced and erosion was healing after 3-5 days topical ozone therapy for infantile atopic dermatitis. The effective rates were 80.0% and 20.0% inthe treatment group and control group for 1 week, and 89.6% and 30.7% for 2 weeks, respectively, with significant difference between the 2 groups (P<0. 001).
 Conclusion: Innovative treatment of infantile atopic dermatitis with topical ozone application is safe and effective, which is worth popularizing in clinic. Article Published Date : Feb 27, 2018

Abstract Title: [Effect of ozone on Staphylococcus aureus colonization in patients with atopic dermatitis]. Abstract Source: Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2018 Feb 28 ;43(2):157-162. PMID: 29559599 Abstract Author(s): Jianyun Lu, Miaomiao Li, Jian Huang, Lihua Gao, Yizhi Pan, Zhibing Fu, Jianhua Dou, Jinhua Huang, Yaping Xiang Article Affiliation: Jianyun Lu Abstract: To verify the effect of ozone on Staphylococcus aureus (S. aureus) colonization in patients with atopic dermatitis (AD) and its correlation with the patient's status.
 Methods: A total of 12 patients with moderate or severe AD, aged from 6 to 65 years, were recruited from outpatient of the Third Xiangya Hospital. The treatment sides were showered with ozonated water and smeared with ozonated oil for 7 days (twice a day), while the control sides were washed with warm running water and smeared with base oil. At different time points, the severity scoring of atopic dermatitis (SCORAD) scores, sleep and pruritus scores were assessed and compared between the two sides. Meanwhile, plate cultivation was used to quantitatively detect the changes of S. aureus colonization in skin lesions.
 Results: After 7 days treatment, erythema and pimples were decreased in the treatment sides. The clear skin texture, smooth skin, improved skin lesions were also observed by dermoscopic examination. The results of reflectance confocal microscopy (RCM) demonstrated thatthe parakeratosis was improved, the structures were clearer, and the inflammatory cells infiltration was reduced after ozone treatment for 7 days. After ozone treatment for 3 and 7 days, the S. aureus colonization in the treatment sides decreased by (75.55±21.81)% and (97.24±2.64)% respectively. Compared to that of control sides, the percentage of S. aureus colony after ozone treatment for 7 days decreased significantly (P<0.01). After ozone treatment for 7 days, the SCORAD scores, sleep and pruritus scores were significantly decreased (all P<0.01). There was a linear correlation between the decreasing percentage of S. aureus colony and the declining percentage of SCORAD scores in AD patients.
 Conclusion: Topical ozone therapy can effectively reduce S. aureus colony in skin lesions and alleviate the severity of AD patients with moderate to severe degree. Article Published Date : Feb 27, 2018

Abstract Title: [Topical ozone therapy: An innovative solution to patients with herpes zoster]. Abstract Source: Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2018 Feb 28 ;43(2):168-172. PMID: 29559601 Abstract Author(s): Jian Huang, Jinhua Huang, Yaping Xiang, Lihua Gao, Yizhi Pan, Jianyun Lu Article Affiliation: Jian Huang Abstract: To observe the clinical efficacy and safety of topical ozone therapy for patients with herpes zoster by reflectance confocal microscopy (RCM).
 Methods: A total of 60 patients with herpes zoster were divided into a control group and an ozone treatment group (n=30). In the control group, patients took oral valacyclovir tablets or granules (0.3 g per day, three times a day) and they were subjected to local weak laser irradiation treatmentplus topical 2% mupirocin ointment twice a day. In the ozone group, the treatment is same as the control group except mupirocin ointment was replaced with topical ozone treatment (hydrotherapy every day plus ozonated oil twice a day). The clinical symptoms, discoid cell and adverse reactions were observed and taken records at day 0, 3, 7 and 14. Statistical analysis was performed to compare the clinical efficacy between the 2 groups. 
 Results: On the seventh day of treatment, the discoid cells of the ozone group disappeared, and the difference between the control group and the ozone groupwas statistically significant (P<0.05). The difference of decreased percentage of pain scores at each time point between the 2 groups was statistically significant (P<0.05). The clinical efficacy was 100% in the ozone group and 86.7% in the control group, with significant difference between the 2 groups (P<0.05).
 Conclusion: Topical ozone therapy in patients with herpes zoster is helpful in relieving pain, shortening the course as well as improving the clinical efficacy without obvious adverse reactions. It is worth to be popularized. Article Published Date : Feb 27, 2018

Abstract Title: The beneficial effects of ozone therapy in acetaminophen-induced hepatotoxicity in mice. Abstract Source: Pharmacol Rep. 2017 Nov 13 ;70(2):340-345. Epub 2017 Nov 13. PMID: 29477043 Abstract Author(s): Aysu Hayriye Tezcan, Omur Ozturk, Sefer Ustebay, Yasemen Adali, Hatice Yagmurdur Article Affiliation: Aysu Hayriye Tezcan Abstract: BACKGROUND: The aim of the present study was to determine the therapeutic effects of medical ozone therapy on acute acetaminophen (APAP)-induced hepatotoxicity which were not clearly demonstrated in prior studies. METHOD: Twenty-four mice were randomly assigned into three equal groups: Group 1 (control), Group 2 (APAP) and Group 3 (APAP +ozone). Hepatotoxicity was induced by APAP given as a single dose of 300 mg/kg intraperitoneally in Groups 2 and 3. Additionally, Group 3 received 20 mcg/0.5 mL ozone intraperitoneal twice a day for the remaining of the study. Other groups received saline injections. On the fourth day of the study, biochemical variables (AST, ALT, ALP) and liver histopathology wasassessed. RESULTS: Intraperitoneal administration of a single dose of APAP induced hepatocellular damage that was shown by both liver enzymes and histopathological changes (p < 0.001). AST, ALT, ALP levels were elevated in both groups 2 and 3 and the difference from group 1 was statistically significant (p < 0.01).Mean ALT and AST levels of group 2 were statistically significantly higher versus group 3 (p < 0.01). In histopathological examinations; necrosis and inflammation were more prominent in Group 2 compared to Group 3 (p < 0.01). CONCLUSION: Ozone showed beneficial effects on APAP hepatotoxicity at a statistically significant level. It is known that ozone has therapeutic effects in various diseases owing to its antioxidant effects. The present study suggests that ozone may be utilized as a routine supplementary therapy in acute APAP hepatotoxicity. Article Published Date : Nov 12, 2017

Abstract Title: Medical ozone therapy reduces oxidative stress and testicular damage in an experimental model of testicular torsion in rats. Abstract Source: Int Braz J Urol. 2017 Nov-Dec;43(6):1160-1166. PMID: 28727368 Abstract Author(s): Mustafa Tusat, Ahmet Mentese, Selim Demir, Ahmet Alver, Mustafa Imamoglu Article Affiliation: Mustafa Tusat Abstract: OBJECTIVE: Testicular torsion (TT) refers to rotation of the testis and twisting of the spermatic cord. TT results in ischemia-reperfusion (I/R) injury involving increased oxidative stress, inflammation and apoptosis, and can even lead to infertility. The aim of this study was to investigate the effect of ozone therapy on testicular damage due to I/R injury in an experimental torsion model. MATERIALS AND METHODS: 24 male Sprague-Dawley rats were divided into 3 groups; sham-operated, torsion/detorsion (T/D), and T/D+ozone. Ozone (1mg/kg) was injected intraperi-toneally 120 minutes before detorsion and for the following 24h. Blood and tissue samples were collected at the end of 24h. Johnsen score, ischemia modified albumin (IMA), total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) levels were determined. RESULTS: Levels of IMA, TOS, OSI, and histopathological scores increased in the serum/tissue of the rats in the experimental T/D group. Serum IMA, TOS, and OSI levels and tissue histo-pathological scores were lower in the rats treated with ozone compared with the T/D group. CONCLUSION: Our study results suggest that ozone therapy may exhibit beneficial effects on both biochemical and histopathological findings. Clinical trials are now necessary to confirm this. Article Published Date : Oct 31, 2017

Abstract Title: Beneficial Effects of Ozone Therapy on Oxidative Stress, Cardiac Functions and Clinical Findings in Patients with Heart Failure Reduced Ejection Fraction. Abstract Source: Cardiovasc Toxicol. 2017 Oct ;17(4):426-433. PMID: 28097518 Abstract Author(s): Mutlu Buyuklu, Fatih Mehmet Kandemir, Turan Set, Eftal Murat Bakırcı, Husnu Degirmenci, Hikmet Hamur, Ergun Topal, Sefa Kucukler, Kultigin Turkmen Article Affiliation: Mutlu Buyuklu Abstract: The aim of study was to determine the effects of ozone therapy on the oxidative stress, cardiac functions and clinical findings in patients with heart failure reduced ejection fraction (HFrEF). A total of 40 patients with New York Heart Association 2 and 3 HF with left ventricular ejection fraction (LVEF)<35%, and 40 subjects without HF as control group were included in the study. Patients with HFrEF were given additional ozone therapy of major and minor administrations along with conventional HF treatment for 5 weeks. Before and after ozone therapy, left ventricular end-systolic and end-diastolic volumes (LVESV, LVEDV) and the 6 minute walk distance (6MWD) and blood levels of the superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GSHPx), malondialdehyde (MDA), nitric oxide (NO) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured. Ozone therapy significantly reduced the serum levels of NO and MDA (p < 0.001, respectively) and significantly increased the levels of SOD, CAT, GSH and GSHPx (p < 0.001, respectively). LVEDV and LVESV were found to be significantly reduced; however, LVEF was not found to be significantly increased (p = 0.567). As the biochemical improvement marker of HF, NT-proBNP was significantly reduced (p < 0.001). The clinical HF improvement marker of 6 minute walk distance was also modestly increased (p < 0.001). Ozone therapy might be beneficial in terms of activating antioxidant system and merit further therapeutic potential to conventional HF treatment in patients with HFrEF. Article Published Date : Sep 30, 2017

Abstract Title: Medical ozone promotes Nrf2 phosphorylation reducing oxidative stress and pro-inflammatory cytokines in multiple sclerosis patients. Abstract Source: Eur J Pharmacol. 2017 Sep 15 ;811:148-154. Epub 2017 Jun 13. PMID: 28623000 Abstract Author(s): Livan Delgado-Roche, Mario Riera-Romo, Fernando Mesta, Yanet Hernández-Matos, Juan M Barrios, Gregorio Martínez-Sánchez, Said M Al-Dalaien Article Affiliation: Livan Delgado-Roche Abstract: Oxidative stress and inflammation play key roles in the pathogenesis of Multiple sclerosis (MS). Different drugs have been used in the clinical practice, however, there is not a completely effective treatment. Due to its potential therapeutic action, medical ozone represents a promising approach for neurodegenerative disorders. The aim of the present study was to address the role of ozone therapy on the cellular redox state in MS patients. Ozone (20μg/ml) was administered three times per week during a month by rectal insufflation. The effect of ozone therapy on biomarkers of oxidative stress and inflammation was addressed by spectrophotometric and immunoenzymatic assays. Furthermore, we investigated the action of ozone on CK2 expression and Nrf2 phosphorylation by western blotting analysis. Medical ozone significantly improved (P<0.05) the activity of antioxidant enzymes and increased the levels of cellular reduced glutathione. In accordance, a significant reduction (P<0.05) of oxidative damage on lipids and proteins was observed in ozone-treated patients. As well, the levels of pro-inflammatory cytokines TNFα and IL-1β were lower after ozone treatment. Ozone therapy incremented the CK2 expression together with Nrf2 phosphorylation in mononuclear cells of MS patients. These findings suggest that ozone´s antioxidant and anti-inflammatory effects might be partially associated with an induction of Nrf2phosphorylation and activation. These results provide new insights on the molecular events modulated by ozone, and pointed out ozone therapy as a potential therapeutic alternative for MS patients. Article Published Date : Sep 14, 2017

Abstract Title: The Histological Effects of Ozone Therapy on Sciatic Nerve Crush Injury in Rats. Abstract Source: World Neurosurg. 2017 Sep ;105:702-708. Epub 2017 Jun 3. PMID: 28587982 Abstract Author(s): Hakan Somay, Selin Tural Emon, Serap Uslu, Metin Orakdogen, Zeynep Cingu Meric, Umit Ince, Tayfun Hakan Article Affiliation: Hakan Somay Abstract: OBJECTIVE: Peripheral nerve injury is a common, important problem that lacks a definitive, effective treatment. It can cause neurologic deficits ranging from paresthesia to paralysis. This study evaluated the effect of ozone therapy on sciatic nerve crush injury in rats. MATERIALS AND METHODS: Twenty-four male rats were divided into control sham surgery, sciatic nerve injury, and sciatic nerve injury with ozone groups (each n = 8). The sciatic nerve injury was inflicted via De Koning's crush-force method. The sciatic nerve injury group received medical air and the sciatic nerve injury ozone group received 0.7 mg/kg ozone. Sciatic nerve samples were obtained 4 weeks after injury. Vascular congestion, vacuolization, edema formation, S100 expression, and the thicknesses of the perineurium and endoneurium and diameter of the injured sciatic nerves were evaluated. RESULTS: The diameter of the sciatic nerve and thicknesses of the perineurium and epineurium were significantly greater in the sciatic nerve injury group (P <0.05) and significantly less in the sciatic nerve injury with ozone group (P<0.001). High S100 immunoreactivity was seen in the sciatic nerve injury group compared with the other 2 groups (P<0.05). The distributions of vascular congestion and vacuolization were significantly less in the sciatic nerve injury with ozone group (P < 0.05). CONCLUSIONS: Ozone therapy improved sciatic nerve injury recovery without causing an increase in fibrotic tissue. Ozone reduced fibrosis, vascular congestion, vacuolization, and edema in rodents. Ozone treatment might be used to assist in sciatic nerve injury. Article Published Date : Aug 31, 2017

Abstract Title: Ozone Prevents Cochlear Damage From Ischemia-Reperfusion Injury in Guinea Pigs. Abstract Source: Artif Organs. 2017 Aug ;41(8):744-752. Epub 2017 Mar 5. PMID: 28261890 Abstract Author(s): Merih Onal, Cagdas Elsurer, Nebil Selimoglu, Mustafa Yilmaz, Ender Erdogan, Jale Bengi Celik, Oznur Kal, Ozkan Onal Article Affiliation: Merih Onal Abstract: The cochlea is an end organ, which is metabolically dependent on a nutrient and oxygen supply to maintain its normal physiological function. Cochlear ischemia and reperfusion (IR) injury is considered one of the most important causes of human idiopathic sudden sensorineural hearing loss. The aim of the present study was to study the efficacy of ozone therapy against cochlear damage caused by IR injury and to investigate the potential clinical use of this treatment for sudden deafness. Twenty-eight guinea pigs were randomized into four groups. The sham group (S) (n = 7) was administered physiological saline intraperitoneally (i.p.) for 7 days. The ozone group (O) (n = 7) was administered 1 mg/kg of ozone i.p. for 7 days. In the IR + O group (n = 7), 1 mg/kg of ozone was administered i.p. for 7 days before IR injury. On the eighth day, the IR + O group was subjected to cochlear ischemia for 15 min by occluding the bilateral vertebral artery and vein with a nontraumatic clamp and then reperfusion for 2 h. The IR group was subjected to cochlear IR injury. After the IR procedure, the guinea pigs were sacrificed on the same day. In a generalhistological evaluation, cochlear and spiral ganglionic tissues were examined with a light microscope, and apoptotic cells were counted by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The apoptotic index (AI) was then calculated. Blood samples were sent for analyses of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase, malondialdehyde (MDA), the total oxidant score (TOS), and total antioxidant capacity (TAC). Data were evaluated statistically using the Kruskal-Wallis test. The AI was highest in the IR group. The AI of the IR + O groupwas lower than that of the IR group. The biochemical antioxidant parameters SOD and GSH-Px and the TAC values were highest in the O group and lowest in the IR group. The MDA level and TOS were highest in the IR group and lowest in the O group. Controlled ozone administration stimulated endogenous antioxidant defense systems, thereby helping the body to combat IR injury. Although this study revealed a statistically significant decrease in cochlear IR damage following ozone therapy, further studies will be necessary to explain the protective mechanisms of ozone therapy in cochlear IR injury. Article Published Date : Jul 31, 2017

Abstract Title: Ozone protects rat heart against ischemia-reperfusion injury: A role for oxidative preconditioning in attenuating mitochondrial injury. Abstract Source: Biomed Pharmacother. 2017 Apr ;88:1090-1097. Epub 2017 Feb 10. PMID: 28192883 Abstract Author(s): Weixin Meng, Ying Xu, Dandan Li, Erjun Zhu, Li Deng, Zonghong Liu, Guowei Zhang, Hongyu Liu Article Affiliation: Weixin Meng Abstract: Ischemia-reperfusion injury (IRI) is a major cause of cardiac dysfunction during cardiovascular surgery, heart transplantation and cardiopulmonary bypass procedures. The purpose of the present study was to explore, firstly, whether ozone induces oxidative preconditioning by activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and, secondly, whether ozone oxidative preconditioning (OzoneOP) can protect the heart against IRI by attenuating mitochondrial damage. Rats were subjected to 30min of cardiac ischemia followed by 2h of reperfusion, with or without prior OzoneOP (100μg/kg/day) for 5 days. Antioxidant capacity, myocardial apoptosis and mitochondrial damage were evaluated and compared at the end of reperfusion. OzoneOP was found to increase antioxidant capacity and to protect the myocardium against IRI by attenuating mitochondrial damage and myocardial apoptosis. The study suggests a potential role for OzoneOP in protecting the heart against IRI during cardiovascular surgery, cardiopulmonary bypass procedures or transplantation. Article Published Date : Mar 31, 2017

Abstract Title: Comparison of laser and ozone treatments on oral mucositis in an experimental model. Abstract Source: Lasers Med Sci. 2017 Apr ;32(3):673-677. Epub 2017 Feb 11. PMID: 28190112 Abstract Author(s): Suzan Bayer, Hakki Oguz Kazancioglu, Ahmet Hüseyin Acar, Nihat Demirtas, Nur Ozten Kandas Article Affiliation: Suzan Bayer Abstract: Oral mucositis (OM) induces severe pain and limits fundamental life behaviors such as eating, drinking, and talking for patients receiving chemotherapy or radiotherapy. In addition, through opportunistic microorganisms, OM frequently leads to systemic infection which then leads to prolonged hospitalization. Severe lesions often adversely affect curative effects in cancer cases. Therefore, the control of OM is important for oral health quality of life and prognosis. Low-level laser therapy (LLLT) and ozone may be useful to accelerate wound healing. In this study, 24 Sprague-Dawley rats were divided into three groups as control, ozone, and laser groups. All groups received 5-fluorouracil intraperitoneally and trauma to the mouth pouch with a needle. After the formation of OM in the mouth, the control group had no treatment; the ozone group was administered ozone, and the laser group, LLLT. Then, all groups were sacrificed and basic fibroblast growth factor (bFGF), transforming growth factor (TGF-β), and platelet-derived growth factor (PDGF) were evaluated in all groups. LLLT was determined to be statistically significantly more effective than ozone on FGF and PDGF. However, in respect of TGF-β, no statistically significant difference was observed between the groups. In conclusion, withinthe limitations of this study, LLLT is more effective than ozone. However, further studies on this subject are required. Article Published Date : Mar 31, 2017

Abstract Title: The NLRP3 inflammasome is a potential target of ozone therapy aiming to ease chronic renal inflammation in chronic kidney disease. Abstract Source: Int Immunopharmacol. 2017 Feb ;43:203-209. Epub 2016 Dec 27. PMID: 28038382 Abstract Author(s): Gang Yu, Zhiming Bai, Zhiyuan Chen, Hui Chen, Guoren Wang, Gang Wang, Zhenxiang Liu Article Affiliation: Gang Yu Abstract: Ozone therapy is an effective medical treatment for various diseases. A previous study has demonstrated its reno-protective effect in chronic kidney disease (CKD), but the mechanism involved is not completely known. This study produced the 5/6 nephrectomized CKD rat model and investigated whether the reno-protective effect of ozone therapy was achieved by its anti-inflammatory property through the modulation of the NLRP3 inflammasome. The results showed that ozone therapy at a low concentration improved renal function and ameliorated renal morphological injury in 5/6 nephrectomized rats. The expression of NLRP3, ASC, and caspase-1-p10 in the kidney of these rats was simultaneously lowered by ozone therapy. Moreover, renal inflammation caused by IL-1β was significantly alleviated by ozone therapy. The Pearson correlation analysis indicated that the protein level of IL-1β was positively correlated with renal injury scores. Taken together, these results indicated that ozone therapy might reduce sterile renal inflammation and slow down CKD progression through the modulation of the NLRP3 inflammasome in 5/6 nephrectomized rats. Article Published Date : Jan 31, 2017

Abstract Title: [The experience with the application of ozone therapy for the treatment of periodontitis in musicians-instrumentalists]. Abstract Source: Vopr Kurortol Fizioter Lech Fiz Kult. 2017 ;94(4):31-34. PMID: 29119958 Abstract Author(s): A V Kislitsyna, A G Volkov, N Zh Dikopova, S S Akhmedbaeva, A L Shishmareva Article Affiliation: A V Kislitsyna Abstract: : Playing various musical instruments is the cause of an additional load that affects the condition of dentition and of all organs and body systems at large. Each group of instruments is known to exert a specific impact on the health of the musicians including the undesirable influence on the state of thir oral cavity, such as a change of occlusion and irritation of oral mucosa. Taken together, these effects contribute to the development of periodontal disease, one of the most common dental disorders. AIM: The objective of the present study was to evaluate the effectiveness of ozone therapy conducted with the use of the generator producing ozone under effect of ultraviolet radiation for the treatment of periodontitis in musicians-instrumentalists. MATERIAL AND METHODS: The study included 42 musicians presenting with the diagnosis of periodontitis who were divided into two groups depending on the severity of the disease. Group 1 was comprised of the subjects with mild periodontitis while group 2 consisted of the musicians having periodontitis of moderate severity. All the participants in the study remained under observation over 6 months during which they were treated by ozone therapy. The results of the treatment were estimated immediately after the onset of therapy as well as within the next 3 and 6 months. The variance analysis with the use of Student's t-test was employed for the statistical treatment of the data obtained. RESULTS: The study has demonstrate that ozone therapy resulted in the reduction of inflammation and normalization of local blood circulation in the periodontal tissues; moreover, it extended and lengthened the periods of remission and stabilization of the process of recovery. CONCLUSION: The results of the study are of primary importance for the maintenance of oral cavity health in musicians-instrumentalists which is indispensable for the maintenance of their successful professional activity. Article Published Date : Dec 31, 2016

Abstract Title: Comparison between intra-articular ozone and placebo in the treatment of knee osteoarthritis: A randomized, double-blinded, placebo-controlled study. Abstract Source: PLoS One. 2017 ;12(7):e0179185. Epub 2017 Jul 24. PMID: 28738079 Abstract Author(s): Carlos César Lopes de Jesus, Fânia Cristina Dos Santos, Luciana Maria Oliveira Bueno de Jesus, Iara Monteiro, Maria Sonia Sousa Castro Sant'Ana, Virginia Fernandes Moça Trevisani Article Affiliation: Carlos César Lopes de Jesus Abstract: OBJECTIVE: The aim of the trial was to determine the effectiveness of oxygen-ozone injections on knee osteoarthritis concerning pain reduction, joint functional improvement, and quality of life. METHODS: In this randomized, double-blinded, placebo controlled clinical trial, 98 patients with symptomatic knee osteoarthritis (OA) were randomized into two groups receiving intra-articular 20μg/ml of ozone (OZ) or placebo (PBO) for 8 weeks. The efficacy outcomes for knee OA were the Visual Analogue Scale (VAS), Lequesne Index, Timed Up and Go Test (TUG Test), SF-36, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Geriatric Pain Measure (GPM). RESULTS: After 8 weeks of treatment, ozone was more effective than the placebo: VAS [mean difference (MD) = 2.16, p<0.003 (CI 95% 0.42-3.89)], GPM [MD = 18.94, p<0.004 (CI 95% 3.43-34.44)], LEQ [MD = 4.05, p<0.001 (CI 95% 1.10-7.00)], WOMAC (P) [median of diff = 9.999, p = 0.019 (CI 95% 0.000-15.000)], WOMAC (JS) [median of diff = 12.499, p<0.001 (CI 95% 0.000-12.500)], WOMAC (PF) = [median of diff = 11.760, p = 0.003 (CI 95% 4.409-19.119)], TUG (no statistical difference) and SF-36 (FC) [(MD = -25.82, p<0.001 (CI 95% 33.65-17.99)], SF-36 (PH) [MD = -40.82, p<0.001 (CI 95% -54.48-27.17)], SF-36 (GSH) [MD = -3.38, p<0.001 (CI 95% -4.83-1.93)], SF-36 (SA) [MD = 2.17, p<0.001 (CI 95% -19.67-8.24), SF-36 (EA) [MD = -35.37, p<0.001 (CI 95% -48.86-21.89)]. Adverse events occurred in 3 patients (2 in the placebo group and 1 in the ozone group) and included only puncture accidents. CONCLUSIONS: The study confirms the efficacy of ozone concerning pain relief, functional improvement, and quality of life in patients with knee osteoarthritis. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number Register ISRCTNR55861167. Article Published Date : Dec 31, 2016

Abstract Title: Protective effects of ellagic acid and ozone on rat ovaries with an ischemia/reperfusion injury. Abstract Source: J Obstet Gynaecol Res. 2016 Jan ;42(1):52-8. Epub 2015 Nov 10. PMID: 26555146 Abstract Author(s): Ilyas Sayar, Senol Bicer, Cebrail Gursul, Mehmet Gürbüzel, Kemal Peker, Arda Işik Article Affiliation: Ilyas Sayar Abstract: AIM: This study investigated the effects of the antioxidant agents, ozone (O) and ellagic acid (EA), on ischemia/reperfusion (I/R) injuries developed from an ovarian torsion-detorsion model. MATERIALS AND METHODS: Arteries in the left ovaries of rats were clamped for two hours to achieve torsion, and then the clamps were removed for a two-hour detorsion period. Thirty-five female Sprague-Dawley rats were randomly divided into five groups: control: administered only with anesthesia, rats were not subjected to torsion-detorsion; I/R: subjected to torsion and subsequent detorsion, without administering any treatment agent; and I/R + EA, I/R + O and I/R + O + EA: subjected to torsion and detorsion processes and administered with EA, O or EA + O at the 75th minute of torsion. The rats were then sacrificed under general anesthesia and the ovarian tissues were excised. The tissues were homogenized and levels of glutathione reductase, catalase, superoxide dismutase and malondialdehyde (MDA) were analyzed. Tissue damage was evaluated in terms of histopathological parameters, such as hemorrhage, congestion, edema and inflammation. RESULTS: Antioxidant enzyme activity and MDA levels in the ovary tissue increased in the I/R group and decreased in the O, EA and O + EA groups (P<0.05). Histopathological examination revealed that tissue damage in the O, EA and O + EA groups decreased in comparison with the I/R group (P<0.05). CONCLUSIONS: These biochemical and histopathological findings suggest that EA and O are effective against ovarian I/R injury. Article Published Date : Dec 31, 2015

Abstract Title: Ozone oxidative post-conditioning reduces oxidative protein damage in patients with disc hernia. Abstract Source: Neurol Res. 2012 Jan ;34(1):59-67. PMID: 22196863 Abstract Author(s): Olga Sonia León Fernández, Marelis Pantoja, María Teresa Díaz Soto, Jaqueline Dranguet, Martina García Insua, Renata Viebhan-Hánsler, Silvia Menéndez Cepero, José L Calunga Fernández Article Affiliation: University of Havana, Cuba. Abstract: UNLABELLED: Introduction/objectives: Although inflammation in disc hernia (DH) has been recognized and it is a well-known process mediated by loss of the cellular redox balance, only a few studies about the impact of chronic oxidative stress on this neurological disorder have been made. Ozone therapy has been widely used with clinical efficacy in DH. This work aimed at characterizing the systemic redox status of patients with low back pain and neck pain as well as studying if ozone oxidative post-conditioning modified the pathological oxidative stress and protected against oxidative protein damage and if there is any relationship between oxidative changes and pain in both DH. METHODS: Redox status of 33 patients with diagnosis of DH by computerized axial tomography, nuclear magnetic resonance, and clinical evaluations was studied. Ozone was administered by paravertebral way. After ozone treatment, plasmatic levels of antioxidant/pro-oxidant markers, pain, and life quality disability parameters were evaluated. RESULTS: One hundred percent of patients showed a severe oxidative stress. Major changes in superoxide dismutase activity, total hydroperoxides, advanced oxidation protein products, fructolysine content, and malondialdehyde were observed. After ozone oxidative post-conditioning, there was a re-establishment of patients' cellular redox balance as well as a decrease in pain in both DH. A relationship between indicators of oxidative protein damage and pain was demonstrated. CONCLUSIONS: Ozone therapy protected against oxidation of proteins and reduced the pain. Relationship between markers of oxidative protein damage, disability parameters, and pain suggests the role of oxidative stress in the pathological processes involved in DH. Article Published Date : Jan 01, 2012

Abstract Title: A metaanalysis of the effectiveness and safety of ozone treatments for herniated lumbar discs. Abstract Source: J Vasc Interv Radiol. 2010 Apr;21(4):534-48. Epub 2010 Feb 25. PMID: 20188591 Abstract Author(s): Jim Steppan, Thomas Meaders, Mario Muto, Kieran J Murphy Article Affiliation: ActiveO, Salt Lake City, Utah, USA. Abstract: PURPOSE: To determine statistically significant effects of oxygen/ozone treatment of herniated discs with respect to pain, function, and complication rate. MATERIALS AND METHODS: Random-effects metaanalyses were used to estimate outcomes for oxygen/ozone treatment of herniated discs. A literature search provided relevant studies that were weighted by a study quality score. Separate metaanalyses were performed for visual analog scale (VAS), Oswestry Disability Index (ODI), and modified MacNab outcome scales, as well as for complication rate. Institutional review board approval was not required for this retrospective analysis. RESULTS: Twelve studies were included in the metaanalyses. The inclusion/exclusion criteria, patient demographics, clinical trial rankings, treatment procedures, outcome measures, and complications are summarized. Metaanalyses were performed on the oxygen/ozone treatment results for almost 8,000 patients from multiple centers. The mean improvement was 3.9 for VAS and 25.7 for ODI. The likelihood of showing improvement on the modified MacNab scale was 79.7%. The means for the VAS and ODI outcomes are well above the minimum clinically important difference and the minimum (significant) detectable change. The likelihood of complications was 0.064%. CONCLUSIONS: Oxygen/ozone treatment of herniated discs is an effective and extremely safe procedure. The estimated improvement in pain and function is impressive in view of the broad inclusion criteria, which included patients ranging in age from 13 to 94 years with all types of disc herniations. Pain and function outcomes are similar to the outcomes for lumbar discs treated with surgical discectomy, but the complication rate is much lower (<0.1%) and the recovery time is significantly shorter. Article Published Date : Apr 01, 2010

Abstract Title: [Treatment of patients with acute and chronic suppurative middle ear diseases using ozone preparations]. Abstract Source: Vestn Otorinolaringol. 2009(3):34-5. PMID: 19692964 Abstract Author(s): E V Sin'kov Abstract: Methods of clinical application of gaseous ozone and ozonated solutions are described with special reference to the treatment of patients with acute and chronic suppurative middle ear diseases. Results of otoscopy, microbiological and cytological studies confirm therapeutic efficiency of the above techniques as accelerating recovery of patients with this pathology. It is recommended to include ozonotherapy as an additional method in the combined treatment of acute and chronic suppurative otitis media. Article Published Date : Jan 01, 2009

Abstract Title: Role of ozone therapy in the treatment of osteonecrosis of the jaws in multiple myeloma patients. Abstract Source: Haematologica. 2007 Sep;92(9):1289-90. PMID: 17768133 Abstract Author(s): Maria Teresa Petrucci, Cristiano Gallucci, Alessandro Agrillo, Maria Cristina Mustazza, Robin Foà Abstract: Current treatments for bisphosphonate-associated osteonecrosis of the jaw (ONJ) in multiple myeloma patients have limited efficacy. The biological effects of ozone indicate it may be therapeutic for ONJ. We, here, report the efficacy of a 15-day course of antibiotics, surgery and ozone therapy in 12 MM patients with ONJ. Article Published Date : Sep 01, 2007

Abstract Title: [Experience in medical ozone use for root canal treatment]. Abstract Source: Am J Perinatol. 2004 Aug;21(6):333-9. PMID: 16353031 Abstract Author(s): I V Bezrukova, N B Petrukhina, P A Voinov Abstract: The results of clinical and laboratory assessment of effectiveness of PSR-diagnosis are presented. The high efficacy of ozone therapy is revealed. The findings demonstrate the reduction of number in the micro-organisms in root canal: Actinobacillus actinomycetemcomitans from 31.25% to 10.21%; Bacteriodes forsythus from 68.75% to 15.50%; Treponema denticola from 37.5% to 11.4%; Porphyromonas gingivalis from 56.25% to 45%; Prevotella intermedia from 16% to 0%. Article Published Date : Aug 01, 2004

Abstract Title: [Use of gaseous ozone and ozonized solutions in the treatment of chronic suppurative otitis media]. Abstract Source: Vestn Otorinolaringol. 1998(6):11-2. PMID: 10081391 Abstract Author(s): Iu M Ovchinnikov, E V Sin'kov Abstract: Ozone as gas and ozonized solutions were employed as treatment modalities in 28 patients with acute and chronic inflammatory diseases of the middle ear. Basing on otoscopy, bacteriological tests of the discharge from the middle ear cavity, number of washings before disappearance of the purulent discharge the conclusion was made that cure of patients on ozone therapy occurs 3-5 days earlier than in ozone-untreated patients. Ozone therapy is a beneficial adjuvant in combined treatment of otitis media. Article Published Date : Jan 01, 1998